MYC (c-Myc) is a nuclear bHLH-leucine zipper transcription factor and major proto-oncogene that regulates cell growth, proliferation, metabolism, and apoptosis. MYC functions primarily through obligate heterodimerization with MAX to bind E-box DNA motifs (CACGTG) at promoters and enhancers, activating transcription of target genes involved in cell cycle progression, ribosome biogenesis, and metabolic programs. MYC can also repress transcription via interaction with MIZ1 (ZBTB17). The protein contains N-terminal transactivation domains with conserved Myc boxes (MBI-MBIV) and a C-terminal bHLH-LZ domain for dimerization and DNA binding. MYC stability is regulated by a phosphodegron at T58/S62 recognized by the E3 ligase FBXW7 for ubiquitin-mediated proteasomal degradation. MYC is deregulated in over 50% of human cancers and regulates approximately 11% of human genes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: MYC binds E-box DNA sequences (CACGTG) in promoters and enhancers as a heterodimer with MAX to regulate transcription. This is a well-established core function supported by extensive structural and functional evidence. Reason: E-box binding and sequence-specific DNA recognition at RNA Pol II promoters is a core molecular function of MYC, essential for its role as a transcriptional regulator. IBA annotation is phylogenetically sound. Supporting Evidence: PMID:12553908 X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. file:human/MYC/MYC-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: MYC functions as a DNA-binding transcription factor that heterodimerizes with MAX to bind E-box sequences and regulate gene expression. This is the core molecular function of MYC. Reason: DNA-binding transcription factor activity is the primary molecular function of MYC. The IBA annotation captures the essential role of MYC as a sequence-specific transcriptional regulator. Supporting Evidence: PMID:12553908 E box recognition by these two structurally similar transcription factor pairs determines whether a cell will divide and proliferate (Myc-Max) or differentiate and become quiescent (Mad-Max). |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: MYC binds DNA via its bHLH-LZ domain as a heterodimer with MAX. This broad term is accurate but less specific than E-box binding. Reason: DNA binding is a well-established function of MYC. While less specific than E-box binding, this IEA annotation is valid and provides useful general information about MYC molecular function. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: MYC is a well-characterized DNA-binding transcription factor. This term is appropriately inferred from InterPro domain annotations. Reason: This IEA annotation from InterPro correctly identifies MYC as a DNA-binding transcription factor based on its bHLH-LZ domain structure. |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000002 | ACCEPT | Summary: MYC heterodimerizes with MAX via its leucine zipper domain for DNA binding and transcriptional activity. Dimerization is essential for MYC function. Reason: Protein dimerization (specifically heterodimerization with MAX) is a core molecular function of MYC that is essential for DNA binding and transcriptional activity. The IEA annotation correctly identifies this function from InterPro domains. |
| GO:0005515 protein binding | IPI PMID:11891322 Small-molecule antagonists of Myc/Max dimerization inhibit M... | REMOVE | Summary: Generic protein binding term from a study on small-molecule antagonists of Myc/Max dimerization. Reason: GO:0005515 protein binding is uninformative and does not describe the specific molecular function. The relevant interaction is already captured by protein dimerization activity (GO:0046983) and the Myc-Max complex annotation. Supporting Evidence: PMID:11891322 Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts. |
| GO:0005515 protein binding | IPI PMID:15992821 A structure-based model of the c-Myc/Bin1 protein interactio... | REMOVE | Summary: Generic protein binding term from a study on c-Myc/Bin1 interaction structure. Reason: GO:0005515 protein binding is uninformative. The specific interaction with BIN1 should be captured by more specific terms. Supporting Evidence: PMID:15992821 A structure-based model of the c-Myc/Bin1 protein interaction shows alternative splicing of Bin1 and c-Myc phosphorylation are key binding determinants. |
| GO:0005515 protein binding | IPI PMID:16352593 Targeting of Miz-1 is essential for Myc-mediated apoptosis. | REMOVE | Summary: Generic protein binding term from a study on Miz-1 targeting for Myc-mediated apoptosis. Reason: GO:0005515 protein binding is uninformative. The functional interaction with MIZ1 is better represented by specific terms like DNA-binding transcription factor binding. Supporting Evidence: PMID:16352593 Dec 13. Targeting of Miz-1 is essential for Myc-mediated apoptosis. |
| GO:0005515 protein binding | IPI PMID:16606833 Identification of small molecules that induce apoptosis in a... | REMOVE | Summary: Generic protein binding term from a study on small molecules inducing Myc-dependent apoptosis. Reason: GO:0005515 protein binding is uninformative and does not specify the functional nature of the interaction. Supporting Evidence: PMID:16606833 Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation. |
| GO:0005515 protein binding | IPI PMID:16996503 Myc stabilization in response to estrogen and phospholipase ... | REMOVE | Summary: Generic protein binding term from a study on Myc stabilization by estrogen and phospholipase D. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:16996503 Epub 2006 Sep 18. Myc stabilization in response to estrogen and phospholipase D in MCF-7 breast cancer cells. |
| GO:0005515 protein binding | IPI PMID:17070091 HPV-18 E7 conjugates to c-Myc and mediates its transcription... | REMOVE | Summary: Generic protein binding term from a study on HPV-18 E7 interaction with c-Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:17070091 Epub 2006 Oct 4. HPV-18 E7 conjugates to c-Myc and mediates its transcriptional activity. |
| GO:0005515 protein binding | IPI PMID:17157259 SNIP1 is a candidate modifier of the transcriptional activit... | REMOVE | Summary: Generic protein binding term from a study on SNIP1 interaction with c-Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:17157259 SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes. |
| GO:0005515 protein binding | IPI PMID:17314511 Large-scale identification of c-MYC-associated proteins usin... | REMOVE | Summary: Generic protein binding term from a large-scale c-MYC interactome study. Reason: GO:0005515 protein binding is uninformative. High-throughput interactome studies do not provide functional context. Supporting Evidence: PMID:17314511 Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach. |
| GO:0005515 protein binding | IPI PMID:17418410 HIF-2alpha promotes hypoxic cell proliferation by enhancing ... | REMOVE | Summary: Generic protein binding term from a study on HIF-2alpha promoting c-myc transcription. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:17418410 HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. |
| GO:0005515 protein binding | IPI PMID:17599065 Inhibition of c-Myc activity by ribosomal protein L11. | REMOVE | Summary: Generic protein binding term from a study on ribosomal protein L11 inhibiting c-Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:17599065 Jun 28. Inhibition of c-Myc activity by ribosomal protein L11. |
| GO:0005515 protein binding | IPI PMID:17632056 CIP2A inhibits PP2A in human malignancies. | REMOVE | Summary: Generic protein binding term from a study on CIP2A inhibiting PP2A and stabilizing MYC. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:17632056 CIP2A inhibits PP2A in human malignancies. |
| GO:0005515 protein binding | IPI PMID:18256156 Epstein-Barr virus nuclear antigen 3C interacts with and enh... | REMOVE | Summary: Generic protein binding term from a study on EBV EBNA3C interaction with c-Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:18256156 Epstein-Barr virus nuclear antigen 3C interacts with and enhances the stability of the c-Myc oncoprotein. |
| GO:0005515 protein binding | IPI PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene en... | REMOVE | Summary: Generic protein binding term from a study on c-Myc repressing FOXO3a-mediated transcription. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. |
| GO:0005515 protein binding | IPI PMID:18413597 Adenovirus E1A targets p400 to induce the cellular oncoprote... | REMOVE | Summary: Generic protein binding term from a study on Adenovirus E1A targeting p400 to induce Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:18413597 Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc. |
| GO:0005515 protein binding | IPI PMID:18620061 Characterizing proteins and their interactions in cells and ... | REMOVE | Summary: Generic protein binding term from a proximity ligation assay study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:18620061 Jul 11. Characterizing proteins and their interactions in cells and tissues using the in situ proximity ligation assay. |
| GO:0005515 protein binding | IPI PMID:18923429 Miz1 and HectH9 regulate the stability of the checkpoint pro... | REMOVE | Summary: Generic protein binding term from a study on Miz1 and HectH9 regulating TopBP1 stability. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:18923429 Miz1 and HectH9 regulate the stability of the checkpoint protein, TopBP1. |
| GO:0005515 protein binding | IPI PMID:19131971 The Axin1 scaffold protein promotes formation of a degradati... | REMOVE | Summary: Generic protein binding term from a study on Axin1 promoting c-Myc degradation. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:19131971 The Axin1 scaffold protein promotes formation of a degradation complex for c-Myc. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Generic protein binding term from a large-scale TF interacting protein regions study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:20195357 A comprehensive resource of interacting protein regions for refining human transcription factor networks. |
| GO:0005515 protein binding | IPI PMID:20208519 Transcription-independent ARF regulation in oncogenic stress... | REMOVE | Summary: Generic protein binding term from a study on ARF regulation in stress-mediated p53 responses. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:20208519 Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses. |
| GO:0005515 protein binding | IPI PMID:20691906 Myc-nick: a cytoplasmic cleavage product of Myc that promote... | REMOVE | Summary: Generic protein binding term from a study on Myc-nick promoting alpha-tubulin acetylation. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:20691906 Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation. |
| GO:0005515 protein binding | IPI PMID:20713710 Noninvasive molecular imaging of c-Myc activation in living ... | REMOVE | Summary: Generic protein binding term from a study on noninvasive imaging of c-Myc activation. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:20713710 Noninvasive molecular imaging of c-Myc activation in living mice. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | REMOVE | Summary: Generic protein binding term from a human MAP kinase interactome study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:20936779 A human MAP kinase interactome. |
| GO:0005515 protein binding | IPI PMID:20970423 NEMO stabilizes c-Myc through direct interaction in the nucl... | REMOVE | Summary: Generic protein binding term from a study on NEMO stabilizing c-Myc in the nucleus. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:20970423 Epub 2010 Oct 21. NEMO stabilizes c-Myc through direct interaction in the nucleus. |
| GO:0005515 protein binding | IPI PMID:21150319 Proteomic profiling of Myc-associated proteins. | REMOVE | Summary: Generic protein binding term from a proteomic profiling of Myc-associated proteins study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:21150319 Dec 15. Proteomic profiling of Myc-associated proteins. |
| GO:0005515 protein binding | IPI PMID:21575199 IΞΊB kinases increase Myc protein stability and enhance progr... | REMOVE | Summary: Generic protein binding term from a study on IkB kinases increasing Myc stability. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:21575199 IΞΊB kinases increase Myc protein stability and enhance progression of breast cancer cells. |
| GO:0005515 protein binding | IPI PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. | REMOVE | Summary: Generic protein binding term from a study on Sirt1 deacetylating c-Myc and promoting Myc/Max association. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Generic protein binding term from a human liver protein interaction network study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:22094256 A systematic screen for CDK4/6 substrates links FOXM1 phosph... | REMOVE | Summary: Generic protein binding term from a CDK4/6 substrate screen study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:22094256 A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells. |
| GO:0005515 protein binding | IPI PMID:23217706 The histone deacetylase SIRT6 is a tumor suppressor that con... | REMOVE | Summary: Generic protein binding term from a study on SIRT6 as a tumor suppressor controlling metabolism. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:23217706 The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. |
| GO:0005515 protein binding | IPI PMID:23455924 A Y2H-seq approach defines the human protein methyltransfera... | REMOVE | Summary: Generic protein binding term from a Y2H-seq protein methyltransferase interactome study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:23455924 A Y2H-seq approach defines the human protein methyltransferase interactome. |
| GO:0005515 protein binding | IPI PMID:23791182 The ubiquitin ligase FBXW7 modulates leukemia-initiating cel... | REMOVE | Summary: Generic protein binding term from a study on FBXW7 regulating MYC stability in leukemia. Reason: GO:0005515 protein binding is uninformative. The FBXW7-MYC interaction is regulatory, not a core function. Supporting Evidence: PMID:23791182 The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. |
| GO:0005515 protein binding | IPI PMID:23804756 Structural and biochemical studies of SLIP1-SLBP identify DB... | REMOVE | Summary: Generic protein binding term from a structural study on SLIP1-SLBP interactions. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:23804756 Jun 26. Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins. |
| GO:0005515 protein binding | IPI PMID:24048479 Deterministic direct reprogramming of somatic cells to pluri... | REMOVE | Summary: Generic protein binding term from a study on deterministic direct reprogramming to pluripotency. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:24048479 Deterministic direct reprogramming of somatic cells to pluripotency. |
| GO:0005515 protein binding | IPI PMID:24951594 Sin3b interacts with Myc and decreases Myc levels. | REMOVE | Summary: Generic protein binding term from a study on Sin3b interacting with Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:24951594 2014 Jun 20. Sin3b interacts with Myc and decreases Myc levels. |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | REMOVE | Summary: Generic protein binding term from a proteomic study on chromatin-associated TF complexes. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. |
| GO:0005515 protein binding | IPI PMID:26267534 Small Molecule Inhibition of ERK Dimerization Prevents Tumor... | REMOVE | Summary: Generic protein binding term from a study on ERK dimerization inhibitors. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:26267534 Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Generic protein binding term from a human interactome stoichiometry study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:26655473 Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy C... | REMOVE | Summary: Generic protein binding term from a study on Pin1 pre-anchoring to unphosphorylated c-Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:26655473 2015 Nov 19. Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity. |
| GO:0005515 protein binding | IPI PMID:26766587 The Interaction of Myc with Miz1 Defines Medulloblastoma Sub... | REMOVE | Summary: Generic protein binding term from a study on Myc-Miz1 interaction defining medulloblastoma subgroups. Reason: GO:0005515 protein binding is uninformative. The Miz1 interaction is better captured by DNA-binding transcription factor binding. Supporting Evidence: PMID:26766587 The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup Identity. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | REMOVE | Summary: Generic protein binding term from a Polycomb complexome mapping study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complexome. |
| GO:0005515 protein binding | IPI PMID:28007894 The pseudophosphatase STYX targets the F-box of FBXW7 and in... | REMOVE | Summary: Generic protein binding term from a study on STYX targeting FBXW7. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:28007894 The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding term from a human binary protein interactome reference map. Reason: GO:0005515 protein binding is uninformative. High-throughput binary interactome data lacks functional context. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Generic protein binding term from a neurodegenerative disease protein interactome study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding term from a dual proteome-scale interactome study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | REMOVE | Summary: Generic protein binding term from a head and neck cancer protein network study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:34591642 Oct 1. A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity. |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | REMOVE | Summary: Generic protein binding term from a proteome-scale binding site mapping study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:35044719 Proteome-scale mapping of binding sites in the unstructured regions of the human proteome. |
| GO:0005515 protein binding | IPI PMID:35140242 Human transcription factor protein interaction networks. | REMOVE | Summary: Generic protein binding term from a human TF protein interaction networks study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:35140242 Human transcription factor protein interaction networks. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding term from the OpenCell endogenous tagging study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Generic protein binding term from a mutation-directed neo-PPI study in cancer. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:35512704 2022 May 4. Systematic discovery of mutation-directed neo-protein-protein interactions in cancer. |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | REMOVE | Summary: Generic protein binding term from a phosphomimetic screening study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:37219487 2023 May 23. Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions. |
| GO:0005515 protein binding | IPI PMID:9184233 Rox, a novel bHLHZip protein expressed in quiescent cells th... | REMOVE | Summary: Generic protein binding term from a study on Rox/Mnt heterodimerizing with Max. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:9184233 Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor. |
| GO:0005515 protein binding | IPI PMID:9708738 The novel ATM-related protein TRRAP is an essential cofactor... | REMOVE | Summary: Generic protein binding term from a study on TRRAP as an essential cofactor for c-Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:9708738 The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. |
| GO:0042802 identical protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | REMOVE | Summary: MYC identical protein binding detected in chromatin-associated TF complex proteomics. Reason: MYC functions primarily as a heterodimer with MAX, not as a homodimer. While MYC can self-associate, this is not its primary functional mode. The identical protein binding annotation is misleading. Supporting Evidence: PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. |
| GO:0042802 identical protein binding | IPI PMID:9184233 Rox, a novel bHLHZip protein expressed in quiescent cells th... | REMOVE | Summary: MYC identical protein binding from a study on Rox/Max heterodimerization. Reason: MYC functions primarily as a heterodimer with MAX. Identical protein binding is not the core mechanism of MYC function. Supporting Evidence: PMID:9184233 Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene en... | ACCEPT | Summary: MYC represses FOXO3a-mediated transcription of p27(Kip1). MYC functions as both a transcriptional activator and repressor, with repression mediated through interaction with MIZ1. Reason: Transcriptional repression is a core function of MYC, particularly through interaction with MIZ1 to repress cell cycle inhibitors like p27. Supporting Evidence: PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:10412034 Induction of apoptosis and differentiation in neuroblastoma ... | ACCEPT | Summary: MYC-mediated transcriptional repression from a study on Bin1-Myc interaction and apoptosis. Reason: MYC-mediated transcriptional repression is a core function. Supporting Evidence: PMID:10412034 Induction of apoptosis and differentiation in neuroblastoma and astrocytoma cells by the overexpression of Bin1, a novel Myc interacting protein. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: MYC negative regulation of transcription inferred from Ensembl Compara orthology. Reason: This IEA annotation correctly reflects MYC repressive function and is consistent with experimental evidence. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: MYC binds E-box sequences in cis-regulatory regions. IEA from Ensembl Compara orthology. Reason: This term correctly describes MYC DNA binding activity at cis-regulatory elements and is consistent with IBA and experimental annotations. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: General cis-regulatory DNA binding from Ensembl Compara orthology. Reason: This broader term for cis-regulatory DNA binding is valid for MYC. |
| GO:0001658 branching involved in ureteric bud morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Developmental process annotation from Ensembl Compara orthology. Reason: MYC plays a role in kidney development but this is a tissue-specific developmental process, not a core molecular function. |
| GO:0001783 B cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC can promote apoptosis under certain conditions, including in B cells (relevant to Burkitt lymphoma). Reason: While MYC has a dual role in promoting both proliferation and apoptosis, B cell apoptosis is a cell-type specific process, not a core function. |
| GO:0001866 NK T cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell-type specific proliferation process from Ensembl Compara orthology. Reason: NK T cell proliferation is a tissue-specific downstream effect, not a core function of MYC. |
| GO:0002904 positive regulation of B cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC promotes apoptosis under certain conditions in B cells. Reason: This is a cell-type specific regulatory process, not a core function. |
| GO:0006366 transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: MYC directly participates in RNA Pol II transcription as a transcription factor. Reason: Transcription by RNA Pol II is a core process in which MYC directly participates as a DNA-binding transcription factor. |
| GO:0006974 DNA damage response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC is involved in DNA damage response pathways. Reason: DNA damage response is a downstream consequence of MYC activity, not its core function. |
| GO:0008283 cell population proliferation | IEA GO_REF:0000107 | ACCEPT | Summary: MYC is a master regulator of cell proliferation. Reason: Cell proliferation is a core downstream biological process regulated by MYC through its transcriptional activity. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | ACCEPT | Summary: MYC positively regulates cell proliferation through transcriptional activation of growth-promoting genes. Reason: Positive regulation of cell proliferation is a core function of MYC as a proto-oncogene. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC can trigger apoptosis in response to DNA damage through ARF/p53 pathway activation. Reason: This is a context-dependent response, not a core function of MYC. |
| GO:0009314 response to radiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: MYC expression and stability are affected by radiation-induced DNA damage. Reason: This is too general and represents an indirect effect rather than a direct MYC function. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: MYC is a major regulator of gene expression, controlling approximately 11% of human genes. Reason: Regulation of gene expression is the core function of MYC as a transcription factor. |
| GO:0014902 myotube differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC expression is regulated during muscle differentiation. Reason: Myotube differentiation is a tissue-specific developmental process, not a core MYC function. |
| GO:0016055 Wnt signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC is a transcriptional target of Wnt signaling and beta-catenin. Reason: While MYC is regulated by Wnt signaling, this annotation is misleading as MYC is a downstream target, not an integral component of the Wnt pathway. |
| GO:0016485 protein processing | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation from Ensembl Compara orthology. Reason: MYC does not directly participate in protein processing. This is likely an indirect downstream effect. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000107 | ACCEPT | Summary: MYC is recognized by E3 ubiquitin ligases including FBXW7 for proteasomal degradation. Reason: MYC binding to ubiquitin protein ligases (especially FBXW7) is essential for its regulation and turnover. |
| GO:0035457 cellular response to interferon-alpha | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: MYC expression may be modulated by interferon signaling. Reason: This is too specific and represents an indirect effect rather than a core MYC function. |
| GO:0035914 skeletal muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC downregulation is required for muscle differentiation. Reason: Tissue-specific differentiation process, not a core MYC function. |
| GO:0042474 middle ear morphogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Developmental annotation from Ensembl Compara orthology. Reason: This is a very specific developmental process that likely represents an indirect effect of MYC on proliferation during ear development. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC has dual roles in regulating both cell proliferation and apoptosis. Reason: MYC regulates apoptosis but this is context-dependent and not its primary function. |
| GO:0043279 response to alkaloid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation from Ensembl Compara orthology. Reason: This is too specific and likely represents an indirect pharmacological effect. |
| GO:0043473 pigmentation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation from Ensembl Compara orthology. Reason: This is a very distal developmental phenotype, not a core function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: MYC is a transcriptional activator that positively regulates target gene transcription via RNA Pol II. Reason: Positive regulation of transcription by RNA Pol II is a core function of MYC as a transcription factor. |
| GO:0048705 skeletal system morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Developmental annotation from Ensembl Compara orthology. Reason: Tissue-specific developmental process, not a core MYC function. |
| GO:0050910 detection of mechanical stimulus involved in sensory perception of sound | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Annotation from Ensembl Compara orthology. Reason: This is a very specific sensory process with no clear direct connection to MYC function. |
| GO:1904699 positive regulation of acinar cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell-type specific proliferation annotation from Ensembl Compara. Reason: This is a tissue-specific manifestation of MYC proliferative function. |
| GO:1990863 acinar cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell-type specific proliferation annotation from Ensembl Compara. Reason: This is a tissue-specific manifestation of MYC proliferative function. |
| GO:2001235 positive regulation of apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC can activate apoptotic signaling under stress conditions. Reason: MYC-induced apoptosis is context-dependent and not its primary function. |
| GO:0016072 rRNA metabolic process | IMP PMID:38225354 Ribogenesis boosts controlled by HEATR1-MYC interplay promot... | ACCEPT | Summary: MYC localizes to the nucleolus via HEATR1 interaction and regulates ribosome biogenesis and rRNA synthesis. Reason: Regulation of ribosome biogenesis is a well-documented core function of MYC, directly linked to its role in promoting cell growth and proliferation. Supporting Evidence: PMID:38225354 Jan 15. Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth. |
| GO:0005515 protein binding | IPI PMID:38225354 Ribogenesis boosts controlled by HEATR1-MYC interplay promot... | REMOVE | Summary: Generic protein binding from a study on HEATR1-MYC interaction in ribogenesis. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:38225354 Jan 15. Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth. |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IMP PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | KEEP AS NON CORE | Summary: MYC represses gene expression by recruiting DNA methyltransferases to target gene promoters. Reason: While MYC can influence DNA methylation patterns, this is a context-specific mechanism of repression, not its primary mode of action. Supporting Evidence: PMID:19786833 Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IMP PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: MYC binds to cis-regulatory regions at target gene promoters. Reason: This is a core molecular function of MYC as a DNA-binding transcription factor. Supporting Evidence: PMID:19786833 Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IMP PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: MYC has transcription repressor activity mediated through MIZ1 interaction and DNMT recruitment. Reason: Transcription repressor activity is a core function of MYC, particularly through its interaction with MIZ1. Supporting Evidence: PMID:19786833 Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. |
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:25438055 AMBRA1 links autophagy to cell proliferation and tumorigenes... | ACCEPT | Summary: MYC regulates G1/S transition through transcriptional control of cyclin/CDK genes and repression of CDK inhibitors. Reason: Regulation of G1/S transition is a core biological process function of MYC in promoting cell cycle progression. Supporting Evidence: PMID:25438055 AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:10723141 Identification of Mad as a repressor of the human telomerase... | ACCEPT | Summary: Direct experimental evidence for MYC DNA-binding transcription factor activity. Reason: This is the core molecular function of MYC. Supporting Evidence: PMID:10723141 Identification of Mad as a repressor of the human telomerase (hTERT) gene. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin... | ACCEPT | Summary: Experimental evidence for MYC transcription factor activity. Reason: Core molecular function of MYC. Supporting Evidence: PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:29203640 Transforming Growth Factor Ξ²-Induced Proliferative Arrest Me... | ACCEPT | Summary: MYC represses transcription of target genes. Reason: Transcription repressor activity (via MIZ1) is a core function of MYC. Supporting Evidence: PMID:29203640 2018 Mar 1. Transforming Growth Factor Ξ²-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC. |
| GO:0001221 transcription coregulator binding | IPI PMID:15674325 PARP-10, a novel Myc-interacting protein with poly(ADP-ribos... | ACCEPT | Summary: MYC interacts with transcription coregulators including TAF1C for rRNA transcription. Reason: Binding to transcription coregulators is essential for MYC transcriptional activity. Supporting Evidence: PMID:15674325 PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:15674325 PARP-10, a novel Myc-interacting protein with poly(ADP-ribos... | ACCEPT | Summary: MYC binds other DNA-binding transcription factors as part of its regulatory mechanism. Reason: This is more informative than generic protein binding and describes functional interactions relevant to MYC activity. Supporting Evidence: PMID:15674325 PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:27791094 Primate-specific miR-515 family members inhibit key genes in... | ACCEPT | Summary: MYC functions as a transcriptional activator at E-box containing promoters. Reason: Transcription activator activity is a core molecular function of MYC. Supporting Evidence: PMID:27791094 Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia. |
| GO:0070888 E-box binding | IDA PMID:27791094 Primate-specific miR-515 family members inhibit key genes in... | ACCEPT | Summary: MYC binds E-box DNA sequences (CACGTG) as a heterodimer with MAX. Reason: E-box binding is the specific DNA binding activity of MYC and represents a core molecular function. Supporting Evidence: PMID:27791094 Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia. |
| GO:0001046 core promoter sequence-specific DNA binding | IDA PMID:30873824 Integrin alpha x stimulates cancer angiogenesis through PI3K... | ACCEPT | Summary: MYC binds core promoter sequences at target genes. Reason: Promoter binding is a core function of MYC as a transcription factor. Supporting Evidence: PMID:30873824 Sep 14. Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression in blood vessel endothelial cells. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: MYC transcription factor activity inferred from sequence and structural similarity. Reason: ISA annotation correctly identifies MYC transcription factor activity based on structural conservation. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: MYC represses transcription through DNA methylation-mediated mechanisms. Reason: Transcriptional repression is a core function of MYC. Supporting Evidence: PMID:19786833 Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. |
| GO:0005515 protein binding | IPI PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | REMOVE | Summary: Generic protein binding from a DNA methylation study. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:19786833 Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IMP PMID:25956029 The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regula... | ACCEPT | Summary: MYC transcription factor activity from a study on GLTSCR2-NPM1-MYC axis. Reason: Core molecular function of MYC. Supporting Evidence: PMID:25956029 2015 May 5. The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regulator of the Oncogenic Nucleophosmin-MYC Axis. |
| GO:0005515 protein binding | IPI PMID:25956029 The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regula... | REMOVE | Summary: Generic protein binding from a study on nucleophosmin-MYC interaction. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:25956029 2015 May 5. The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regulator of the Oncogenic Nucleophosmin-MYC Axis. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | ACCEPT | Summary: MYC represses transcription at specific target genes. Reason: Transcriptional repression is a core function of MYC. Supporting Evidence: PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | ACCEPT | Summary: MYC binds other transcription factors as part of its regulatory function. Reason: This is more informative than generic protein binding. Supporting Evidence: PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:10723141 Identification of Mad as a repressor of the human telomerase... | ACCEPT | Summary: Direct evidence for MYC binding to cis-regulatory regions. Reason: Core molecular function of MYC. Supporting Evidence: PMID:10723141 Identification of Mad as a repressor of the human telomerase (hTERT) gene. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:10723141 Identification of Mad as a repressor of the human telomerase... | ACCEPT | Summary: MYC activates transcription at target genes. Reason: Transcription activator activity is a core function of MYC. Supporting Evidence: PMID:10723141 Identification of Mad as a repressor of the human telomerase (hTERT) gene. |
| GO:0010468 regulation of gene expression | IDA PMID:21447833 TIP110/p110nrb/SART3/p110 regulation of hematopoiesis throug... | ACCEPT | Summary: MYC regulates expression of many target genes. Reason: Gene expression regulation is the core function of MYC as a transcription factor. Supporting Evidence: PMID:21447833 2011 Mar 29. TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC. |
| GO:0000165 MAPK cascade | IMP PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to... | KEEP AS NON CORE | Summary: MYC stability is regulated by MAPK signaling through phosphorylation. Reason: MYC is regulated by MAPK signaling but is not a direct component of the MAPK cascade. Supporting Evidence: PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. |
| GO:0005515 protein binding | IPI PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to... | REMOVE | Summary: Generic protein binding from a study on FBXW7 and USP28 regulation of MYC. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. |
| GO:0044877 protein-containing complex binding | IDA PMID:18987311 The parafibromin tumor suppressor protein inhibits cell prol... | ACCEPT | Summary: MYC binds to protein complexes as part of its function. Reason: This is more informative than generic protein binding and reflects MYC interaction with multiprotein complexes. Supporting Evidence: PMID:18987311 The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene. |
| GO:0003677 DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: MYC DNA binding inferred from sequence similarity. Reason: DNA binding is a core function of MYC. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin... | ACCEPT | Summary: MYC represses transcription at specific promoters. Reason: Transcriptional repression is a core function of MYC. Supporting Evidence: PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. |
| GO:0005515 protein binding | IPI PMID:20551172 Myc protein is stabilized by suppression of a novel E3 ligas... | REMOVE | Summary: Generic protein binding from a study on TRPC4AP E3 ligase complex. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:20551172 Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells. |
| GO:0070888 E-box binding | IDA PMID:18818310 AP4 encodes a c-MYC-inducible repressor of p21. | ACCEPT | Summary: Direct evidence for MYC binding to E-box sequences. Reason: E-box binding is the core DNA binding specificity of MYC. Supporting Evidence: PMID:18818310 AP4 encodes a c-MYC-inducible repressor of p21. |
| GO:0005515 protein binding | IPI PMID:15103331 Phosphorylation-dependent degradation of c-Myc is mediated b... | REMOVE | Summary: Generic protein binding from a study on FBXW7-mediated MYC degradation. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:15103331 Apr 22. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. |
| GO:0001658 branching involved in ureteric bud morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MYC role in kidney development inferred from sequence similarity. Reason: Tissue-specific developmental process, not a core function. |
| GO:0003677 DNA binding | TAS PMID:10597290 Nmi protein interacts with regions that differ between MycN ... | ACCEPT | Summary: MYC DNA binding established by traceable author statement. Reason: DNA binding is a core function of MYC. Supporting Evidence: PMID:10597290 Nmi protein interacts with regions that differ between MycN and Myc and is localized in the cytoplasm of neuroblastoma cells in contrast to nuclear MycN. |
| GO:0005515 protein binding | IPI PMID:10597290 Nmi protein interacts with regions that differ between MycN ... | REMOVE | Summary: Generic protein binding from a study on E7 oncoprotein interaction with MYC. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:10597290 Nmi protein interacts with regions that differ between MycN and Myc and is localized in the cytoplasm of neuroblastoma cells in contrast to nuclear MycN. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:15994933 Identification of a novel c-Myc protein interactor, JPO2, wi... | ACCEPT | Summary: MYC promotes cell proliferation through transcriptional activation of growth genes. Reason: Positive regulation of cell proliferation is a core biological process function of MYC. Supporting Evidence: PMID:15994933 Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells. |
| GO:0005515 protein binding | IPI PMID:9308237 Association of Myc with the zinc-finger protein Miz-1 define... | REMOVE | Summary: Generic protein binding from a study on Myc-Max-Mad network. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:9308237 Association of Myc with the zinc-finger protein Miz-1 defines a novel pathway for gene regulation by Myc. |
| GO:0005515 protein binding | IPI PMID:12706874 Yaf2 inhibits Myc biological function. | REMOVE | Summary: Generic protein binding from a study on transrepression of Smad transcriptional activity by Myc. Reason: GO:0005515 protein binding is uninformative. Supporting Evidence: PMID:12706874 Yaf2 inhibits Myc biological function. |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | ACCEPT | Summary: MYC positively regulates cell proliferation, a core function inferred by phylogenetic analysis. Reason: Positive regulation of cell proliferation is a core function of MYC as a proto-oncogene. IBA annotation is phylogenetically sound. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: MYC regulates RNA Pol II transcription, a core function inferred by phylogenetic analysis. Reason: Regulation of transcription by RNA Pol II is the core function of MYC as a transcription factor. IBA annotation is phylogenetically sound. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: MYC localizes to the nucleus to function as a transcription factor. Reason: Nuclear localization is essential for MYC transcriptional activity. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: MYC localizes to the nucleoplasm where it functions as a transcriptional regulator. Reason: Nucleoplasm localization is consistent with MYC function. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: MYC associates with chromosomes/chromatin at target gene loci. Reason: Chromosome association is essential for MYC DNA binding and transcriptional activity. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: MYC localizes to the nucleolus for rRNA transcription regulation. Reason: Nucleolar localization is important for MYC function in ribosome biogenesis. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A fraction of MYC can be found in the cytoplasm. Reason: While MYC can be cytoplasmic (especially Myc-nick isoform), its primary localization is nuclear. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: MYC regulates DNA-templated transcription as a transcription factor. Reason: This is the core function of MYC. |
| GO:0005634 nucleus | IDA PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene en... | ACCEPT | Summary: Nuclear localization is essential for MYC's function as a transcriptional regulator Reason: Nuclear localization is core to MYC's role in transcriptional regulation and gene expression control Supporting Evidence: PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. |
| GO:0090571 RNA polymerase II transcription repressor complex | IPI PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene en... | ACCEPT | Summary: MYC is a component of transcription repressor complexes with MIZ1 to repress target genes. Reason: MYC participates in repressor complexes, which is essential for its repressive function. Supporting Evidence: PMID:18393360 c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. |
| GO:0005634 nucleus | NAS PMID:8425218 Mad: a heterodimeric partner for Max that antagonizes Myc tr... | ACCEPT | Summary: Nuclear localization of MYC. Reason: Nuclear localization is essential for MYC function. Supporting Evidence: PMID:8425218 Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. |
| GO:0005634 nucleus | IDA PMID:8782822 BIN1 is a novel MYC-interacting protein with features of a t... | ACCEPT | Summary: Direct assay evidence for MYC nuclear localization. Reason: Nuclear localization is core to MYC function. Supporting Evidence: PMID:8782822 BIN1 is a novel MYC-interacting protein with features of a tumour suppressor. |
| GO:0010564 regulation of cell cycle process | IDA PMID:8782822 BIN1 is a novel MYC-interacting protein with features of a t... | ACCEPT | Summary: MYC regulates cell cycle progression through transcriptional control of cyclins and CDK inhibitors. Reason: Cell cycle regulation is a core function of MYC as a growth regulator. Supporting Evidence: PMID:8782822 BIN1 is a novel MYC-interacting protein with features of a tumour suppressor. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:8425218 Mad: a heterodimeric partner for Max that antagonizes Myc tr... | ACCEPT | Summary: MYC positively regulates transcription of target genes. Reason: Positive transcriptional regulation is a core function of MYC. Supporting Evidence: PMID:8425218 Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. |
| GO:0071943 Myc-Max complex | IPI PMID:12553908 X-ray structures of Myc-Max and Mad-Max recognizing DNA. Mol... | ACCEPT | Summary: MYC forms a heterodimeric complex with MAX for DNA binding and transcriptional activity. Reason: The Myc-Max complex is the functional unit for MYC transcriptional activity. This is a core cellular component annotation. Supporting Evidence: PMID:12553908 X-ray structures of Myc-Max and Mad-Max recognizing DNA. |
| GO:0090571 RNA polymerase II transcription repressor complex | IPI PMID:15992821 A structure-based model of the c-Myc/Bin1 protein interactio... | ACCEPT | Summary: MYC participates in transcription repressor complexes with BIN1. Reason: MYC is part of repressor complexes for transcriptional repression function. Supporting Evidence: PMID:15992821 A structure-based model of the c-Myc/Bin1 protein interaction shows alternative splicing of Bin1 and c-Myc phosphorylation are key binding determinants. |
| GO:0000791 euchromatin | IEA GO_REF:0000107 | ACCEPT | Summary: MYC preferentially associates with active euchromatin at target genes. Reason: Euchromatin association is consistent with MYC role as a transcriptional activator. |
| GO:0002053 positive regulation of mesenchymal cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cell-type specific proliferation annotation from Ensembl Compara. Reason: Tissue-specific manifestation of MYC proliferative function. |
| GO:0005819 spindle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: MYC may localize to spindle during mitosis. Reason: Spindle localization is not a well-characterized or core aspect of MYC function. |
| GO:0016604 nuclear body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC localizes to nuclear bodies. Reason: While MYC can localize to nuclear bodies including nucleolus, this is not the primary localization. |
| GO:0030424 axon | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Neuronal-specific localization annotation. Reason: Axon localization is not a well-characterized or core aspect of MYC function. |
| GO:0032206 positive regulation of telomere maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC regulates TERT expression and telomere maintenance. Reason: While MYC transcriptionally activates TERT, telomere maintenance is a downstream effect. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: MYC positively regulates transcription at many target genes. Reason: Positive transcriptional regulation is a core function of MYC. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: MYC may localize to perinuclear region. Reason: This is not a primary or well-characterized localization for MYC. |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: MYC promotes transcription initiation at target gene promoters. Reason: MYC regulates transcription initiation as part of its core function. |
| GO:0071943 Myc-Max complex | IEA GO_REF:0000107 | ACCEPT | Summary: MYC forms the Myc-Max heterodimer complex for transcriptional regulation. Reason: The Myc-Max complex is the functional unit for MYC activity. |
| GO:0090096 positive regulation of metanephric cap mesenchymal cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Kidney-specific proliferation annotation from Ensembl Compara. Reason: This highly tissue-specific and developmental stage-specific term is an over-annotation. While MYC is important for proliferation in many contexts including kidney development, annotating to this very specific term is overly granular. |
| GO:1904672 regulation of somatic stem cell population maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: MYC regulates stem cell self-renewal and maintenance. Reason: While MYC is one of the Yamanaka factors for iPSC reprogramming, stem cell maintenance is a context-specific function. |
| GO:0000785 chromatin | IDA PMID:30158517 MYC dephosphorylation by the PP1/PNUTS phosphatase complex r... | ACCEPT | Summary: MYC directly binds to chromatin to regulate target gene expression Reason: Chromatin association is essential for MYC's function as a transcription factor that directly regulates gene expression Supporting Evidence: PMID:30158517 MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: MYC localizes to the nucleoplasm where it forms transcriptional complexes Reason: Nucleoplasm localization is consistent with MYC's role in forming transcriptional regulatory complexes |
| GO:0005730 nucleolus | IDA PMID:38225354 Ribogenesis boosts controlled by HEATR1-MYC interplay promot... | ACCEPT | Summary: MYC localizes to the nucleolus via HEATR1 interaction for ribosome biogenesis regulation. Reason: Nucleolar localization is important for MYC function in rRNA transcription and ribosome biogenesis. Supporting Evidence: PMID:38225354 Jan 15. Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth. |
| GO:0032206 positive regulation of telomere maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MYC regulates telomere maintenance through TERT transcription. Reason: Telomere maintenance is a downstream effect of MYC transcriptional activity, not a core function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: MYC positively regulates transcription by RNA Pol II. Reason: This is a core function of MYC as a transcription factor. |
| GO:0005634 nucleus | IDA PMID:11793365 Expression of frizzled-related protein and Wnt-signalling mo... | ACCEPT | Summary: MYC nuclear localization demonstrated by direct assay. Reason: Nuclear localization is essential for MYC function. Supporting Evidence: PMID:11793365 Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours. |
| GO:0060633 negative regulation of transcription initiation by RNA polymerase II | IDA PMID:29203640 Transforming Growth Factor Ξ²-Induced Proliferative Arrest Me... | ACCEPT | Summary: MYC represses transcription initiation at specific target genes. Reason: Negative regulation of transcription initiation is a core repressive function of MYC. Supporting Evidence: PMID:29203640 2018 Mar 1. Transforming Growth Factor Ξ²-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC. |
| GO:1902255 positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator | IDA PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of norm... | KEEP AS NON CORE | Summary: MYC can activate apoptosis through p53-dependent pathways. Reason: MYC-induced apoptosis via p53 is a context-dependent function, not the primary role of MYC. Supporting Evidence: PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. |
| GO:1902895 positive regulation of miRNA transcription | IDA PMID:27791094 Primate-specific miR-515 family members inhibit key genes in... | KEEP AS NON CORE | Summary: MYC regulates transcription of miRNAs as part of its transcriptional program. Reason: miRNA transcription regulation is a specific aspect of MYC transcriptional activity. Supporting Evidence: PMID:27791094 Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia. |
| GO:0000785 chromatin | IMP PMID:12837246 Multiple tumor suppressor pathways negatively regulate telom... | ACCEPT | Summary: MYC associates with chromatin at target gene promoters. Reason: Chromatin association is essential for MYC transcriptional activity. Supporting Evidence: PMID:12837246 Multiple tumor suppressor pathways negatively regulate telomerase. |
| GO:1904672 regulation of somatic stem cell population maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MYC regulates stem cell maintenance (Yamanaka factor). Reason: Stem cell maintenance is a context-specific function. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: MYC chromatin association inferred from structural annotation. Reason: Chromatin association is core to MYC function. |
| GO:0005730 nucleolus | IDA PMID:25775507 The nucleolar ubiquitin-specific protease USP36 deubiquitina... | ACCEPT | Summary: MYC localizes to nucleolus and is stabilized by USP36. Reason: Nucleolar localization is important for MYC function in ribosome biogenesis. Supporting Evidence: PMID:25775507 The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc. |
| GO:0032986 protein-DNA complex disassembly | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | KEEP AS NON CORE | Summary: MYC promotes protein-DNA complex disassembly at repressed promoters. Reason: This is a specific mechanism of MYC repressive function. Supporting Evidence: PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth. |
| GO:0032991 protein-containing complex | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | ACCEPT | Summary: MYC is part of protein-containing transcriptional complexes. Reason: MYC functions within multiprotein complexes for transcriptional regulation. Supporting Evidence: PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth. |
| GO:0010628 positive regulation of gene expression | IDA PMID:15459207 ERK1/2 regulates intracellular ATP levels through alpha-enol... | ACCEPT | Summary: MYC positively regulates gene expression. Reason: Positive regulation of gene expression is a core function of MYC. Supporting Evidence: PMID:15459207 2004 Sep 30. ERK1/2 regulates intracellular ATP levels through alpha-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation. |
| GO:0010628 positive regulation of gene expression | IGI PMID:15459207 ERK1/2 regulates intracellular ATP levels through alpha-enol... | ACCEPT | Summary: MYC positive regulation of gene expression supported by genetic interaction. Reason: Core function of MYC. Supporting Evidence: PMID:15459207 2004 Sep 30. ERK1/2 regulates intracellular ATP levels through alpha-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation. |
| GO:0070371 ERK1 and ERK2 cascade | IDA PMID:15459207 ERK1/2 regulates intracellular ATP levels through alpha-enol... | KEEP AS NON CORE | Summary: MYC is involved in ERK1/2 signaling cascades. Reason: MYC is regulated by and influences ERK signaling but is not a direct component. Supporting Evidence: PMID:15459207 2004 Sep 30. ERK1/2 regulates intracellular ATP levels through alpha-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation. |
| GO:0071456 cellular response to hypoxia | IDA PMID:15459207 ERK1/2 regulates intracellular ATP levels through alpha-enol... | KEEP AS NON CORE | Summary: MYC is involved in cellular response to hypoxia. Reason: Hypoxia response is a context-specific function. Supporting Evidence: PMID:15459207 2004 Sep 30. ERK1/2 regulates intracellular ATP levels through alpha-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5696914 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core to MYC function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:10723141 Identification of Mad as a repressor of the human telomerase... | ACCEPT | Summary: MYC positively regulates RNA Pol II transcription. Reason: Core function of MYC. Supporting Evidence: PMID:10723141 Identification of Mad as a repressor of the human telomerase (hTERT) gene. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1484099 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1980067 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2220985 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4411357 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687083 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5687113 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6790036 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8865265 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8865280 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8932400 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9011975 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9725332 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9762097 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9816153 | ACCEPT | Summary: MYC nucleoplasm localization from Reactome pathway. Reason: Nucleoplasm localization is core. |
| GO:0005634 nucleus | IDA PMID:15358760 Sterol-responsive element-binding protein (SREBP) 2 down-reg... | ACCEPT | Summary: MYC nuclear localization by direct assay. Reason: Nuclear localization is essential for MYC function. Supporting Evidence: PMID:15358760 2004 Sep 8. Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: a novel role of SREBP in regulating cholesterol metabolism. |
| GO:0006338 chromatin remodeling | IDA PMID:21533051 Multiple Wnt/Γ-catenin responsive enhancers align with the M... | ACCEPT | Summary: MYC promotes chromatin remodeling at target genes. Reason: Chromatin remodeling is part of MYC transcriptional activation mechanism. Supporting Evidence: PMID:21533051 Multiple Wnt/Γ-catenin responsive enhancers align with the MYC promoter through long-range chromatin loops. |
| GO:0006974 DNA damage response | IDA PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to... | KEEP AS NON CORE | Summary: MYC is involved in DNA damage response signaling. Reason: DNA damage response is context-specific, not a core MYC function. Supporting Evidence: PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. |
| GO:0032991 protein-containing complex | IDA PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to... | ACCEPT | Summary: MYC is part of protein complexes for its regulation. Reason: MYC functions within protein complexes. Supporting Evidence: PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. |
| GO:0034644 cellular response to UV | IEP PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to... | MARK AS OVER ANNOTATED | Summary: MYC expression is affected by UV radiation. Reason: UV response is a general stress response, not a core MYC function. Supporting Evidence: PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. |
| GO:0048146 positive regulation of fibroblast proliferation | IMP PMID:15674325 PARP-10, a novel Myc-interacting protein with poly(ADP-ribos... | KEEP AS NON CORE | Summary: MYC promotes fibroblast proliferation. Reason: Cell-type specific proliferation effect. Supporting Evidence: PMID:15674325 PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. |
| GO:0048146 positive regulation of fibroblast proliferation | IDA PMID:18987311 The parafibromin tumor suppressor protein inhibits cell prol... | KEEP AS NON CORE | Summary: MYC promotes fibroblast proliferation. Reason: Cell-type specific proliferation effect. Supporting Evidence: PMID:18987311 The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene. |
| GO:0050679 positive regulation of epithelial cell proliferation | IDA PMID:18987311 The parafibromin tumor suppressor protein inhibits cell prol... | KEEP AS NON CORE | Summary: MYC promotes epithelial cell proliferation. Reason: Cell-type specific proliferation effect. Supporting Evidence: PMID:18987311 The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene. |
| GO:0070848 response to growth factor | TAS PMID:18987311 The parafibromin tumor suppressor protein inhibits cell prol... | KEEP AS NON CORE | Summary: MYC is induced in response to growth factor signaling. Reason: Growth factor response is an upstream regulatory event, not a core MYC function. Supporting Evidence: PMID:18987311 The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene. |
| GO:0071466 cellular response to xenobiotic stimulus | IDA PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to... | MARK AS OVER ANNOTATED | Summary: MYC levels change in response to xenobiotic stress. Reason: Xenobiotic response is a general stress response, not a core MYC function. Supporting Evidence: PMID:17873522 Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. |
| GO:0032873 negative regulation of stress-activated MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MYC can modulate stress-activated MAPK signaling. Reason: MAPK regulation is context-dependent and not a core MYC function. |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MYC can inhibit apoptosis under certain conditions. Reason: MYC has dual effects on apoptosis (can both promote and inhibit); this is context-dependent. |
| GO:0006879 intracellular iron ion homeostasis | IDA PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin... | KEEP AS NON CORE | Summary: MYC regulates iron homeostasis genes. Reason: Iron homeostasis regulation is a specific metabolic function of MYC, not its primary role. Supporting Evidence: PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. |
| GO:0044346 fibroblast apoptotic process | TAS PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of norm... | KEEP AS NON CORE | Summary: MYC promotes fibroblast apoptosis under certain conditions. Reason: Cell-type specific apoptotic function. Supporting Evidence: PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. |
| GO:0045656 negative regulation of monocyte differentiation | IMP PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin... | KEEP AS NON CORE | Summary: MYC inhibits monocyte differentiation to maintain proliferative state. Reason: Cell-type specific differentiation effect. Supporting Evidence: PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of norm... | ACCEPT | Summary: MYC positively regulates transcription. Reason: Positive transcription regulation is a core function of MYC. Supporting Evidence: PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin... | ACCEPT | Summary: MYC positively regulates RNA Pol II transcription. Reason: Core function of MYC. Supporting Evidence: PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. |
| GO:0048146 positive regulation of fibroblast proliferation | IDA PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin... | KEEP AS NON CORE | Summary: MYC promotes fibroblast proliferation. Reason: Cell-type specific proliferation effect. Supporting Evidence: PMID:9924025 Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. |
| GO:0048147 negative regulation of fibroblast proliferation | IDA PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of norm... | KEEP AS NON CORE | Summary: MYC can negatively regulate fibroblast proliferation in certain contexts (apoptosis). Reason: Context-dependent effect on proliferation. Supporting Evidence: PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. |
| GO:0051276 chromosome organization | IDA PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of norm... | KEEP AS NON CORE | Summary: MYC affects chromosome organization at target loci. Reason: Chromosome organization is a downstream effect of MYC chromatin binding. Supporting Evidence: PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. |
| GO:0051782 negative regulation of cell division | IDA PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of norm... | MARK AS OVER ANNOTATED | Summary: MYC primarily promotes cell proliferation rather than inhibiting cell division. This annotation is paradoxical given MYC's well-established role as a driver of cell cycle progression and proliferation. Reason: MYC is predominantly a positive regulator of cell division and proliferation. While MYC can induce growth arrest in certain contexts (e.g., at very high levels or in cells lacking survival signals), negative regulation of cell division is not a core function and this annotation may reflect specific experimental conditions rather than physiological MYC function. Supporting Evidence: PMID:10962037 Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. |
| GO:0005654 nucleoplasm | IDA PMID:17558397 The ubiquitin-specific protease USP28 is required for MYC st... | ACCEPT | Summary: MYC is a nuclear transcription factor that localizes to the nucleoplasm where it binds chromatin and regulates transcription. Reason: Nucleoplasm localization is essential for MYC function as a transcription factor. UniProt confirms nuclear localization, and MYC contains a nuclear localization signal (NLS) that directs it to the nucleus. Supporting Evidence: PMID:17558397 The ubiquitin-specific protease USP28 is required for MYC stability. |
| GO:0005730 nucleolus | IDA PMID:17558397 The ubiquitin-specific protease USP28 is required for MYC st... | ACCEPT | Summary: MYC has been detected in the nucleolus where it regulates ribosomal RNA transcription and ribosome biogenesis. Reason: Nucleolar localization is important for MYC function in ribosome biogenesis and rRNA transcription regulation, consistent with other nucleolus annotations. Supporting Evidence: PMID:17558397 The ubiquitin-specific protease USP28 is required for MYC stability. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:17558397 The ubiquitin-specific protease USP28 is required for MYC st... | ACCEPT | Summary: MYC-MAX heterodimers activate transcription by binding E-box elements and recruiting transcriptional coactivators including histone acetyltransferases. Reason: Positive regulation of transcription is a core function of MYC. MYC-MAX complexes bind E-box DNA elements at target gene promoters and recruit coactivators (including TRRAP-containing HAT complexes) to activate gene expression, particularly genes involved in cell growth and proliferation. Supporting Evidence: PMID:17558397 The ubiquitin-specific protease USP28 is required for MYC stability. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:18291362 Sulindac suppresses beta-catenin expression in human cancer ... | MARK AS OVER ANNOTATED | Summary: MYC expression can be modulated in response to xenobiotic exposure, likely reflecting stress or proliferative responses. Reason: IEP (Inferred from Expression Pattern) evidence indicates MYC expression changes in response to xenobiotic stimulus. However, MYC expression changes in many contexts as a general growth/stress response. This is not a core function of MYC but rather reflects its role as an immediate-early gene responsive to various stimuli. Supporting Evidence: PMID:18291362 Epub 2008 Feb 5. Sulindac suppresses beta-catenin expression in human cancer cells. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:18818310 AP4 encodes a c-MYC-inducible repressor of p21. | ACCEPT | Summary: MYC-MAX heterodimers bind E-box elements to activate transcription of target genes promoting cell growth and proliferation. Reason: Positive regulation of transcription is a core function of MYC. This IDA evidence from an independent study further supports MYC's well-established role as a transcriptional activator. Supporting Evidence: PMID:18818310 AP4 encodes a c-MYC-inducible repressor of p21. |
| GO:0002053 positive regulation of mesenchymal cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: MYC promotes proliferation in mesenchymal cells through its general role as a transcriptional activator of cell cycle and growth genes. Reason: MYC is a general promoter of cell proliferation across many cell types. While this ISS annotation is likely correct, positive regulation of mesenchymal cell proliferation specifically is a cell type-specific manifestation of MYC's broader proliferative function rather than a core function. |
| GO:0090096 positive regulation of metanephric cap mesenchymal cell proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: MYC promotes cell proliferation in metanephric cap mesenchyme during kidney development. Reason: This highly tissue-specific and developmental stage-specific term is an over-annotation. While MYC is important for proliferation in many contexts including kidney development, annotating to this very specific term based on sequence similarity (ISS) is overly granular. MYC's general proliferative function is the core annotation. |
| GO:0032204 regulation of telomere maintenance | IMP PMID:17765874 c-Myc interacts with TRF1/PIN2 and regulates telomere length... | KEEP AS NON CORE | Summary: MYC activates telomerase expression by binding to the TERT promoter, contributing to telomere maintenance and cellular immortalization. Reason: MYC directly regulates TERT (telomerase reverse transcriptase) expression, contributing to telomere maintenance. This is an important function in the context of MYC-driven immortalization and cancer, but represents a specific downstream target rather than a core molecular function of MYC. Supporting Evidence: PMID:17765874 c-Myc interacts with TRF1/PIN2 and regulates telomere length. |
| GO:0005634 nucleus | IDA PMID:15994933 Identification of a novel c-Myc protein interactor, JPO2, wi... | ACCEPT | Summary: MYC is a nuclear transcription factor that requires nuclear localization for its function in regulating gene expression. Reason: Nuclear localization is fundamental to MYC function as a transcription factor. MYC contains a nuclear localization signal and exerts its primary function in the nucleus by binding DNA and regulating transcription. Supporting Evidence: PMID:15994933 Identification of a novel c-Myc protein interactor, JPO2, with transforming activity in medulloblastoma cells. |
| GO:0005634 nucleus | TAS PMID:9187264 Histamine modulates the expression of c-fos through cyclic A... | ACCEPT | Summary: MYC is a nuclear transcription factor established through extensive literature. Reason: Nuclear localization is well-established for MYC and essential for its function. TAS evidence from a review article confirms the consensus in the field. Supporting Evidence: PMID:9187264 Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937. |
| GO:0065003 protein-containing complex assembly | IEA | NEW | Summary: Essential for protein-containing complex assembly, particularly Myc-Max complex formation required for transcriptional regulation Reason: MYC functions primarily through heterodimerization with MAX to form the Myc-Max transcriptional complex. This protein-containing complex assembly is fundamental to MYC's mechanism of action, as the Myc-Max heterodimer is required for DNA binding and transcriptional regulation. The complex formation is essential for both transcriptional activation and repression activities. Supporting Evidence: PMID:12553908 X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. PMID:21807113 Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. |
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