MYC

The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of growth-related genes (PubMed:24940000, PubMed:25956029). Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000, PubMed:25956029). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells (By similarity). Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which in turn regulate splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808).

A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1.

Burkitt lymphoma

BL

A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass.

None

The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.

Phosphorylated by PRKDC (PubMed:1597196). Phosphorylation at Ser-344 by PIM2 leads to the stabilization of MYC (By similarity). Phosphorylation at Ser-77 by CDK2 prevents Ras-induced senescence (PubMed:19966300, PubMed:20713526). Phosphorylated at Ser-77 by DYRK2; this primes the protein for subsequent phosphorylation by GSK3B at Thr-73 (PubMed:22307329). Phosphorylation at Thr-73 and Ser-77 by GSK3 is required for ubiquitination and degradation by the proteasome (PubMed:15103331, PubMed:17558397, PubMed:8386367). Dephosphorylation at Ser-77 by protein phosphatase 2A (PPP2CA) promotes its degradation; interaction with PPP2CA is enhanced by AMBRA1 (PubMed:25438055, PubMed:25803737).

Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-73 and Ser-77, leading to its degradation by the proteasome (PubMed:15103331, PubMed:17558397, PubMed:25775507). In the nucleoplasm, ubiquitination is counteracted by USP28, which interacts with isoform 1 of FBXW7 (FBW7alpha), leading to its deubiquitination and preventing degradation (PubMed:17558397, PubMed:17873522). In the nucleolus, however, ubiquitination is not counteracted by USP28 but by USP36, due to the lack of interaction between isoform 3 of FBXW7 (FBW7gamma) and USP28, explaining the selective MYC degradation in the nucleolus (PubMed:17558397, PubMed:25775507). Also polyubiquitinated by the DCX(TRPC4AP) complex (PubMed:20551172, PubMed:29779948). Ubiquitinated by UBR5 when not forming a heterodimer with another bHLH protein, leading to its degradation: UBR5 recognizes and binds a degron that is only available upon heterodimer dissociation (PubMed:33208877, PubMed:37478862). Ubiquitinated by TRIM6 in a phosphorylation-independent manner (By similarity).

• Nucleus
• Nucleoplasm
• Nucleus
• Nucleolus
• Nucleus
• Cytoplasm
• Localization to the nucleolus is dependent on HEATR1.

BHLHE39, MYC, Myc proto-oncogene protein, Class E basic helix-loop-helix protein 39, Proto-oncogene c-Myc, Transcription factor p64, bHLHe39

• entrezGene:4613
• entrezGene:4610
• entrezGene:4609
• omim:164850
• omim:164840
• omim:190080
• swissprot:P01106
• swissprot:P12524
• swissprot:P04198

Proteins

Epigenetics

• Oncology

48804Da