MYC_PTEHP
ID MYC_PTEHP Reviewed; 440 AA.
AC Q9MZT8;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 108.
DE RecName: Full=Myc proto-oncogene protein;
DE AltName: Full=Proto-oncogene c-Myc;
DE AltName: Full=Transcription factor p64;
GN Name=MYC;
OS Pteropus hypomelanus (Island flying fox) (Variable flying fox).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Chiroptera; Megachiroptera; Pteropodidae;
OC Pteropodinae; Pteropus.
OX NCBI_TaxID=9405;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12116424; DOI=10.1080/10635159950127367;
RA Miyamoto M.M., Porter C.A., Goodman M.;
RT "c-myc gene sequences and the phylogeny of bats and other eutherian
RT mammals.";
RL Syst. Biol. 49:501-514(2000).
CC -!- FUNCTION: Transcription factor that binds DNA in a non-specific manner,
CC yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'.
CC Activates the transcription of growth-related genes. Binds to the VEGFA
CC promoter, promoting VEGFA production and subsequent sprouting
CC angiogenesis. Regulator of somatic reprogramming, controls self-renewal
CC of embryonic stem cells. Functions with TAF6L to activate target gene
CC expression through RNA polymerase II pause release (By similarity).
CC Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which
CC in turn regulate splicing of pyruvate kinase PKM by binding
CC repressively to sequences flanking PKM exon 9, inhibiting exon 9
CC inclusion and resulting in exon 10 inclusion and production of the PKM
CC M2 isoform (By similarity). {ECO:0000250|UniProtKB:P01106,
CC ECO:0000250|UniProtKB:P01108}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Binds DNA as a heterodimer with MAX (By similarity). Interacts
CC with TAF1C and SPAG9. Interacts with PARP10. Interacts with KDM5A and
CC KDM5B. Interacts (when phosphorylated at Thr-58 and Ser-62) with FBXW7.
CC Interacts with PIM2. Interacts with RIOX1. The heterodimer MYC:MAX
CC interacts with ABI1; the interaction may enhance MYC:MAX
CC transcriptional activity. Interacts with TRIM6 (By similarity).
CC Interacts with NPM1; the binary complex is recruited to the promoter of
CC MYC target genes and enhances their transcription (By similarity).
CC {ECO:0000250|UniProtKB:P01106, ECO:0000250|UniProtKB:P01108}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:P01106}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:P01106}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P01106}.
CC -!- PTM: Phosphorylated by PRKDC (By similarity). Phosphorylation at Ser-
CC 330 by PIM2 leads to the stabilization of MYC (By similarity).
CC Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence.
CC Phosphorylated at Ser-62 by DYRK2; this primes the protein for
CC subsequent phosphorylation by GSK3B at Thr-58. Phosphorylation at Thr-
CC 58 and Ser-62 by GSK3 is required for ubiquitination and degradation by
CC the proteasome. Dephosphorylation at Ser-62 by protein phosphatase 2A
CC (PPP2CA) promotes its degradation; interaction with PPP2CA is enhanced
CC by AMBRA1 (By similarity). {ECO:0000250|UniProtKB:P01106,
CC ECO:0000250|UniProtKB:P01108}.
CC -!- PTM: Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at
CC Thr-58 and Ser-62, leading to its degradation by the proteasome.
CC Ubiquitination is counteracted by USP28 in the nucleoplasm and USP36 in
CC the nucleolus, both interacting with of FBXW7, leading to its
CC deubiquitination and preventing degradation. Also polyubiquitinated by
CC the DCX(TRPC4AP) complex. Ubiquitinated by TRIM6 in a phosphorylation-
CC independent manner. {ECO:0000250|UniProtKB:P01106,
CC ECO:0000250|UniProtKB:P01108}.
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DR EMBL; AF160487; AAF80395.1; -; Genomic_DNA.
DR EMBL; AF160486; AAF80395.1; JOINED; Genomic_DNA.
DR AlphaFoldDB; Q9MZT8; -.
DR SMR; Q9MZT8; -.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0051276; P:chromosome organization; ISS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0051782; P:negative regulation of cell division; ISS:UniProtKB.
DR GO; GO:0045656; P:negative regulation of monocyte differentiation; ISS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:1904672; P:regulation of somatic stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0032204; P:regulation of telomere maintenance; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010332; P:response to gamma radiation; ISS:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003327; Myc-LZ.
DR InterPro; IPR002418; Tscrpt_reg_Myc.
DR InterPro; IPR012682; Tscrpt_reg_Myc_N.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF02344; Myc-LZ; 1.
DR Pfam; PF01056; Myc_N; 1.
DR PIRSF; PIRSF001705; Myc_protein; 1.
DR PRINTS; PR00044; LEUZIPPRMYC.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 3: Inferred from homology;
KW Acetylation; Activator; DNA-binding; Glycoprotein; Isopeptide bond;
KW Nucleus; Phosphoprotein; Proto-oncogene; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..440
FT /note="Myc proto-oncogene protein"
FT /id="PRO_0000127299"
FT DOMAIN 355..407
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 202..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 414..435
FT /note="Leucine-zipper"
FT MOTIF 101..109
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT COMPBIAS 202..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..362
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 58
FT /note="Phosphothreonine; by GSK3; alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 62
FT /note="Phosphoserine; by DYRK2, GSK3 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 144
FT /note="N6-acetyllysine; by PCAF; alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 149
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 158
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 276
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 318
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 324
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 330
FT /note="Phosphoserine; by PIM2; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P01108"
FT MOD_RES 372
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT CARBOHYD 58
FT /note="O-linked (GlcNAc) threonine; alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 52
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT CROSSLNK 144
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT CROSSLNK 149
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P01106"
SQ SEQUENCE 440 AA; 48796 MW; 95D61CEA3A7347AF CRC64;
MPLNVSFASR NYDLDYDSVQ PYFYCDEEEN FYHQQQQSEL QPPAPSEDIW KKFELLPTPP
LSPSRRSGLC SPSYVAAFAS FSPRDDDDGG GGSFSSADQL EMVTELLGGD MVNQSFICDP
DDETFIKNII IQDCMWSGFS AAAKLVSEKL ASYQAARKDG GSRSPARGHS ACSTSSLYLQ
DLSAAASECI DPSVVFPYPL NDSSSPKPCA SPDSTAFSPS SDSLLSSAAS SPRASPEPLV
LHEETPPTTS SDSEEEQEDE EEIDVVSVEK RQPPAKRSES GSPSAGSHSK PPHSPLVLKR
CHVSTHQHNY AAPPSTRKDY PPTKRAKLDS GRVLKQISNN RKCASPRSSD TEENDKRRTH
NVLERQRRNE LKRSFFALRD QIPELENNEK APKVVILKKA TAYILAIQAE EQKLISEKDL
LRKRREQLKH KLEQLRNSCA
