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 24-JAN-2024, entry version 207. 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. 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; 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; 153. DR DIP; DIP-53627N; -. DR IntAct; Q01664; 53. DR MINT; Q01664; -. DR STRING; 9606.ENSP00000204517; -. DR GlyGen; Q01664; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000204517; -. DR PeptideAtlas; Q01664; -. DR ProteomicsDB; 57980; -. DR Pumba; Q01664; -. DR Antibodypedia; 894; 339 antibodies from 26 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 AGR; HGNC:11745; -. 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; RMIFEDQ; -. DR OrthoDB; 2881824at2759; -. DR PhylomeDB; Q01664; -. DR TreeFam; TF316489; -. DR PathwayCommons; Q01664; -. DR SignaLink; Q01664; -. DR SIGNOR; Q01664; -. DR BioGRID-ORCS; 7023; 191 hits in 1200 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 153 other cell types or tissues. DR ExpressionAtlas; Q01664; baseline and differential. 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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. 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:0045893; P:positive regulation of DNA-templated transcription; 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 CDD; cd11419; bHLHzip_TFAP4; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR PANTHER; PTHR15741; BASIC HELIX-LOOP-HELIX ZIP TRANSCRIPTION FACTOR; 1. DR PANTHER; PTHR15741:SF27; TRANSCRIPTION FACTOR AP-4; 1. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. DR Genevisible; Q01664; HS. 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 //