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
c-MYC, a basic helix–loop–helix zipper transcription factor, is believed to regulate an estimated 15% of genes in the human genome via binding to E-boxes within target promoters ( 48 )
PMID:18818310
c-MYC directly regulates the expression of AP4 via CACGTG motifs in the first intron of the AP4 gene.

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 and Mad-Max recognizing DNA
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)

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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)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

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

Target Gene/Protein Identity (from UniProt):

UniProt Accession: 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: c-MYC, a basic helix–loop–helix zipper transcription factor, is believed to regulate an estimated 15% of genes in the human genome via binding to E-boxes within target promoters ( 48 )
  - reference_id: PMID:18818310
    supporting_text: c-MYC directly regulates the expression of AP4 via CACGTG motifs in the first intron of the AP4 gene.
  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 and Mad-Max recognizing DNA
    full_text_unavailable: true
  - 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