Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0071943 Myc-Max complex	IBA GO_REF:0000033	ACCEPT	Summary: Myc-Max complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0008284 positive regulation of cell population proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	Summary: DNA-binding transcription factor activity is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005654 nucleoplasm	IEA GO_REF:0000044	ACCEPT	Summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005694 chromosome	IEA GO_REF:0000044	ACCEPT	Summary: chromosome is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005730 nucleolus	IEA GO_REF:0000044	ACCEPT	Summary: nucleolus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: cytoplasm reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0005739 mitochondrion	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: mitochondrion likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0046983 protein dimerization activity	IEA GO_REF:0000002	ACCEPT	Summary: protein dimerization activity is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0005515 protein binding	IPI PMID:19269368 The TRIM-NHL protein TRIM32 activates microRNAs and prevents...	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0005515 protein binding	IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous...	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0005515 protein binding	IPI PMID:20434984 c-Myc regulates transcriptional pause release.	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0005515 protein binding	IPI PMID:20946988 A Myc network accounts for similarities between embryonic st...	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0005515 protein binding	IPI PMID:36124234 Integrative analysis reveals histone demethylase LSD1 promot...	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0005515 protein binding	IPI PMID:9764821 The C. elegans MDL-1 and MXL-1 proteins can functionally sub...	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0000082 G1/S transition of mitotic cell cycle	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: G1/S transition of mitotic cell cycle is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0000122 negative regulation of transcription by RNA polymerase II	ISO GO_REF:0000096	ACCEPT	Summary: negative regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0000122 negative regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	ACCEPT	Summary: negative regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0000165 MAPK cascade	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: MAPK cascade reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0000320 re-entry into mitotic cell cycle	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: re-entry into mitotic cell cycle reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0000785 chromatin	ISO GO_REF:0000119	ACCEPT	Summary: chromatin is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO GO_REF:0000119	ACCEPT	Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISO GO_REF:0000119	ACCEPT	Summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0001046 core promoter sequence-specific DNA binding	ISO GO_REF:0000119	ACCEPT	Summary: core promoter sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0001221 transcription coregulator binding	ISO GO_REF:0000119	ACCEPT	Summary: transcription coregulator binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific	ISO GO_REF:0000119	ACCEPT	Summary: DNA-binding transcription repressor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific	ISO GO_REF:0000119	ACCEPT	Summary: DNA-binding transcription activator activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0002082 regulation of oxidative phosphorylation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: regulation of oxidative phosphorylation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0003677 DNA binding	ISO GO_REF:0000096	ACCEPT	Summary: DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0003690 double-stranded DNA binding	ISO GO_REF:0000096	ACCEPT	Summary: double-stranded DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0003700 DNA-binding transcription factor activity	ISO GO_REF:0000096	ACCEPT	Summary: DNA-binding transcription factor activity is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005634 nucleus	ISO GO_REF:0000119	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005654 nucleoplasm	ISO GO_REF:0000119	ACCEPT	Summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005730 nucleolus	ISO GO_REF:0000119	ACCEPT	Summary: nucleolus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006006 glucose metabolic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: glucose metabolic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006338 chromatin remodeling	ISO GO_REF:0000119	ACCEPT	Summary: chromatin remodeling is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006351 DNA-templated transcription	ISO GO_REF:0000096	ACCEPT	Summary: DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006352 DNA-templated transcription initiation	ISO GO_REF:0000096	MODIFY	Summary: Myc is well supported as a nuclear Myc-Max DNA-binding transcription regulator, but the evidence does not establish the initiation-specific process captured by this term. Reason: Replace the initiation-specific annotation with a broader RNA polymerase II transcription-regulation term that matches the supported Myc transcription factor biology. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006355 regulation of DNA-templated transcription	ISO GO_REF:0000096	ACCEPT	Summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006366 transcription by RNA polymerase II	ISO GO_REF:0000096	ACCEPT	Summary: transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006848 pyruvate transport	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: pyruvate transport likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006865 amino acid transport	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: amino acid transport reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006879 intracellular iron ion homeostasis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: intracellular iron ion homeostasis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006974 DNA damage response	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: DNA damage response reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0007007 inner mitochondrial membrane organization	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: inner mitochondrial membrane organization likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0007346 regulation of mitotic cell cycle	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: regulation of mitotic cell cycle reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0008284 positive regulation of cell population proliferation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0010564 regulation of cell cycle process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of cell cycle process is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0010628 positive regulation of gene expression	ISO GO_REF:0000119	ACCEPT	Summary: positive regulation of gene expression is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0010629 negative regulation of gene expression	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: negative regulation of gene expression reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0010918 positive regulation of mitochondrial membrane potential	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of mitochondrial membrane potential reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0014911 positive regulation of smooth muscle cell migration	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of smooth muscle cell migration reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0016072 rRNA metabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Myc regulates ribosome biogenesis and nucleolar transcription programs, but rRNA metabolism is a downstream growth program rather than the core Myc-Max DNA-binding function. Reason: Retain as non-core because Myc can drive ribosome-biogenesis programs, while the primary molecular function remains sequence-specific transcriptional regulation through Myc-Max. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md Functional-annotation implication: this strengthens the mechanistic annotation of Myc as a regulator of ribosome biogenesis/nucleolar transcription programs, with clinically relevant downstream dependencies.
GO:0032204 regulation of telomere maintenance	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: regulation of telomere maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0032986 protein-DNA complex disassembly	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: protein-DNA complex disassembly reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0032991 protein-containing complex	ISO GO_REF:0000119	ACCEPT	Summary: protein-containing complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0042802 identical protein binding	ISO GO_REF:0000119	REMOVE	Summary: identical protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0043565 sequence-specific DNA binding	ISO GO_REF:0000096	ACCEPT	Summary: sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of gene expression via chromosomal CpG island methylation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0044877 protein-containing complex binding	ISO GO_REF:0000096	ACCEPT	Summary: protein-containing complex binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0044877 protein-containing complex binding	ISO GO_REF:0000119	ACCEPT	Summary: protein-containing complex binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0045656 negative regulation of monocyte differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of monocyte differentiation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0045787 positive regulation of cell cycle	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of cell cycle reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0045821 positive regulation of glycolytic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of glycolytic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0045893 positive regulation of DNA-templated transcription	ISO GO_REF:0000096	ACCEPT	Summary: positive regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0045893 positive regulation of DNA-templated transcription	ISO GO_REF:0000119	ACCEPT	Summary: positive regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000096	ACCEPT	Summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	ACCEPT	Summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0046325 negative regulation of D-glucose import across plasma membrane	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: negative regulation of D-glucose import across plasma membrane likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0046722 lactic acid secretion	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: lactic acid secretion likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0048146 positive regulation of fibroblast proliferation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0048146 positive regulation of fibroblast proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0048147 negative regulation of fibroblast proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: negative regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0048661 positive regulation of smooth muscle cell proliferation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of smooth muscle cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0050679 positive regulation of epithelial cell proliferation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of epithelial cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0051276 chromosome organization	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: chromosome organization reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0051782 negative regulation of cell division	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of cell division likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0060252 positive regulation of glial cell proliferation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of glial cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0060633 negative regulation of transcription initiation by RNA polymerase II	ISO GO_REF:0000119	MODIFY	Summary: Myc can repress RNA polymerase II transcription in some contexts, but the cited evidence does not justify the more specific transcription-initiation mechanism. Reason: Replace the initiation-specific repression annotation with the broader supported negative regulation of RNA polymerase II transcription. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. file:mouse/Myc/Myc-deep-research-falcon.md MBIIIa–MIZ-1-associated repression in some contexts.
GO:0070371 ERK1 and ERK2 cascade	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ERK1 and ERK2 cascade reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0070888 E-box binding	ISO GO_REF:0000119	ACCEPT	Summary: E-box binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0071456 cellular response to hypoxia	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cellular response to hypoxia reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0071466 cellular response to xenobiotic stimulus	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: cellular response to xenobiotic stimulus likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0140297 DNA-binding transcription factor binding	ISO GO_REF:0000119	ACCEPT	Summary: DNA-binding transcription factor binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:1901857 positive regulation of cellular respiration	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of cellular respiration reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:1902255 positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:1902895 positive regulation of miRNA transcription	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of miRNA transcription reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:1903862 positive regulation of oxidative phosphorylation	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of oxidative phosphorylation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:1904036 negative regulation of epithelial cell apoptotic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: negative regulation of epithelial cell apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:1905761 SCF ubiquitin ligase complex binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: SCF ubiquitin ligase complex binding reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:2001171 positive regulation of ATP biosynthetic process	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of ATP biosynthetic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0071943 Myc-Max complex	ISO GO_REF:0000119	ACCEPT	Summary: Myc-Max complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0090571 RNA polymerase II transcription repressor complex	ISO GO_REF:0000119	ACCEPT	Summary: RNA polymerase II transcription repressor complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0005634 nucleus	IDA PMID:20434984 c-Myc regulates transcriptional pause release.	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0045893 positive regulation of DNA-templated transcription	IDA PMID:20434984 c-Myc regulates transcriptional pause release.	MODIFY	Summary: PMID:20434984 supports Myc regulation of Pol II promoter-proximal pause release rather than a broad transcription-positive-regulation assertion. Reason: Use the more specific transcription-elongation term because the paper reports Myc acting mainly at Pol II pause release instead of recruitment. Proposed replacements: positive regulation of transcription elongation by RNA polymerase II Supporting Evidence: PMID:20434984 c-Myc regulates transcriptional pause release. PMID:20434984 c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes.
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: proteasome-mediated ubiquitin-dependent protein catabolic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0016072 rRNA metabolic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Myc regulates ribosome biogenesis and nucleolar transcription programs, but rRNA metabolism is a downstream growth program rather than the core Myc-Max DNA-binding function. Reason: Retain as non-core because Myc can drive ribosome-biogenesis programs, while the primary molecular function remains sequence-specific transcriptional regulation through Myc-Max. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md Functional-annotation implication: this strengthens the mechanistic annotation of Myc as a regulator of ribosome biogenesis/nucleolar transcription programs, with clinically relevant downstream dependencies.
GO:0032206 positive regulation of telomere maintenance	IMP PMID:9637678 Myc activates telomerase.	KEEP AS NON CORE	Summary: positive regulation of telomere maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:9637678 Myc activates telomerase.	ACCEPT	Summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISS GO_REF:0000024	ACCEPT	Summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0001866 NK T cell proliferation	IMP PMID:19423665 Intrathymic proliferation wave essential for Valpha14+ natur...	KEEP AS NON CORE	Summary: NK T cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0000082 G1/S transition of mitotic cell cycle	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: G1/S transition of mitotic cell cycle is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0005515 protein binding	IPI PMID:23277542 Domain-specific c-Myc ubiquitylation controls c-Myc transcri...	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0006355 regulation of DNA-templated transcription	IDA PMID:31005419 TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cell...	ACCEPT	Summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:1904672 regulation of somatic stem cell population maintenance	IDA PMID:31005419 TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cell...	KEEP AS NON CORE	Summary: regulation of somatic stem cell population maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-9634437	ACCEPT	Summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0060261 positive regulation of transcription initiation by RNA polymerase II	IDA PMID:26691508 Physical Interactions and Functional Coordination between th...	MODIFY	Summary: PMID:26691508 supports Myc-dependent activation of Set1/Mll core subunit expression during reprogramming, but not the specific mechanism of RNA polymerase II transcription initiation. Reason: Replace the initiation-specific term with a broader transcriptional activation term; independent Myc evidence also emphasizes Pol II pause release rather than recruitment/initiation at target genes. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:26691508 Thus, Myc directly promotes the expression of two core subunits of the H3K4 methyltransferase complexes with a potential functional implication. PMID:20434984 c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA PMID:18625840 Nucleophosmin and its AML-associated mutant regulate c-Myc t...	ACCEPT	Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005515 protein binding	IPI PMID:26523946 Combined Overexpression of JARID2, PRDM14, ESRRB, and SALL4A...	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0005634 nucleus	IDA PMID:18625840 Nucleophosmin and its AML-associated mutant regulate c-Myc t...	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005634 nucleus	IDA PMID:22328504 TRIM6 interacts with Myc and maintains the pluripotency of m...	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:22328504 TRIM6 interacts with Myc and maintains the pluripotency of m...	KEEP AS NON CORE	Summary: TRIM6 ubiquitin-ligase binding is a regulatory ES-cell interaction for Myc, not a core Myc function. Reason: The paper supports TRIM6 interaction that attenuates Myc transcriptional activity in embryonic stem cells; this regulatory interaction should not be treated as core Myc-Max DNA-binding transcription factor activity. Supporting Evidence: PMID:22328504 TRIM6, one of the TRIM family ubiquitin ligases, was selectively expressed in ES cells and interacted with Myc PMID:22328504 TRIM6 regulates the transcriptional activity of Myc during the maintenance of ES cell pluripotency
GO:0048471 perinuclear region of cytoplasm	IDA PMID:22328504 TRIM6 interacts with Myc and maintains the pluripotency of m...	MARK AS OVER ANNOTATED	Summary: perinuclear region of cytoplasm likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0035457 cellular response to interferon-alpha	IDA PMID:24795346 Posttranscriptional regulation of c-Myc expression in adult ...	MARK AS OVER ANNOTATED	Summary: cellular response to interferon-alpha likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0000791 euchromatin	IDA PMID:22723415 Wnt/β-catenin signaling regulates telomerase in stem cells a...	ACCEPT	Summary: euchromatin is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0042981 regulation of apoptotic process	IMP PMID:23277542 Domain-specific c-Myc ubiquitylation controls c-Myc transcri...	KEEP AS NON CORE	Summary: regulation of apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:23277542 Domain-specific c-Myc ubiquitylation controls c-Myc transcri...	ACCEPT	Summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005634 nucleus	IDA PMID:23770341 Overexpression of c-myc in hepatocytes promotes activation o...	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0010468 regulation of gene expression	ISO PMID:21447833 TIP110/p110nrb/SART3/p110 regulation of hematopoiesis throug...	ACCEPT	Summary: regulation of gene expression is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage	IDA PMID:14517295 c-Myc augments gamma irradiation-induced apoptosis by suppre...	KEEP AS NON CORE	Summary: intrinsic apoptotic signaling pathway in response to DNA damage reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage	IMP PMID:14517295 c-Myc augments gamma irradiation-induced apoptosis by suppre...	KEEP AS NON CORE	Summary: intrinsic apoptotic signaling pathway in response to DNA damage reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:2001235 positive regulation of apoptotic signaling pathway	IDA PMID:14517295 c-Myc augments gamma irradiation-induced apoptosis by suppre...	KEEP AS NON CORE	Summary: positive regulation of apoptotic signaling pathway reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:2001235 positive regulation of apoptotic signaling pathway	IMP PMID:14517295 c-Myc augments gamma irradiation-induced apoptosis by suppre...	KEEP AS NON CORE	Summary: positive regulation of apoptotic signaling pathway reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0035914 skeletal muscle cell differentiation	IMP PMID:22147266 Analysis of early C2C12 myogenesis identifies stably and dif...	KEEP AS NON CORE	Summary: skeletal muscle cell differentiation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0000987 cis-regulatory region sequence-specific DNA binding	IDA PMID:15511642 A role for nucleoprotein Zap3 in the reduction of telomerase...	ACCEPT	Summary: cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005515 protein binding	IPI PMID:18438430 Pim kinase-dependent inhibition of c-Myc degradation.	REMOVE	Summary: protein binding is not a useful retained annotation for Myc in this review. Reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.
GO:0006974 DNA damage response	IDA PMID:20212154 p38 MAPK/MK2-mediated induction of miR-34c following DNA dam...	KEEP AS NON CORE	Summary: DNA damage response reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0000165 MAPK cascade	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: MAPK cascade reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006338 chromatin remodeling	ISS GO_REF:0000024	ACCEPT	Summary: chromatin remodeling is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0006879 intracellular iron ion homeostasis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: intracellular iron ion homeostasis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006974 DNA damage response	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: DNA damage response reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0032204 regulation of telomere maintenance	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: regulation of telomere maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0044877 protein-containing complex binding	ISS GO_REF:0000024	ACCEPT	Summary: protein-containing complex binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
GO:0045656 negative regulation of monocyte differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: negative regulation of monocyte differentiation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0048146 positive regulation of fibroblast proliferation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0050679 positive regulation of epithelial cell proliferation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: positive regulation of epithelial cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0051276 chromosome organization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: chromosome organization reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0051782 negative regulation of cell division	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: negative regulation of cell division likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0070888 E-box binding	ISS GO_REF:0000024	ACCEPT	Summary: E-box binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005634 nucleus	IDA PMID:19796622 Uncovering early response of gene regulatory networks in ESC...	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0009314 response to radiation	IMP PMID:14517295 c-Myc augments gamma irradiation-induced apoptosis by suppre...	MARK AS OVER ANNOTATED	Summary: response to radiation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0016055 Wnt signaling pathway	IDA PMID:19056892 A functional link between Wnt signaling and SKP2-independent...	KEEP AS NON CORE	Summary: Wnt signaling pathway reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0005654 nucleoplasm	ISS GO_REF:0000024	ACCEPT	Summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005730 nucleolus	ISS GO_REF:0000024	ACCEPT	Summary: nucleolus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0045893 positive regulation of DNA-templated transcription	ISS GO_REF:0000024	ACCEPT	Summary: positive regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0090096 positive regulation of metanephric cap mesenchymal cell proliferation	IMP PMID:19161241 C-myc as a modulator of renal stem/progenitor cell populatio...	MARK AS OVER ANNOTATED	Summary: positive regulation of metanephric cap mesenchymal cell proliferation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0001658 branching involved in ureteric bud morphogenesis	IMP PMID:19161241 C-myc as a modulator of renal stem/progenitor cell populatio...	KEEP AS NON CORE	Summary: branching involved in ureteric bud morphogenesis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0002053 positive regulation of mesenchymal cell proliferation	IMP PMID:19161241 C-myc as a modulator of renal stem/progenitor cell populatio...	KEEP AS NON CORE	Summary: positive regulation of mesenchymal cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0000122 negative regulation of transcription by RNA polymerase II	IDA PMID:12196193 c-Myc represses the murine Nramp1 promoter.	ACCEPT	Summary: negative regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0030424 axon	IDA PMID:10482234 Requirement for the homeobox gene Hb9 in the consolidation o...	MARK AS OVER ANNOTATED	Summary: axon likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0002904 positive regulation of B cell apoptotic process	IGI PMID:11604501 Bax loss impairs Myc-induced apoptosis and circumvents the s...	KEEP AS NON CORE	Summary: positive regulation of B cell apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:12235125 Beta-catenin-induced melanoma growth requires the downstream...	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:14517295 c-Myc augments gamma irradiation-induced apoptosis by suppre...	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0008284 positive regulation of cell population proliferation	IGI PMID:17596282 Unique mechanisms of growth regulation and tumor suppression...	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0043085 positive regulation of catalytic activity	IMP PMID:17382917 c-Myc is essential for urokinase plasminogen activator expre...	KEEP AS NON CORE	Summary: positive regulation of catalytic activity reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:17382917 c-Myc is essential for urokinase plasminogen activator expre...	ACCEPT	Summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0010468 regulation of gene expression	IDA PMID:11438662 Apoptosis triggered by Myc-induced suppression of Bcl-X(L) o...	ACCEPT	Summary: regulation of gene expression is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005634 nucleus	IDA PMID:17631878 Epidermal hyperplasia and expansion of the interfollicular s...	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0001783 B cell apoptotic process	IMP PMID:12970677 c-Myc-deficient B lymphocytes are resistant to spontaneous a...	KEEP AS NON CORE	Summary: B cell apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0016485 protein processing	IMP PMID:12970677 c-Myc-deficient B lymphocytes are resistant to spontaneous a...	MARK AS OVER ANNOTATED	Summary: protein processing likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0043279 response to alkaloid	IMP PMID:12970677 c-Myc-deficient B lymphocytes are resistant to spontaneous a...	MARK AS OVER ANNOTATED	Summary: response to alkaloid likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0042474 middle ear morphogenesis	IMP PMID:17523175 Neural crest cell deficiency of c-myc causes skull and heari...	MARK AS OVER ANNOTATED	Summary: middle ear morphogenesis likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0043473 pigmentation	IMP PMID:17523175 Neural crest cell deficiency of c-myc causes skull and heari...	MARK AS OVER ANNOTATED	Summary: pigmentation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0048705 skeletal system morphogenesis	IMP PMID:17523175 Neural crest cell deficiency of c-myc causes skull and heari...	KEEP AS NON CORE	Summary: skeletal system morphogenesis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0050910 detection of mechanical stimulus involved in sensory perception of sound	IMP PMID:17523175 Neural crest cell deficiency of c-myc causes skull and heari...	MARK AS OVER ANNOTATED	Summary: detection of mechanical stimulus involved in sensory perception of sound likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0006355 regulation of DNA-templated transcription	IGI PMID:8521822 Mad3 and Mad4: novel Max-interacting transcriptional repress...	ACCEPT	Summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0016604 nuclear body	IDA PMID:15735755 PML interacts with Myc, and Myc target gene expression is al...	KEEP AS NON CORE	Summary: nuclear body reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0005634 nucleus	ISO PMID:15994933 Identification of a novel c-Myc protein interactor, JPO2, wi...	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0008284 positive regulation of cell population proliferation	ISO PMID:15994933 Identification of a novel c-Myc protein interactor, JPO2, wi...	KEEP AS NON CORE	Summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function. Reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity. Supporting Evidence: file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
GO:0003677 DNA binding	IDA PMID:12970171 Deletion of Mnt leads to disrupted cell cycle control and tu...	ACCEPT	Summary: DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0005819 spindle	IDA PMID:15509711 Serine-threonine kinases and transcription factors active in...	MARK AS OVER ANNOTATED	Summary: spindle likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0009314 response to radiation	IDA PMID:14517295 c-Myc augments gamma irradiation-induced apoptosis by suppre...	MARK AS OVER ANNOTATED	Summary: response to radiation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program. Reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0003677 DNA binding	IDA PMID:14560010 Miz1 is required for early embryonic development during gast...	ACCEPT	Summary: DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
GO:0042981 regulation of apoptotic process	IDA PMID:12235125 Beta-catenin-induced melanoma growth requires the downstream...	KEEP AS NON CORE	Summary: regulation of apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity. Reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
GO:0005634 nucleus	IDA PMID:11872843 Colorectal cancer in mice genetically deficient in the mucin...	ACCEPT	Summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes. Reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization. Supporting Evidence: file:mouse/Myc/Myc-deep-research-bioreason.md Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression. file:mouse/Myc/Myc-uniprot.txt Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. file:mouse/Myc/Myc-deep-research-falcon.md c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.

Core Functions

Myc functions as a DNA-binding RNA polymerase II transcription factor by heterodimerizing with Max and binding E-box motifs at promoters and enhancers.

Molecular Function:

DNA-binding transcription factor activity, RNA polymerase II-specific

Directly Involved In:

positive regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II regulation of transcription by RNA polymerase II

Cellular Locations:

nucleus nucleoplasm chromatin

In Complex:

Myc-Max complex

Supporting Evidence:

file:mouse/Myc/Myc-uniprot.txt
Transcription factor ... specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
file:mouse/Myc/Myc-deep-research-bioreason.md
Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
file:mouse/Myc/Myc-deep-research-falcon.md
c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.

Myc enables Myc-Max complex formation through protein dimerization, which is required for efficient DNA binding and transcriptional regulation.

Molecular Function:

protein dimerization activity

Cellular Locations:

nucleus nucleoplasm

In Complex:

Myc-Max complex

Supporting Evidence:

file:mouse/Myc/Myc-uniprot.txt
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX.
file:mouse/Myc/Myc-deep-research-falcon.md
c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

PMID:10482234

Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity.

PMID:11438662

Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis.

PMID:11604501

Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis.

PMID:11872843

Colorectal cancer in mice genetically deficient in the mucin Muc2.

PMID:12196193

c-Myc represses the murine Nramp1 promoter.

PMID:12235125

Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.

PMID:12970171

Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis.

PMID:12970677

c-Myc-deficient B lymphocytes are resistant to spontaneous and induced cell death.

PMID:14517295

c-Myc augments gamma irradiation-induced apoptosis by suppressing Bcl-XL.

PMID:14560010

Miz1 is required for early embryonic development during gastrulation.

PMID:15509711

Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells.

PMID:15511642

A role for nucleoprotein Zap3 in the reduction of telomerase activity during embryonic stem cell differentiation.

PMID:15735755

PML interacts with Myc, and Myc target gene expression is altered in PML-null fibroblasts.

PMID:15994933

Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells.

PMID:17382917

c-Myc is essential for urokinase plasminogen activator expression on hypoxia-induced vascular smooth muscle cells.

PMID:17523175

Neural crest cell deficiency of c-myc causes skull and hearing defects.

PMID:17596282

Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.

PMID:17631878

Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1.

PMID:18438430

Pim kinase-dependent inhibition of c-Myc degradation.

PMID:18625840

Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7 gamma.

PMID:19056892

A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.

PMID:19161241

C-myc as a modulator of renal stem/progenitor cell population.

PMID:19269368

The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors.

PMID:19423665

Intrathymic proliferation wave essential for Valpha14+ natural killer T cell development depends on c-Myc.

PMID:19796622

Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.

PMID:20211142

An atlas of combinatorial transcriptional regulation in mouse and man.

PMID:20212154

p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication.

PMID:20434984

c-Myc regulates transcriptional pause release.

PMID:20946988

A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs.

PMID:21447833

TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC.

PMID:22147266

Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.

PMID:22328504

TRIM6 interacts with Myc and maintains the pluripotency of mouse embryonic stem cells.

PMID:22723415

Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells.

PMID:23277542

Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity.

PMID:23770341

Overexpression of c-myc in hepatocytes promotes activation of hepatic stellate cells and facilitates the onset of liver fibrosis.

PMID:24795346

Posttranscriptional regulation of c-Myc expression in adult murine HSCs during homeostasis and interferon-α-induced stress response.

PMID:26523946

Combined Overexpression of JARID2, PRDM14, ESRRB, and SALL4A Dramatically Improves Efficiency and Kinetics of Reprogramming to Induced Pluripotent Stem Cells.

PMID:26691508

Physical Interactions and Functional Coordination between the Core Subunits of Set1/Mll Complexes and the Reprogramming Factors.

PMID:31005419

TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network.

PMID:36124234

Integrative analysis reveals histone demethylase LSD1 promotes RNA polymerase II pausing.

PMID:8521822

Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation.

PMID:9637678

Myc activates telomerase.

PMID:9764821

The C. elegans MDL-1 and MXL-1 proteins can functionally substitute for vertebrate MAD and MAX.

Reactome:R-MMU-9634437

Myc gene expression is enhanced by E2f1, phospho-Stat3, and Cebpb and repressed by Cebpa

file:mouse/Myc/Myc-uniprot.txt

UniProt record for mouse Myc

Myc is a transcription factor that recognizes E-box-like core sequences and requires Max dimerization for efficient DNA binding.

"Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX."

file:mouse/Myc/Myc-deep-research-bioreason.md

Bioreason deep research report on mouse Myc

Myc is a nuclear bHLH-LZ transcription factor whose core activity is Myc-Max DNA binding and transcriptional regulation.

file:mouse/Myc/Myc-deep-research-falcon.md

Falcon deep research report on mouse Myc

Myc is a nuclear bHLH-LZ transcription factor whose core activity is Myc-Max DNA binding and transcriptional regulation.

"c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration."

Suggested Experiments

Experiment: Use Myc and Max perturbation with CUT&RUN/ChIP-seq plus nascent RNA profiling in mouse cells to separate direct Myc-Max target transcription from secondary metabolic and cell-cycle effects.

Experiment: Compare wild-type Myc with dimerization-defective and DNA-binding-defective mutants in mouse cells to test which GO process annotations require direct Myc-Max DNA binding.

📚 Additional Documentation

Deep Research Bioreason

(Myc-deep-research-bioreason.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:29 AM

Organism: Mus musculus

Sequence:

MDFLWALETPQTATTMPLNVNFTNRNYDLDYDSVQPYFICDEEENFYHQQQQSELQPPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVATSFSPREDDDGGGGNFSTADQLEMMTELLGGDMVNQSFICDPDDETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSTSLSPARGHSVCSTSSLYLQDLTAAASECIDPSVVFPYPLNDSSSPKSCTSSDSTAFSPSSDSLLSSESSPRASPEPLVLHEETPPTTSSDSEEEQEDEEEIDVVSVEKRQTPAKRSESGSSPSRGHSKPPHSPLVLKRCHVSTHQHNYAAPPSTRKDYPAAKRAKLDSGRVLKQISNNRKCSSPRSSDTEENDKRRTHNVLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILSIQADEHKLTSEKDLLRKRREQLKHKLEQLRNSGA

Thinking Trace

I begin with the InterPro architecture. Two broad family signatures, IPR002418 (Transcription regulator Myc family, residues 16–452) and IPR050433 (Myc family transcription factors, residues 22–452), cover nearly the entire protein, establishing membership in the Myc lineage of transcriptional regulators. Within this scaffold, IPR012682 (Transcription regulator Myc, N-terminal domain, residues 17–360) defines the characteristic N-terminal module that mediates transcriptional activation through cofactor recruitment and short linear motifs. The C-terminal half is organized around a DNA-interacting core: IPR036638 (Helix-loop-helix DNA-binding domain superfamily, residues 361–454) and IPR011598 (Myc-type basic helix-loop-helix domain, residues 369–427) together specify a basic region that contacts E-box DNA followed by an HLH dimerization module. Immediately downstream, IPR003327 (Leucine zipper, Myc, residues 423–452) provides a coiled-coil zipper that stabilizes higher-order dimers and enhances sequence-specific DNA binding and promoter selectivity. The ordered layout—N-terminal activation domain leading into a C-terminal bHLH followed by a leucine zipper—creates a modular transcription factor that binds E-box motifs and recruits transcriptional machinery.

This domain architecture dictates molecular function. The bHLH and leucine-zipper ensemble (IPR036638, IPR011598, IPR003327) causes sequence-specific DNA recognition and obligate dimerization, supporting DNA-binding transcription factor activity with RNA polymerase II specificity. The expansive N-terminal region (IPR012682) supplies interaction surfaces that assemble coactivators and chromatin regulators, reinforcing the assignment of RNA polymerase II transcription factor activity and sequence-specific DNA binding. Thus, the mechanistic core is a bHLH-zipper-driven dimer that binds regulatory DNA and modulates transcription initiation and elongation.

From function to process, Myc-family N-terminal activation modules typically stimulate gene expression programs that drive growth and biosynthesis. By recruiting coactivators and chromatin-modifying complexes via IPR012682, this factor positively regulates transcription by RNA polymerase II and broadly coordinates transcriptional outputs that promote cell proliferation and metabolic remodeling. Consequently, it participates in positive regulation of transcription and contributes to the regulation of cell population proliferation.

Cellular location follows from the need to access chromatin and RNA polymerase II. The presence of DNA-binding and activation modules necessitates a nuclear site of action, consistent with nuclear accumulation where promoter and enhancer targets reside. Therefore, the cellular component is the nucleus.

Integrating these observations yields a mechanistic hypothesis: the protein forms bHLH-zipper dimers that bind E-box elements at target promoters and enhancers, then uses its N-terminal activation domain to recruit histone acetyltransferases and chromatin remodelers, thereby enhancing RNA polymerase II transcription and driving proliferative gene programs. Likely partners include other bHLH-zipper transcription factors and co-regulators that stabilize dimers and bridge to the transcriptional apparatus, such as TRRAP-containing acetyltransferase assemblies and Mediator-associated components that together potentiate growth-associated transcriptional networks.

Functional Summary

A nuclear transcriptional regulator that uses a C-terminal basic helix-loop-helix and leucine zipper module to dimerize and bind E-box DNA elements, while an extensive N-terminal activation region recruits coactivators and chromatin-modifying complexes. Through this architecture, it stimulates RNA polymerase II–dependent transcriptional programs that promote growth and proliferation by coordinating expression of biosynthetic and cell-cycle–associated genes within the nucleus.

UniProt Summary

Is a transcriptional activator.

InterPro Domains

Transcription regulator Myc (IPR002418, family) — residues 16-452
Transcription regulator Myc, N-terminal (IPR012682, domain) — residues 17-360
Myc family transcription factors (IPR050433, family) — residues 22-452
Helix-loop-helix DNA-binding domain superfamily (IPR036638, homologous_superfamily) — residues 361-454
Myc-type, basic helix-loop-helix (bHLH) domain (IPR011598, domain) — residues 369-427
Leucine zipper, Myc (IPR003327, domain) — residues 423-452

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), heterocyclic compound binding (GO:1901363), organic cyclic compound binding (GO:0097159), protein binding (GO:0005515), nucleic acid binding (GO:0003676), enzyme binding (GO:0019899), ubiquitin-like protein ligase binding (GO:0044389), transcription regulatory region nucleic acid binding (GO:0001067), DNA binding (GO:0003677), ubiquitin protein ligase binding (GO:0031625), double-stranded DNA binding (GO:0003690), sequence-specific DNA binding (GO:0043565), transcription cis-regulatory region binding (GO:0000976), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)

Biological Process: biological_process (GO:0008150), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), signaling (GO:0023052), multicellular organismal process (GO:0032501), biological regulation (GO:0065007), response to stimulus (GO:0050896), developmental process (GO:0032502), cellular process (GO:0009987), pigmentation (GO:0043473), metabolic process (GO:0008152), immune system process (GO:0002376), negative regulation of biological process (GO:0048519), response to external stimulus (GO:0009605), anatomical structure development (GO:0048856), anatomical structure morphogenesis (GO:0009653), response to chemical (GO:0042221), leukocyte activation (GO:0045321), cell population proliferation (GO:0008283), positive regulation of multicellular organismal process (GO:0051240), nitrogen compound metabolic process (GO:0006807), regulation of multicellular organismal process (GO:0051239), negative regulation of metabolic process (GO:0009892), cell-cell signaling (GO:0007267), regulation of developmental process (GO:0050793), positive regulation of cellular process (GO:0048522), cell death (GO:0008219), regulation of cellular process (GO:0050794), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), regulation of signaling (GO:0023051), negative regulation of cellular process (GO:0048523), signal transduction (GO:0007165), cellular developmental process (GO:0048869), response to abiotic stimulus (GO:0009628), positive regulation of signaling (GO:0023056), cell activation (GO:0001775), multicellular organism development (GO:0007275), biosynthetic process (GO:0009058), positive regulation of response to stimulus (GO:0048584), regulation of metabolic process (GO:0019222), organic substance metabolic process (GO:0071704), system process (GO:0003008), cellular metabolic process (GO:0044237), positive regulation of metabolic process (GO:0009893), regulation of molecular function (GO:0065009), response to stress (GO:0006950), detection of stimulus (GO:0051606), morphogenesis of a branching structure (GO:0001763), positive regulation of developmental process (GO:0051094), cell communication (GO:0007154), primary metabolic process (GO:0044238), detection of external stimulus (GO:0009581), positive regulation of cell death (GO:0010942), tissue morphogenesis (GO:0048729), programmed cell death (GO:0012501), response to radiation (GO:0009314), response to xenobiotic stimulus (GO:0009410), cell differentiation (GO:0030154), system development (GO:0048731), animal organ development (GO:0048513), regulation of signal transduction (GO:0009966), regulation of macromolecule metabolic process (GO:0060255), detection of abiotic stimulus (GO:0009582), cellular aromatic compound metabolic process (GO:0006725), regulation of binding (GO:0051098), lymphocyte activation (GO:0046649), tube development (GO:0035295), animal organ morphogenesis (GO:0009887), organic cyclic compound metabolic process (GO:1901360), leukocyte proliferation (GO:0070661), negative regulation of macromolecule metabolic process (GO:0010605), apoptotic signaling pathway (GO:0097190), nephron morphogenesis (GO:0072028), regulation of nitrogen compound metabolic process (GO:0051171), cell surface receptor signaling pathway (GO:0007166), embryo development (GO:0009790), nephron development (GO:0072006), positive regulation of cell population proliferation (GO:0008284), positive regulation of nitrogen compound metabolic process (GO:0051173), tube morphogenesis (GO:0035239), positive regulation of signal transduction (GO:0009967), regulation of catalytic activity (GO:0050790), negative regulation of nitrogen compound metabolic process (GO:0051172), positive regulation of molecular function (GO:0044093), organic substance biosynthetic process (GO:1901576), organonitrogen compound metabolic process (GO:1901564), intracellular signal transduction (GO:0035556), positive regulation of macromolecule metabolic process (GO:0010604), cell-cell signaling by wnt (GO:0198738), heterocycle metabolic process (GO:0046483), negative regulation of molecular function (GO:0044092), protein metabolic process (GO:0019538), cell surface receptor signaling pathway involved in cell-cell signaling (GO:1905114), morphogenesis of a branching epithelium (GO:0061138), cellular biosynthetic process (GO:0044249), cellular nitrogen compound metabolic process (GO:0034641), negative regulation of cellular metabolic process (GO:0031324), response to organic substance (GO:0010033), macromolecule metabolic process (GO:0043170), detection of stimulus involved in sensory perception (GO:0050906), positive regulation of biosynthetic process (GO:0009891), muscle structure development (GO:0061061), embryonic morphogenesis (GO:0048598), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), tissue development (GO:0009888), response to nitrogen compound (GO:1901698), nucleobase-containing compound metabolic process (GO:0006139), positive regulation of cellular metabolic process (GO:0031325), regulation of cell communication (GO:0010646), cellular response to chemical stimulus (GO:0070887), cellular response to stress (GO:0033554), epithelial cell proliferation (GO:0050673), regulation of biosynthetic process (GO:0009889), regulation of cellular metabolic process (GO:0031323), negative regulation of biosynthetic process (GO:0009890), positive regulation of cell communication (GO:0010647), nervous system process (GO:0050877), regulation of primary metabolic process (GO:0080090), response to mechanical stimulus (GO:0009612), regulation of kidney development (GO:0090183), regulation of stem cell population maintenance (GO:2000036), macromolecule biosynthetic process (GO:0009059), organic cyclic compound biosynthetic process (GO:1901362), epithelial tube morphogenesis (GO:0060562), skeletal system morphogenesis (GO:0048705), nephron epithelium development (GO:0072009), regulation of macromolecule biosynthetic process (GO:0010556), negative regulation of binding (GO:0051100), regulation of protein metabolic process (GO:0051246), regulation of programmed cell death (GO:0043067), Wnt signaling pathway (GO:0016055), nephron epithelium morphogenesis (GO:0072088), sensory organ morphogenesis (GO:0090596), positive regulation of mesenchymal cell proliferation (GO:0002053), morphogenesis of an epithelium (GO:0002009), detection of mechanical stimulus (GO:0050982), regulation of protein binding (GO:0043393), regulation of epithelial cell proliferation (GO:0050678), kidney morphogenesis (GO:0060993), regulation of gene expression (GO:0010468), detection of mechanical stimulus involved in sensory perception of sound (GO:0050910), branching morphogenesis of an epithelial tube (GO:0048754), detection of mechanical stimulus involved in sensory perception (GO:0050974), embryonic organ development (GO:0048568), renal tubule development (GO:0061326), skeletal system development (GO:0001501), muscle cell differentiation (GO:0042692), nucleic acid metabolic process (GO:0090304), heterocycle biosynthetic process (GO:0018130), intrinsic apoptotic signaling pathway (GO:0097193), mesonephric tubule development (GO:0072164), negative regulation of cellular biosynthetic process (GO:0031327), regulation of RNA metabolic process (GO:0051252), positive regulation of catalytic activity (GO:0043085), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), gene expression (GO:0010467), renal system development (GO:0072001), response to cytokine (GO:0034097), cellular response to xenobiotic stimulus (GO:0071466), lymphocyte proliferation (GO:0046651), proteolysis (GO:0006508), regulation of DNA metabolic process (GO:0051052), cellular response to DNA damage stimulus (GO:0006974), cellular response to organic substance (GO:0071310), positive regulation of DNA metabolic process (GO:0051054), embryonic organ morphogenesis (GO:0048562), regulation of hydrolase activity (GO:0051336), positive regulation of programmed cell death (GO:0043068), aromatic compound biosynthetic process (GO:0019438), sensory organ development (GO:0007423), positive regulation of apoptotic signaling pathway (GO:2001235), protein maturation (GO:0051604), middle ear morphogenesis (GO:0042474), regulation of mesenchymal cell proliferation (GO:0010464), regulation of apoptotic signaling pathway (GO:2001233), mononuclear cell proliferation (GO:0032943), sensory perception (GO:0007600), skeletal muscle cell differentiation (GO:0035914), positive regulation of epithelial cell proliferation (GO:0050679), nucleobase-containing compound biosynthetic process (GO:0034654), positive regulation of macromolecule biosynthetic process (GO:0010557), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), positive regulation of RNA metabolic process (GO:0051254), response to organonitrogen compound (GO:0010243), muscle tissue development (GO:0060537), apoptotic process (GO:0006915), regulation of cellular biosynthetic process (GO:0031326), positive regulation of protein metabolic process (GO:0051247), T cell activation (GO:0042110), regulation of nucleobase-containing compound metabolic process (GO:0019219), negative regulation of macromolecule biosynthetic process (GO:0010558), cellular nitrogen compound biosynthetic process (GO:0044271), regulation of transferase activity (GO:0051338), muscle organ development (GO:0007517), epithelium development (GO:0060429), negative regulation of RNA metabolic process (GO:0051253), kidney development (GO:0001822), positive regulation of cellular biosynthetic process (GO:0031328), regulation of telomerase activity (GO:0051972), nephron tubule development (GO:0072080), regulation of apoptotic process (GO:0042981), RNA metabolic process (GO:0016070), regulation of proteolysis (GO:0030162), mesonephros development (GO:0001823), regulation of peptidase activity (GO:0052547), regulation of RNA biosynthetic process (GO:2001141), ear development (GO:0043583), cellular response to cytokine stimulus (GO:0071345), positive regulation of DNA biosynthetic process (GO:2000573), skeletal muscle tissue development (GO:0007519), renal tubule morphogenesis (GO:0061333), T cell proliferation (GO:0042098), branching involved in ureteric bud morphogenesis (GO:0001658), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), ureteric bud development (GO:0001657), positive regulation of RNA biosynthetic process (GO:1902680), positive regulation of hydrolase activity (GO:0051345), negative regulation of RNA biosynthetic process (GO:1902679), mesonephric tubule morphogenesis (GO:0072171), positive regulation of apoptotic process (GO:0043065), response to alkaloid (GO:0043279), positive regulation of transferase activity (GO:0051347), skeletal muscle organ development (GO:0060538), kidney epithelium development (GO:0072073), regulation of DNA-templated transcription (GO:0006355), ear morphogenesis (GO:0042471), positive regulation of proteolysis (GO:0045862), striated muscle cell differentiation (GO:0051146), regulation of DNA biosynthetic process (GO:2000278), leukocyte apoptotic process (GO:0071887), response to interferon-alpha (GO:0035455), RNA biosynthetic process (GO:0032774), nucleic acid-templated transcription (GO:0097659), sensory perception of mechanical stimulus (GO:0050954), nephron tubule morphogenesis (GO:0072078), alpha-beta T cell activation (GO:0046631), protein processing (GO:0016485), negative regulation of protein binding (GO:0032091), positive regulation of peptidase activity (GO:0010952), regulation of endopeptidase activity (GO:0052548), myotube differentiation (GO:0014902), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of leukocyte apoptotic process (GO:2000108), lymphocyte apoptotic process (GO:0070227), sensory perception of sound (GO:0007605), ureteric bud morphogenesis (GO:0060675), mesonephric epithelium development (GO:0072163), positive regulation of nucleic acid-templated transcription (GO:1903508), positive regulation of telomerase activity (GO:0051973), regulation of leukocyte apoptotic process (GO:2000106), regulation of nucleic acid-templated transcription (GO:1903506), DNA-templated transcription (GO:0006351), cellular response to interferon-alpha (GO:0035457), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription initiation (GO:2000142), negative regulation of nucleic acid-templated transcription (GO:1903507), positive regulation of DNA-templated transcription initiation (GO:2000144), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of lymphocyte apoptotic process (GO:0070228), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription initiation by RNA polymerase II (GO:0060260), transcription by RNA polymerase II (GO:0006366), positive regulation of endopeptidase activity (GO:0010950), regulation of cysteine-type endopeptidase activity (GO:2000116), positive regulation of lymphocyte apoptotic process (GO:0070230), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), positive regulation of cysteine-type endopeptidase activity (GO:2001056), regulation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0043281), regulation of B cell apoptotic process (GO:0002902), positive regulation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0043280), activation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0006919)

Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cell projection (GO:0042995), chromatin (GO:0000785), perinuclear region of cytoplasm (GO:0048471), nuclear protein-containing complex (GO:0140513), cytoplasm (GO:0005737), transcription regulator complex (GO:0005667), membrane-enclosed lumen (GO:0031974), nuclear body (GO:0016604), nucleoplasm (GO:0005654), euchromatin (GO:0000791), plasma membrane bounded cell projection (GO:0120025), intracellular organelle (GO:0043229), RNA polymerase II transcription regulator complex (GO:0090575), non-membrane-bounded organelle (GO:0043228), organelle lumen (GO:0043233), membrane-bounded organelle (GO:0043227), intracellular membrane-bounded organelle (GO:0043231), intracellular non-membrane-bounded organelle (GO:0043232), neuron projection (GO:0043005), intracellular organelle lumen (GO:0070013), nucleus (GO:0005634), cytoskeleton (GO:0005856), nuclear lumen (GO:0031981), spindle (GO:0005819), chromosome (GO:0005694), axon (GO:0030424), microtubule cytoskeleton (GO:0015630)

Generated by BioReason

Deep Research Bioreason Rl

(Myc-deep-research-bioreason-rl.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:29 AM

Organism: Mus musculus

Sequence:

MDFLWALETPQTATTMPLNVNFTNRNYDLDYDSVQPYFICDEEENFYHQQQQSELQPPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVATSFSPREDDDGGGGNFSTADQLEMMTELLGGDMVNQSFICDPDDETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSTSLSPARGHSVCSTSSLYLQDLTAAASECIDPSVVFPYPLNDSSSPKSCTSSDSTAFSPSSDSLLSSESSPRASPEPLVLHEETPPTTSSDSEEEQEDEEEIDVVSVEKRQTPAKRSESGSSPSRGHSKPPHSPLVLKRCHVSTHQHNYAAPPSTRKDYPAAKRAKLDSGRVLKQISNNRKCSSPRSSDTEENDKRRTHNVLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILSIQADEHKLTSEKDLLRKRREQLKHKLEQLRNSGA

Thinking Trace

Functional Summary

UniProt Summary

Is a transcriptional activator.

InterPro Domains

Transcription regulator Myc (IPR002418, family) — residues 16-452
Transcription regulator Myc, N-terminal (IPR012682, domain) — residues 17-360
Myc family transcription factors (IPR050433, family) — residues 22-452
Helix-loop-helix DNA-binding domain superfamily (IPR036638, homologous_superfamily) — residues 361-454
Myc-type, basic helix-loop-helix (bHLH) domain (IPR011598, domain) — residues 369-427
Leucine zipper, Myc (IPR003327, domain) — residues 423-452

GO Terms

Generated by BioReason

Deep Research Falcon

(Myc-deep-research-falcon.md)

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gene_id: Myc
gene_symbol: Myc
uniprot_accession: P01108
protein_description: 'RecName: Full=Myc proto-oncogene protein; AltName: Full=Proto-oncogene
c-Myc; AltName: Full=Transcription factor p64;'
gene_info: Name=Myc;
organism_full: Mus musculus (Mouse).
protein_family: Not specified in UniProt
protein_domains: bHLH_dom. (IPR011598); HLH_DNA-bd_sf. (IPR036638); Myc-LZ. (IPR003327);
Myc_transcription_factors. (IPR050433); Tscrpt_reg_Myc. (IPR002418)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P01108
Protein Description: RecName: Full=Myc proto-oncogene protein; AltName: Full=Proto-oncogene c-Myc; AltName: Full=Transcription factor p64;
Gene Information: Name=Myc;
Organism (full): Mus musculus (Mouse).
Protein Family: Not specified in UniProt
Key Domains: bHLH_dom. (IPR011598); HLH_DNA-bd_sf. (IPR036638); Myc-LZ. (IPR003327); Myc_transcription_factors. (IPR050433); Tscrpt_reg_Myc. (IPR002418)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Myc" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Myc' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Myc (gene ID: Myc, UniProt: P01108) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P01108
Protein Description: RecName: Full=Myc proto-oncogene protein; AltName: Full=Proto-oncogene c-Myc; AltName: Full=Transcription factor p64;
Gene Information: Name=Myc;
Organism (full): Mus musculus (Mouse).
Protein Family: Not specified in UniProt
Key Domains: bHLH_dom. (IPR011598); HLH_DNA-bd_sf. (IPR036638); Myc-LZ. (IPR003327); Myc_transcription_factors. (IPR050433); Tscrpt_reg_Myc. (IPR002418)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Myc" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene Myc (gene ID: Myc, UniProt: P01108) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Research Report: Mouse Myc (UniProt P01108) — Functional Annotation Synthesis (2023–2024 prioritized)

0. Target verification (critical disambiguation)

This report concerns Mus musculus Myc encoding Myc proto-oncogene protein (c-Myc), UniProt P01108, including the alternate name transcription factor p64 and other c-Myc isoforms discussed in the literature (p64/p67/p55). The protein is a canonical MYC-family bHLH–leucine zipper transcription factor, distinct from mouse Mycn (N-Myc) and Mycl (L-Myc) paralogs. (kubickova2023isoformdirectedcontrolof pages 2-4, jha2023mycfunctionand pages 1-2, zacariasfluck2024mycthereis pages 1-2)

1. Key concepts and definitions (current understanding)

1.1 What Myc is (molecular function)

Myc/c-Myc is a sequence-specific DNA-binding transcription factor and is widely conceptualized as a global transcriptional amplifier: rather than turning on an entirely unique gene set, MYC preferentially boosts transcription from genes that are already active/open in chromatin, with binding enriched at loci bearing active histone marks (e.g., H3K4me3, H3K27ac) and excluded from repressive chromatin. (jha2023mycfunctionand pages 2-3, jha2023mycfunctionand pages 1-2)

1.2 Domain architecture and mechanistic definitions

Mouse c-Myc is described as a 439-aa protein with:
- An N-terminal transactivation domain (TAD) containing conserved Myc boxes (MB0/MBI/MBII are emphasized in the N-terminus), which control cofactor recruitment and protein stability. (jha2023mycfunctionand pages 2-3, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2)
- A central regulatory region including MBIII/MBIV (or MBIIIa/MBIIIb/MBIV), mediating additional cofactor interactions. (jha2023mycfunctionand pages 2-3, ascanelli2024manipulatingmycfor pages 1-2)
- A C-terminal basic helix–loop–helix leucine zipper (bHLH-LZ / bHLH-ZIP) DNA-binding/dimerization domain required for function. (jha2023mycfunctionand pages 2-3, kubickova2023isoformdirectedcontrolof pages 2-4, jha2023mycfunctionand pages 1-2)

Mechanistically, c-Myc is an obligate heterodimer: it cannot efficiently homodimerize or bind DNA alone and requires MAX to form a MYC:MAX complex. This complex binds E-box motifs, with a canonical consensus 5′-CACGTG-3′, enabling transcriptional activation. (jha2023mycfunctionand pages 2-3, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2, zacariasfluck2024mycthereis pages 1-2)

A useful visual model of MYC:MAX promoter and enhancer binding in transcriptional amplification is provided in Jha et al. 2023 (Figures 1–2). (jha2023mycfunctionand media 99ef2bf9, jha2023mycfunctionand media ac4350d2)

1.3 Cofactors and pathway-level roles

MYC function is mediated through Myc-box-dependent recruitment of transcriptional and chromatin machinery. Examples highlighted in recent syntheses include:
- MBII interactions with TRRAP and multiple acetyltransferase/co-activator complexes (e.g., GCN5, TIP60, CBP/p300) and SKP2-associated regulatory functions. (jha2023mycfunctionand pages 2-3, ascanelli2024manipulatingmycfor pages 1-2)
- MBIIIb–WDR5 interaction, linked to H3K4 methylation-associated transcriptional control. (jha2023mycfunctionand pages 2-3, ascanelli2024manipulatingmycfor pages 1-2)
- MBIV–HCF-1 involvement in transcriptional activity and apoptosis-associated outputs. (jha2023mycfunctionand pages 2-3)
- MBIIIa–MIZ-1-associated repression in some contexts. (ascanelli2024manipulatingmycfor pages 1-2)
- Connection to transcriptional pause release via P-TEFb. (ascanelli2024manipulatingmycfor pages 1-2)

1.4 Isoforms and nomenclature (important for annotation)

The c-Myc locus produces multiple isoforms, including p67 (c-Myc1), p64 (c-Myc2), and p55 (c-MycS); p64 is explicitly consistent with the UniProt alternate name “transcription factor p64.” (kubickova2023isoformdirectedcontrolof pages 2-4)

1.5 Subcellular localization

Canonical c-Myc functions primarily in the nucleus as a DNA-binding transcription regulator. (kubickova2023isoformdirectedcontrolof pages 2-4, ascanelli2024manipulatingmycfor pages 1-2)
A processed form termed MYC-nick (generated by proteolytic cleavage) lacks the NLS and can be cytoplasmic, indicating that some Myc-derived products may have non-nuclear localization. (jha2023mycfunctionand pages 2-3, ascanelli2024manipulatingmycfor pages 1-2)

2. Recent developments and latest research (prioritizing 2023–2024)

2.1 Immune biology: coupling proliferation to genome integrity (mouse in vivo)

Dar et al. (Nature Communications; 2023-11 publication month per record) report that during antiviral responses, c-Myc induces Cul4b and other CRL4 complex members in activated CD8+ T cells, mechanistically linking rapid clonal expansion to DNA damage response/genome integrity pathways. Cul4b-deficient CD8+ T cells fail to expand and cannot clear LCMV Armstrong, accumulating DNA damage and undergoing proliferative catastrophe. (dar2023cmycusescul4b pages 1-2)

Quantitative context from this study: antigen-specific CD8+ T cells expand from <~1,000 to >10^7 by day 8, with a shortened ~4 h cell cycle and ~15–20 divisions during acute infection—conditions that create substantial replication stress risk that the Myc→Cul4b axis helps mitigate. (dar2023cmycusescul4b pages 1-2)

Functional-annotation implication: beyond “pro-proliferative transcription factor,” Myc should be annotated as coordinating cell-cycle progression with genome maintenance/replication-stress management in high-proliferation physiological states. (dar2023cmycusescul4b pages 1-2)

2.2 Hematologic malignancy models: MYC-driven ribosome biogenesis and Pol I vulnerability

Behrens et al. (Science Advances; 2024-03) show that in BCR::ABL1-driven B-ALL, c-MYC (with ERG) coordinates a transcriptional network with a prominent role in ribosome biogenesis and RNA polymerase I (Pol I) machinery; genetic deletion of Erg or c-Myc prevented or delayed disease onset in the murine P190 model. (behrens2024ergandcmyc pages 7-8)

They validate a pharmacologic vulnerability using Pol I inhibitors (CX-5461 and others), with reported CX-5461 IC50s in murine P190 lines ranging 99–406 nM (examples: 99 nM, 135 nM) and in human lines including 230 nM and 861 nM; actinomycin D and BMH-21 also inhibited at sub-nanomolar to tens of nanomolar ranges (example actinomycin D 0.27 nM; BMH-21 22 nM). (behrens2024ergandcmyc pages 7-8)

Functional-annotation implication: this strengthens the mechanistic annotation of Myc as a regulator of ribosome biogenesis/nucleolar transcription programs, with clinically relevant downstream dependencies. (behrens2024ergandcmyc pages 1-2, behrens2024ergandcmyc pages 7-8)

2.3 Organism-level physiology: Myc dosage, cancer incidence, and aging hallmarks (mouse genetics)

Prochownik & Wang (Frontiers in Cell and Developmental Biology; 2023-08) synthesize evidence from mouse knockout models indicating Myc dosage has complex organismal effects. They report that near-total postnatal Myc loss can yield longer-lived mice with >3-fold lower lifetime cancer incidence, yet with accelerated emergence of multiple “aging hallmarks” (mitochondrial/ribosomal decline, ROS, genotoxic damage, metabolic rewiring, senescence). (prochownik2023lessonsinaging pages 1-2)

Functional-annotation implication: Myc supports tissue maintenance programs (ribosome/mitochondria/metabolism) that can be decoupled genetically from cancer susceptibility, informing interpretation of Myc’s “normal” physiological function in adult tissues. (prochownik2023lessonsinaging pages 1-2)

2.4 Translational MYC targeting: Omomyc-derived inhibitor OMO-103 in humans

Garralda et al. (Nature Medicine; 2024-02) report a first-in-human Phase 1 trial (NCT04808362) of OMO-103, a 91-aa MYC inhibitor derived from Omomyc. Patients received weekly IV infusions across six dose levels, with 22 patients enrolled and RP2D = 6.48 mg/kg; pharmacokinetics suggested tumor exposure (detectable in biopsies up to 19 days after last infusion) and a serum terminal half-life of ~40 h. Clinical activity signals included stable disease in 8/12 patients reaching a 9-week assessment and one case with 49% reduction in total tumor volume at best response. (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3)

Functional-annotation implication: these data support the real-world tractability of perturbing the MYC:MAX/E-box network and provide quantitative benchmarks for “MYC inhibition” implementation. (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3)

2.5 Programmable epigenomic silencing of MYC transcription in cancer models

Senapedis et al. (Nature Communications; 2024-09) present a programmable epigenomic “controller” concept that targets regulatory DNA elements within MYC insulated genomic domains to induce durable transcriptional downregulation via mechanisms including CpG methylation and KRAB-mediated heterochromatin formation, with antitumor activity in HCC models (monotherapy and combinations). (senapedis2024targetedtranscriptionaldownregulation pages 1-2)

Functional-annotation implication: this highlights the importance of cis-regulatory architecture and epigenetic control of MYC expression in disease contexts, emphasizing that MYC function is tightly gated upstream at the transcriptional/3D-genome level. (senapedis2024targetedtranscriptionaldownregulation pages 1-2)

2.6 Expanding non-cancer framing (regeneration and other diseases)

Two 2024 reviews explicitly emphasize the breadth of MYC biology beyond cancer: one focusing on non-oncologic disease links and physiological functions, and another emphasizing Myc’s role downstream of multiple signaling pathways as a lever in regeneration and tissue repair, while warning that tuning is needed to avoid oncogenesis. (ascanelli2024manipulatingmycfor pages 1-2, zacariasfluck2024mycthereis pages 1-2)

3. Current applications and real-world implementations

3.1 Mouse genetics and disease models

Myc conditional genetics remains central to mechanistic mapping in vivo (e.g., immune responses and cancer models). Dar et al. (2023) demonstrate how Myc-driven proliferation in T cells requires parallel activation of genome integrity pathways to avoid catastrophic failure during antiviral expansion. (dar2023cmycusescul4b pages 1-2)

3.2 Therapeutic targeting strategies (clinical and preclinical)

Direct MYC inhibition (protein drug): OMO-103 has progressed to human testing with defined IV dosing, PK, and preliminary activity readouts. (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3)

Downstream dependency targeting: In MYC-dependent leukemia programs, inhibition of ribosome biogenesis machinery (Pol I transcription) yields potent in vitro growth inhibition at nanomolar or sub-nanomolar concentrations depending on inhibitor, providing a translationally relevant “indirect MYC targeting” route. (behrens2024ergandcmyc pages 7-8)

Epigenomic repression approaches: Programmable epigenomic controllers represent a modality for durable downregulation of MYC mRNA transcription in preclinical models. (senapedis2024targetedtranscriptionaldownregulation pages 1-2)

3.3 ClinicalTrials.gov implementations (OMO-103)

ClinicalTrials.gov records document multiple ongoing or recent OMO-103 studies:
- NCT04808362 (posted 2021; TERMINATED): Phase 1/2 open-label dose-escalation/expansion, weekly IV infusion; 22 enrolled; terminated after Phase 1 completion due to strategy shift. (NCT04808362 chunk 1)
- NCT06059001 (posted 2023; ACTIVE_NOT_RECRUITING): Phase 1b in metastatic PDAC combining OMO-103 with gemcitabine/nab-paclitaxel; planned 26 participants; start 2023-08-31; primary endpoint safety/tolerability (AEs/SAEs). (NCT06059001 chunk 1)
- NCT06650514 (posted 2024; RECRUITING): Phase 2 single-arm pilot in advanced high-grade osteosarcoma; planned 10 evaluable patients; dosing 6.5 mg/kg weekly IV; primary endpoint 16-week PFS rate; planned start 2024-12-27. (NCT06650514 chunk 1)
- NCT07089940 (posted 2026; RECRUITING): early phase 1 PDAC study emphasizing PD effects in tumor biopsies; planned enrollment 12. (NCT07089940 chunk 1)

4. Expert synthesis and analysis (authoritative perspectives)

4.1 “Transcriptional amplifier” model remains influential, with methodological cautions

Recent expert syntheses emphasize MYC as a transcriptional amplifier of already active genes, mediated by promoter/enhancer occupancy and extensive cofactor integration. They also stress technical caveats in defining “MYC target genes,” including variation in ChIP peak counts and the importance of normalization (e.g., spike-ins) for quantitative comparisons. (jha2023mycfunctionand pages 2-3, jha2023mycfunctionand pages 1-2)

4.2 Myc integrates signaling pathways into coherent growth programs

A 2024 regeneration-focused review frames Myc as a central node downstream of multiple signaling pathways (WNT, RAS/RAF/MAPK, JAK/STAT, TGF-β, NF-κB) that transduces external pro-proliferative cues into transcriptional programs for growth, development, homeostasis, and regeneration—while highlighting the need for tight regulation to avoid oncogenesis. (ascanelli2024manipulatingmycfor pages 1-2)

4.3 Physiological breadth beyond cancer

A 2024 review explicitly argues that while cancer dominates MYC discourse, MYC’s roles in proliferation, differentiation, metabolism, ribogenesis, and aspects of development (e.g., bone/vascular biology) imply importance in non-oncologic diseases and potentially protective contexts as well. (zacariasfluck2024mycthereis pages 1-2)

5. Relevant statistics and data points (recent studies)

Antiviral clonal expansion stress context: CD8+ T cells can expand from <~1,000 to >10^7 antigen-specific cells by day 8 in acute LCMV infection, with a ~4 h cell cycle and ~15–20 divisions, motivating Myc-linked genome-protection pathways. (dar2023cmycusescul4b pages 1-2)
MYC/ERG-dependent leukemia vulnerabilities: Pol I inhibition yields CX-5461 IC50s 99–406 nM (murine P190) and 230 nM / 861 nM (human lines in study), with actinomycin D and BMH-21 showing potent inhibition in the sub-nM to tens of nM range. (behrens2024ergandcmyc pages 7-8)
Organismal outcomes in Myc KO models: Myc loss associated with >3-fold lower lifetime cancer incidence yet accelerated aging hallmarks (reviewed from mouse KO literature). (prochownik2023lessonsinaging pages 1-2)
Clinical proof-of-concept for MYC inhibition: OMO-103 Phase 1 enrolled 22 patients; RP2D 6.48 mg/kg; tumor biopsy detectability up to 19 days; serum half-life ~40 h; stable disease in 8/12 at 9-week assessment; 49% best tumor volume reduction in one patient. (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3)

6. Practical functional-annotation summary (what to annotate for UniProt P01108)

Feature	Summary for mouse c-Myc (Myc, UniProt P01108)	Evidence
Recommended identity / synonyms	Mouse Myc encodes Myc proto-oncogene protein / proto-oncogene c-Myc / transcription factor p64; literature often uses MYC or c-Myc. It is the canonical Myc family member distinct from Mycn/N-Myc and Mycl/L-Myc.	(kubickova2023isoformdirectedcontrolof pages 2-4, jha2023mycfunctionand pages 1-2, zacariasfluck2024mycthereis pages 1-2)
Isoforms / products	The c-Myc locus produces multiple protein isoforms, including p67 (c-Myc1), p64 (c-Myc2), and p55 (c-MycS); p64 aligns with the UniProt alternate name “transcription factor p64.”	(kubickova2023isoformdirectedcontrolof pages 2-4)
Overall architecture	c-Myc is a 439-aa transcription factor with an N-terminal transactivation domain (TAD), a central regulatory region, and a C-terminal DNA-binding/dimerization module containing the basic helix-loop-helix leucine zipper (bHLH-LZ / bHLH-ZIP).	(jha2023mycfunctionand pages 2-3, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2, zacariasfluck2024mycthereis pages 1-2)
N-terminal TAD / Myc boxes	The N-terminus contains conserved Myc boxes, including MB0, MBI, MBII; MBI/MBII are central to transactivation and regulation, and deletions in Myc boxes reduce transactivation. The N-terminal intrinsically disordered region also contains degron motifs.	(jha2023mycfunctionand pages 2-3, kubickova2023isoformdirectedcontrolof pages 2-4, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2)
Central regulatory region	The middle portion contains MBIII/MBIV (or MBIIIa/MBIIIb and MBIV in finer annotation), which contribute to cofactor recruitment and transcriptional control.	(jha2023mycfunctionand pages 2-3, ascanelli2024manipulatingmycfor pages 1-2)
C-terminal bHLH-LZ	The C-terminal bHLH-LZ domain mediates sequence-specific DNA binding and heterodimerization; this is the defining DNA-binding module for c-Myc family transcriptional activity.	(jha2023mycfunctionand pages 2-3, kubickova2023isoformdirectedcontrolof pages 2-4, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2, zacariasfluck2024mycthereis pages 1-2)
Obligate partner	c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.	(jha2023mycfunctionand pages 2-3, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2, zacariasfluck2024mycthereis pages 1-2)
DNA motif recognized	The MYC:MAX heterodimer preferentially binds the canonical E-box motif, especially 5'-CACGTG-3'.	(jha2023mycfunctionand pages 2-3, kubickova2023isoformdirectedcontrolof pages 2-4, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2, zacariasfluck2024mycthereis pages 1-2)
Major co-factors / cofactors by region	MBII recruits/cooperates with TRRAP, GCN5, TIP60, CBP/p300, SKP2; MBIIIb interacts with WDR5; MBIV engages HCF-1; MBIIIa mediates repression through MIZ-1; MYC also promotes pause release through P-TEFb.	(jha2023mycfunctionand pages 2-3, ascanelli2024manipulatingmycfor pages 1-2)
Functional interpretation	c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration.	(jha2023mycfunctionand pages 2-3, kubickova2023isoformdirectedcontrolof pages 2-4, jha2023mycfunctionand pages 1-2, ascanelli2024manipulatingmycfor pages 1-2, zacariasfluck2024mycthereis pages 1-2)
Subcellular localization	The canonical protein is primarily nuclear, consistent with its role as a DNA-binding transcription factor.	(kubickova2023isoformdirectedcontrolof pages 2-4, ascanelli2024manipulatingmycfor pages 1-2)
Processed cytoplasmic form	Proteolytic cleavage can generate MYC-nick, a form lacking the NLS and found in the cytoplasm, indicating that not all Myc-derived products are strictly nuclear.	(jha2023mycfunctionand pages 2-3, ascanelli2024manipulatingmycfor pages 1-2)

Table: This table summarizes the core identity, structural features, binding partners, DNA motif recognition, cofactors, and localization of mouse c-Myc (UniProt P01108). It is designed as a concise functional-annotation reference grounded in the cited sources.

Year	System/model	Main finding (mechanism)	Quantitative/statistical highlights	Relevance to Myc functional annotation	Source (with DOI URL)
2023	Mouse antiviral CD8+ T cells during acute LCMV infection; Cul4b-deficient vs control T cells	c-Myc upregulates Cul4b and other CRL4 complex components after T-cell activation, coupling rapid clonal expansion to DNA-damage control; without Cul4b, activated CD8+ T cells accumulate replication stress/DNA damage, fail to expand, and undergo proliferative catastrophe (dar2023cmycusescul4b pages 1-2)	Antigen-specific CD8+ T cells expand from <~1,000 to >10^7 cells by day 8, with a shortened ~4 h cell cycle and ~15–20 divisions during acute infection; Cul4b-deficient cells fail to clear LCMV in vivo (dar2023cmycusescul4b pages 1-2)	Supports annotation of Myc as a nuclear transcriptional regulator that links proliferation to genome maintenance/DNA-damage response, not just cell-cycle activation	Dar et al., 2023, Nature Communications — https://doi.org/10.1038/s41467-023-42765-7 (dar2023cmycusescul4b pages 1-2)
2023	Mouse Myc haploinsufficient and postnatal near-total Myc knockout models	Myc dosage strongly affects organismal physiology: reduced Myc lowers cancer burden but accelerates multiple aging hallmarks, indicating that normal Myc activity sustains mitochondrial/ribosomal integrity and metabolic homeostasis in vivo (prochownik2023lessonsinaging pages 1-2)	Near-total postnatal Myc loss produced mice with >3-fold lower lifetime cancer incidence yet premature-aging phenotypes; Myc+/− mice lived longer and accumulated age-related phenotypes more slowly (prochownik2023lessonsinaging pages 1-2)	Refines annotation from “oncogene” to a broader physiological regulator of ribosome biogenesis, mitochondrial function, metabolism, and tissue maintenance	Prochownik & Wang, 2023, Frontiers in Cell and Developmental Biology — https://doi.org/10.3389/fcell.2023.1244321 (prochownik2023lessonsinaging pages 1-2)
2024	Murine P190 BCR::ABL1 B-ALL and human Ph+ B-ALL models	c-MYC and ERG co-regulate a leukemic transcriptional network, prominently ribosome biogenesis and RNA polymerase I (Pol I) machinery; genetic deletion of c-Myc delays/prevents disease, and Pol I inhibition exposes a therapeutic vulnerability (behrens2024ergandcmyc pages 7-8)	Genetic deletion of Erg or c-Myc prevented or delayed leukemia onset; CX-5461 IC50s in murine P190 lines were 99–406 nM (examples: 99 nM, 135 nM), and in human lines 230 nM and 861 nM; actinomycin D IC50 example 0.27 nM; BMH-21 IC50 example 22 nM (behrens2024ergandcmyc pages 7-8)	Strong evidence that Myc functionally drives ribosome biogenesis/nucleolar transcription programs and that this node can be exploited pharmacologically	Behrens et al., 2024, Science Advances — https://doi.org/10.1126/sciadv.adj8803 (behrens2024ergandcmyc pages 7-8)
2024	First-in-human phase 1 trial in advanced solid tumors (all-comers metastatic solid tumors)	OMO-103, an Omomyc-derived MYC inhibitor, showed clinical feasibility of directly targeting MYC; pharmacokinetic and biopsy data supported tumor exposure and target engagement (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3)	22 patients enrolled across 6 dose levels (0.48, 1.44, 2.88, 4.32, 6.48, 9.72 mg/kg); weekly 30–45 min IV dosing; no MTD reached; RP2D = 6.48 mg/kg; OMO-103 detectable in tumor biopsies up to 19 days after last infusion; serum terminal half-life ~40 h; of 19 evaluable patients, 12 reached the 9-week activity assessment and 8/12 had stable disease; one patient had 49% reduction in total tumor volume at best response (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3)	Real-world validation that Myc’s MAX/E-box transcriptional network is pharmacologically actionable in humans, reinforcing the biological centrality of Myc-driven transcriptional control	Garralda et al., 2024, Nature Medicine — https://doi.org/10.1038/s41591-024-02805-1 (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3)
2024	Hepatocellular carcinoma cell and animal models using programmable epigenomic controllers	MYC transcription can be durably reduced by targeting regulatory DNA elements within MYC insulated genomic domains; combined DNA methylation and KRAB-based repression produced stronger silencing and antitumor activity (senapedis2024targetedtranscriptionaldownregulation pages 1-2)	Dual-repressor OTX-2002 / OTX-2002-DS showed stronger MYC downregulation than single components in Hep3B cells; significant antitumor activity was observed in vitro and in vivo, including activity in combination with tyrosine kinase or immune checkpoint inhibitors, although exact effect sizes are not given in the excerpt (senapedis2024targetedtranscriptionaldownregulation pages 1-2)	Shows that Myc function depends on cis-regulatory chromatin architecture and supports annotation of Myc as a gene whose activity is tightly controlled at the transcriptional/epigenomic level	Senapedis et al., 2024, Nature Communications — https://doi.org/10.1038/s41467-024-52202-y (senapedis2024targetedtranscriptionaldownregulation pages 1-2)

Table: This table summarizes recent high-value findings on MYC/c-Myc from mouse and mammalian studies, emphasizing mechanisms, quantitative results, and how each study informs functional annotation of mouse Myc (UniProt P01108). It is useful for linking core molecular function to current in vivo biology and translational applications.

7. Visual evidence (MYC:MAX and transcription amplification model)

The Jha et al. 2023 figures provide a concise schematic of how MYC:MAX binding at promoters and enhancers can shift transcriptional output from baseline activation to amplification, and how this integrates with transcriptional machinery/cofactors. (jha2023mycfunctionand media 99ef2bf9, jha2023mycfunctionand media ac4350d2)

8. References (URLs and publication dates where available from retrieved records)

Jha RK, Kouzine F, Levens D. MYC function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology. 2023-10. https://doi.org/10.3389/fcell.2023.1268275 (jha2023mycfunctionand pages 2-3, jha2023mycfunctionand pages 1-2, jha2023mycfunctionand media 99ef2bf9, jha2023mycfunctionand media ac4350d2)
Kubíčková A, De Sanctis JB, Hajdúch M. Isoform-Directed Control of c-Myc Functions. International Journal of Molecular Sciences. 2023-12. https://doi.org/10.3390/ijms242417524 (kubickova2023isoformdirectedcontrolof pages 2-4)
Prochownik EV, Wang H. Lessons in aging from Myc knockout mouse models. Frontiers in Cell and Developmental Biology. 2023-08. https://doi.org/10.3389/fcell.2023.1244321 (prochownik2023lessonsinaging pages 1-2)
Dar AA et al. c-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8+ T cell immunity. Nature Communications. 2023-11. https://doi.org/10.1038/s41467-023-42765-7 (dar2023cmycusescul4b pages 1-2)
Ascanelli C, Dahir R, Wilson CH. Manipulating Myc for reparative regeneration. Frontiers in Cell and Developmental Biology. 2024-03. https://doi.org/10.3389/fcell.2024.1357589 (ascanelli2024manipulatingmycfor pages 1-2)
Zacarías-Fluck MF, Soucek L, Whitfield JR. MYC: there is more to it than cancer. Frontiers in Cell and Developmental Biology. 2024-03. https://doi.org/10.3389/fcell.2024.1342872 (zacariasfluck2024mycthereis pages 1-2)
Behrens K et al. ERG and c-MYC regulate a critical gene network in BCR::ABL1-driven B cell acute lymphoblastic leukemia. Science Advances. 2024-03. https://doi.org/10.1126/sciadv.adj8803 (behrens2024ergandcmyc pages 1-2, behrens2024ergandcmyc pages 7-8)
Garralda E et al. MYC targeting by OMO-103 in solid tumors: a phase 1 trial. Nature Medicine. 2024-02. https://doi.org/10.1038/s41591-024-02805-1 (garralda2024myctargetingby pages 1-2, garralda2024myctargetingby pages 2-3, garralda2024myctargetingby pages 10-11)
Senapedis W et al. Targeted transcriptional downregulation of MYC using epigenomic controllers demonstrates antitumor activity in hepatocellular carcinoma models. Nature Communications. 2024-09. https://doi.org/10.1038/s41467-024-52202-y (senapedis2024targetedtranscriptionaldownregulation pages 1-2)
ClinicalTrials.gov: NCT06650514 (posted 2024): https://clinicaltrials.gov/study/NCT06650514 (NCT06650514 chunk 1)
ClinicalTrials.gov: NCT04808362 (posted 2021): https://clinicaltrials.gov/study/NCT04808362 (NCT04808362 chunk 1)
ClinicalTrials.gov: NCT06059001 (posted 2023): https://clinicaltrials.gov/study/NCT06059001 (NCT06059001 chunk 1)
ClinicalTrials.gov: NCT07089940 (posted 2026): https://clinicaltrials.gov/study/NCT07089940 (NCT07089940 chunk 1)

References

(kubickova2023isoformdirectedcontrolof pages 2-4): Agáta Kubíčková, Juan Bautista De Sanctis, and Marián Hajdúch. Isoform-directed control of c-myc functions: understanding the balance from proliferation to growth arrest. International Journal of Molecular Sciences, 24:17524, Dec 2023. URL: https://doi.org/10.3390/ijms242417524, doi:10.3390/ijms242417524. This article has 17 citations.
(jha2023mycfunctionand pages 1-2): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 101 citations.
(zacariasfluck2024mycthereis pages 1-2): Mariano F. Zacarías-Fluck, Laura Soucek, and Jonathan R. Whitfield. Myc: there is more to it than cancer. Frontiers in Cell and Developmental Biology, Mar 2024. URL: https://doi.org/10.3389/fcell.2024.1342872, doi:10.3389/fcell.2024.1342872. This article has 36 citations.
(jha2023mycfunctionand pages 2-3): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 101 citations.
(ascanelli2024manipulatingmycfor pages 1-2): Camilla Ascanelli, Rowda Dahir, and Catherine H. Wilson. Manipulating myc for reparative regeneration. Frontiers in Cell and Developmental Biology, Mar 2024. URL: https://doi.org/10.3389/fcell.2024.1357589, doi:10.3389/fcell.2024.1357589. This article has 10 citations.
(jha2023mycfunctionand media 99ef2bf9): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 101 citations.
(jha2023mycfunctionand media ac4350d2): Rajiv Kumar Jha, Fedor Kouzine, and David Levens. Myc function and regulation in physiological perspective. Frontiers in Cell and Developmental Biology, Oct 2023. URL: https://doi.org/10.3389/fcell.2023.1268275, doi:10.3389/fcell.2023.1268275. This article has 101 citations.
(dar2023cmycusescul4b pages 1-2): Asif A. Dar, Dale D. Kim, Scott M. Gordon, Kathleen Klinzing, Siera Rosen, Ipsita Guha, Nadia Porter, Yohaniz Ortega, Katherine S. Forsyth, Jennifer Roof, Hossein Fazelinia, Lynn A. Spruce, Laurence C. Eisenlohr, Edward M. Behrens, and Paula M. Oliver. C-myc uses cul4b to preserve genome integrity and promote antiviral cd8+ t cell immunity. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-42765-7, doi:10.1038/s41467-023-42765-7. This article has 9 citations and is from a highest quality peer-reviewed journal.
(behrens2024ergandcmyc pages 7-8): Kira Behrens, Natalie Brajanovski, Zhen Xu, Elizabeth M. Viney, Ladina DiRago, Soroor Hediyeh-Zadeh, Melissa J. Davis, Richard B. Pearson, Elaine Sanij, Warren S. Alexander, and Ashley P. Ng. Erg and c-myc regulate a critical gene network in bcr::abl1-driven b cell acute lymphoblastic leukemia. Science Advances, Mar 2024. URL: https://doi.org/10.1126/sciadv.adj8803, doi:10.1126/sciadv.adj8803. This article has 17 citations and is from a highest quality peer-reviewed journal.
(behrens2024ergandcmyc pages 1-2): Kira Behrens, Natalie Brajanovski, Zhen Xu, Elizabeth M. Viney, Ladina DiRago, Soroor Hediyeh-Zadeh, Melissa J. Davis, Richard B. Pearson, Elaine Sanij, Warren S. Alexander, and Ashley P. Ng. Erg and c-myc regulate a critical gene network in bcr::abl1-driven b cell acute lymphoblastic leukemia. Science Advances, Mar 2024. URL: https://doi.org/10.1126/sciadv.adj8803, doi:10.1126/sciadv.adj8803. This article has 17 citations and is from a highest quality peer-reviewed journal.
(prochownik2023lessonsinaging pages 1-2): Edward V. Prochownik and Huabo Wang. Lessons in aging from myc knockout mouse models. Frontiers in Cell and Developmental Biology, Aug 2023. URL: https://doi.org/10.3389/fcell.2023.1244321, doi:10.3389/fcell.2023.1244321. This article has 17 citations.
(garralda2024myctargetingby pages 1-2): Elena Garralda, Marie-Eve Beaulieu, Víctor Moreno, Sílvia Casacuberta-Serra, Sandra Martínez-Martín, Laia Foradada, Guzman Alonso, Daniel Massó-Vallés, Sergio López-Estévez, Toni Jauset, Elena Corral de la Fuente, Bernard Doger, Tatiana Hernández, Raquel Perez-Lopez, Oriol Arqués, Virginia Castillo Cano, Josefa Morales, Jonathan R. Whitfield, Manuela Niewel, Laura Soucek, and Emiliano Calvo. Myc targeting by omo-103 in solid tumors: a phase 1 trial. Nature Medicine, 30:762-771, Feb 2024. URL: https://doi.org/10.1038/s41591-024-02805-1, doi:10.1038/s41591-024-02805-1. This article has 191 citations and is from a highest quality peer-reviewed journal.
(garralda2024myctargetingby pages 2-3): Elena Garralda, Marie-Eve Beaulieu, Víctor Moreno, Sílvia Casacuberta-Serra, Sandra Martínez-Martín, Laia Foradada, Guzman Alonso, Daniel Massó-Vallés, Sergio López-Estévez, Toni Jauset, Elena Corral de la Fuente, Bernard Doger, Tatiana Hernández, Raquel Perez-Lopez, Oriol Arqués, Virginia Castillo Cano, Josefa Morales, Jonathan R. Whitfield, Manuela Niewel, Laura Soucek, and Emiliano Calvo. Myc targeting by omo-103 in solid tumors: a phase 1 trial. Nature Medicine, 30:762-771, Feb 2024. URL: https://doi.org/10.1038/s41591-024-02805-1, doi:10.1038/s41591-024-02805-1. This article has 191 citations and is from a highest quality peer-reviewed journal.
(senapedis2024targetedtranscriptionaldownregulation pages 1-2): William Senapedis, Kayleigh M. Gallagher, Elmer Figueroa, Jeremiah D. Farelli, Robert Lyng, J. Graeme Hodgson, Charles W. O’Donnell, Joseph V. Newman, Madison Pacaro, Stephen K. Siecinski, Justin Chen, and Thomas G. McCauley. Targeted transcriptional downregulation of myc using epigenomic controllers demonstrates antitumor activity in hepatocellular carcinoma models. Nature Communications, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52202-y, doi:10.1038/s41467-024-52202-y. This article has 17 citations and is from a highest quality peer-reviewed journal.
(NCT04808362 chunk 1): Phase 1/2 Study to Evaluate Safety, PK and Efficacy of the MYC-Inhibitor OMO-103 in Solid Tumours. Peptomyc S.L.. 2021. ClinicalTrials.gov Identifier: NCT04808362
(NCT06059001 chunk 1): Study to Evaluate the Safety, PK, and Efficacy of the Myc Inhibitor OMO-103 Administered iv in Patients With PDAC. Peptomyc S.L.. 2023. ClinicalTrials.gov Identifier: NCT06059001
(NCT06650514 chunk 1): A Phase 2 Pilot Study to Evaluate the Safety and the Anti-Tumour Activity of the Myc Inhibitor OMO-103 Administered Intravenously in Patients With Advanced High-Grade Osteosarcoma. Vall d'Hebron Institute of Oncology. 2024. ClinicalTrials.gov Identifier: NCT06650514
(NCT07089940 chunk 1): Charles D Lopez. OMO-103 for the Treatment of Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma. OHSU Knight Cancer Institute. 2026. ClinicalTrials.gov Identifier: NCT07089940
(garralda2024myctargetingby pages 10-11): Elena Garralda, Marie-Eve Beaulieu, Víctor Moreno, Sílvia Casacuberta-Serra, Sandra Martínez-Martín, Laia Foradada, Guzman Alonso, Daniel Massó-Vallés, Sergio López-Estévez, Toni Jauset, Elena Corral de la Fuente, Bernard Doger, Tatiana Hernández, Raquel Perez-Lopez, Oriol Arqués, Virginia Castillo Cano, Josefa Morales, Jonathan R. Whitfield, Manuela Niewel, Laura Soucek, and Emiliano Calvo. Myc targeting by omo-103 in solid tumors: a phase 1 trial. Nature Medicine, 30:762-771, Feb 2024. URL: https://doi.org/10.1038/s41591-024-02805-1, doi:10.1038/s41591-024-02805-1. This article has 191 citations and is from a highest quality peer-reviewed journal.

Citations

jha2023mycfunctionand pages 2-3
ascanelli2024manipulatingmycfor pages 1-2
kubickova2023isoformdirectedcontrolof pages 2-4
behrens2024ergandcmyc pages 7-8
prochownik2023lessonsinaging pages 1-2
senapedis2024targetedtranscriptionaldownregulation pages 1-2
zacariasfluck2024mycthereis pages 1-2
jha2023mycfunctionand pages 1-2
behrens2024ergandcmyc pages 1-2
garralda2024myctargetingby pages 1-2
garralda2024myctargetingby pages 2-3
garralda2024myctargetingby pages 10-11
https://doi.org/10.1038/s41467-023-42765-7
https://doi.org/10.3389/fcell.2023.1244321
https://doi.org/10.1126/sciadv.adj8803
https://doi.org/10.1038/s41591-024-02805-1
https://doi.org/10.1038/s41467-024-52202-y
https://doi.org/10.3389/fcell.2023.1268275
https://doi.org/10.3390/ijms242417524
https://doi.org/10.3389/fcell.2024.1357589
https://doi.org/10.3389/fcell.2024.1342872
https://clinicaltrials.gov/study/NCT06650514
https://clinicaltrials.gov/study/NCT04808362
https://clinicaltrials.gov/study/NCT06059001
https://clinicaltrials.gov/study/NCT07089940
https://doi.org/10.3390/ijms242417524,
https://doi.org/10.3389/fcell.2023.1268275,
https://doi.org/10.3389/fcell.2024.1342872,
https://doi.org/10.3389/fcell.2024.1357589,
https://doi.org/10.1038/s41467-023-42765-7,
https://doi.org/10.1126/sciadv.adj8803,
https://doi.org/10.3389/fcell.2023.1244321,
https://doi.org/10.1038/s41591-024-02805-1,
https://doi.org/10.1038/s41467-024-52202-y,

Bioreason Rl Review

(Myc-bioreason-rl-review.md)

BioReason-Pro RL Review: Myc (mouse)

Source: Myc-deep-research-bioreason-rl.md

Correctness: 5/5
Completeness: 4/5

Functional Summary Review

The BioReason functional summary is accurate and well-constructed:

A nuclear transcriptional regulator that uses a C-terminal basic helix-loop-helix and leucine zipper module to dimerize and bind E-box DNA elements, while an extensive N-terminal activation region recruits coactivators and chromatin-modifying complexes. Through this architecture, it stimulates RNA polymerase II-dependent transcriptional programs that promote growth and proliferation by coordinating expression of biosynthetic and cell-cycle-associated genes within the nucleus.

This correctly identifies: (1) the bHLH-leucine zipper DNA-binding/dimerization module, (2) the N-terminal transactivation domain, (3) E-box binding specificity, (4) RNA polymerase II transcriptional activation, (5) nuclear localization, and (6) the biological output of growth and proliferation gene programs. These align with curated annotations including GO:0003700 (DNA-binding transcription factor activity, via GO_REF:0000002), GO:0005634 (nucleus), and GO:0006355 (regulation of DNA-templated transcription, via GO_REF:0000002).

The mention of "chromatin-modifying complexes" is accurate -- Myc recruits TRRAP/HAT complexes. The description of coordinating "biosynthetic and cell-cycle-associated genes" captures the established Myc transcriptional program well.

Minor gaps: The summary does not mention the obligate heterodimerization partner Max, which is essential for Myc's DNA-binding activity. The curated review includes GO:0046983 (protein dimerization activity, via GO_REF:0000002). Myc's roles in apoptosis induction (when survival signals are absent) and its involvement in ribosome biogenesis are also omitted.

Comparison with interpro2go:

The curated review has three GO_REF:0000002 annotations: GO:0003700 (DNA-binding transcription factor activity), GO:0006355 (regulation of DNA-templated transcription), and GO:0046983 (protein dimerization activity). BioReason's summary is fully consistent with the first two and implicitly covers the third (dimerization via the bHLH-leucine zipper). BioReason adds mechanistic context about E-box binding and chromatin modifier recruitment that interpro2go cannot provide. However, the explicit dimerization function could have been stated more clearly.

Notes on thinking trace

The trace correctly identifies the Myc-family N-terminal activation domain (IPR012682) and the bHLH-zip C-terminal architecture. The hypothesis about TRRAP-containing acetyltransferase assemblies and Mediator components is accurate and shows good biological knowledge integration. The reasoning chain from domain architecture to transcriptional activation to growth programs is well-constructed.

📄 View Raw YAML

id: P01108
gene_symbol: Myc
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: 'Mouse Myc encodes c-Myc, a nuclear basic helix-loop-helix leucine zipper transcription factor. Myc heterodimerizes with Max to bind E-box DNA motifs and regulate RNA polymerase II transcriptional programs controlling growth, proliferation, ribosome biogenesis, metabolism, apoptosis, and stem-cell state. The core activity is Myc-Max DNA-binding transcriptional regulation; many developmental, cell-cycle, and metabolic annotations are downstream or context-specific outputs.'
alternative_products:
- name: 2 (c-myc 1 {ECO:0000303|PubMed:3277717})
  id: P01108-1
- name: 1 (c-myc 2 {ECO:0000303|PubMed:3277717})
  id: P01108-2
  sequence_note: VSP_061781
- name: '3'
  id: P01108-3
  sequence_note: VSP_061782
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0071943
    label: Myc-Max complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Myc-Max complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: DNA-binding transcription factor activity is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: chromosome is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: nucleolus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: cytoplasm reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: mitochondrion likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0046983
    label: protein dimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: protein dimerization activity is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19269368
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20211142
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20434984
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20946988
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36124234
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9764821
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0000082
    label: G1/S transition of mitotic cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: G1/S transition of mitotic cell cycle is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: MAPK cascade reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0000320
    label: re-entry into mitotic cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: re-entry into mitotic cell cycle reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: chromatin is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0001046
    label: core promoter sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: core promoter sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0001221
    label: transcription coregulator binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: transcription coregulator binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0001227
    label: DNA-binding transcription repressor activity, RNA polymerase II-specific
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: DNA-binding transcription repressor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0001228
    label: DNA-binding transcription activator activity, RNA polymerase II-specific
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: DNA-binding transcription activator activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0002082
    label: regulation of oxidative phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of oxidative phosphorylation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0003690
    label: double-stranded DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: double-stranded DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: DNA-binding transcription factor activity is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleolus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006006
    label: glucose metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: glucose metabolic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006338
    label: chromatin remodeling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: chromatin remodeling is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006352
    label: DNA-templated transcription initiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Myc is well supported as a nuclear Myc-Max DNA-binding transcription regulator, but the evidence does not establish the initiation-specific process captured by this term.
    action: MODIFY
    reason: Replace the initiation-specific annotation with a broader RNA polymerase II transcription-regulation term that matches the supported Myc transcription factor biology.
    proposed_replacement_terms:
    - id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006366
    label: transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006848
    label: pyruvate transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: pyruvate transport likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006865
    label: amino acid transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: amino acid transport reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006879
    label: intracellular iron ion homeostasis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: intracellular iron ion homeostasis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: DNA damage response reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0007007
    label: inner mitochondrial membrane organization
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: inner mitochondrial membrane organization likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0007346
    label: regulation of mitotic cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of mitotic cell cycle reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0010564
    label: regulation of cell cycle process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of cell cycle process is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of gene expression is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of gene expression reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0010918
    label: positive regulation of mitochondrial membrane potential
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of mitochondrial membrane potential reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0014911
    label: positive regulation of smooth muscle cell migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of smooth muscle cell migration reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0016072
    label: rRNA metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Myc regulates ribosome biogenesis and nucleolar transcription programs, but rRNA metabolism is a downstream growth program rather than the core Myc-Max DNA-binding function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Myc can drive ribosome-biogenesis programs, while the primary molecular function remains sequence-specific transcriptional regulation through Myc-Max.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'Functional-annotation implication: this strengthens the mechanistic annotation of Myc as a regulator of ribosome biogenesis/nucleolar transcription programs, with clinically relevant downstream dependencies.'
- term:
    id: GO:0032204
    label: regulation of telomere maintenance
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of telomere maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0032986
    label: protein-DNA complex disassembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein-DNA complex disassembly reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein-containing complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: identical protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of gene expression via chromosomal CpG island methylation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein-containing complex binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein-containing complex binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0045656
    label: negative regulation of monocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of monocyte differentiation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0045787
    label: positive regulation of cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cell cycle reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0045821
    label: positive regulation of glycolytic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of glycolytic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0046325
    label: negative regulation of D-glucose import across plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of D-glucose import across plasma membrane likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0046722
    label: lactic acid secretion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: lactic acid secretion likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0048147
    label: negative regulation of fibroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0048661
    label: positive regulation of smooth muscle cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of smooth muscle cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of epithelial cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0051276
    label: chromosome organization
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: chromosome organization reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0051782
    label: negative regulation of cell division
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: negative regulation of cell division likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0060252
    label: positive regulation of glial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of glial cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0060633
    label: negative regulation of transcription initiation by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Myc can repress RNA polymerase II transcription in some contexts, but the cited evidence does not justify the more specific transcription-initiation mechanism.
    action: MODIFY
    reason: Replace the initiation-specific repression annotation with the broader supported negative regulation of RNA polymerase II transcription.
    proposed_replacement_terms:
    - id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: MBIIIa–MIZ-1-associated repression in some contexts.
- term:
    id: GO:0070371
    label: ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ERK1 and ERK2 cascade reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0070888
    label: E-box binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: E-box binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to hypoxia reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0071466
    label: cellular response to xenobiotic stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to xenobiotic stimulus likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0140297
    label: DNA-binding transcription factor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: DNA-binding transcription factor binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:1901857
    label: positive regulation of cellular respiration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cellular respiration reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:1902255
    label: positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:1902895
    label: positive regulation of miRNA transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of miRNA transcription reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:1903862
    label: positive regulation of oxidative phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of oxidative phosphorylation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:1904036
    label: negative regulation of epithelial cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of epithelial cell apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:1905761
    label: SCF ubiquitin ligase complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: SCF ubiquitin ligase complex binding reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:2001171
    label: positive regulation of ATP biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of ATP biosynthetic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0071943
    label: Myc-Max complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Myc-Max complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0090571
    label: RNA polymerase II transcription repressor complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: RNA polymerase II transcription repressor complex is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20434984
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:20434984
  review:
    summary: PMID:20434984 supports Myc regulation of Pol II promoter-proximal pause release rather than a broad transcription-positive-regulation assertion.
    action: MODIFY
    reason: Use the more specific transcription-elongation term because the paper reports Myc acting mainly at Pol II pause release instead of recruitment.
    supported_by:
    - reference_id: PMID:20434984
      supporting_text: c-Myc regulates transcriptional pause release.
    - reference_id: PMID:20434984
      supporting_text: c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes.
    proposed_replacement_terms:
    - id: GO:0032968
      label: positive regulation of transcription elongation by RNA polymerase II
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: proteasome-mediated ubiquitin-dependent protein catabolic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0016072
    label: rRNA metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Myc regulates ribosome biogenesis and nucleolar transcription programs, but rRNA metabolism is a downstream growth program rather than the core Myc-Max DNA-binding function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Myc can drive ribosome-biogenesis programs, while the primary molecular function remains sequence-specific transcriptional regulation through Myc-Max.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'Functional-annotation implication: this strengthens the mechanistic annotation of Myc as a regulator of ribosome biogenesis/nucleolar transcription programs, with clinically relevant downstream dependencies.'
- term:
    id: GO:0032206
    label: positive regulation of telomere maintenance
  evidence_type: IMP
  original_reference_id: PMID:9637678
  review:
    summary: positive regulation of telomere maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:9637678
  review:
    summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0001866
    label: NK T cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:19423665
  review:
    summary: NK T cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0000082
    label: G1/S transition of mitotic cell cycle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: G1/S transition of mitotic cell cycle is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23277542
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:31005419
  review:
    summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:1904672
    label: regulation of somatic stem cell population maintenance
  evidence_type: IDA
  original_reference_id: PMID:31005419
  review:
    summary: regulation of somatic stem cell population maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9634437
  review:
    summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0060261
    label: positive regulation of transcription initiation by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:26691508
  review:
    summary: PMID:26691508 supports Myc-dependent activation of Set1/Mll core subunit expression during reprogramming, but not the specific mechanism of RNA polymerase II transcription initiation.
    action: MODIFY
    reason: Replace the initiation-specific term with a broader transcriptional activation term; independent Myc evidence also emphasizes Pol II pause release rather than recruitment/initiation at target genes.
    proposed_replacement_terms:
    - id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    supported_by:
    - reference_id: PMID:26691508
      supporting_text: Thus, Myc directly promotes the expression of two core subunits of the H3K4 methyltransferase complexes with a potential functional implication.
    - reference_id: PMID:20434984
      supporting_text: c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:18625840
  review:
    summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26523946
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18625840
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:22328504
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:22328504
  review:
    summary: TRIM6 ubiquitin-ligase binding is a regulatory ES-cell interaction for Myc, not a core Myc function.
    action: KEEP_AS_NON_CORE
    reason: The paper supports TRIM6 interaction that attenuates Myc transcriptional activity in embryonic stem cells; this regulatory interaction should not be treated as core Myc-Max DNA-binding transcription factor activity.
    supported_by:
    - reference_id: PMID:22328504
      supporting_text: TRIM6, one of the TRIM family ubiquitin ligases, was selectively expressed in ES cells and interacted with Myc
    - reference_id: PMID:22328504
      supporting_text: TRIM6 regulates the transcriptional activity of Myc during the maintenance of ES cell pluripotency
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:22328504
  review:
    summary: perinuclear region of cytoplasm likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0035457
    label: cellular response to interferon-alpha
  evidence_type: IDA
  original_reference_id: PMID:24795346
  review:
    summary: cellular response to interferon-alpha likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0000791
    label: euchromatin
  evidence_type: IDA
  original_reference_id: PMID:22723415
  review:
    summary: euchromatin is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:23277542
  review:
    summary: regulation of apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:23277542
  review:
    summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:23770341
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: ISO
  original_reference_id: PMID:21447833
  review:
    summary: regulation of gene expression is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0008630
    label: intrinsic apoptotic signaling pathway in response to DNA damage
  evidence_type: IDA
  original_reference_id: PMID:14517295
  review:
    summary: intrinsic apoptotic signaling pathway in response to DNA damage reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0008630
    label: intrinsic apoptotic signaling pathway in response to DNA damage
  evidence_type: IMP
  original_reference_id: PMID:14517295
  review:
    summary: intrinsic apoptotic signaling pathway in response to DNA damage reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:2001235
    label: positive regulation of apoptotic signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:14517295
  review:
    summary: positive regulation of apoptotic signaling pathway reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:2001235
    label: positive regulation of apoptotic signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:14517295
  review:
    summary: positive regulation of apoptotic signaling pathway reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0035914
    label: skeletal muscle cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:22147266
  review:
    summary: skeletal muscle cell differentiation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15511642
  review:
    summary: cis-regulatory region sequence-specific DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18438430
  review:
    summary: protein binding is not a useful retained annotation for Myc in this review.
    action: REMOVE
    reason: The annotation is too generic, unsupported as a direct Myc activity, or represents an interaction/process better captured by specific transcription factor and Myc-Max terms.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc is primarily a nuclear bHLH-leucine zipper transcription factor; generic binding, localization, and metabolic-output terms should not replace its direct DNA-binding transcriptional role.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: 'The report supports more informative terms for Myc than generic protein binding: bHLH-LZ-mediated MAX heterodimerization, Myc-Max complex formation, E-box DNA binding, and transcriptional regulation.'
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IDA
  original_reference_id: PMID:20212154
  review:
    summary: DNA damage response reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: MAPK cascade reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006338
    label: chromatin remodeling
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: chromatin remodeling is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0006879
    label: intracellular iron ion homeostasis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: intracellular iron ion homeostasis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: DNA damage response reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0032204
    label: regulation of telomere maintenance
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: regulation of telomere maintenance reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: protein-containing complex binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- term:
    id: GO:0045656
    label: negative regulation of monocyte differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: negative regulation of monocyte differentiation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of fibroblast proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0050679
    label: positive regulation of epithelial cell proliferation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of epithelial cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0051276
    label: chromosome organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: chromosome organization reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0051782
    label: negative regulation of cell division
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: negative regulation of cell division likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0070888
    label: E-box binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: E-box binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19796622
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0009314
    label: response to radiation
  evidence_type: IMP
  original_reference_id: PMID:14517295
  review:
    summary: response to radiation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0016055
    label: Wnt signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:19056892
  review:
    summary: Wnt signaling pathway reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: nucleoplasm is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: nucleolus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0090096
    label: positive regulation of metanephric cap mesenchymal cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:19161241
  review:
    summary: positive regulation of metanephric cap mesenchymal cell proliferation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0001658
    label: branching involved in ureteric bud morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:19161241
  review:
    summary: branching involved in ureteric bud morphogenesis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0002053
    label: positive regulation of mesenchymal cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:19161241
  review:
    summary: positive regulation of mesenchymal cell proliferation reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:12196193
  review:
    summary: negative regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0030424
    label: axon
  evidence_type: IDA
  original_reference_id: PMID:10482234
  review:
    summary: axon likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0002904
    label: positive regulation of B cell apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:11604501
  review:
    summary: positive regulation of B cell apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:12235125
  review:
    summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:14517295
  review:
    summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IGI
  original_reference_id: PMID:17596282
  review:
    summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0043085
    label: positive regulation of catalytic activity
  evidence_type: IMP
  original_reference_id: PMID:17382917
  review:
    summary: positive regulation of catalytic activity reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:17382917
  review:
    summary: positive regulation of transcription by RNA polymerase II is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IDA
  original_reference_id: PMID:11438662
  review:
    summary: regulation of gene expression is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17631878
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0001783
    label: B cell apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:12970677
  review:
    summary: B cell apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: IMP
  original_reference_id: PMID:12970677
  review:
    summary: protein processing likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0043279
    label: response to alkaloid
  evidence_type: IMP
  original_reference_id: PMID:12970677
  review:
    summary: response to alkaloid likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0042474
    label: middle ear morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:17523175
  review:
    summary: middle ear morphogenesis likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0043473
    label: pigmentation
  evidence_type: IMP
  original_reference_id: PMID:17523175
  review:
    summary: pigmentation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0048705
    label: skeletal system morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:17523175
  review:
    summary: skeletal system morphogenesis reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0050910
    label: detection of mechanical stimulus involved in sensory perception of sound
  evidence_type: IMP
  original_reference_id: PMID:17523175
  review:
    summary: detection of mechanical stimulus involved in sensory perception of sound likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IGI
  original_reference_id: PMID:8521822
  review:
    summary: regulation of DNA-templated transcription is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IDA
  original_reference_id: PMID:15735755
  review:
    summary: nuclear body reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: PMID:15994933
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: PMID:15994933
  review:
    summary: positive regulation of cell population proliferation is a well-known downstream Myc output, but not the direct core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The review defines the core function as Myc-Max E-box DNA-binding transcriptional regulation; proliferation and cell-cycle outputs should be retained as non-core consequences unless supported as the direct molecular activity.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:12970171
  review:
    summary: DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IDA
  original_reference_id: PMID:15509711
  review:
    summary: spindle likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0009314
    label: response to radiation
  evidence_type: IDA
  original_reference_id: PMID:14517295
  review:
    summary: response to radiation likely overstates a direct role for Myc and is better interpreted as an indirect consequence of its transcriptional program.
    action: MARK_AS_OVER_ANNOTATED
    reason: The core evidence supports Myc as a transcription factor; this term is too downstream, pathway-level, or weakly connected to a direct molecular function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IDA
  original_reference_id: PMID:14560010
  review:
    summary: DNA binding is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:12235125
  review:
    summary: regulation of apoptotic process reflects a downstream, cell-type-specific, or pathway-level output of Myc transcriptional regulation rather than the core molecular activity.
    action: KEEP_AS_NON_CORE
    reason: Myc drives broad growth, proliferation, metabolism, apoptosis, and differentiation programs; this annotation can be retained as non-core but should not define the primary function.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc controls broad transcriptional programs for growth, proliferation, metabolism, apoptosis, and differentiation; many process annotations are downstream or context-specific outputs rather than core molecular functions.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: The report distinguishes Myc core function as nuclear transcriptional regulation from downstream programs in proliferation, metabolism, ribosome biogenesis, apoptosis, development, and tissue homeostasis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:11872843
  review:
    summary: nucleus is consistent with Myc as a nuclear Myc-Max DNA-binding transcription factor that regulates RNA polymerase II target genes.
    action: ACCEPT
    reason: The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
    supported_by:
    - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
      supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
    - reference_id: file:mouse/Myc/Myc-uniprot.txt
      supporting_text: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
    - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
      supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier, with canonical nuclear localization and MYC:MAX E-box binding.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: PMID:10482234
  title: Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity.
  findings: []
- id: PMID:11438662
  title: Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis.
  findings: []
- id: PMID:11604501
  title: Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis.
  findings: []
- id: PMID:11872843
  title: Colorectal cancer in mice genetically deficient in the mucin Muc2.
  findings: []
- id: PMID:12196193
  title: c-Myc represses the murine Nramp1 promoter.
  findings: []
- id: PMID:12235125
  title: Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor.
  findings: []
- id: PMID:12970171
  title: Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis.
  findings: []
- id: PMID:12970677
  title: c-Myc-deficient B lymphocytes are resistant to spontaneous and induced cell death.
  findings: []
- id: PMID:14517295
  title: c-Myc augments gamma irradiation-induced apoptosis by suppressing Bcl-XL.
  findings: []
- id: PMID:14560010
  title: Miz1 is required for early embryonic development during gastrulation.
  findings: []
- id: PMID:15509711
  title: Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells.
  findings: []
- id: PMID:15511642
  title: A role for nucleoprotein Zap3 in the reduction of telomerase activity during embryonic stem cell differentiation.
  findings: []
- id: PMID:15735755
  title: PML interacts with Myc, and Myc target gene expression is altered in PML-null fibroblasts.
  findings: []
- id: PMID:15994933
  title: Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells.
  findings: []
- id: PMID:17382917
  title: c-Myc is essential for urokinase plasminogen activator expression on hypoxia-induced vascular smooth muscle cells.
  findings: []
- id: PMID:17523175
  title: Neural crest cell deficiency of c-myc causes skull and hearing defects.
  findings: []
- id: PMID:17596282
  title: Unique mechanisms of growth regulation and tumor suppression upon Apc inactivation in the pancreas.
  findings: []
- id: PMID:17631878
  title: Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1.
  findings: []
- id: PMID:18438430
  title: Pim kinase-dependent inhibition of c-Myc degradation.
  findings: []
- id: PMID:18625840
  title: Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7 gamma.
  findings: []
- id: PMID:19056892
  title: A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors.
  findings: []
- id: PMID:19161241
  title: C-myc as a modulator of renal stem/progenitor cell population.
  findings: []
- id: PMID:19269368
  title: The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors.
  findings: []
- id: PMID:19423665
  title: Intrathymic proliferation wave essential for Valpha14+ natural killer T cell development depends on c-Myc.
  findings: []
- id: PMID:19796622
  title: Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
  findings: []
- id: PMID:20211142
  title: An atlas of combinatorial transcriptional regulation in mouse and man.
  findings: []
- id: PMID:20212154
  title: p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication.
  findings: []
- id: PMID:20434984
  title: c-Myc regulates transcriptional pause release.
  findings: []
- id: PMID:20946988
  title: A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs.
  findings: []
- id: PMID:21447833
  title: TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC.
  findings: []
- id: PMID:22147266
  title: Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation.
  findings: []
- id: PMID:22328504
  title: TRIM6 interacts with Myc and maintains the pluripotency of mouse embryonic stem cells.
  findings: []
- id: PMID:22723415
  title: Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells.
  findings: []
- id: PMID:23277542
  title: Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity.
  findings: []
- id: PMID:23770341
  title: Overexpression of c-myc in hepatocytes promotes activation of hepatic stellate cells and facilitates the onset of liver fibrosis.
  findings: []
- id: PMID:24795346
  title: Posttranscriptional regulation of c-Myc expression in adult murine HSCs during homeostasis and interferon-α-induced stress response.
  findings: []
- id: PMID:26523946
  title: Combined Overexpression of JARID2, PRDM14, ESRRB, and SALL4A Dramatically Improves Efficiency and Kinetics of Reprogramming to Induced Pluripotent Stem Cells.
  findings: []
- id: PMID:26691508
  title: Physical Interactions and Functional Coordination between the Core Subunits of Set1/Mll Complexes and the Reprogramming Factors.
  findings: []
- id: PMID:31005419
  title: TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network.
  findings: []
- id: PMID:36124234
  title: Integrative analysis reveals histone demethylase LSD1 promotes RNA polymerase II pausing.
  findings: []
- id: PMID:8521822
  title: 'Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation.'
  findings: []
- id: PMID:9637678
  title: Myc activates telomerase.
  findings: []
- id: PMID:9764821
  title: The C. elegans MDL-1 and MXL-1 proteins can functionally substitute for vertebrate MAD and MAX.
  findings: []
- id: Reactome:R-MMU-9634437
  title: Myc gene expression is enhanced by E2f1, phospho-Stat3, and Cebpb and repressed by Cebpa
  findings: []
- id: file:mouse/Myc/Myc-uniprot.txt
  title: UniProt record for mouse Myc
  findings:
  - statement: Myc is a transcription factor that recognizes E-box-like core sequences and requires Max dimerization for efficient DNA binding.
    supporting_text: Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX.
- id: file:mouse/Myc/Myc-deep-research-bioreason.md
  title: Bioreason deep research report on mouse Myc
  findings:
  - statement: Myc is a nuclear bHLH-LZ transcription factor whose core activity is Myc-Max DNA binding and transcriptional regulation.
- id: file:mouse/Myc/Myc-deep-research-falcon.md
  title: Falcon deep research report on mouse Myc
  findings:
  - statement: Myc is a nuclear bHLH-LZ transcription factor whose core activity is Myc-Max DNA binding and transcriptional regulation.
    supporting_text: c-Myc is best annotated as a sequence-specific nuclear transcription regulator / transcriptional amplifier that controls genes involved in cell cycle entry, proliferation, metabolism, ribosome biogenesis, differentiation, apoptosis, development, tissue homeostasis, and regeneration.
core_functions:
- description: Myc functions as a DNA-binding RNA polymerase II transcription factor by heterodimerizing with Max and binding E-box motifs at promoters and enhancers.
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  - id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  - id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  - id: GO:0000785
    label: chromatin
  in_complex:
    id: GO:0071943
    label: Myc-Max complex
  supported_by:
  - reference_id: file:mouse/Myc/Myc-uniprot.txt
    supporting_text: Transcription factor ... specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
  - reference_id: file:mouse/Myc/Myc-deep-research-bioreason.md
    supporting_text: Myc binds E-box DNA sequences as a heterodimer with MAX and regulates RNA polymerase II target gene expression.
  - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
    supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
- description: Myc enables Myc-Max complex formation through protein dimerization, which is required for efficient DNA binding and transcriptional regulation.
  molecular_function:
    id: GO:0046983
    label: protein dimerization activity
  directly_involved_in: []
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  in_complex:
    id: GO:0071943
    label: Myc-Max complex
  supported_by:
  - reference_id: file:mouse/Myc/Myc-uniprot.txt
    supporting_text: Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX.
  - reference_id: file:mouse/Myc/Myc-deep-research-falcon.md
    supporting_text: c-Myc does not efficiently homodimerize or bind DNA alone; it requires MAX as an obligate heterodimerization partner for promoter binding and transcriptional activation.
proposed_new_terms: []
suggested_questions:
- question: Which mouse Myc metabolic and mitochondrial GO annotations represent direct Myc target-gene regulation versus downstream effects of altered growth state?
- question: Which Myc repressive functions through Miz1 or other cofactors should be represented as distinct non-core transcriptional mechanisms?
suggested_experiments:
- description: Use Myc and Max perturbation with CUT&RUN/ChIP-seq plus nascent RNA profiling in mouse cells to separate direct Myc-Max target transcription from secondary metabolic and cell-cycle effects.
- description: Compare wild-type Myc with dimerization-defective and DNA-binding-defective mutants in mouse cells to test which GO process annotations require direct Myc-Max DNA binding.

Myc

Gene Description

Existing Annotations Review

Core Functions

Myc functions as a DNA-binding RNA polymerase II transcription factor by heterodimerizing with Max and binding E-box motifs at promoters and enhancers.

Myc enables Myc-Max complex formation through protein dimerization, which is required for efficient DNA binding and transcriptional regulation.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Deep Research Bioreason

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Deep Research Bioreason Rl

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Research Report: Mouse Myc (UniProt P01108) — Functional Annotation Synthesis (2023–2024 prioritized)

0. Target verification (critical disambiguation)

1. Key concepts and definitions (current understanding)

1.1 What Myc is (molecular function)

1.2 Domain architecture and mechanistic definitions

1.3 Cofactors and pathway-level roles

1.4 Isoforms and nomenclature (important for annotation)

1.5 Subcellular localization

2. Recent developments and latest research (prioritizing 2023–2024)

2.1 Immune biology: coupling proliferation to genome integrity (mouse in vivo)

2.2 Hematologic malignancy models: MYC-driven ribosome biogenesis and Pol I vulnerability

2.3 Organism-level physiology: Myc dosage, cancer incidence, and aging hallmarks (mouse genetics)

2.4 Translational MYC targeting: Omomyc-derived inhibitor OMO-103 in humans

2.5 Programmable epigenomic silencing of MYC transcription in cancer models

2.6 Expanding non-cancer framing (regeneration and other diseases)

3. Current applications and real-world implementations

3.1 Mouse genetics and disease models

3.2 Therapeutic targeting strategies (clinical and preclinical)

3.3 ClinicalTrials.gov implementations (OMO-103)

4. Expert synthesis and analysis (authoritative perspectives)

4.1 “Transcriptional amplifier” model remains influential, with methodological cautions

4.2 Myc integrates signaling pathways into coherent growth programs

4.3 Physiological breadth beyond cancer

5. Relevant statistics and data points (recent studies)

6. Practical functional-annotation summary (what to annotate for UniProt P01108)

7. Visual evidence (MYC:MAX and transcription amplification model)

8. References (URLs and publication dates where available from retrieved records)

Citations

Bioreason Rl Review

BioReason-Pro RL Review: Myc (mouse)

Functional Summary Review

Notes on thinking trace

📄 View Raw YAML