TFAP4_HUMAN
ID TFAP4_HUMAN Reviewed; 338 AA.
AC Q01664; O60409;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Transcription factor AP-4;
DE AltName: Full=Activating enhancer-binding protein 4;
DE AltName: Full=Class C basic helix-loop-helix protein 41;
DE Short=bHLHc41;
GN Name=TFAP4; Synonyms=BHLHC41;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7933101; DOI=10.1128/jvi.68.11.7188-7199.1994;
RA Ou S.H., Garcia-Martinez L.F., Paulssen E.J., Gaynor R.B.;
RT "Role of flanking E box motifs in human immunodeficiency virus type 1 TATA
RT element function.";
RL J. Virol. 68:7188-7199(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-218.
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-338, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2123466; DOI=10.1101/gad.4.10.1741;
RA Hu Y.-F., Luescher B., Admon A., Mermod N., Tjian R.;
RT "Transcription factor AP-4 contains multiple dimerization domains that
RT regulate dimer specificity.";
RL Genes Dev. 4:1741-1752(1990).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-139, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123; SER-124 AND SER-139, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-139, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-147; LYS-187; LYS-189 AND
RP LYS-285, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Transcription factor that activates both viral and cellular
CC genes by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Homodimer.
CC -!- INTERACTION:
CC Q01664; Q96IF1: AJUBA; NbExp=3; IntAct=EBI-2514218, EBI-949782;
CC Q01664; Q96B26: EXOSC8; NbExp=6; IntAct=EBI-2514218, EBI-371922;
CC Q01664; P55040: GEM; NbExp=2; IntAct=EBI-2514218, EBI-744104;
CC Q01664; Q08379: GOLGA2; NbExp=6; IntAct=EBI-2514218, EBI-618309;
CC Q01664; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2514218, EBI-6509505;
CC Q01664; Q92876: KLK6; NbExp=3; IntAct=EBI-2514218, EBI-2432309;
CC Q01664; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-2514218, EBI-348259;
CC Q01664; P17568: NDUFB7; NbExp=3; IntAct=EBI-2514218, EBI-1246238;
CC Q01664; P26045: PTPN3; NbExp=3; IntAct=EBI-2514218, EBI-1047946;
CC Q01664; Q5VUG0: SFMBT2; NbExp=3; IntAct=EBI-2514218, EBI-12025260;
CC Q01664; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-2514218, EBI-750487;
CC Q01664; Q13077: TRAF1; NbExp=6; IntAct=EBI-2514218, EBI-359224;
CC Q01664; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-2514218, EBI-3650647;
CC Q01664; Q2NL98: VMAC; NbExp=3; IntAct=EBI-2514218, EBI-2803134;
CC -!- SUBCELLULAR LOCATION: Nucleus.
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DR EMBL; S73885; AAB32235.1; -; mRNA.
DR EMBL; AC004653; AAC17116.1; -; Genomic_DNA.
DR EMBL; BC010576; AAH10576.1; -; mRNA.
DR EMBL; X57435; CAA40683.1; -; mRNA.
DR CCDS; CCDS10510.1; -.
DR PIR; I56893; I56893.
DR RefSeq; NP_003214.1; NM_003223.2.
DR AlphaFoldDB; Q01664; -.
DR SMR; Q01664; -.
DR BioGRID; 112881; 147.
DR DIP; DIP-53627N; -.
DR IntAct; Q01664; 52.
DR MINT; Q01664; -.
DR STRING; 9606.ENSP00000204517; -.
DR GlyGen; Q01664; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q01664; -.
DR PhosphoSitePlus; Q01664; -.
DR BioMuta; TFAP4; -.
DR DMDM; 1729833; -.
DR EPD; Q01664; -.
DR jPOST; Q01664; -.
DR MassIVE; Q01664; -.
DR MaxQB; Q01664; -.
DR PaxDb; Q01664; -.
DR PeptideAtlas; Q01664; -.
DR PRIDE; Q01664; -.
DR ProteomicsDB; 57980; -.
DR Antibodypedia; 894; 316 antibodies from 25 providers.
DR DNASU; 7023; -.
DR Ensembl; ENST00000204517.11; ENSP00000204517.6; ENSG00000090447.12.
DR GeneID; 7023; -.
DR KEGG; hsa:7023; -.
DR MANE-Select; ENST00000204517.11; ENSP00000204517.6; NM_003223.3; NP_003214.1.
DR UCSC; uc010uxg.3; human.
DR CTD; 7023; -.
DR DisGeNET; 7023; -.
DR GeneCards; TFAP4; -.
DR HGNC; HGNC:11745; TFAP4.
DR HPA; ENSG00000090447; Low tissue specificity.
DR MIM; 600743; gene.
DR neXtProt; NX_Q01664; -.
DR OpenTargets; ENSG00000090447; -.
DR PharmGKB; PA36462; -.
DR VEuPathDB; HostDB:ENSG00000090447; -.
DR eggNOG; KOG0561; Eukaryota.
DR GeneTree; ENSGT00390000015189; -.
DR HOGENOM; CLU_064747_0_0_1; -.
DR InParanoid; Q01664; -.
DR OMA; DQGREEP; -.
DR OrthoDB; 1565841at2759; -.
DR PhylomeDB; Q01664; -.
DR TreeFam; TF316489; -.
DR PathwayCommons; Q01664; -.
DR SignaLink; Q01664; -.
DR SIGNOR; Q01664; -.
DR BioGRID-ORCS; 7023; 175 hits in 1119 CRISPR screens.
DR GeneWiki; TFAP4; -.
DR GenomeRNAi; 7023; -.
DR Pharos; Q01664; Tbio.
DR PRO; PR:Q01664; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q01664; protein.
DR Bgee; ENSG00000090447; Expressed in olfactory bulb and 152 other tissues.
DR ExpressionAtlas; Q01664; baseline and differential.
DR Genevisible; Q01664; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:ARUK-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IDA:UniProtKB.
DR GO; GO:0043922; P:negative regulation by host of viral transcription; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043923; P:positive regulation by host of viral transcription; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:2001269; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Direct protein sequencing; DNA-binding; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..338
FT /note="Transcription factor AP-4"
FT /id="PRO_0000127458"
FT DOMAIN 48..99
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 100..120
FT /note="Leucine-zipper 1"
FT REGION 118..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..179
FT /note="Leucine-zipper 2"
FT REGION 283..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..141
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..297
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 321..338
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 123
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 147
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 187
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 189
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 285
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 218
FT /note="Q -> H (in dbSNP:rs251732)"
FT /evidence="ECO:0000269|PubMed:15616553"
FT /id="VAR_059346"
SQ SEQUENCE 338 AA; 38726 MW; 540C008658596B83 CRC64;
MEYFMVPTQK VPSLQHFRKT EKEVIGGLCS LANIPLTPET QRDQERRIRR EIANSNERRR
MQSINAGFQS LKTLIPHTDG EKLSKAAILQ QTAEYIFSLE QEKTRLLQQN TQLKRFIQEL
SGSSPKRRRA EDKDEGIGSP DIWEDEKAED LRREMIELRQ QLDKERSVRM MLEEQVRSLE
AHMYPEKLKV IAQQVQLQQQ QEQVRLLHQE KLEREQQQLR TQLLPPPAPT HHPTVIVPAP
PPPPSHHINV VTMGPSSVIN SVSTSRQNLD TIVQAIQHIE GTQEKQELEE EQRRAVIVKP
VRSCPEAPTS DTASDSEASD SDAMDQSREE PSGDGELP
