Existing Annotations Review

Core Functions

DNA-binding transcription factor activity forming heterodimers with MAX to bind E-box sequences and regulate target gene expression

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

Substrates:

deoxyribonucleic acid

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:27791094
Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia.
PMID:18818310
AP4 encodes a c-MYC-inducible repressor of p21.

E-box DNA binding activity recognizing CANNTG sequences in target gene promoters and enhancers

Molecular Function:

E-box binding

Directly Involved In:

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

Cellular Locations:

nucleus chromatin

Substrates:

deoxyribonucleic acid

Supporting Evidence:

PMID:27791094
E-box binding and transcriptional activation of target genes
PMID:18818310
E-box sequence recognition and binding specificity

Protein dimerization activity forming heterodimers with MAX protein for DNA binding and transcriptional regulation

Molecular Function:

protein dimerization activity

Directly Involved In:

protein-containing complex assembly

Cellular Locations:

nucleus nucleoplasm

In Complex:

Myc-Max complex

Substrates:

MAX protein

Supporting Evidence:

PMID:12553908
X-ray structures of Myc-Max heterodimers demonstrate molecular basis for dimerization
PMID:21807113
Sirt1 deacetylates c-Myc and promotes c-Myc/Max association

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:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.

GO_REF:0000113

Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods.

PMID:10412034

Induction of apoptosis and differentiation in neuroblastoma and astrocytoma cells by the overexpression of Bin1, a novel Myc interacting protein.

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.

PMID:10723141

Identification of Mad as a repressor of the human telomerase (hTERT) gene.

PMID:11891322

Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts.

PMID:12706874

Yaf2 inhibits Myc biological function.

PMID:15103331

Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7.

PMID:15674325

PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation.

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.

PMID:15994933

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

PMID:16352593

Targeting of Miz-1 is essential for Myc-mediated apoptosis.

PMID:16606833

Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation.

PMID:16996503

Myc stabilization in response to estrogen and phospholipase D in MCF-7 breast cancer cells.

PMID:17070091

HPV-18 E7 conjugates to c-Myc and mediates its transcriptional activity.

PMID:17157259

SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes.

PMID:17314511

Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach.

PMID:17418410

HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity.

PMID:17599065

Inhibition of c-Myc activity by ribosomal protein L11.

PMID:17632056

CIP2A inhibits PP2A in human malignancies.

PMID:17873522

Fbw7 and Usp28 regulate myc protein stability in response to DNA damage.

PMID:18256156

Epstein-Barr virus nuclear antigen 3C interacts with and enhances the stability of the c-Myc oncoprotein.

PMID:18393360

c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.

PMID:18413597

Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc.

PMID:18620061

Characterizing proteins and their interactions in cells and tissues using the in situ proximity ligation assay.

PMID:18818310

AP4 encodes a c-MYC-inducible repressor of p21.

PMID:18923429

Miz1 and HectH9 regulate the stability of the checkpoint protein, TopBP1.

PMID:18987311

The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene.

PMID:19131971

The Axin1 scaffold protein promotes formation of a degradation complex for c-Myc.

PMID:19160485

A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth.

PMID:19786833

Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation.

PMID:20195357

A comprehensive resource of interacting protein regions for refining human transcription factor networks.

PMID:20208519

Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses.

PMID:20551172

Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells.

PMID:20691906

Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation.

PMID:20713710

Noninvasive molecular imaging of c-Myc activation in living mice.

PMID:20936779

A human MAP kinase interactome.

PMID:20970423

NEMO stabilizes c-Myc through direct interaction in the nucleus.

PMID:21150319

Proteomic profiling of Myc-associated proteins.

PMID:21447833

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

PMID:21575199

IκB kinases increase Myc protein stability and enhance progression of breast cancer cells.

PMID:21807113

Sirt1 deacetylates c-Myc and promotes c-Myc/Max association.

PMID:21988832

Toward an understanding of the protein interaction network of the human liver.

PMID:22094256

A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.

PMID:23217706

The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism.

PMID:23455924

A Y2H-seq approach defines the human protein methyltransferase interactome.

PMID:23791182

The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability.

PMID:23804756

Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins.

PMID:24048479

Deterministic direct reprogramming of somatic cells to pluripotency.

PMID:24951594

Sin3b interacts with Myc and decreases Myc levels.

PMID:25438055

AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation.

PMID:25609649

Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

PMID:25956029

The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regulator of the Oncogenic Nucleophosmin-MYC Axis.

PMID:26267534

Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

PMID:26655473

Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity.

PMID:26766587

The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup Identity.

PMID:27705803

A High-Density Map for Navigating the Human Polycomb Complexome.

PMID:27791094

Primate-specific miR-515 family members inhibit key genes in human trophoblast differentiation and are upregulated in preeclampsia.

PMID:28007894

The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function.

PMID:29203640

Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC.

PMID:30873824

Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression in blood vessel endothelial cells.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34591642

A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.

PMID:35044719

Proteome-scale mapping of binding sites in the unstructured regions of the human proteome.

PMID:35140242

Human transcription factor protein interaction networks.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:35512704

Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.

PMID:37219487

Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.

PMID:38225354

Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth.

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.

PMID:9308237

Association of Myc with the zinc-finger protein Miz-1 defines a novel pathway for gene regulation by Myc.

PMID:9708738

The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins.

PMID:9924025

Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC.

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:0000052

Gene Ontology annotation based on curation of immunofluorescence data

PMID:10962037

Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts.

PMID:11793365

Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours.

PMID:12553908

X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors.

PMID:12837246

Multiple tumor suppressor pathways negatively regulate telomerase.

PMID:15358760

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.

PMID:15459207

ERK1/2 regulates intracellular ATP levels through alpha-enolase expression in cardiomyocytes exposed to ischemic hypoxia and reoxygenation.

PMID:17558397

The ubiquitin-specific protease USP28 is required for MYC stability.

PMID:17765874

c-Myc interacts with TRF1/PIN2 and regulates telomere length.

PMID:18291362

Sulindac suppresses beta-catenin expression in human cancer cells.

PMID:21533051

Multiple Wnt/ß-catenin responsive enhancers align with the MYC promoter through long-range chromatin loops.

PMID:25775507

The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc.

PMID:30158517

MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability.

PMID:8425218

Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity.

PMID:8782822

BIN1 is a novel MYC-interacting protein with features of a tumour suppressor.

PMID:9187264

Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937.

Reactome:R-HSA-1484099

MYC trancscription is negatively regulated by SMAD2/3:SMAD4:RBL1:E2F4/5:DP1/2 complex

Reactome:R-HSA-1980067

NOTCH1 stimulates MYC transcription

Reactome:R-HSA-2220985

NOTCH1 PEST domain mutants stimulate MYC transcription

Reactome:R-HSA-4411357

TCF7L1/TCF7L2/LEF1:CTNNB1 promote transcription of the MYC gene

Reactome:R-HSA-5687083

MYC binds MAPKAPK5 gene

Reactome:R-HSA-5687113

MYC mRNA translation is negatively regulated by miR-34B and C

Reactome:R-HSA-5696914

USP28 deubiquitinates CLSPN and MYC

Reactome:R-HSA-6790036

Expression of STAT3-upregulated nuclear proteins

Reactome:R-HSA-8865265

TFAP2C homodimer binds MYC and KDM5B

Reactome:R-HSA-8865280

TFAP2C homodimer binds the CDKN1A (p21) gene promoter

Reactome:R-HSA-8932400

MYC:MAX binds the CDC25A gene

Reactome:R-HSA-9011975

Estrogen-responsive MYC gene expression

Reactome:R-HSA-9725332

MYC/MYCN bind the ALK gene

Reactome:R-HSA-9762097

MYC binds the NFE2L2 promoter

Reactome:R-HSA-9816153

MYC,MYCN bind MIR9-3 gene locus

file:human/MYC/MYC-deep-research-falcon.md

Deep research report on MYC

📚 Additional Documentation

Deep Research Bioreason

(MYC-deep-research-bioreason.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:50 AM

Organism: Homo sapiens

Sequence:

MDFFRVVENQQPPATMPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGGDMVNQSFICDPDDETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSGSPNPARGHSVCSTSSLYLQDLSAAASECIDPSVVFPYPLNDSSSPKSCASQDSSAFSPSSDSLLSSTESSPQGSPEPLVLHEETPPTTSSDSEEEQEDEEEIDVVSVEKRQAPGKRSESGSPSAGGHSKPPHSPLVLKRCHVSTHQHNYAAPPSTRKDYPAAKRVKLDSVRVLRQISNNRKCTSPRSSDTEENVKRRTHNVLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILSVQAEEQKLISEEDLLRKRREQLKHKLEQLRNSCA

Thinking Trace

I begin by examining the InterPro architecture. The polypeptide is dominated by Myc-family signatures: IPR002418 (Transcription regulator Myc family, residues 16–452) and IPR050433 (Myc family transcription factors, residues 22–452) encompass essentially the full length, indicating a canonical Myc-like transcriptional regulator. The N-terminal half is reinforced by IPR012682 (Transcription regulator Myc, N-terminal domain, residues 17–360), a region known in Myc proteins to harbor transcriptional activation surfaces and short linear motifs that recruit co-regulators. The C-terminal half transitions into a DNA-recognition and dimerization module: IPR036638 (Helix-loop-helix DNA-binding domain superfamily, residues 361–454) provides the structural scaffold for sequence-specific DNA binding; embedded within it, IPR011598 (Myc-type, basic helix-loop-helix domain, residues 369–427) supplies the basic residues that contact DNA and the helix-loop-helix for dimer formation. Immediately following, IPR003327 (Leucine zipper, Myc, residues 423–453) forms the leucine zipper that stabilizes homo- or heterodimers and positions the basic region for high-affinity binding to E-box motifs (5′-CAC[GT]TG-3′). The ordered layout—N-terminal activation platform followed by a C-terminal bHLH-zipper DNA-binding/dimerization module—causally establishes a sequence-specific transcription factor that functions by dimeric DNA engagement and recruitment of transcriptional machinery.

This architecture dictates molecular function. The bHLH-zipper core (IPR011598 and IPR003327) binds DNA in a sequence-specific manner and requires dimerization to achieve high specificity and affinity, fulfilling DNA-binding transcription factor activity and explaining RNA polymerase II regulatory role through promoter/enhancer occupancy. The expansive Myc-family N-terminus (IPR012682 within IPR002418/IPR050433) creates interaction surfaces for co-activators and co-repressors, supporting protein binding and cooperative assembly of transcriptional complexes.

From function to process, Myc-family transcriptional regulators typically drive programs that coordinate growth and biosynthesis. By binding E-boxes and recruiting co-regulators through the N-terminal activation domain, this protein modulates transcriptional networks that promote cell proliferation and tune cell cycle progression. Thus it operates in regulation of transcription by RNA polymerase II and downstream biological programs including cell proliferation and regulation of the cell cycle.

Cellular location follows directly. A DNA-binding transcriptional regulator must act where chromatin and the transcriptional apparatus reside; the presence of a nuclear bHLH-zipper DNA-binding module and the Myc-family activation domain together predict a nuclear residency. This aligns with a soluble, chromatin-associated nuclear factor rather than a membrane or cytosolic enzyme.

Mechanistically, I hypothesize that the protein dimerizes via its leucine zipper to form high-affinity complexes at E-box-containing promoters and enhancers. The N-terminal domain recruits histone acetyltransferase co-activators and mediator components, shifting local chromatin toward an active state and boosting RNA polymerase II initiation and elongation. Likely partners include other bHLH-zipper transcription factors and co-regulators that stabilize or potentiate Myc-driven transcriptional outputs. This cooperative assembly enables precise transcriptional control that manifests as enhanced proliferative transcriptional programs within the nucleus.

Functional Summary

A nuclear transcriptional regulator that binds E-box DNA elements as a dimer and stimulates RNA polymerase II–dependent transcriptional programs. Its N-terminal activation region recruits co-regulatory machinery, while a C-terminal basic helix–loop–helix–leucine zipper module enforces sequence-specific DNA binding and dimerization. Together these features drive gene-expression circuits that promote proliferative and cell-cycle-associated pathways within the nucleus.

UniProt Summary

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 423-453

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), transcription regulator activity (GO:0140110), RNA polymerase II transcription factor activity, sequence-specific DNA binding (GO:0003700), organic cyclic compound binding (GO:0097159), molecular function activator activity (GO:0140677), heterocyclic compound binding (GO:1901363), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), transcription factor binding (GO:0008134), DNA-binding transcription repressor activity (GO:0001217), nucleic acid binding (GO:0003676), DNA-binding transcription activator activity (GO:0001216), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), transcription regulatory region nucleic acid binding (GO:0001067), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), transcription coregulator binding (GO:0001221), sequence-specific DNA binding (GO:0043565), transcription cis-regulatory region binding (GO:0000976), double-stranded DNA binding (GO:0003690), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), core promoter sequence-specific DNA binding (GO:0001046), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), E-box binding (GO:0070888)

Biological Process: biological_process (GO:0008150), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), signaling (GO:0023052), biological regulation (GO:0065007), response to stimulus (GO:0050896), cellular process (GO:0009987), homeostatic process (GO:0042592), negative regulation of biological process (GO:0048519), response to chemical (GO:0042221), cell cycle process (GO:0022402), cellular component organization or biogenesis (GO:0071840), negative regulation of multicellular organismal process (GO:0051241), regulation of multicellular organismal process (GO:0051239), negative regulation of metabolic process (GO:0009892), regulation of developmental process (GO:0050793), cellular homeostasis (GO:0019725), negative regulation of immune system process (GO:0002683), response to endogenous stimulus (GO:0009719), 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 developmental process (GO:0051093), negative regulation of cellular process (GO:0048523), signal transduction (GO:0007165), response to abiotic stimulus (GO:0009628), positive regulation of signaling (GO:0023056), positive regulation of response to stimulus (GO:0048584), regulation of metabolic process (GO:0019222), cell cycle (GO:0007049), regulation of immune system process (GO:0002682), chemical homeostasis (GO:0048878), positive regulation of metabolic process (GO:0009893), regulation of molecular function (GO:0065009), response to stress (GO:0006950), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), regulation of cell division (GO:0051302), response to hypoxia (GO:0001666), positive regulation of cell death (GO:0010942), programmed cell death (GO:0012501), response to xenobiotic stimulus (GO:0009410), response to radiation (GO:0009314), regulation of response to stress (GO:0080134), response to oxygen levels (GO:0070482), response to growth factor (GO:0070848), regulation of signal transduction (GO:0009966), regulation of macromolecule metabolic process (GO:0060255), regulation of hemopoiesis (GO:1903706), negative regulation of hemopoiesis (GO:1903707), regulation of cell cycle (GO:0051726), intracellular chemical homeostasis (GO:0055082), negative regulation of macromolecule metabolic process (GO:0010605), cellular response to abiotic stimulus (GO:0071214), regulation of nitrogen compound metabolic process (GO:0051171), regulation of cell differentiation (GO:0045595), cellular component organization (GO:0016043), regulation of cellular component organization (GO:0051128), regulation of cell cycle process (GO:0010564), positive regulation of cell population proliferation (GO:0008284), positive regulation of nitrogen compound metabolic process (GO:0051173), monoatomic ion homeostasis (GO:0050801), 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), mitotic cell cycle process (GO:1903047), intracellular signal transduction (GO:0035556), positive regulation of macromolecule metabolic process (GO:0010604), negative regulation of cell population proliferation (GO:0008285), regulation of cellular response to stress (GO:0080135), inorganic ion homeostasis (GO:0098771), negative regulation of cell division (GO:0051782), negative regulation of cellular metabolic process (GO:0031324), positive regulation of biosynthetic process (GO:0009891), positive regulation of response to DNA damage stimulus (GO:2001022), regulation of multicellular organismal development (GO:2000026), cellular response to environmental stimulus (GO:0104004), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), 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), negative regulation of cell differentiation (GO:0045596), regulation of biosynthetic process (GO:0009889), cell cycle phase transition (GO:0044770), regulation of cellular metabolic process (GO:0031323), positive regulation of cell communication (GO:0010647), negative regulation of biosynthetic process (GO:0009890), regulation of primary metabolic process (GO:0080090), mitotic cell cycle (GO:0000278), regulation of fibroblast proliferation (GO:0048145), regulation of macromolecule biosynthetic process (GO:0010556), cellular response to oxygen levels (GO:0071453), cell cycle G1/S phase transition (GO:0044843), regulation of protein metabolic process (GO:0051246), regulation of programmed cell death (GO:0043067), MAPK cascade (GO:0000165), regulation of epithelial cell proliferation (GO:0050678), regulation of gene expression (GO:0010468), iron ion homeostasis (GO:0055072), regulation of myeloid cell differentiation (GO:0045637), negative regulation of myeloid cell differentiation (GO:0045638), response to decreased oxygen levels (GO:0036293), regulation of leukocyte differentiation (GO:1902105), negative regulation of fibroblast proliferation (GO:0048147), positive regulation of intracellular signal transduction (GO:1902533), negative regulation of cellular biosynthetic process (GO:0031327), protein-containing complex organization (GO:0043933), regulation of RNA metabolic process (GO:0051252), positive regulation of fibroblast proliferation (GO:0048146), positive regulation of catalytic activity (GO:0043085), response to ionizing radiation (GO:0010212), cellular component disassembly (GO:0022411), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), cellular response to radiation (GO:0071478), cellular response to hypoxia (GO:0071456), response to light stimulus (GO:0009416), cellular response to xenobiotic stimulus (GO:0071466), negative regulation of leukocyte differentiation (GO:1902106), regulation of DNA metabolic process (GO:0051052), cellular response to DNA damage stimulus (GO:0006974), positive regulation of DNA metabolic process (GO:0051054), positive regulation of programmed cell death (GO:0043068), regulation of hydrolase activity (GO:0051336), regulation of cell development (GO:0060284), positive regulation of apoptotic signaling pathway (GO:2001235), chromatin organization (GO:0006325), positive regulation of gene expression (GO:0010628), intracellular monoatomic ion homeostasis (GO:0006873), regulation of apoptotic signaling pathway (GO:2001233), regulation of response to DNA damage stimulus (GO:2001020), positive regulation of epithelial cell proliferation (GO:0050679), positive regulation of macromolecule biosynthetic process (GO:0010557), mitotic cell cycle phase transition (GO:0044772), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), positive regulation of RNA metabolic process (GO:0051254), monoatomic cation homeostasis (GO:0055080), regulation of cellular biosynthetic process (GO:0031326), apoptotic process (GO:0006915), positive regulation of protein metabolic process (GO:0051247), regulation of nucleobase-containing compound metabolic process (GO:0019219), regulation of organelle organization (GO:0033043), negative regulation of macromolecule biosynthetic process (GO:0010558), organelle organization (GO:0006996), negative regulation of cell development (GO:0010721), negative regulation of RNA metabolic process (GO:0051253), positive regulation of cellular biosynthetic process (GO:0031328), regulation of intracellular signal transduction (GO:1902531), regulation of apoptotic process (GO:0042981), regulation of proteolysis (GO:0030162), regulation of peptidase activity (GO:0052547), regulation of RNA biosynthetic process (GO:2001141), intracellular monoatomic cation homeostasis (GO:0030003), positive regulation of DNA biosynthetic process (GO:2000573), chromatin remodeling (GO:0006338), ERK1 and ERK2 cascade (GO:0070371), regulation of DNA methylation (GO:0044030), positive regulation of miRNA metabolic process (GO:2000630), G1/S transition of mitotic cell cycle (GO:0000082), positive regulation of signal transduction by p53 class mediator (GO:1901798), response to UV (GO:0009411), positive regulation of RNA biosynthetic process (GO:1902680), positive regulation of hydrolase activity (GO:0051345), negative regulation of RNA biosynthetic process (GO:1902679), regulation of chromosome organization (GO:0033044), negative regulation of myeloid leukocyte differentiation (GO:0002762), regulation of intrinsic apoptotic signaling pathway (GO:2001242), positive regulation of apoptotic process (GO:0043065), regulation of signal transduction by p53 class mediator (GO:1901796), regulation of telomere maintenance (GO:0032204), protein-DNA complex subunit organization (GO:0071824), regulation of DNA-templated transcription (GO:0006355), response to gamma radiation (GO:0010332), chromosome organization (GO:0051276), intracellular iron ion homeostasis (GO:0006879), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), cellular response to light stimulus (GO:0071482), cellular response to decreased oxygen levels (GO:0036294), positive regulation of proteolysis (GO:0045862), regulation of DNA biosynthetic process (GO:2000278), regulation of miRNA metabolic process (GO:2000628), protein-containing complex disassembly (GO:0032984), regulation of myeloid leukocyte differentiation (GO:0002761), positive regulation of peptidase activity (GO:0010952), regulation of endopeptidase activity (GO:0052548), negative regulation of DNA-templated transcription (GO:0045892), regulation of monocyte differentiation (GO:0045655), positive regulation of nucleic acid-templated transcription (GO:1903508), regulation of nucleic acid-templated transcription (GO:1903506), regulation of miRNA transcription (GO:1902893), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902253), positive regulation of miRNA transcription (GO:1902895), negative regulation of nucleic acid-templated transcription (GO:1903507), protein-DNA complex disassembly (GO:0032986), cellular response to UV (GO:0034644), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of endopeptidase activity (GO:0010950), regulation of cysteine-type endopeptidase activity (GO:2000116), positive regulation of cysteine-type endopeptidase activity (GO:2001056), regulation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0043281), positive regulation of cysteine-type endopeptidase activity involved in apoptotic process (GO:0043280)

Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), chromatin (GO:0000785), nuclear protein-containing complex (GO:0140513), transcription regulator complex (GO:0005667), membrane-enclosed lumen (GO:0031974), nucleoplasm (GO:0005654), RNA polymerase II transcription repressor complex (GO:0090571), RNA polymerase II transcription regulator complex (GO:0090575), organelle lumen (GO:0043233), intracellular organelle (GO:0043229), transcription repressor complex (GO:0017053), membrane-bounded organelle (GO:0043227), non-membrane-bounded organelle (GO:0043228), intracellular membrane-bounded organelle (GO:0043231), intracellular organelle lumen (GO:0070013), intracellular non-membrane-bounded organelle (GO:0043232), nuclear lumen (GO:0031981), nucleolus (GO:0005730), chromosome (GO:0005694), nucleus (GO:0005634)

Generated by BioReason

Deep Research Bioreason Rl

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

BioReason Chat Export

Exported on March 22, 2026 at 01:50 AM

Organism: Homo sapiens

Sequence:

MDFFRVVENQQPPATMPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGGDMVNQSFICDPDDETFIKNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSGSPNPARGHSVCSTSSLYLQDLSAAASECIDPSVVFPYPLNDSSSPKSCASQDSSAFSPSSDSLLSSTESSPQGSPEPLVLHEETPPTTSSDSEEEQEDEEEIDVVSVEKRQAPGKRSESGSPSAGGHSKPPHSPLVLKRCHVSTHQHNYAAPPSTRKDYPAAKRVKLDSVRVLRQISNNRKCTSPRSSDTEENVKRRTHNVLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILSVQAEEQKLISEEDLLRKRREQLKHKLEQLRNSCA

Thinking Trace

Functional Summary

UniProt Summary

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 423-453

GO Terms

Generated by BioReason

Deep Research Falcon

(MYC-deep-research-falcon.md)

provider: falcon
model: Edison Scientific Literature
cached: false
start_time: '2025-12-26T19:52:13.895043'
end_time: '2025-12-26T20:00:24.753491'
duration_seconds: 490.86
template_file: templates/gene_research_go_focused.md
template_variables:
organism: human
gene_id: MYC
gene_symbol: MYC
uniprot_accession: P01106
protein_description: 'RecName: Full=Myc proto-oncogene protein; AltName: Full=Class
E basic helix-loop-helix protein 39; Short=bHLHe39; AltName: Full=Proto-oncogene
c-Myc; AltName: Full=Transcription factor p64;'
gene_info: Name=MYC; Synonyms=BHLHE39;
organism_full: Homo sapiens (Human).
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)
provider_config:
timeout: 600
max_retries: 3
parameters:
allowed_domains: []
temperature: 0.1
citation_count: 20

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: P01106
Protein Description: RecName: Full=Myc proto-oncogene protein; AltName: Full=Class E basic helix-loop-helix protein 39; Short=bHLHe39; AltName: Full=Proto-oncogene c-Myc; AltName: Full=Transcription factor p64;
Gene Information: Name=MYC; Synonyms=BHLHE39;
Organism (full): Homo sapiens (Human).
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: Homo sapiens (Human).
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: P01106) in human.

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: P01106
Protein Description: RecName: Full=Myc proto-oncogene protein; AltName: Full=Class E basic helix-loop-helix protein 39; Short=bHLHe39; AltName: Full=Proto-oncogene c-Myc; AltName: Full=Transcription factor p64;
Gene Information: Name=MYC; Synonyms=BHLHE39;
Organism (full): Homo sapiens (Human).
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: Homo sapiens (Human).
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: P01106) in human.

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.

Plan and verification. We verified the target: Homo sapiens MYC (UniProt P01106) encodes the Myc proto-oncogene protein, a nuclear bHLH–leucine zipper transcription factor that heterodimerizes with MAX to bind E-box DNA elements and can repress via MIZ1; it contains conserved Myc boxes and is regulated by a T58/S62 phosphodegron recognized by FBXW7 (issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11, jha2023mycfunctionand pages 14-14).

Category	Summary	Key evidence
Core identity & domains	Gene: MYC (human). Key domains: N-terminal transactivation region with conserved Myc boxes (MBI–MBIV) and C-terminal basic helix–loop–helix leucine zipper (bHLH-LZ) for dimerization/DNA binding.	(issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7)
Mechanism (DNA binding & partners)	Forms obligate heterodimer with MAX to bind canonical E-box motifs (e.g., CACGTG) and activates transcription; interacts with MIZ1 to repress specific targets; nuclear localization at promoters/enhancers/super-enhancers.	(jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11)
Post-translational regulation	Regulated by phosphorylation at S62/T58 (GSK3β-linked priming) creating a phospho-degron recognized by FBXW7 leading to ubiquitin-mediated proteasomal degradation.	(jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15)
2023–2024 advances	Phase-separation/condensate behavior modulates MYC/N-MYC-driven transcriptional programs; genome-wide CRISPR/DepMap screens identify nucleocytoplasmic transport as a MYC synthetic-lethal pathway with XPO1 as a druggable node; building translational dependency maps links cell-line dependencies to TCGA patient tumors.	(jha2023mycfunctionand pages 14-15, deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8, issa2024genomicdependenciesin pages 127-129)
Applications / clinical implementations	Direct inhibitor: Omomyc-derived miniprotein OMO-103 completed Phase 1 (first-in-human) with RP2D DL5 (6.48 mg/kg); indirect approaches include XPO1 inhibitors, BET bromodomain and CDK9 inhibitors and degraders/PROTACs in development.	(garralda2024myctargetingby pages 1-2, deutzmann2024nucleartocytoplasmic pages 1-2, weber2023strategiestotarget pages 1-3, yu2025rethinkingmycinhibition pages 4-5)
Quantitative statistics	OMO-103 Phase 1: 22 patients enrolled, 19 evaluable, 12 reached 9-week assessment, 8 had stable disease, 1 achieved 49% tumor-volume reduction; estimated MYC overexpression contributes to >50% of cancers and MYC-network alterations in >70% of HCC; MYC regulates on the order of >11% of human genes.	(garralda2024myctargetingby pages 1-2, deutzmann2024nucleartocytoplasmic pages 1-2, issa2024genomicdependenciesin pages 31-35)

Table: Compact, evidence-linked summary of human MYC (P01106) covering domains, mechanism, key 2023–2024 advances, clinical applications (OMO-103), and quantitative statistics; citations link to the supporting context IDs.

Comprehensive research report

Key concepts and definitions (current understanding)
Identity and domains: MYC is a human bHLH-LZ transcription factor with an N-terminal transactivation domain harboring conserved Myc boxes (MBI–MBIV) and a C‑terminal bHLH‑LZ that mediates MAX dimerization and sequence-specific DNA binding to E-boxes (canonical CACGTG) at promoters and enhancers/super-enhancers (issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7).
Partners and DNA binding: MYC forms obligate heterodimers with MAX to bind E-box motifs; it can also interact with MIZ1 to repress transcription of cell-cycle inhibitors, integrating activation and repression programs in the nucleus (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11).
Cellular localization and function: MYC acts in the nucleus as a transcriptional amplifier influencing cell-cycle progression, ribosome biogenesis, and metabolic programs; it engages basal transcription machinery (e.g., TBP, P-TEFb) and enhancer architecture (super-enhancers) (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11).
Post-translational regulation and turnover: Phosphorylation at Ser62 and Thr58 forms a phospho-degron; GSK3β-dependent phosphorylation primes FBXW7 recognition and ubiquitin–proteasome degradation, tightly controlling MYC stability (jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15).
Recent developments and latest research (prioritizing 2023–2024)
MYC condensates and phase separation: Emerging work shows that phase separation of Myc/N‑Myc can modulate target-selective transcriptional programs, linking intrinsically disordered regions and condensate biology to MYC-driven gene control (jha2023mycfunctionand pages 14-15). While functional consequences are still being refined, these studies support a condensate-based layer of MYC regulation that may intersect with enhancer topology.
Pan-cancer dependencies and translational maps: Recent efforts to translate cell-line essentiality into patient tumors have produced translational dependency maps connecting gene dependencies to TCGA tumors; MYC-associated programs emerge as core vulnerabilities across cancers, providing a framework for clinical prioritization (issa2024genomicdependenciesin pages 127-129).
Synthetic lethality via nucleocytoplasmic transport in MYC-high HCC (2024): A genome-wide CRISPR screen in a MYC-driven hepatocellular carcinoma model identified 1,808 MYC synthetic-lethal (MYC‑SL) genes with a prominent nucleocytoplasmic transport node; inhibiting Exportin‑1 (XPO1) caused marked tumor regression in a MYC-transgenic HCC model and reduced growth in HCC PDXs, with XPO1 high expression correlating with poor prognosis specifically in MYC‑high HCC (Nature Communications, Feb 2024; https://doi.org/10.1038/s41467-024-45128-y) (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).
Regulatory RNAs and PTM crosstalk: Recent syntheses underscore long noncoding RNA effects on MYC expression/activity and SUMO–CDK9 axis crosstalk affecting transcriptional amplification, reflecting multilayered post-transcriptional and PTM control of the MYC network (jha2023mycfunctionand pages 14-15).
Current applications and real-world implementations
Direct MYC inhibitors: Omomyc/OMO‑103. A first-in-human Phase 1 trial (Nature Medicine, Feb 2024; NCT04808362) tested OMO‑103 (91 aa Omomyc-derived miniprotein). Twenty-two patients enrolled; of 19 evaluable, 12 reached the predefined 9-week assessment; eight had stable disease and one achieved a 49% tumor-volume reduction; most adverse events were grade 1 infusion reactions. Pharmacokinetics showed a ~40 h serum half-life; recommended Phase 2 dose: 6.48 mg/kg (DL5). URL: https://doi.org/10.1038/s41591-024-02805-1 (garralda2024myctargetingby pages 1-2).
Indirect strategies and synthetic-lethal targeting: XPO1 inhibition as a MYC‑SL approach in MYC‑high HCC demonstrates in vivo tumor regression and PDX growth inhibition, nominating nucleocytoplasmic transport as a druggable MYC dependency (Nature Communications 2024: https://doi.org/10.1038/s41467-024-45128-y) (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8). Reviews catalog indirect modalities, including BET and CDK9 inhibitors, and emergent degraders/PROTACs directed at MYC or its co-dependencies (Frontiers in Oncology, 2023: https://doi.org/10.3389/fonc.2023.1142111) (weber2023strategiestotarget pages 1-3). Additional overviews summarize PROTAC and epigenomic strategies in early clinical testing (yu2025rethinkingmycinhibition pages 4-5).
Ongoing/announced trials: The Omomyc program continues into disease-focused studies following NCT04808362; multiple early-phase efforts explore indirect MYC suppression (e.g., BET/CDK9) and MYC‑centric degraders as summarized in recent reviews (garralda2024myctargetingby pages 1-2, yu2025rethinkingmycinhibition pages 4-5).
Expert opinions and analysis from authoritative sources
Authoritative trial report: Nature Medicine’s Phase 1 OMO‑103 publication provides clinical-grade evidence of feasibility, tolerability, target engagement, and preliminary antitumor activity for direct MYC inhibition in solid tumors (garralda2024myctargetingby pages 1-2).
Mechanistic consensus syntheses: Contemporary reviews detail MYC’s multi-modal regulation as a nuclear bHLH-LZ factor integrating activation via MAX and repression via MIZ1, with critical control by phospho‑degron/FBXW7 pathways and engagement with enhancer architecture and transcriptional machinery (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11).
Translational dependency and SL analysis: Nature Communications (2024) offers high-quality experimental evidence that MYC‑high tumors depend on nucleocytoplasmic transport, providing a practical therapeutic entry point (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).
Relevant statistics and data (recent)
OMO‑103 (Phase 1): 22 patients enrolled; 19 evaluable; 12 reached 9-week assessment; 8/12 stable disease; 1 patient with 49% volume reduction; RP2D 6.48 mg/kg; serum t1/2 ~40 h; common TRAEs grade 1 infusion reactions (garralda2024myctargetingby pages 1-2).
MYC dysregulation prevalence (HCC and general): The MYC network is altered in >70% of HCC; MYC overexpression contributes to >50% of human cancers overall, underscoring pan-cancer centrality (deutzmann2024nucleartocytoplasmic pages 1-2).
Scope of MYC regulation: MYC/MAX binding regulates on the order of >11% of human genes (genome-wide mapping/E-box occupancy estimates), illustrating its broad transcriptional reach (issa2024genomicdependenciesin pages 31-35).

Mechanistic placement in pathways and subcellular localization
- Primary role: Nuclear transcription factor that directly binds E-box motifs as a MYC:MAX heterodimer to activate genes involved in cell-cycle progression, biomass accumulation (ribosome biogenesis), and metabolism; represses via MIZ1 complexes, balancing proliferative outputs (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11, issa2024genomicdependenciesin pages 31-35).
- Regulation by PTMs: MYC protein stability is determined by sequential Ser62/Thr58 phosphorylation, promoting FBXW7-mediated ubiquitination and proteasomal degradation (jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15). This turnover gate keeps oncogenic thresholds and creates pharmacologic opportunities via E3 ligase axes.

Clinical and translational implications
- Direct MYC inhibition is now clinically feasible (OMO‑103), with early signals of disease stabilization and acceptable safety; defining biomarkers of benefit will be critical in Phase 2 (garralda2024myctargetingby pages 1-2).
- Indirect targeting of MYC dependencies (e.g., XPO1) is supported by in vivo efficacy, particularly in MYC‑high contexts such as HCC, suggesting patient selection by MYC activity may optimize responses (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).

URLs and publication dates (selection)
- OMO‑103 Phase 1 (Nature Medicine), published Feb 6, 2024: https://doi.org/10.1038/s41591-024-02805-1 (garralda2024myctargetingby pages 1-2).
- MYC nucleocytoplasmic transport dependency (Nature Communications), published Feb 2024: https://doi.org/10.1038/s41467-024-45128-y (deutzmann2024nucleartocytoplasmic pages 1-2, deutzmann2024nucleartocytoplasmic pages 7-8).
- Mechanistic review (Frontiers in Cell and Developmental Biology), Oct 2023: https://doi.org/10.3389/fcell.2023.1268275 (jha2023mycfunctionand pages 6-7, jha2023mycfunctionand pages 11-11, jha2023mycfunctionand pages 14-14, jha2023mycfunctionand pages 14-15).
- Targeting strategies review (Frontiers in Oncology), Mar 2023: https://doi.org/10.3389/fonc.2023.1142111 (weber2023strategiestotarget pages 1-3).

Notes on identification and ambiguity
- The gene symbol MYC here is unambiguous: human Homo sapiens MYC (UniProt P01106), encoding c‑Myc; all cited mechanisms and trials correspond to human MYC biology (issa2024genomicdependenciesin pages 31-35, jha2023mycfunctionand pages 6-7).

References

(issa2024genomicdependenciesin pages 31-35): LHB Issa. Genomic dependencies in myc overexpressing multiple myeloma. Unknown journal, 2024.
(jha2023mycfunctionand pages 6-7): 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 80 citations and is from a poor quality or predatory journal.
(jha2023mycfunctionand pages 11-11): 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 80 citations and is from a poor quality or predatory journal.
(jha2023mycfunctionand pages 14-14): 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 80 citations and is from a poor quality or predatory journal.
(jha2023mycfunctionand pages 14-15): 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 80 citations and is from a poor quality or predatory journal.
(deutzmann2024nucleartocytoplasmic pages 1-2): Anja Deutzmann, Delaney K. Sullivan, Renumathy Dhanasekaran, Wei Li, Xinyu Chen, Ling Tong, Wadie D. Mahauad-Fernandez, John Bell, Adriane Mosley, Angela N. Koehler, Yulin Li, and Dean W. Felsher. Nuclear to cytoplasmic transport is a druggable dependency in myc-driven hepatocellular carcinoma. Nature Communications, Feb 2024. URL: https://doi.org/10.1038/s41467-024-45128-y, doi:10.1038/s41467-024-45128-y. This article has 13 citations and is from a highest quality peer-reviewed journal.
(deutzmann2024nucleartocytoplasmic pages 7-8): Anja Deutzmann, Delaney K. Sullivan, Renumathy Dhanasekaran, Wei Li, Xinyu Chen, Ling Tong, Wadie D. Mahauad-Fernandez, John Bell, Adriane Mosley, Angela N. Koehler, Yulin Li, and Dean W. Felsher. Nuclear to cytoplasmic transport is a druggable dependency in myc-driven hepatocellular carcinoma. Nature Communications, Feb 2024. URL: https://doi.org/10.1038/s41467-024-45128-y, doi:10.1038/s41467-024-45128-y. This article has 13 citations and is from a highest quality peer-reviewed journal.
(issa2024genomicdependenciesin pages 127-129): LHB Issa. Genomic dependencies in myc overexpressing multiple myeloma. Unknown journal, 2024.
(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 149 citations and is from a highest quality peer-reviewed journal.
(weber2023strategiestotarget pages 1-3): Leonie I. Weber and Markus Hartl. Strategies to target the cancer driver myc in tumor cells. Frontiers in Oncology, Mar 2023. URL: https://doi.org/10.3389/fonc.2023.1142111, doi:10.3389/fonc.2023.1142111. This article has 28 citations and is from a poor quality or predatory journal.
(yu2025rethinkingmycinhibition pages 4-5): Jing Yu, Dan Liu, Yujian Yuan, Chunxia Sun, and Zihan Su. Rethinking myc inhibition: a multi-dimensional approach to overcome cancer’s master regulator. Frontiers in Cell and Developmental Biology, Apr 2025. URL: https://doi.org/10.3389/fcell.2025.1601975, doi:10.3389/fcell.2025.1601975. This article has 3 citations and is from a poor quality or predatory journal.

Citations

jha2023mycfunctionand pages 14-15
issa2024genomicdependenciesin pages 127-129
garralda2024myctargetingby pages 1-2
weber2023strategiestotarget pages 1-3
yu2025rethinkingmycinhibition pages 4-5
deutzmann2024nucleartocytoplasmic pages 1-2
issa2024genomicdependenciesin pages 31-35
jha2023mycfunctionand pages 6-7
jha2023mycfunctionand pages 11-11
jha2023mycfunctionand pages 14-14
deutzmann2024nucleartocytoplasmic pages 7-8
https://doi.org/10.1038/s41467-024-45128-y
https://doi.org/10.1038/s41591-024-02805-1
https://doi.org/10.3389/fonc.2023.1142111
https://doi.org/10.3389/fcell.2023.1268275
https://doi.org/10.3389/fcell.2023.1268275,
https://doi.org/10.1038/s41467-024-45128-y,
https://doi.org/10.1038/s41591-024-02805-1,
https://doi.org/10.3389/fonc.2023.1142111,
https://doi.org/10.3389/fcell.2025.1601975,

Bioreason Rl Review

(MYC-bioreason-rl-review.md)

BioReason-Pro RL Review: MYC (human)

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

Correctness: 5/5
Completeness: 4/5

Functional Summary Review

The BioReason functional summary states:

A nuclear transcriptional regulator that binds E-box DNA elements as a dimer and stimulates RNA polymerase II-dependent transcriptional programs. Its N-terminal activation region recruits co-regulatory machinery, while a C-terminal basic helix-loop-helix-leucine zipper module enforces sequence-specific DNA binding and dimerization. Together these features drive gene-expression circuits that promote proliferative and cell-cycle-associated pathways within the nucleus.

This is an accurate and complete summary of MYC's core function. The curated review describes MYC as "a nuclear bHLH-leucine zipper transcription factor and major proto-oncogene that regulates cell growth, proliferation, metabolism, and apoptosis" that "functions primarily through obligate heterodimerization with MAX to bind E-box DNA motifs (CACGTG)." BioReason captures all these elements: bHLH-LZ architecture, E-box binding, dimerization requirement, nuclear localization, and transcriptional activation of proliferative programs.

The mention of "RNA polymerase II-dependent transcriptional programs" is correct and aligns with DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981) in the curated review.

Minor gaps:
1. BioReason does not mention MYC's requirement for MAX as a dimerization partner -- it says "dimer" generically
2. MYC's role in transcriptional repression (via MIZ1 complex) is absent
3. The role in ribosome biogenesis, metabolism, and apoptosis regulation is not captured
4. MYC's function as an amplifier of existing transcriptional programs (rather than a simple activator) is not mentioned

Comparison with interpro2go:

The interpro2go annotations from IPR011598 (Myc-type bHLH) and IPR003327 (Leucine zipper, Myc) would map to DNA binding, transcription factor activity, and E-box binding. BioReason reproduces this logic faithfully and adds appropriate context about the N-terminal activation domain and co-regulator recruitment. The predicted GO terms include E-box binding (GO:0070888) and RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), which are appropriate and match the curated review.

Notes on thinking trace

The trace is well-structured, proceeding from family assignment to domain analysis to functional inference. The hypothesis about histone acetyltransferase co-activator recruitment is accurate for MYC biology.

📄 View Raw YAML

id: P01106
gene_symbol: MYC
aliases:
  - c-Myc
  - proto-oncogene c-Myc
  - transcription factor p64
  - v-myc myelocytomatosis viral oncogene homolog
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
  - 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: 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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12553908
          supporting_text: X-ray structures of Myc-Max and Mad-Max recognizing 
            DNA. Molecular bases of regulation by proto-oncogenic transcription 
            factors.
        - reference_id: file:human/MYC/MYC-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - 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: 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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:12553908
          supporting_text: 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).
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      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.
      action: ACCEPT
      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.
  - term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: MYC is a well-characterized DNA-binding transcription factor. 
        This term is appropriately inferred from InterPro domain annotations.
      action: ACCEPT
      reason: This IEA annotation from InterPro correctly identifies MYC as a 
        DNA-binding transcription factor based on its bHLH-LZ domain structure.
  - term:
      id: GO:0046983
      label: protein dimerization activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: MYC heterodimerizes with MAX via its leucine zipper domain for 
        DNA binding and transcriptional activity. Dimerization is essential for 
        MYC function.
      action: ACCEPT
      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.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11891322
    review:
      summary: Generic protein binding term from a study on small-molecule 
        antagonists of Myc/Max dimerization.
      action: REMOVE
      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.
      supported_by:
        - reference_id: PMID:11891322
          supporting_text: Small-molecule antagonists of Myc/Max dimerization 
            inhibit Myc-induced transformation of chicken embryo fibroblasts.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15992821
    review:
      summary: Generic protein binding term from a study on c-Myc/Bin1 
        interaction structure.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative. The specific 
        interaction with BIN1 should be captured by more specific terms.
      supported_by:
        - reference_id: PMID:15992821
          supporting_text: A structure-based model of the c-Myc/Bin1 protein 
            interaction shows alternative splicing of Bin1 and c-Myc 
            phosphorylation are key binding determinants.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16352593
    review:
      summary: Generic protein binding term from a study on Miz-1 targeting for 
        Myc-mediated apoptosis.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative. The functional 
        interaction with MIZ1 is better represented by specific terms like 
        DNA-binding transcription factor binding.
      supported_by:
        - reference_id: PMID:16352593
          supporting_text: Dec 13. Targeting of Miz-1 is essential for 
            Myc-mediated apoptosis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16606833
    review:
      summary: Generic protein binding term from a study on small molecules 
        inducing Myc-dependent apoptosis.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative and does not specify 
        the functional nature of the interaction.
      supported_by:
        - reference_id: PMID:16606833
          supporting_text: Identification of small molecules that induce 
            apoptosis in a Myc-dependent manner and inhibit Myc-driven 
            transformation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16996503
    review:
      summary: Generic protein binding term from a study on Myc stabilization by
        estrogen and phospholipase D.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:16996503
          supporting_text: Epub 2006 Sep 18. Myc stabilization in response to 
            estrogen and phospholipase D in MCF-7 breast cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17070091
    review:
      summary: Generic protein binding term from a study on HPV-18 E7 
        interaction with c-Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:17070091
          supporting_text: Epub 2006 Oct 4. HPV-18 E7 conjugates to c-Myc and 
            mediates its transcriptional activity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17157259
    review:
      summary: Generic protein binding term from a study on SNIP1 interaction 
        with c-Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:17157259
          supporting_text: SNIP1 is a candidate modifier of the transcriptional 
            activity of c-Myc on E box-dependent target genes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17314511
    review:
      summary: Generic protein binding term from a large-scale c-MYC interactome
        study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative. High-throughput 
        interactome studies do not provide functional context.
      supported_by:
        - reference_id: PMID:17314511
          supporting_text: Large-scale identification of c-MYC-associated 
            proteins using a combined TAP/MudPIT approach.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17418410
    review:
      summary: Generic protein binding term from a study on HIF-2alpha promoting
        c-myc transcription.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:17418410
          supporting_text: HIF-2alpha promotes hypoxic cell proliferation by 
            enhancing c-myc transcriptional activity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17599065
    review:
      summary: Generic protein binding term from a study on ribosomal protein 
        L11 inhibiting c-Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:17599065
          supporting_text: Jun 28. Inhibition of c-Myc activity by ribosomal 
            protein L11.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17632056
    review:
      summary: Generic protein binding term from a study on CIP2A inhibiting 
        PP2A and stabilizing MYC.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:17632056
          supporting_text: CIP2A inhibits PP2A in human malignancies.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18256156
    review:
      summary: Generic protein binding term from a study on EBV EBNA3C 
        interaction with c-Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:18256156
          supporting_text: Epstein-Barr virus nuclear antigen 3C interacts with 
            and enhances the stability of the c-Myc oncoprotein.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18393360
    review:
      summary: Generic protein binding term from a study on c-Myc repressing 
        FOXO3a-mediated transcription.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:18393360
          supporting_text: c-Myc represses FOXO3a-mediated transcription of the 
            gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18413597
    review:
      summary: Generic protein binding term from a study on Adenovirus E1A 
        targeting p400 to induce Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:18413597
          supporting_text: Adenovirus E1A targets p400 to induce the cellular 
            oncoprotein Myc.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18620061
    review:
      summary: Generic protein binding term from a proximity ligation assay 
        study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:18620061
          supporting_text: Jul 11. Characterizing proteins and their 
            interactions in cells and tissues using the in situ proximity 
            ligation assay.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18923429
    review:
      summary: Generic protein binding term from a study on Miz1 and HectH9 
        regulating TopBP1 stability.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:18923429
          supporting_text: Miz1 and HectH9 regulate the stability of the 
            checkpoint protein, TopBP1.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19131971
    review:
      summary: Generic protein binding term from a study on Axin1 promoting 
        c-Myc degradation.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:19131971
          supporting_text: The Axin1 scaffold protein promotes formation of a 
            degradation complex for c-Myc.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20195357
    review:
      summary: Generic protein binding term from a large-scale TF interacting 
        protein regions study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:20195357
          supporting_text: A comprehensive resource of interacting protein 
            regions for refining human transcription factor networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20208519
    review:
      summary: Generic protein binding term from a study on ARF regulation in 
        stress-mediated p53 responses.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:20208519
          supporting_text: Transcription-independent ARF regulation in oncogenic
            stress-mediated p53 responses.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20691906
    review:
      summary: Generic protein binding term from a study on Myc-nick promoting 
        alpha-tubulin acetylation.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:20691906
          supporting_text: 'Myc-nick: a cytoplasmic cleavage product of Myc that promotes
            alpha-tubulin acetylation and cell differentiation.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20713710
    review:
      summary: Generic protein binding term from a study on noninvasive imaging 
        of c-Myc activation.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:20713710
          supporting_text: Noninvasive molecular imaging of c-Myc activation in 
            living mice.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20936779
    review:
      summary: Generic protein binding term from a human MAP kinase interactome 
        study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:20936779
          supporting_text: A human MAP kinase interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20970423
    review:
      summary: Generic protein binding term from a study on NEMO stabilizing 
        c-Myc in the nucleus.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:20970423
          supporting_text: Epub 2010 Oct 21. NEMO stabilizes c-Myc through 
            direct interaction in the nucleus.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21150319
    review:
      summary: Generic protein binding term from a proteomic profiling of 
        Myc-associated proteins study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:21150319
          supporting_text: Dec 15. Proteomic profiling of Myc-associated 
            proteins.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21575199
    review:
      summary: Generic protein binding term from a study on IkB kinases 
        increasing Myc stability.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:21575199
          supporting_text: IκB kinases increase Myc protein stability and 
            enhance progression of breast cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21807113
    review:
      summary: Generic protein binding term from a study on Sirt1 deacetylating 
        c-Myc and promoting Myc/Max association.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:21807113
          supporting_text: Sirt1 deacetylates c-Myc and promotes c-Myc/Max 
            association.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21988832
    review:
      summary: Generic protein binding term from a human liver protein 
        interaction network study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:21988832
          supporting_text: Toward an understanding of the protein interaction 
            network of the human liver.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22094256
    review:
      summary: Generic protein binding term from a CDK4/6 substrate screen 
        study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:22094256
          supporting_text: A systematic screen for CDK4/6 substrates links FOXM1
            phosphorylation to senescence suppression in cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23217706
    review:
      summary: Generic protein binding term from a study on SIRT6 as a tumor 
        suppressor controlling metabolism.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:23217706
          supporting_text: The histone deacetylase SIRT6 is a tumor suppressor 
            that controls cancer metabolism.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23455924
    review:
      summary: Generic protein binding term from a Y2H-seq protein 
        methyltransferase interactome study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:23455924
          supporting_text: A Y2H-seq approach defines the human protein 
            methyltransferase interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23791182
    review:
      summary: Generic protein binding term from a study on FBXW7 regulating MYC
        stability in leukemia.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative. The FBXW7-MYC 
        interaction is regulatory, not a core function.
      supported_by:
        - reference_id: PMID:23791182
          supporting_text: The ubiquitin ligase FBXW7 modulates 
            leukemia-initiating cell activity by regulating MYC stability.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23804756
    review:
      summary: Generic protein binding term from a structural study on 
        SLIP1-SLBP interactions.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:23804756
          supporting_text: Jun 26. Structural and biochemical studies of 
            SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24048479
    review:
      summary: Generic protein binding term from a study on deterministic direct
        reprogramming to pluripotency.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:24048479
          supporting_text: Deterministic direct reprogramming of somatic cells 
            to pluripotency.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24951594
    review:
      summary: Generic protein binding term from a study on Sin3b interacting 
        with Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:24951594
          supporting_text: 2014 Jun 20. Sin3b interacts with Myc and decreases 
            Myc levels.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25609649
    review:
      summary: Generic protein binding term from a proteomic study on 
        chromatin-associated TF complexes.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:25609649
          supporting_text: Proteomic analyses reveal distinct 
            chromatin-associated and soluble transcription factor complexes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26267534
    review:
      summary: Generic protein binding term from a study on ERK dimerization 
        inhibitors.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:26267534
          supporting_text: Small Molecule Inhibition of ERK Dimerization 
            Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26496610
    review:
      summary: Generic protein binding term from a human interactome 
        stoichiometry study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:26496610
          supporting_text: Oct 22. A human interactome in three quantitative 
            dimensions organized by stoichiometries and abundances.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26655473
    review:
      summary: Generic protein binding term from a study on Pin1 pre-anchoring 
        to unphosphorylated c-Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:26655473
          supporting_text: 2015 Nov 19. Pre-Anchoring of Pin1 to 
            Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26766587
    review:
      summary: Generic protein binding term from a study on Myc-Miz1 interaction
        defining medulloblastoma subgroups.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative. The Miz1 interaction 
        is better captured by DNA-binding transcription factor binding.
      supported_by:
        - reference_id: PMID:26766587
          supporting_text: The Interaction of Myc with Miz1 Defines 
            Medulloblastoma Subgroup Identity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:27705803
    review:
      summary: Generic protein binding term from a Polycomb complexome mapping 
        study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:27705803
          supporting_text: A High-Density Map for Navigating the Human Polycomb 
            Complexome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28007894
    review:
      summary: Generic protein binding term from a study on STYX targeting 
        FBXW7.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:28007894
          supporting_text: The pseudophosphatase STYX targets the F-box of FBXW7
            and inhibits SCFFBXW7 function.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32296183
    review:
      summary: Generic protein binding term from a human binary protein 
        interactome reference map.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative. High-throughput 
        binary interactome data lacks functional context.
      supported_by:
        - reference_id: PMID:32296183
          supporting_text: Apr 8. A reference map of the human binary protein 
            interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32814053
    review:
      summary: Generic protein binding term from a neurodegenerative disease 
        protein interactome study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:32814053
          supporting_text: Interactome Mapping Provides a Network of 
            Neurodegenerative Disease Proteins and Uncovers Widespread Protein 
            Aggregation in Affected Brains.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: Generic protein binding term from a dual proteome-scale 
        interactome study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:34591642
    review:
      summary: Generic protein binding term from a head and neck cancer protein 
        network study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:34591642
          supporting_text: Oct 1. A protein network map of head and neck cancer 
            reveals PIK3CA mutant drug sensitivity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35044719
    review:
      summary: Generic protein binding term from a proteome-scale binding site 
        mapping study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:35044719
          supporting_text: Proteome-scale mapping of binding sites in the 
            unstructured regions of the human proteome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35140242
    review:
      summary: Generic protein binding term from a human TF protein interaction 
        networks study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:35140242
          supporting_text: Human transcription factor protein interaction 
            networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35271311
    review:
      summary: Generic protein binding term from the OpenCell endogenous tagging
        study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:35271311
          supporting_text: '2022 Mar 11. OpenCell: Endogenous tagging for the cartography
            of human cellular organization.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35512704
    review:
      summary: Generic protein binding term from a mutation-directed neo-PPI 
        study in cancer.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:35512704
          supporting_text: 2022 May 4. Systematic discovery of mutation-directed
            neo-protein-protein interactions in cancer.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:37219487
    review:
      summary: Generic protein binding term from a phosphomimetic screening 
        study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:37219487
          supporting_text: 2023 May 23. Large-scale phosphomimetic screening 
            identifies phospho-modulated motif-based protein interactions.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:9184233
    review:
      summary: Generic protein binding term from a study on Rox/Mnt 
        heterodimerizing with Max.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:9184233
          supporting_text: 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.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:9708738
    review:
      summary: Generic protein binding term from a study on TRRAP as an 
        essential cofactor for c-Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:9708738
          supporting_text: The novel ATM-related protein TRRAP is an essential 
            cofactor for the c-Myc and E2F oncoproteins.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:25609649
    review:
      summary: MYC identical protein binding detected in chromatin-associated TF
        complex proteomics.
      action: REMOVE
      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.
      supported_by:
        - reference_id: PMID:25609649
          supporting_text: Proteomic analyses reveal distinct 
            chromatin-associated and soluble transcription factor complexes.
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IPI
    original_reference_id: PMID:9184233
    review:
      summary: MYC identical protein binding from a study on Rox/Max 
        heterodimerization.
      action: REMOVE
      reason: MYC functions primarily as a heterodimer with MAX. Identical 
        protein binding is not the core mechanism of MYC function.
      supported_by:
        - reference_id: PMID:9184233
          supporting_text: 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.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:18393360
    review:
      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.
      action: ACCEPT
      reason: Transcriptional repression is a core function of MYC, particularly
        through interaction with MIZ1 to repress cell cycle inhibitors like p27.
      supported_by:
        - reference_id: PMID:18393360
          supporting_text: c-Myc represses FOXO3a-mediated transcription of the 
            gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:10412034
    review:
      summary: MYC-mediated transcriptional repression from a study on Bin1-Myc 
        interaction and apoptosis.
      action: ACCEPT
      reason: MYC-mediated transcriptional repression is a core function.
      supported_by:
        - reference_id: PMID:10412034
          supporting_text: Induction of apoptosis and differentiation in 
            neuroblastoma and astrocytoma cells by the overexpression of Bin1, a
            novel Myc interacting protein.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC negative regulation of transcription inferred from Ensembl 
        Compara orthology.
      action: ACCEPT
      reason: This IEA annotation correctly reflects MYC repressive function and
        is consistent with experimental evidence.
  - term:
      id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA 
        binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC binds E-box sequences in cis-regulatory regions. IEA from 
        Ensembl Compara orthology.
      action: ACCEPT
      reason: This term correctly describes MYC DNA binding activity at 
        cis-regulatory elements and is consistent with IBA and experimental 
        annotations.
  - term:
      id: GO:0000987
      label: cis-regulatory region sequence-specific DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: General cis-regulatory DNA binding from Ensembl Compara 
        orthology.
      action: ACCEPT
      reason: This broader term for cis-regulatory DNA binding is valid for MYC.
  - term:
      id: GO:0001658
      label: branching involved in ureteric bud morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Developmental process annotation from Ensembl Compara orthology.
      action: KEEP_AS_NON_CORE
      reason: MYC plays a role in kidney development but this is a 
        tissue-specific developmental process, not a core molecular function.
  - term:
      id: GO:0001783
      label: B cell apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC can promote apoptosis under certain conditions, including in 
        B cells (relevant to Burkitt lymphoma).
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0001866
      label: NK T cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Cell-type specific proliferation process from Ensembl Compara 
        orthology.
      action: KEEP_AS_NON_CORE
      reason: NK T cell proliferation is a tissue-specific downstream effect, 
        not a core function of MYC.
  - term:
      id: GO:0002904
      label: positive regulation of B cell apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC promotes apoptosis under certain conditions in B cells.
      action: KEEP_AS_NON_CORE
      reason: This is a cell-type specific regulatory process, not a core 
        function.
  - term:
      id: GO:0006366
      label: transcription by RNA polymerase II
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC directly participates in RNA Pol II transcription as a 
        transcription factor.
      action: ACCEPT
      reason: Transcription by RNA Pol II is a core process in which MYC 
        directly participates as a DNA-binding transcription factor.
  - term:
      id: GO:0006974
      label: DNA damage response
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC is involved in DNA damage response pathways.
      action: KEEP_AS_NON_CORE
      reason: DNA damage response is a downstream consequence of MYC activity, 
        not its core function.
  - term:
      id: GO:0008283
      label: cell population proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC is a master regulator of cell proliferation.
      action: ACCEPT
      reason: Cell proliferation is a core downstream biological process 
        regulated by MYC through its transcriptional activity.
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC positively regulates cell proliferation through 
        transcriptional activation of growth-promoting genes.
      action: ACCEPT
      reason: Positive regulation of cell proliferation is a core function of 
        MYC as a proto-oncogene.
  - term:
      id: GO:0008630
      label: intrinsic apoptotic signaling pathway in response to DNA damage
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC can trigger apoptosis in response to DNA damage through 
        ARF/p53 pathway activation.
      action: KEEP_AS_NON_CORE
      reason: This is a context-dependent response, not a core function of MYC.
  - term:
      id: GO:0009314
      label: response to radiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC expression and stability are affected by radiation-induced 
        DNA damage.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is too general and represents an indirect effect rather than 
        a direct MYC function.
  - term:
      id: GO:0010468
      label: regulation of gene expression
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC is a major regulator of gene expression, controlling 
        approximately 11% of human genes.
      action: ACCEPT
      reason: Regulation of gene expression is the core function of MYC as a 
        transcription factor.
  - term:
      id: GO:0014902
      label: myotube differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC expression is regulated during muscle differentiation.
      action: KEEP_AS_NON_CORE
      reason: Myotube differentiation is a tissue-specific developmental 
        process, not a core MYC function.
  - term:
      id: GO:0016055
      label: Wnt signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC is a transcriptional target of Wnt signaling and 
        beta-catenin.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0016485
      label: protein processing
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Annotation from Ensembl Compara orthology.
      action: MARK_AS_OVER_ANNOTATED
      reason: MYC does not directly participate in protein processing. This is 
        likely an indirect downstream effect.
  - term:
      id: GO:0031625
      label: ubiquitin protein ligase binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC is recognized by E3 ubiquitin ligases including FBXW7 for 
        proteasomal degradation.
      action: ACCEPT
      reason: MYC binding to ubiquitin protein ligases (especially FBXW7) is 
        essential for its regulation and turnover.
  - term:
      id: GO:0035457
      label: cellular response to interferon-alpha
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC expression may be modulated by interferon signaling.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is too specific and represents an indirect effect rather than
        a core MYC function.
  - term:
      id: GO:0035914
      label: skeletal muscle cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC downregulation is required for muscle differentiation.
      action: KEEP_AS_NON_CORE
      reason: Tissue-specific differentiation process, not a core MYC function.
  - term:
      id: GO:0042474
      label: middle ear morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Developmental annotation from Ensembl Compara orthology.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is a very specific developmental process that likely 
        represents an indirect effect of MYC on proliferation during ear 
        development.
  - term:
      id: GO:0042981
      label: regulation of apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC has dual roles in regulating both cell proliferation and 
        apoptosis.
      action: KEEP_AS_NON_CORE
      reason: MYC regulates apoptosis but this is context-dependent and not its 
        primary function.
  - term:
      id: GO:0043279
      label: response to alkaloid
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Annotation from Ensembl Compara orthology.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is too specific and likely represents an indirect 
        pharmacological effect.
  - term:
      id: GO:0043473
      label: pigmentation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Annotation from Ensembl Compara orthology.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is a very distal developmental phenotype, not a core 
        function.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC is a transcriptional activator that positively regulates 
        target gene transcription via RNA Pol II.
      action: ACCEPT
      reason: Positive regulation of transcription by RNA Pol II is a core 
        function of MYC as a transcription factor.
  - term:
      id: GO:0048705
      label: skeletal system morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Developmental annotation from Ensembl Compara orthology.
      action: KEEP_AS_NON_CORE
      reason: Tissue-specific developmental process, not a core MYC function.
  - term:
      id: GO:0050910
      label: detection of mechanical stimulus involved in sensory perception of 
        sound
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Annotation from Ensembl Compara orthology.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is a very specific sensory process with no clear direct 
        connection to MYC function.
  - term:
      id: GO:1904699
      label: positive regulation of acinar cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Cell-type specific proliferation annotation from Ensembl Compara.
      action: KEEP_AS_NON_CORE
      reason: This is a tissue-specific manifestation of MYC proliferative 
        function.
  - term:
      id: GO:1990863
      label: acinar cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Cell-type specific proliferation annotation from Ensembl Compara.
      action: KEEP_AS_NON_CORE
      reason: This is a tissue-specific manifestation of MYC proliferative 
        function.
  - term:
      id: GO:2001235
      label: positive regulation of apoptotic signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC can activate apoptotic signaling under stress conditions.
      action: KEEP_AS_NON_CORE
      reason: MYC-induced apoptosis is context-dependent and not its primary 
        function.
  - term:
      id: GO:0016072
      label: rRNA metabolic process
    evidence_type: IMP
    original_reference_id: PMID:38225354
    review:
      summary: MYC localizes to the nucleolus via HEATR1 interaction and 
        regulates ribosome biogenesis and rRNA synthesis.
      action: ACCEPT
      reason: Regulation of ribosome biogenesis is a well-documented core 
        function of MYC, directly linked to its role in promoting cell growth 
        and proliferation.
      supported_by:
        - reference_id: PMID:38225354
          supporting_text: Jan 15. Ribogenesis boosts controlled by HEATR1-MYC 
            interplay promote transition into brain tumour growth.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:38225354
    review:
      summary: Generic protein binding from a study on HEATR1-MYC interaction in
        ribogenesis.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:38225354
          supporting_text: Jan 15. Ribogenesis boosts controlled by HEATR1-MYC 
            interplay promote transition into brain tumour growth.
  - term:
      id: GO:0044027
      label: negative regulation of gene expression via chromosomal CpG island 
        methylation
    evidence_type: IMP
    original_reference_id: PMID:19786833
    review:
      summary: MYC represses gene expression by recruiting DNA 
        methyltransferases to target gene promoters.
      action: KEEP_AS_NON_CORE
      reason: While MYC can influence DNA methylation patterns, this is a 
        context-specific mechanism of repression, not its primary mode of 
        action.
      supported_by:
        - reference_id: PMID:19786833
          supporting_text: Dnmt3/transcription factor interactions as crucial 
            players in targeted DNA methylation.
  - term:
      id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA 
        binding
    evidence_type: IMP
    original_reference_id: PMID:19786833
    review:
      summary: MYC binds to cis-regulatory regions at target gene promoters.
      action: ACCEPT
      reason: This is a core molecular function of MYC as a DNA-binding 
        transcription factor.
      supported_by:
        - reference_id: PMID:19786833
          supporting_text: Dnmt3/transcription factor interactions as crucial 
            players in targeted DNA methylation.
  - term:
      id: GO:0001227
      label: DNA-binding transcription repressor activity, RNA polymerase 
        II-specific
    evidence_type: IMP
    original_reference_id: PMID:19786833
    review:
      summary: MYC has transcription repressor activity mediated through MIZ1 
        interaction and DNMT recruitment.
      action: ACCEPT
      reason: Transcription repressor activity is a core function of MYC, 
        particularly through its interaction with MIZ1.
      supported_by:
        - reference_id: PMID:19786833
          supporting_text: Dnmt3/transcription factor interactions as crucial 
            players in targeted DNA methylation.
  - term:
      id: GO:0000082
      label: G1/S transition of mitotic cell cycle
    evidence_type: IDA
    original_reference_id: PMID:25438055
    review:
      summary: MYC regulates G1/S transition through transcriptional control of 
        cyclin/CDK genes and repression of CDK inhibitors.
      action: ACCEPT
      reason: Regulation of G1/S transition is a core biological process 
        function of MYC in promoting cell cycle progression.
      supported_by:
        - reference_id: PMID:25438055
          supporting_text: AMBRA1 links autophagy to cell proliferation and 
            tumorigenesis by promoting c-Myc dephosphorylation and degradation.
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:10723141
    review:
      summary: Direct experimental evidence for MYC DNA-binding transcription 
        factor activity.
      action: ACCEPT
      reason: This is the core molecular function of MYC.
      supported_by:
        - reference_id: PMID:10723141
          supporting_text: Identification of Mad as a repressor of the human 
            telomerase (hTERT) gene.
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:9924025
    review:
      summary: Experimental evidence for MYC transcription factor activity.
      action: ACCEPT
      reason: Core molecular function of MYC.
      supported_by:
        - reference_id: PMID:9924025
          supporting_text: Coordinated regulation of iron-controlling genes, 
            H-ferritin and IRP2, by c-MYC.
  - term:
      id: GO:0001227
      label: DNA-binding transcription repressor activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:29203640
    review:
      summary: MYC represses transcription of target genes.
      action: ACCEPT
      reason: Transcription repressor activity (via MIZ1) is a core function of 
        MYC.
      supported_by:
        - reference_id: PMID:29203640
          supporting_text: 2018 Mar 1. Transforming Growth Factor β-Induced 
            Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation 
            and Its Antagonism by MYC.
  - term:
      id: GO:0001221
      label: transcription coregulator binding
    evidence_type: IPI
    original_reference_id: PMID:15674325
    review:
      summary: MYC interacts with transcription coregulators including TAF1C for
        rRNA transcription.
      action: ACCEPT
      reason: Binding to transcription coregulators is essential for MYC 
        transcriptional activity.
      supported_by:
        - reference_id: PMID:15674325
          supporting_text: PARP-10, a novel Myc-interacting protein with 
            poly(ADP-ribose) polymerase activity, inhibits transformation.
  - term:
      id: GO:0140297
      label: DNA-binding transcription factor binding
    evidence_type: IPI
    original_reference_id: PMID:15674325
    review:
      summary: MYC binds other DNA-binding transcription factors as part of its 
        regulatory mechanism.
      action: ACCEPT
      reason: This is more informative than generic protein binding and 
        describes functional interactions relevant to MYC activity.
      supported_by:
        - reference_id: PMID:15674325
          supporting_text: PARP-10, a novel Myc-interacting protein with 
            poly(ADP-ribose) polymerase activity, inhibits transformation.
  - term:
      id: GO:0001228
      label: DNA-binding transcription activator activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:27791094
    review:
      summary: MYC functions as a transcriptional activator at E-box containing 
        promoters.
      action: ACCEPT
      reason: Transcription activator activity is a core molecular function of 
        MYC.
      supported_by:
        - reference_id: PMID:27791094
          supporting_text: Primate-specific miR-515 family members inhibit key 
            genes in human trophoblast differentiation and are upregulated in 
            preeclampsia.
  - term:
      id: GO:0070888
      label: E-box binding
    evidence_type: IDA
    original_reference_id: PMID:27791094
    review:
      summary: MYC binds E-box DNA sequences (CACGTG) as a heterodimer with MAX.
      action: ACCEPT
      reason: E-box binding is the specific DNA binding activity of MYC and 
        represents a core molecular function.
      supported_by:
        - reference_id: PMID:27791094
          supporting_text: Primate-specific miR-515 family members inhibit key 
            genes in human trophoblast differentiation and are upregulated in 
            preeclampsia.
  - term:
      id: GO:0001046
      label: core promoter sequence-specific DNA binding
    evidence_type: IDA
    original_reference_id: PMID:30873824
    review:
      summary: MYC binds core promoter sequences at target genes.
      action: ACCEPT
      reason: Promoter binding is a core function of MYC as a transcription 
        factor.
      supported_by:
        - reference_id: PMID:30873824
          supporting_text: Sep 14. Integrin alpha x stimulates cancer 
            angiogenesis through PI3K/Akt signaling-mediated VEGFR2/VEGF-A 
            overexpression in blood vessel endothelial cells.
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: ISA
    original_reference_id: GO_REF:0000113
    review:
      summary: MYC transcription factor activity inferred from sequence and 
        structural similarity.
      action: ACCEPT
      reason: ISA annotation correctly identifies MYC transcription factor 
        activity based on structural conservation.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IMP
    original_reference_id: PMID:19786833
    review:
      summary: MYC represses transcription through DNA methylation-mediated 
        mechanisms.
      action: ACCEPT
      reason: Transcriptional repression is a core function of MYC.
      supported_by:
        - reference_id: PMID:19786833
          supporting_text: Dnmt3/transcription factor interactions as crucial 
            players in targeted DNA methylation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19786833
    review:
      summary: Generic protein binding from a DNA methylation study.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:19786833
          supporting_text: Dnmt3/transcription factor interactions as crucial 
            players in targeted DNA methylation.
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IMP
    original_reference_id: PMID:25956029
    review:
      summary: MYC transcription factor activity from a study on 
        GLTSCR2-NPM1-MYC axis.
      action: ACCEPT
      reason: Core molecular function of MYC.
      supported_by:
        - reference_id: PMID:25956029
          supporting_text: 2015 May 5. The Nucleolar Protein GLTSCR2 Is an 
            Upstream Negative Regulator of the Oncogenic Nucleophosmin-MYC Axis.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25956029
    review:
      summary: Generic protein binding from a study on nucleophosmin-MYC 
        interaction.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:25956029
          supporting_text: 2015 May 5. The Nucleolar Protein GLTSCR2 Is an 
            Upstream Negative Regulator of the Oncogenic Nucleophosmin-MYC Axis.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:19160485
    review:
      summary: MYC represses transcription at specific target genes.
      action: ACCEPT
      reason: Transcriptional repression is a core function of MYC.
      supported_by:
        - reference_id: PMID:19160485
          supporting_text: A ribosomal protein L23-nucleophosmin circuit 
            coordinates Mizl function with cell growth.
  - term:
      id: GO:0140297
      label: DNA-binding transcription factor binding
    evidence_type: IPI
    original_reference_id: PMID:19160485
    review:
      summary: MYC binds other transcription factors as part of its regulatory 
        function.
      action: ACCEPT
      reason: This is more informative than generic protein binding.
      supported_by:
        - reference_id: PMID:19160485
          supporting_text: A ribosomal protein L23-nucleophosmin circuit 
            coordinates Mizl function with cell growth.
  - term:
      id: GO:0000978
      label: RNA polymerase II cis-regulatory region sequence-specific DNA 
        binding
    evidence_type: IDA
    original_reference_id: PMID:10723141
    review:
      summary: Direct evidence for MYC binding to cis-regulatory regions.
      action: ACCEPT
      reason: Core molecular function of MYC.
      supported_by:
        - reference_id: PMID:10723141
          supporting_text: Identification of Mad as a repressor of the human 
            telomerase (hTERT) gene.
  - term:
      id: GO:0001228
      label: DNA-binding transcription activator activity, RNA polymerase 
        II-specific
    evidence_type: IDA
    original_reference_id: PMID:10723141
    review:
      summary: MYC activates transcription at target genes.
      action: ACCEPT
      reason: Transcription activator activity is a core function of MYC.
      supported_by:
        - reference_id: PMID:10723141
          supporting_text: Identification of Mad as a repressor of the human 
            telomerase (hTERT) gene.
  - term:
      id: GO:0010468
      label: regulation of gene expression
    evidence_type: IDA
    original_reference_id: PMID:21447833
    review:
      summary: MYC regulates expression of many target genes.
      action: ACCEPT
      reason: Gene expression regulation is the core function of MYC as a 
        transcription factor.
      supported_by:
        - reference_id: PMID:21447833
          supporting_text: 2011 Mar 29. TIP110/p110nrb/SART3/p110 regulation of 
            hematopoiesis through CMYC.
  - term:
      id: GO:0000165
      label: MAPK cascade
    evidence_type: IMP
    original_reference_id: PMID:17873522
    review:
      summary: MYC stability is regulated by MAPK signaling through 
        phosphorylation.
      action: KEEP_AS_NON_CORE
      reason: MYC is regulated by MAPK signaling but is not a direct component 
        of the MAPK cascade.
      supported_by:
        - reference_id: PMID:17873522
          supporting_text: Fbw7 and Usp28 regulate myc protein stability in 
            response to DNA damage.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17873522
    review:
      summary: Generic protein binding from a study on FBXW7 and USP28 
        regulation of MYC.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:17873522
          supporting_text: Fbw7 and Usp28 regulate myc protein stability in 
            response to DNA damage.
  - term:
      id: GO:0044877
      label: protein-containing complex binding
    evidence_type: IDA
    original_reference_id: PMID:18987311
    review:
      summary: MYC binds to protein complexes as part of its function.
      action: ACCEPT
      reason: This is more informative than generic protein binding and reflects
        MYC interaction with multiprotein complexes.
      supported_by:
        - reference_id: PMID:18987311
          supporting_text: The parafibromin tumor suppressor protein inhibits 
            cell proliferation by repression of the c-myc proto-oncogene.
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC DNA binding inferred from sequence similarity.
      action: ACCEPT
      reason: DNA binding is a core function of MYC.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:9924025
    review:
      summary: MYC represses transcription at specific promoters.
      action: ACCEPT
      reason: Transcriptional repression is a core function of MYC.
      supported_by:
        - reference_id: PMID:9924025
          supporting_text: Coordinated regulation of iron-controlling genes, 
            H-ferritin and IRP2, by c-MYC.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20551172
    review:
      summary: Generic protein binding from a study on TRPC4AP E3 ligase 
        complex.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:20551172
          supporting_text: Myc protein is stabilized by suppression of a novel 
            E3 ligase complex in cancer cells.
  - term:
      id: GO:0070888
      label: E-box binding
    evidence_type: IDA
    original_reference_id: PMID:18818310
    review:
      summary: Direct evidence for MYC binding to E-box sequences.
      action: ACCEPT
      reason: E-box binding is the core DNA binding specificity of MYC.
      supported_by:
        - reference_id: PMID:18818310
          supporting_text: AP4 encodes a c-MYC-inducible repressor of p21.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15103331
    review:
      summary: Generic protein binding from a study on FBXW7-mediated MYC 
        degradation.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:15103331
          supporting_text: Apr 22. Phosphorylation-dependent degradation of 
            c-Myc is mediated by the F-box protein Fbw7.
  - term:
      id: GO:0001658
      label: branching involved in ureteric bud morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC role in kidney development inferred from sequence similarity.
      action: KEEP_AS_NON_CORE
      reason: Tissue-specific developmental process, not a core function.
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: TAS
    original_reference_id: PMID:10597290
    review:
      summary: MYC DNA binding established by traceable author statement.
      action: ACCEPT
      reason: DNA binding is a core function of MYC.
      supported_by:
        - reference_id: PMID:10597290
          supporting_text: 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.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:10597290
    review:
      summary: Generic protein binding from a study on E7 oncoprotein 
        interaction with MYC.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:10597290
          supporting_text: 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.
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IDA
    original_reference_id: PMID:15994933
    review:
      summary: MYC promotes cell proliferation through transcriptional 
        activation of growth genes.
      action: ACCEPT
      reason: Positive regulation of cell proliferation is a core biological 
        process function of MYC.
      supported_by:
        - reference_id: PMID:15994933
          supporting_text: Identification of a novel c-Myc protein interactor, 
            JPO2, with transforming activity in medulloblastoma cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:9308237
    review:
      summary: Generic protein binding from a study on Myc-Max-Mad network.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:9308237
          supporting_text: Association of Myc with the zinc-finger protein Miz-1
            defines a novel pathway for gene regulation by Myc.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12706874
    review:
      summary: Generic protein binding from a study on transrepression of Smad 
        transcriptional activity by Myc.
      action: REMOVE
      reason: GO:0005515 protein binding is uninformative.
      supported_by:
        - reference_id: PMID:12706874
          supporting_text: Yaf2 inhibits Myc biological function.
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: MYC positively regulates cell proliferation, a core function 
        inferred by phylogenetic analysis.
      action: ACCEPT
      reason: Positive regulation of cell proliferation is a core function of 
        MYC as a proto-oncogene. IBA annotation is phylogenetically sound.
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: MYC regulates RNA Pol II transcription, a core function inferred 
        by phylogenetic analysis.
      action: ACCEPT
      reason: Regulation of transcription by RNA Pol II is the core function of 
        MYC as a transcription factor. IBA annotation is phylogenetically sound.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: MYC localizes to the nucleus to function as a transcription 
        factor.
      action: ACCEPT
      reason: Nuclear localization is essential for MYC transcriptional 
        activity.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: MYC localizes to the nucleoplasm where it functions as a 
        transcriptional regulator.
      action: ACCEPT
      reason: Nucleoplasm localization is consistent with MYC function.
  - term:
      id: GO:0005694
      label: chromosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: MYC associates with chromosomes/chromatin at target gene loci.
      action: ACCEPT
      reason: Chromosome association is essential for MYC DNA binding and 
        transcriptional activity.
  - term:
      id: GO:0005730
      label: nucleolus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: MYC localizes to the nucleolus for rRNA transcription regulation.
      action: ACCEPT
      reason: Nucleolar localization is important for MYC function in ribosome 
        biogenesis.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: A fraction of MYC can be found in the cytoplasm.
      action: KEEP_AS_NON_CORE
      reason: While MYC can be cytoplasmic (especially Myc-nick isoform), its 
        primary localization is nuclear.
  - term:
      id: GO:0006355
      label: regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: MYC regulates DNA-templated transcription as a transcription 
        factor.
      action: ACCEPT
      reason: This is the core function of MYC.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:18393360
    review:
      summary: Nuclear localization is essential for MYC's function as a 
        transcriptional regulator
      action: ACCEPT
      reason: Nuclear localization is core to MYC's role in transcriptional 
        regulation and gene expression control
      supported_by:
        - reference_id: PMID:18393360
          supporting_text: c-Myc represses FOXO3a-mediated transcription of the 
            gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.
  - term:
      id: GO:0090571
      label: RNA polymerase II transcription repressor complex
    evidence_type: IPI
    original_reference_id: PMID:18393360
    review:
      summary: MYC is a component of transcription repressor complexes with MIZ1
        to repress target genes.
      action: ACCEPT
      reason: MYC participates in repressor complexes, which is essential for 
        its repressive function.
      supported_by:
        - reference_id: PMID:18393360
          supporting_text: c-Myc represses FOXO3a-mediated transcription of the 
            gene encoding the p27(Kip1) cyclin dependent kinase inhibitor.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: NAS
    original_reference_id: PMID:8425218
    review:
      summary: Nuclear localization of MYC.
      action: ACCEPT
      reason: Nuclear localization is essential for MYC function.
      supported_by:
        - reference_id: PMID:8425218
          supporting_text: 'Mad: a heterodimeric partner for Max that antagonizes
            Myc transcriptional activity.'
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:8782822
    review:
      summary: Direct assay evidence for MYC nuclear localization.
      action: ACCEPT
      reason: Nuclear localization is core to MYC function.
      supported_by:
        - reference_id: PMID:8782822
          supporting_text: BIN1 is a novel MYC-interacting protein with features
            of a tumour suppressor.
  - term:
      id: GO:0010564
      label: regulation of cell cycle process
    evidence_type: IDA
    original_reference_id: PMID:8782822
    review:
      summary: MYC regulates cell cycle progression through transcriptional 
        control of cyclins and CDK inhibitors.
      action: ACCEPT
      reason: Cell cycle regulation is a core function of MYC as a growth 
        regulator.
      supported_by:
        - reference_id: PMID:8782822
          supporting_text: BIN1 is a novel MYC-interacting protein with features
            of a tumour suppressor.
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:8425218
    review:
      summary: MYC positively regulates transcription of target genes.
      action: ACCEPT
      reason: Positive transcriptional regulation is a core function of MYC.
      supported_by:
        - reference_id: PMID:8425218
          supporting_text: 'Mad: a heterodimeric partner for Max that antagonizes
            Myc transcriptional activity.'
  - term:
      id: GO:0071943
      label: Myc-Max complex
    evidence_type: IPI
    original_reference_id: PMID:12553908
    review:
      summary: MYC forms a heterodimeric complex with MAX for DNA binding and 
        transcriptional activity.
      action: ACCEPT
      reason: The Myc-Max complex is the functional unit for MYC transcriptional
        activity. This is a core cellular component annotation.
      supported_by:
        - reference_id: PMID:12553908
          supporting_text: X-ray structures of Myc-Max and Mad-Max recognizing 
            DNA.
  - term:
      id: GO:0090571
      label: RNA polymerase II transcription repressor complex
    evidence_type: IPI
    original_reference_id: PMID:15992821
    review:
      summary: MYC participates in transcription repressor complexes with BIN1.
      action: ACCEPT
      reason: MYC is part of repressor complexes for transcriptional repression 
        function.
      supported_by:
        - reference_id: PMID:15992821
          supporting_text: A structure-based model of the c-Myc/Bin1 protein 
            interaction shows alternative splicing of Bin1 and c-Myc 
            phosphorylation are key binding determinants.
  - term:
      id: GO:0000791
      label: euchromatin
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC preferentially associates with active euchromatin at target 
        genes.
      action: ACCEPT
      reason: Euchromatin association is consistent with MYC role as a 
        transcriptional activator.
  - term:
      id: GO:0002053
      label: positive regulation of mesenchymal cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Cell-type specific proliferation annotation from Ensembl Compara.
      action: KEEP_AS_NON_CORE
      reason: Tissue-specific manifestation of MYC proliferative function.
  - term:
      id: GO:0005819
      label: spindle
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC may localize to spindle during mitosis.
      action: MARK_AS_OVER_ANNOTATED
      reason: Spindle localization is not a well-characterized or core aspect of
        MYC function.
  - term:
      id: GO:0016604
      label: nuclear body
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC localizes to nuclear bodies.
      action: KEEP_AS_NON_CORE
      reason: While MYC can localize to nuclear bodies including nucleolus, this
        is not the primary localization.
  - term:
      id: GO:0030424
      label: axon
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Neuronal-specific localization annotation.
      action: MARK_AS_OVER_ANNOTATED
      reason: Axon localization is not a well-characterized or core aspect of 
        MYC function.
  - term:
      id: GO:0032206
      label: positive regulation of telomere maintenance
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC regulates TERT expression and telomere maintenance.
      action: KEEP_AS_NON_CORE
      reason: While MYC transcriptionally activates TERT, telomere maintenance 
        is a downstream effect.
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC positively regulates transcription at many target genes.
      action: ACCEPT
      reason: Positive transcriptional regulation is a core function of MYC.
  - term:
      id: GO:0048471
      label: perinuclear region of cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC may localize to perinuclear region.
      action: MARK_AS_OVER_ANNOTATED
      reason: This is not a primary or well-characterized localization for MYC.
  - term:
      id: GO:0060261
      label: positive regulation of transcription initiation by RNA polymerase 
        II
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC promotes transcription initiation at target gene promoters.
      action: ACCEPT
      reason: MYC regulates transcription initiation as part of its core 
        function.
  - term:
      id: GO:0071943
      label: Myc-Max complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC forms the Myc-Max heterodimer complex for transcriptional 
        regulation.
      action: ACCEPT
      reason: The Myc-Max complex is the functional unit for MYC activity.
  - term:
      id: GO:0090096
      label: positive regulation of metanephric cap mesenchymal cell 
        proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: Kidney-specific proliferation annotation from Ensembl Compara.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:1904672
      label: regulation of somatic stem cell population maintenance
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: MYC regulates stem cell self-renewal and maintenance.
      action: KEEP_AS_NON_CORE
      reason: While MYC is one of the Yamanaka factors for iPSC reprogramming, 
        stem cell maintenance is a context-specific function.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IDA
    original_reference_id: PMID:30158517
    review:
      summary: MYC directly binds to chromatin to regulate target gene 
        expression
      action: ACCEPT
      reason: Chromatin association is essential for MYC's function as a 
        transcription factor that directly regulates gene expression
      supported_by:
        - reference_id: PMID:30158517
          supporting_text: MYC dephosphorylation by the PP1/PNUTS phosphatase 
            complex regulates chromatin binding and protein stability.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: MYC localizes to the nucleoplasm where it forms transcriptional 
        complexes
      action: ACCEPT
      reason: Nucleoplasm localization is consistent with MYC's role in forming 
        transcriptional regulatory complexes
  - term:
      id: GO:0005730
      label: nucleolus
    evidence_type: IDA
    original_reference_id: PMID:38225354
    review:
      summary: MYC localizes to the nucleolus via HEATR1 interaction for 
        ribosome biogenesis regulation.
      action: ACCEPT
      reason: Nucleolar localization is important for MYC function in rRNA 
        transcription and ribosome biogenesis.
      supported_by:
        - reference_id: PMID:38225354
          supporting_text: Jan 15. Ribogenesis boosts controlled by HEATR1-MYC 
            interplay promote transition into brain tumour growth.
  - term:
      id: GO:0032206
      label: positive regulation of telomere maintenance
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC regulates telomere maintenance through TERT transcription.
      action: KEEP_AS_NON_CORE
      reason: Telomere maintenance is a downstream effect of MYC transcriptional
        activity, not a core function.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC positively regulates transcription by RNA Pol II.
      action: ACCEPT
      reason: This is a core function of MYC as a transcription factor.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:11793365
    review:
      summary: MYC nuclear localization demonstrated by direct assay.
      action: ACCEPT
      reason: Nuclear localization is essential for MYC function.
      supported_by:
        - reference_id: PMID:11793365
          supporting_text: Expression of frizzled-related protein and 
            Wnt-signalling molecules in invasive human breast tumours.
  - term:
      id: GO:0060633
      label: negative regulation of transcription initiation by RNA polymerase 
        II
    evidence_type: IDA
    original_reference_id: PMID:29203640
    review:
      summary: MYC represses transcription initiation at specific target genes.
      action: ACCEPT
      reason: Negative regulation of transcription initiation is a core 
        repressive function of MYC.
      supported_by:
        - reference_id: PMID:29203640
          supporting_text: 2018 Mar 1. Transforming Growth Factor β-Induced 
            Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation 
            and Its Antagonism by MYC.
  - term:
      id: GO:1902255
      label: positive regulation of intrinsic apoptotic signaling pathway by p53
        class mediator
    evidence_type: IDA
    original_reference_id: PMID:10962037
    review:
      summary: MYC can activate apoptosis through p53-dependent pathways.
      action: KEEP_AS_NON_CORE
      reason: MYC-induced apoptosis via p53 is a context-dependent function, not
        the primary role of MYC.
      supported_by:
        - reference_id: PMID:10962037
          supporting_text: Overexpression of MYC causes p53-dependent G2 arrest 
            of normal fibroblasts.
  - term:
      id: GO:1902895
      label: positive regulation of miRNA transcription
    evidence_type: IDA
    original_reference_id: PMID:27791094
    review:
      summary: MYC regulates transcription of miRNAs as part of its 
        transcriptional program.
      action: KEEP_AS_NON_CORE
      reason: miRNA transcription regulation is a specific aspect of MYC 
        transcriptional activity.
      supported_by:
        - reference_id: PMID:27791094
          supporting_text: Primate-specific miR-515 family members inhibit key 
            genes in human trophoblast differentiation and are upregulated in 
            preeclampsia.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IMP
    original_reference_id: PMID:12837246
    review:
      summary: MYC associates with chromatin at target gene promoters.
      action: ACCEPT
      reason: Chromatin association is essential for MYC transcriptional 
        activity.
      supported_by:
        - reference_id: PMID:12837246
          supporting_text: Multiple tumor suppressor pathways negatively 
            regulate telomerase.
  - term:
      id: GO:1904672
      label: regulation of somatic stem cell population maintenance
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC regulates stem cell maintenance (Yamanaka factor).
      action: KEEP_AS_NON_CORE
      reason: Stem cell maintenance is a context-specific function.
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: ISA
    original_reference_id: GO_REF:0000113
    review:
      summary: MYC chromatin association inferred from structural annotation.
      action: ACCEPT
      reason: Chromatin association is core to MYC function.
  - term:
      id: GO:0005730
      label: nucleolus
    evidence_type: IDA
    original_reference_id: PMID:25775507
    review:
      summary: MYC localizes to nucleolus and is stabilized by USP36.
      action: ACCEPT
      reason: Nucleolar localization is important for MYC function in ribosome 
        biogenesis.
      supported_by:
        - reference_id: PMID:25775507
          supporting_text: The nucleolar ubiquitin-specific protease USP36 
            deubiquitinates and stabilizes c-Myc.
  - term:
      id: GO:0032986
      label: protein-DNA complex disassembly
    evidence_type: IDA
    original_reference_id: PMID:19160485
    review:
      summary: MYC promotes protein-DNA complex disassembly at repressed 
        promoters.
      action: KEEP_AS_NON_CORE
      reason: This is a specific mechanism of MYC repressive function.
      supported_by:
        - reference_id: PMID:19160485
          supporting_text: A ribosomal protein L23-nucleophosmin circuit 
            coordinates Mizl function with cell growth.
  - term:
      id: GO:0032991
      label: protein-containing complex
    evidence_type: IDA
    original_reference_id: PMID:19160485
    review:
      summary: MYC is part of protein-containing transcriptional complexes.
      action: ACCEPT
      reason: MYC functions within multiprotein complexes for transcriptional 
        regulation.
      supported_by:
        - reference_id: PMID:19160485
          supporting_text: A ribosomal protein L23-nucleophosmin circuit 
            coordinates Mizl function with cell growth.
  - term:
      id: GO:0010628
      label: positive regulation of gene expression
    evidence_type: IDA
    original_reference_id: PMID:15459207
    review:
      summary: MYC positively regulates gene expression.
      action: ACCEPT
      reason: Positive regulation of gene expression is a core function of MYC.
      supported_by:
        - reference_id: PMID:15459207
          supporting_text: 2004 Sep 30. ERK1/2 regulates intracellular ATP 
            levels through alpha-enolase expression in cardiomyocytes exposed to
            ischemic hypoxia and reoxygenation.
  - term:
      id: GO:0010628
      label: positive regulation of gene expression
    evidence_type: IGI
    original_reference_id: PMID:15459207
    review:
      summary: MYC positive regulation of gene expression supported by genetic 
        interaction.
      action: ACCEPT
      reason: Core function of MYC.
      supported_by:
        - reference_id: PMID:15459207
          supporting_text: 2004 Sep 30. ERK1/2 regulates intracellular ATP 
            levels through alpha-enolase expression in cardiomyocytes exposed to
            ischemic hypoxia and reoxygenation.
  - term:
      id: GO:0070371
      label: ERK1 and ERK2 cascade
    evidence_type: IDA
    original_reference_id: PMID:15459207
    review:
      summary: MYC is involved in ERK1/2 signaling cascades.
      action: KEEP_AS_NON_CORE
      reason: MYC is regulated by and influences ERK signaling but is not a 
        direct component.
      supported_by:
        - reference_id: PMID:15459207
          supporting_text: 2004 Sep 30. ERK1/2 regulates intracellular ATP 
            levels through alpha-enolase expression in cardiomyocytes exposed to
            ischemic hypoxia and reoxygenation.
  - term:
      id: GO:0071456
      label: cellular response to hypoxia
    evidence_type: IDA
    original_reference_id: PMID:15459207
    review:
      summary: MYC is involved in cellular response to hypoxia.
      action: KEEP_AS_NON_CORE
      reason: Hypoxia response is a context-specific function.
      supported_by:
        - reference_id: PMID:15459207
          supporting_text: 2004 Sep 30. ERK1/2 regulates intracellular ATP 
            levels through alpha-enolase expression in cardiomyocytes exposed to
            ischemic hypoxia and reoxygenation.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5696914
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core to MYC function.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:10723141
    review:
      summary: MYC positively regulates RNA Pol II transcription.
      action: ACCEPT
      reason: Core function of MYC.
      supported_by:
        - reference_id: PMID:10723141
          supporting_text: Identification of Mad as a repressor of the human 
            telomerase (hTERT) gene.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1484099
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1980067
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2220985
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-4411357
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5687083
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5687113
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6790036
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8865265
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8865280
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8932400
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9011975
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9725332
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9762097
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9816153
    review:
      summary: MYC nucleoplasm localization from Reactome pathway.
      action: ACCEPT
      reason: Nucleoplasm localization is core.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:15358760
    review:
      summary: MYC nuclear localization by direct assay.
      action: ACCEPT
      reason: Nuclear localization is essential for MYC function.
      supported_by:
        - reference_id: PMID:15358760
          supporting_text: '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.'
  - term:
      id: GO:0006338
      label: chromatin remodeling
    evidence_type: IDA
    original_reference_id: PMID:21533051
    review:
      summary: MYC promotes chromatin remodeling at target genes.
      action: ACCEPT
      reason: Chromatin remodeling is part of MYC transcriptional activation 
        mechanism.
      supported_by:
        - reference_id: PMID:21533051
          supporting_text: Multiple Wnt/ß-catenin responsive enhancers align 
            with the MYC promoter through long-range chromatin loops.
  - term:
      id: GO:0006974
      label: DNA damage response
    evidence_type: IDA
    original_reference_id: PMID:17873522
    review:
      summary: MYC is involved in DNA damage response signaling.
      action: KEEP_AS_NON_CORE
      reason: DNA damage response is context-specific, not a core MYC function.
      supported_by:
        - reference_id: PMID:17873522
          supporting_text: Fbw7 and Usp28 regulate myc protein stability in 
            response to DNA damage.
  - term:
      id: GO:0032991
      label: protein-containing complex
    evidence_type: IDA
    original_reference_id: PMID:17873522
    review:
      summary: MYC is part of protein complexes for its regulation.
      action: ACCEPT
      reason: MYC functions within protein complexes.
      supported_by:
        - reference_id: PMID:17873522
          supporting_text: Fbw7 and Usp28 regulate myc protein stability in 
            response to DNA damage.
  - term:
      id: GO:0034644
      label: cellular response to UV
    evidence_type: IEP
    original_reference_id: PMID:17873522
    review:
      summary: MYC expression is affected by UV radiation.
      action: MARK_AS_OVER_ANNOTATED
      reason: UV response is a general stress response, not a core MYC function.
      supported_by:
        - reference_id: PMID:17873522
          supporting_text: Fbw7 and Usp28 regulate myc protein stability in 
            response to DNA damage.
  - term:
      id: GO:0048146
      label: positive regulation of fibroblast proliferation
    evidence_type: IMP
    original_reference_id: PMID:15674325
    review:
      summary: MYC promotes fibroblast proliferation.
      action: KEEP_AS_NON_CORE
      reason: Cell-type specific proliferation effect.
      supported_by:
        - reference_id: PMID:15674325
          supporting_text: PARP-10, a novel Myc-interacting protein with 
            poly(ADP-ribose) polymerase activity, inhibits transformation.
  - term:
      id: GO:0048146
      label: positive regulation of fibroblast proliferation
    evidence_type: IDA
    original_reference_id: PMID:18987311
    review:
      summary: MYC promotes fibroblast proliferation.
      action: KEEP_AS_NON_CORE
      reason: Cell-type specific proliferation effect.
      supported_by:
        - reference_id: PMID:18987311
          supporting_text: The parafibromin tumor suppressor protein inhibits 
            cell proliferation by repression of the c-myc proto-oncogene.
  - term:
      id: GO:0050679
      label: positive regulation of epithelial cell proliferation
    evidence_type: IDA
    original_reference_id: PMID:18987311
    review:
      summary: MYC promotes epithelial cell proliferation.
      action: KEEP_AS_NON_CORE
      reason: Cell-type specific proliferation effect.
      supported_by:
        - reference_id: PMID:18987311
          supporting_text: The parafibromin tumor suppressor protein inhibits 
            cell proliferation by repression of the c-myc proto-oncogene.
  - term:
      id: GO:0070848
      label: response to growth factor
    evidence_type: TAS
    original_reference_id: PMID:18987311
    review:
      summary: MYC is induced in response to growth factor signaling.
      action: KEEP_AS_NON_CORE
      reason: Growth factor response is an upstream regulatory event, not a core
        MYC function.
      supported_by:
        - reference_id: PMID:18987311
          supporting_text: The parafibromin tumor suppressor protein inhibits 
            cell proliferation by repression of the c-myc proto-oncogene.
  - term:
      id: GO:0071466
      label: cellular response to xenobiotic stimulus
    evidence_type: IDA
    original_reference_id: PMID:17873522
    review:
      summary: MYC levels change in response to xenobiotic stress.
      action: MARK_AS_OVER_ANNOTATED
      reason: Xenobiotic response is a general stress response, not a core MYC 
        function.
      supported_by:
        - reference_id: PMID:17873522
          supporting_text: Fbw7 and Usp28 regulate myc protein stability in 
            response to DNA damage.
  - term:
      id: GO:0032873
      label: negative regulation of stress-activated MAPK cascade
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC can modulate stress-activated MAPK signaling.
      action: KEEP_AS_NON_CORE
      reason: MAPK regulation is context-dependent and not a core MYC function.
  - term:
      id: GO:0043066
      label: negative regulation of apoptotic process
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC can inhibit apoptosis under certain conditions.
      action: KEEP_AS_NON_CORE
      reason: MYC has dual effects on apoptosis (can both promote and inhibit); 
        this is context-dependent.
  - term:
      id: GO:0006879
      label: intracellular iron ion homeostasis
    evidence_type: IDA
    original_reference_id: PMID:9924025
    review:
      summary: MYC regulates iron homeostasis genes.
      action: KEEP_AS_NON_CORE
      reason: Iron homeostasis regulation is a specific metabolic function of 
        MYC, not its primary role.
      supported_by:
        - reference_id: PMID:9924025
          supporting_text: Coordinated regulation of iron-controlling genes, 
            H-ferritin and IRP2, by c-MYC.
  - term:
      id: GO:0044346
      label: fibroblast apoptotic process
    evidence_type: TAS
    original_reference_id: PMID:10962037
    review:
      summary: MYC promotes fibroblast apoptosis under certain conditions.
      action: KEEP_AS_NON_CORE
      reason: Cell-type specific apoptotic function.
      supported_by:
        - reference_id: PMID:10962037
          supporting_text: Overexpression of MYC causes p53-dependent G2 arrest 
            of normal fibroblasts.
  - term:
      id: GO:0045656
      label: negative regulation of monocyte differentiation
    evidence_type: IMP
    original_reference_id: PMID:9924025
    review:
      summary: MYC inhibits monocyte differentiation to maintain proliferative 
        state.
      action: KEEP_AS_NON_CORE
      reason: Cell-type specific differentiation effect.
      supported_by:
        - reference_id: PMID:9924025
          supporting_text: Coordinated regulation of iron-controlling genes, 
            H-ferritin and IRP2, by c-MYC.
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:10962037
    review:
      summary: MYC positively regulates transcription.
      action: ACCEPT
      reason: Positive transcription regulation is a core function of MYC.
      supported_by:
        - reference_id: PMID:10962037
          supporting_text: Overexpression of MYC causes p53-dependent G2 arrest 
            of normal fibroblasts.
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IMP
    original_reference_id: PMID:9924025
    review:
      summary: MYC positively regulates RNA Pol II transcription.
      action: ACCEPT
      reason: Core function of MYC.
      supported_by:
        - reference_id: PMID:9924025
          supporting_text: Coordinated regulation of iron-controlling genes, 
            H-ferritin and IRP2, by c-MYC.
  - term:
      id: GO:0048146
      label: positive regulation of fibroblast proliferation
    evidence_type: IDA
    original_reference_id: PMID:9924025
    review:
      summary: MYC promotes fibroblast proliferation.
      action: KEEP_AS_NON_CORE
      reason: Cell-type specific proliferation effect.
      supported_by:
        - reference_id: PMID:9924025
          supporting_text: Coordinated regulation of iron-controlling genes, 
            H-ferritin and IRP2, by c-MYC.
  - term:
      id: GO:0048147
      label: negative regulation of fibroblast proliferation
    evidence_type: IDA
    original_reference_id: PMID:10962037
    review:
      summary: MYC can negatively regulate fibroblast proliferation in certain 
        contexts (apoptosis).
      action: KEEP_AS_NON_CORE
      reason: Context-dependent effect on proliferation.
      supported_by:
        - reference_id: PMID:10962037
          supporting_text: Overexpression of MYC causes p53-dependent G2 arrest 
            of normal fibroblasts.
  - term:
      id: GO:0051276
      label: chromosome organization
    evidence_type: IDA
    original_reference_id: PMID:10962037
    review:
      summary: MYC affects chromosome organization at target loci.
      action: KEEP_AS_NON_CORE
      reason: Chromosome organization is a downstream effect of MYC chromatin 
        binding.
      supported_by:
        - reference_id: PMID:10962037
          supporting_text: Overexpression of MYC causes p53-dependent G2 arrest 
            of normal fibroblasts.
  - term:
      id: GO:0051782
      label: negative regulation of cell division
    evidence_type: IDA
    original_reference_id: PMID:10962037
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:10962037
          supporting_text: Overexpression of MYC causes p53-dependent G2 arrest 
            of normal fibroblasts.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: PMID:17558397
    review:
      summary: MYC is a nuclear transcription factor that localizes to the 
        nucleoplasm where it binds chromatin and regulates transcription.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:17558397
          supporting_text: The ubiquitin-specific protease USP28 is required for
            MYC stability.
  - term:
      id: GO:0005730
      label: nucleolus
    evidence_type: IDA
    original_reference_id: PMID:17558397
    review:
      summary: MYC has been detected in the nucleolus where it regulates 
        ribosomal RNA transcription and ribosome biogenesis.
      action: ACCEPT
      reason: Nucleolar localization is important for MYC function in ribosome 
        biogenesis and rRNA transcription regulation, consistent with other 
        nucleolus annotations.
      supported_by:
        - reference_id: PMID:17558397
          supporting_text: The ubiquitin-specific protease USP28 is required for
            MYC stability.
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:17558397
    review:
      summary: MYC-MAX heterodimers activate transcription by binding E-box 
        elements and recruiting transcriptional coactivators including histone 
        acetyltransferases.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:17558397
          supporting_text: The ubiquitin-specific protease USP28 is required for
            MYC stability.
  - term:
      id: GO:0009410
      label: response to xenobiotic stimulus
    evidence_type: IEP
    original_reference_id: PMID:18291362
    review:
      summary: MYC expression can be modulated in response to xenobiotic 
        exposure, likely reflecting stress or proliferative responses.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:18291362
          supporting_text: Epub 2008 Feb 5. Sulindac suppresses beta-catenin 
            expression in human cancer cells.
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:18818310
    review:
      summary: MYC-MAX heterodimers bind E-box elements to activate 
        transcription of target genes promoting cell growth and proliferation.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18818310
          supporting_text: AP4 encodes a c-MYC-inducible repressor of p21.
  - term:
      id: GO:0002053
      label: positive regulation of mesenchymal cell proliferation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC promotes proliferation in mesenchymal cells through its 
        general role as a transcriptional activator of cell cycle and growth 
        genes.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0090096
      label: positive regulation of metanephric cap mesenchymal cell 
        proliferation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: MYC promotes cell proliferation in metanephric cap mesenchyme 
        during kidney development.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0032204
      label: regulation of telomere maintenance
    evidence_type: IMP
    original_reference_id: PMID:17765874
    review:
      summary: MYC activates telomerase expression by binding to the TERT 
        promoter, contributing to telomere maintenance and cellular 
        immortalization.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:17765874
          supporting_text: c-Myc interacts with TRF1/PIN2 and regulates telomere
            length.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:15994933
    review:
      summary: MYC is a nuclear transcription factor that requires nuclear 
        localization for its function in regulating gene expression.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:15994933
          supporting_text: Identification of a novel c-Myc protein interactor, 
            JPO2, with transforming activity in medulloblastoma cells.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: TAS
    original_reference_id: PMID:9187264
    review:
      summary: MYC is a nuclear transcription factor established through 
        extensive literature.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:9187264
          supporting_text: Histamine modulates the expression of c-fos through 
            cyclic AMP production via the H2 receptor in the human promonocytic 
            cell line U937.
  - term:
      id: GO:0065003
      label: protein-containing complex assembly
    evidence_type: IEA
    review:
      summary: Essential for protein-containing complex assembly, particularly 
        Myc-Max complex formation required for transcriptional regulation
      action: NEW
      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.
      supported_by:
        - reference_id: PMID:12553908
          supporting_text: X-ray structures of Myc-Max and Mad-Max recognizing 
            DNA. Molecular bases of regulation by proto-oncogenic transcription 
            factors.
        - reference_id: PMID:21807113
          supporting_text: Sirt1 deacetylates c-Myc and promotes c-Myc/Max 
            association.
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:0000107
    title: Automatic transfer of experimentally verified manual GO annotation 
      data to orthologs using Ensembl Compara.
    findings: []
  - id: GO_REF:0000113
    title: Gene Ontology annotation of human sequence-specific DNA binding 
      transcription factors (DbTFs) based on the TFClass database
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods.
    findings: []
  - id: PMID:10412034
    title: Induction of apoptosis and differentiation in neuroblastoma and 
      astrocytoma cells by the overexpression of Bin1, a novel Myc interacting 
      protein.
    findings: []
  - id: PMID:10597290
    title: 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.
    findings: []
  - id: PMID:10723141
    title: Identification of Mad as a repressor of the human telomerase (hTERT) 
      gene.
    findings: []
  - id: PMID:11891322
    title: Small-molecule antagonists of Myc/Max dimerization inhibit 
      Myc-induced transformation of chicken embryo fibroblasts.
    findings: []
  - id: PMID:12706874
    title: Yaf2 inhibits Myc biological function.
    findings: []
  - id: PMID:15103331
    title: Phosphorylation-dependent degradation of c-Myc is mediated by the 
      F-box protein Fbw7.
    findings: []
  - id: PMID:15674325
    title: PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) 
      polymerase activity, inhibits transformation.
    findings: []
  - id: PMID:15992821
    title: A structure-based model of the c-Myc/Bin1 protein interaction shows 
      alternative splicing of Bin1 and c-Myc phosphorylation are key binding 
      determinants.
    findings: []
  - id: PMID:15994933
    title: Identification of a novel c-Myc protein interactor, JPO2, with 
      transforming activity in medulloblastoma cells.
    findings: []
  - id: PMID:16352593
    title: Targeting of Miz-1 is essential for Myc-mediated apoptosis.
    findings: []
  - id: PMID:16606833
    title: Identification of small molecules that induce apoptosis in a 
      Myc-dependent manner and inhibit Myc-driven transformation.
    findings: []
  - id: PMID:16996503
    title: Myc stabilization in response to estrogen and phospholipase D in 
      MCF-7 breast cancer cells.
    findings: []
  - id: PMID:17070091
    title: HPV-18 E7 conjugates to c-Myc and mediates its transcriptional 
      activity.
    findings: []
  - id: PMID:17157259
    title: SNIP1 is a candidate modifier of the transcriptional activity of 
      c-Myc on E box-dependent target genes.
    findings: []
  - id: PMID:17314511
    title: Large-scale identification of c-MYC-associated proteins using a 
      combined TAP/MudPIT approach.
    findings: []
  - id: PMID:17418410
    title: HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc 
      transcriptional activity.
    findings: []
  - id: PMID:17599065
    title: Inhibition of c-Myc activity by ribosomal protein L11.
    findings: []
  - id: PMID:17632056
    title: CIP2A inhibits PP2A in human malignancies.
    findings: []
  - id: PMID:17873522
    title: Fbw7 and Usp28 regulate myc protein stability in response to DNA 
      damage.
    findings: []
  - id: PMID:18256156
    title: Epstein-Barr virus nuclear antigen 3C interacts with and enhances the
      stability of the c-Myc oncoprotein.
    findings: []
  - id: PMID:18393360
    title: c-Myc represses FOXO3a-mediated transcription of the gene encoding 
      the p27(Kip1) cyclin dependent kinase inhibitor.
    findings: []
  - id: PMID:18413597
    title: Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc.
    findings: []
  - id: PMID:18620061
    title: Characterizing proteins and their interactions in cells and tissues 
      using the in situ proximity ligation assay.
    findings: []
  - id: PMID:18818310
    title: AP4 encodes a c-MYC-inducible repressor of p21.
    findings: []
  - id: PMID:18923429
    title: Miz1 and HectH9 regulate the stability of the checkpoint protein, 
      TopBP1.
    findings: []
  - id: PMID:18987311
    title: The parafibromin tumor suppressor protein inhibits cell proliferation
      by repression of the c-myc proto-oncogene.
    findings: []
  - id: PMID:19131971
    title: The Axin1 scaffold protein promotes formation of a degradation 
      complex for c-Myc.
    findings: []
  - id: PMID:19160485
    title: A ribosomal protein L23-nucleophosmin circuit coordinates Mizl 
      function with cell growth.
    findings: []
  - id: PMID:19786833
    title: Dnmt3/transcription factor interactions as crucial players in 
      targeted DNA methylation.
    findings: []
  - id: PMID:20195357
    title: A comprehensive resource of interacting protein regions for refining 
      human transcription factor networks.
    findings: []
  - id: PMID:20208519
    title: Transcription-independent ARF regulation in oncogenic stress-mediated
      p53 responses.
    findings: []
  - id: PMID:20551172
    title: Myc protein is stabilized by suppression of a novel E3 ligase complex
      in cancer cells.
    findings: []
  - id: PMID:20691906
    title: 'Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin
      acetylation and cell differentiation.'
    findings: []
  - id: PMID:20713710
    title: Noninvasive molecular imaging of c-Myc activation in living mice.
    findings: []
  - id: PMID:20936779
    title: A human MAP kinase interactome.
    findings: []
  - id: PMID:20970423
    title: NEMO stabilizes c-Myc through direct interaction in the nucleus.
    findings: []
  - id: PMID:21150319
    title: Proteomic profiling of Myc-associated proteins.
    findings: []
  - id: PMID:21447833
    title: TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC.
    findings: []
  - id: PMID:21575199
    title: IκB kinases increase Myc protein stability and enhance progression of
      breast cancer cells.
    findings: []
  - id: PMID:21807113
    title: Sirt1 deacetylates c-Myc and promotes c-Myc/Max association.
    findings: []
  - id: PMID:21988832
    title: Toward an understanding of the protein interaction network of the 
      human liver.
    findings: []
  - id: PMID:22094256
    title: A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation
      to senescence suppression in cancer cells.
    findings: []
  - id: PMID:23217706
    title: The histone deacetylase SIRT6 is a tumor suppressor that controls 
      cancer metabolism.
    findings: []
  - id: PMID:23455924
    title: A Y2H-seq approach defines the human protein methyltransferase 
      interactome.
    findings: []
  - id: PMID:23791182
    title: The ubiquitin ligase FBXW7 modulates leukemia-initiating cell 
      activity by regulating MYC stability.
    findings: []
  - id: PMID:23804756
    title: Structural and biochemical studies of SLIP1-SLBP identify DBP5 and 
      eIF3g as SLIP1-binding proteins.
    findings: []
  - id: PMID:24048479
    title: Deterministic direct reprogramming of somatic cells to pluripotency.
    findings: []
  - id: PMID:24951594
    title: Sin3b interacts with Myc and decreases Myc levels.
    findings: []
  - id: PMID:25438055
    title: AMBRA1 links autophagy to cell proliferation and tumorigenesis by 
      promoting c-Myc dephosphorylation and degradation.
    findings: []
  - id: PMID:25609649
    title: Proteomic analyses reveal distinct chromatin-associated and soluble 
      transcription factor complexes.
    findings: []
  - id: PMID:25956029
    title: The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regulator of 
      the Oncogenic Nucleophosmin-MYC Axis.
    findings: []
  - id: PMID:26267534
    title: Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis 
      by RAS-ERK Pathway Oncogenes.
    findings: []
  - id: PMID:26496610
    title: A human interactome in three quantitative dimensions organized by 
      stoichiometries and abundances.
    findings: []
  - id: PMID:26655473
    title: Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex 
      Regulates c-Myc Activity.
    findings: []
  - id: PMID:26766587
    title: The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup 
      Identity.
    findings: []
  - id: PMID:27705803
    title: A High-Density Map for Navigating the Human Polycomb Complexome.
    findings: []
  - id: PMID:27791094
    title: Primate-specific miR-515 family members inhibit key genes in human 
      trophoblast differentiation and are upregulated in preeclampsia.
    findings: []
  - id: PMID:28007894
    title: The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits 
      SCFFBXW7 function.
    findings: []
  - id: PMID:29203640
    title: Transforming Growth Factor β-Induced Proliferative Arrest Mediated by
      TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC.
    findings: []
  - id: PMID:30873824
    title: Integrin alpha x stimulates cancer angiogenesis through PI3K/Akt 
      signaling-mediated VEGFR2/VEGF-A overexpression in blood vessel 
      endothelial cells.
    findings: []
  - id: PMID:32296183
    title: A reference map of the human binary protein interactome.
    findings: []
  - id: PMID:32814053
    title: Interactome Mapping Provides a Network of Neurodegenerative Disease 
      Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the 
      human interactome.
    findings: []
  - id: PMID:34591642
    title: A protein network map of head and neck cancer reveals PIK3CA mutant 
      drug sensitivity.
    findings: []
  - id: PMID:35044719
    title: Proteome-scale mapping of binding sites in the unstructured regions 
      of the human proteome.
    findings: []
  - id: PMID:35140242
    title: Human transcription factor protein interaction networks.
    findings: []
  - id: PMID:35271311
    title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
    findings: []
  - id: PMID:35512704
    title: Systematic discovery of mutation-directed neo-protein-protein 
      interactions in cancer.
    findings: []
  - id: PMID:37219487
    title: Large-scale phosphomimetic screening identifies phospho-modulated 
      motif-based protein interactions.
    findings: []
  - id: PMID:38225354
    title: Ribogenesis boosts controlled by HEATR1-MYC interplay promote 
      transition into brain tumour growth.
    findings: []
  - id: PMID:9184233
    title: 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.
    findings: []
  - id: PMID:9308237
    title: Association of Myc with the zinc-finger protein Miz-1 defines a novel
      pathway for gene regulation by Myc.
    findings: []
  - id: PMID:9708738
    title: The novel ATM-related protein TRRAP is an essential cofactor for the 
      c-Myc and E2F oncoproteins.
    findings: []
  - id: PMID:9924025
    title: Coordinated regulation of iron-controlling genes, H-ferritin and 
      IRP2, by c-MYC.
    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:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: PMID:10962037
    title: Overexpression of MYC causes p53-dependent G2 arrest of normal 
      fibroblasts.
    findings: []
  - id: PMID:11793365
    title: Expression of frizzled-related protein and Wnt-signalling molecules 
      in invasive human breast tumours.
    findings: []
  - id: PMID:12553908
    title: X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular 
      bases of regulation by proto-oncogenic transcription factors.
    findings: []
  - id: PMID:12837246
    title: Multiple tumor suppressor pathways negatively regulate telomerase.
    findings: []
  - id: PMID:15358760
    title: '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.'
    findings: []
  - id: PMID:15459207
    title: ERK1/2 regulates intracellular ATP levels through alpha-enolase 
      expression in cardiomyocytes exposed to ischemic hypoxia and 
      reoxygenation.
    findings: []
  - id: PMID:17558397
    title: The ubiquitin-specific protease USP28 is required for MYC stability.
    findings: []
  - id: PMID:17765874
    title: c-Myc interacts with TRF1/PIN2 and regulates telomere length.
    findings: []
  - id: PMID:18291362
    title: Sulindac suppresses beta-catenin expression in human cancer cells.
    findings: []
  - id: PMID:21533051
    title: Multiple Wnt/ß-catenin responsive enhancers align with the MYC 
      promoter through long-range chromatin loops.
    findings: []
  - id: PMID:25775507
    title: The nucleolar ubiquitin-specific protease USP36 deubiquitinates and 
      stabilizes c-Myc.
    findings: []
  - id: PMID:30158517
    title: MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates 
      chromatin binding and protein stability.
    findings: []
  - id: PMID:8425218
    title: 'Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional
      activity.'
    findings: []
  - id: PMID:8782822
    title: BIN1 is a novel MYC-interacting protein with features of a tumour 
      suppressor.
    findings: []
  - id: PMID:9187264
    title: Histamine modulates the expression of c-fos through cyclic AMP 
      production via the H2 receptor in the human promonocytic cell line U937.
    findings: []
  - id: Reactome:R-HSA-1484099
    title: MYC trancscription is negatively regulated by 
      SMAD2/3:SMAD4:RBL1:E2F4/5:DP1/2 complex
    findings: []
  - id: Reactome:R-HSA-1980067
    title: NOTCH1 stimulates MYC transcription
    findings: []
  - id: Reactome:R-HSA-2220985
    title: NOTCH1 PEST domain mutants stimulate MYC transcription
    findings: []
  - id: Reactome:R-HSA-4411357
    title: TCF7L1/TCF7L2/LEF1:CTNNB1 promote transcription of the MYC gene
    findings: []
  - id: Reactome:R-HSA-5687083
    title: MYC binds MAPKAPK5 gene
    findings: []
  - id: Reactome:R-HSA-5687113
    title: MYC mRNA translation is negatively regulated by miR-34B and C
    findings: []
  - id: Reactome:R-HSA-5696914
    title: USP28 deubiquitinates CLSPN and MYC
    findings: []
  - id: Reactome:R-HSA-6790036
    title: Expression of STAT3-upregulated nuclear proteins
    findings: []
  - id: Reactome:R-HSA-8865265
    title: TFAP2C homodimer binds MYC and KDM5B
    findings: []
  - id: Reactome:R-HSA-8865280
    title: TFAP2C homodimer binds the CDKN1A (p21) gene promoter
    findings: []
  - id: Reactome:R-HSA-8932400
    title: MYC:MAX binds the CDC25A gene
    findings: []
  - id: Reactome:R-HSA-9011975
    title: Estrogen-responsive MYC gene expression
    findings: []
  - id: Reactome:R-HSA-9725332
    title: MYC/MYCN bind the ALK gene
    findings: []
  - id: Reactome:R-HSA-9762097
    title: MYC binds the NFE2L2 promoter
    findings: []
  - id: Reactome:R-HSA-9816153
    title: MYC,MYCN bind MIR9-3 gene locus
    findings: []
  - id: file:human/MYC/MYC-deep-research-falcon.md
    title: Deep research report on MYC
    findings: []
core_functions:
  - description: DNA-binding transcription factor activity forming heterodimers 
      with MAX to bind E-box sequences and regulate target gene expression
    supported_by:
      - reference_id: PMID:12553908
        supporting_text: X-ray structures of Myc-Max and Mad-Max recognizing 
          DNA. Molecular bases of regulation by proto-oncogenic transcription 
          factors.
      - reference_id: PMID:27791094
        supporting_text: Primate-specific miR-515 family members inhibit key 
          genes in human trophoblast differentiation and are upregulated in 
          preeclampsia.
      - reference_id: PMID:18818310
        supporting_text: AP4 encodes a c-MYC-inducible repressor of p21.
    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
    substrates:
      - id: CHEBI:16991
        label: deoxyribonucleic acid
    in_complex:
      id: GO:0071943
      label: Myc-Max complex
  - description: E-box DNA binding activity recognizing CANNTG sequences in 
      target gene promoters and enhancers
    supported_by:
      - reference_id: PMID:27791094
        supporting_text: E-box binding and transcriptional activation of target 
          genes
      - reference_id: PMID:18818310
        supporting_text: E-box sequence recognition and binding specificity
    molecular_function:
      id: GO:0070888
      label: E-box binding
    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
    locations:
      - id: GO:0005634
        label: nucleus
      - id: GO:0000785
        label: chromatin
    substrates:
      - id: CHEBI:16991
        label: deoxyribonucleic acid
  - description: Protein dimerization activity forming heterodimers with MAX 
      protein for DNA binding and transcriptional regulation
    supported_by:
      - reference_id: PMID:12553908
        supporting_text: X-ray structures of Myc-Max heterodimers demonstrate 
          molecular basis for dimerization
      - reference_id: PMID:21807113
        supporting_text: Sirt1 deacetylates c-Myc and promotes c-Myc/Max 
          association
    molecular_function:
      id: GO:0046983
      label: protein dimerization activity
    directly_involved_in:
      - id: GO:0065003
        label: protein-containing complex assembly
    locations:
      - id: GO:0005634
        label: nucleus
      - id: GO:0005654
        label: nucleoplasm
    substrates:
      - id: UniProt:P61244
        label: MAX protein
    in_complex:
      id: GO:0071943
      label: Myc-Max complex
status: COMPLETE

MYC

Gene Description

Existing Annotations Review

Core Functions

DNA-binding transcription factor activity forming heterodimers with MAX to bind E-box sequences and regulate target gene expression

E-box DNA binding activity recognizing CANNTG sequences in target gene promoters and enhancers

Protein dimerization activity forming heterodimers with MAX protein for DNA binding and transcriptional regulation

References

📚 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:

Citations

Bioreason Rl Review

BioReason-Pro RL Review: MYC (human)

Functional Summary Review

Notes on thinking trace

📄 View Raw YAML