MYC_PANTR
ID MYC_PANTR Reviewed; 439 AA.
AC P23583; A2T708; Q8MJ74;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Myc proto-oncogene protein;
DE AltName: Full=Proto-oncogene c-Myc;
DE AltName: Full=Transcription factor p64;
GN Name=MYC;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1999286; DOI=10.1016/0378-1119(91)90056-h;
RA Argaut C., Rigolet M., Eladari M.E., Galibert F.;
RT "Cloning and nucleotide sequence of the chimpanzee c-myc gene.";
RL Gene 97:231-237(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Nickel G.C., Tefft D.L., Trevarthen K., Funt J., Adams M.D.;
RT "Positive selection in transcription factor genes on the human lineage.";
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 276-433.
RX PubMed=12384613; DOI=10.1093/nar/gnf110;
RA Smith S.J., Vigilant L., Morin P.A.;
RT "The effects of sequence length and oligonucleotide mismatches on 5'
RT exonuclease assay efficiency.";
RL Nucleic Acids Res. 30:E111-E111(2002).
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 Interacts with CIP2A; leading to the stabilization of MYC (By
CC similarity). {ECO:0000250|UniProtKB:P01106,
CC 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 329 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M38057; AAA72907.1; -; Genomic_DNA.
DR EMBL; DQ977348; ABM91963.1; -; Genomic_DNA.
DR EMBL; AF519445; AAN03870.1; -; Genomic_DNA.
DR PIR; JU0449; JU0449.
DR AlphaFoldDB; P23583; -.
DR BMRB; P23583; -.
DR STRING; 9598.ENSPTRP00000035190; -.
DR PaxDb; P23583; -.
DR eggNOG; KOG2483; Eukaryota.
DR InParanoid; P23583; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; 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:0043066; P:negative regulation of apoptotic process; 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:0032873; P:negative regulation of stress-activated MAPK cascade; 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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010332; P:response to gamma radiation; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; 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; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..439
FT /note="Myc proto-oncogene protein"
FT /id="PRO_0000127297"
FT DOMAIN 354..406
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 201..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 334..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..434
FT /note="Leucine-zipper"
FT MOTIF 100..108
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT COMPBIAS 201..234
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 345..360
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 8
FT /note="Phosphothreonine"
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 143
FT /note="N6-acetyllysine; by PCAF; alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 148
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 157
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 275
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 317
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 323
FT /note="N6-acetyllysine; by PCAF"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT MOD_RES 329
FT /note="Phosphoserine; by PIM2; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P01108"
FT MOD_RES 371
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 143
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT CROSSLNK 148
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT CROSSLNK 298
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P01106"
FT CONFLICT 202
FT /note="S -> G (in Ref. 2; ABM91963)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="A -> V (in Ref. 2; ABM91963)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 439 AA; 48846 MW; E217FFCBCE24A560 CRC64;
MPLNVSFTNR NYDLDYDSVQ PYFYCDEEEN FYQQQQQSEL QPPAPSEDIW KKFELLPTPP
LSPSRRSGLC SPSYVAVTPF SLRGDNDGGG GSFSTADQLE MVTELLGGDM VNQSFICDPD
DETFIKNIII QDCMWSGFSA AAKLVSEKLA SYQAARKDSG SPNPARGHSV CSTSSLYLQD
LSAAASECID PSVVFPYPLN DSSSPKSCPS QDSSAFSPSS DSLLSSTESS PQGSPEPLVL
HEETPPTTSS DSEEEQEDEE EIDVVSVEKR QAPGKRSESG SPSAGGHSKP PHSPLVLKRC
HVSTHQHNYA APPSTRKDYP AAKRVKLDSV RVLRQISNNR KCTSPRSSDT EENDKRRTHN
VLERQRRNEL KRSFFALRDQ IPELENNEKA PKVVILKKAT AYILSVQAEE QKLISEEDLL
RKRREQLKHK LEQLRNSCA
