ID AP2A_HUMAN Reviewed; 437 AA. AC P05549; Q13777; Q5TAV5; Q8N1C6; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 221. DE RecName: Full=Transcription factor AP-2-alpha; DE Short=AP2-alpha; DE AltName: Full=AP-2 transcription factor; DE AltName: Full=Activating enhancer-binding protein 2-alpha; DE AltName: Full=Activator protein 2; DE Short=AP-2; GN Name=TFAP2A; Synonyms=AP2TF, TFAP2; 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] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3063603; DOI=10.1101/gad.2.12a.1557; RA Williams T., Admon A., Luescher B., Tjian R.; RT "Cloning and expression of AP-2, a cell-type-specific transcription factor RT that activates inducible enhancer elements."; RL Genes Dev. 2:1557-1569(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Teratocarcinoma; RX PubMed=8321221; DOI=10.1128/mcb.13.7.4174-4185.1993; RA Buettner R., Kannan P., Imhof A., Bauer R., Yim S.O., Glockshuber R., RA Van Dyke M.W., Tainsky M.A.; RT "An alternatively spliced mRNA from the AP-2 gene encodes a negative RT regulator of transcriptional activation by AP-2."; RL Mol. Cell. Biol. 13:4174-4185(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8190633; DOI=10.1093/nar/22.8.1413; RA Bauer R., Imhof A., Pscherer A., Kopp H., Moser M., Seegers S., RA Kerscher M., Tainsky M.A., Hofstaedter F., Buettner R.; RT "The genomic structure of the human AP-2 transcription factor."; RL Nucleic Acids Res. 22:1413-1420(1994). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Prostate; 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 [7] RP SUBUNIT. RX PubMed=1998122; DOI=10.1126/science.1998122; RA Williams T., Tjian R.; RT "Characterization of a dimerization motif in AP-2 and its function in RT heterologous DNA-binding proteins."; RL Science 251:1067-1071(1991). RN [8] RP DNA-BINDING. RX PubMed=2010091; DOI=10.1101/gad.5.4.670; RA Williams T., Tjian R.; RT "Analysis of the DNA-binding and activation properties of the human RT transcription factor AP-2."; RL Genes Dev. 5:670-682(1991). RN [9] RP PHOSPHORYLATION AT SER-239, AND MUTAGENESIS OF SER-239. RX PubMed=10037142; DOI=10.1016/s0014-5793(99)00021-6; RA Garcia M.A., Campillos M., Marina A., Valdivieso F., Vazquez J.; RT "Transcription factor AP-2 activity is modulated by protein kinase A- RT mediated phosphorylation."; RL FEBS Lett. 444:27-31(1999). RN [10] RP FUNCTION, AND INTERACTION WITH CITED2. RX PubMed=11694877; DOI=10.1038/ng768; RA Bamforth S.D., Braganca J., Eloranta J.J., Murdoch J.N., Marques F.I., RA Kranc K.R., Farza H., Henderson D.J., Hurst H.C., Bhattacharya S.; RT "Cardiac malformations, adrenal agenesis, neural crest defects and RT exencephaly in mice lacking Cited2, a new Tfap2 co-activator."; RL Nat. Genet. 29:469-474(2001). RN [11] RP INTERACTION WITH CITED4. RX PubMed=11744733; DOI=10.1074/jbc.m110850200; RA Braganca J., Swingler T., Marques F.I.R., Jones T., Eloranta J.J., RA Hurst H.C., Shioda T., Bhattacharya S.; RT "Human CREB-binding protein/p300-interacting transactivator with ED-rich RT tail (CITED) 4, a new member of the CITED family, functions as a co- RT activator for transcription factor AP-2."; RL J. Biol. Chem. 277:8559-8565(2002). RN [12] RP INTERACTION WITH UBE2I, AND SUMOYLATION AT LYS-10. RX PubMed=12072434; DOI=10.1074/jbc.m202780200; RA Eloranta J.J., Hurst H.C.; RT "Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 RT and is sumolated in vivo."; RL J. Biol. Chem. 277:30798-30804(2002). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, AND INTERACTION WITH CITED2 RP AND EP300. RX PubMed=12586840; DOI=10.1074/jbc.m208144200; RA Braganca J., Eloranta J.J., Bamforth S.D., Ibbitt J.C., Hurst H.C., RA Bhattacharya S.; RT "Physical and functional interactions among AP-2 transcription factors, RT p300/CREB-binding protein, and CITED2."; RL J. Biol. Chem. 278:16021-16029(2003). RN [14] RP INTERACTION WITH RALBP1. RX PubMed=12775724; DOI=10.1074/jbc.m302191200; RA Rosse C., L'Hoste S., Offner N., Picard A., Camonis J.; RT "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to RT phosphorylate epsin during the switch off of endocytosis in mitosis."; RL J. Biol. Chem. 278:30597-30604(2003). RN [15] RP INTERACTION WITH WWOX, AND DOMAIN. RX PubMed=15548692; DOI=10.1158/0008-5472.can-04-2055; RA Aqeilan R.I., Palamarchuk A., Weigel R.J., Herrero J.J., Pekarsky Y., RA Croce C.M.; RT "Physical and functional interactions between the Wwox tumor suppressor RT protein and the AP-2gamma transcription factor."; RL Cancer Res. 64:8256-8261(2004). RN [16] RP IDENTIFICATION BY 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 [17] RP INTERACTION WITH KCTD1. RX PubMed=19115315; DOI=10.1002/jcb.22002; RA Ding X., Luo C., Zhou J., Zhong Y., Hu X., Zhou F., Ren K., Gan L., He A., RA Zhu J., Gao X., Zhang J.; RT "The interaction of KCTD1 with transcription factor AP-2alpha inhibits its RT transactivation."; RL J. Cell. Biochem. 106:285-295(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [19] RP INTERACTION WITH KCTD15. RX PubMed=23382213; DOI=10.1073/pnas.1300203110; RA Zarelli V.E., Dawid I.B.; RT "Inhibition of neural crest formation by Kctd15 involves regulation of RT transcription factor AP-2."; RL Proc. Natl. Acad. Sci. U.S.A. 110:2870-2875(2013). RN [20] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-10; LYS-177 AND LYS-184, AND RP 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). RN [21] RP VARIANTS BOFS PRO-249; GLY-254; GLY-255 AND GLU-262. RX PubMed=18423521; DOI=10.1016/j.ajhg.2008.03.005; RA Milunsky J.M., Maher T.A., Zhao G., Roberts A.E., Stalker H.J., Zori R.T., RA Burch M.N., Clemens M., Mulliken J.B., Smith R., Lin A.E.; RT "TFAP2A mutations result in branchio-oculo-facial syndrome."; RL Am. J. Hum. Genet. 82:1171-1177(2008). CC -!- FUNCTION: Sequence-specific DNA-binding protein that interacts with CC inducible viral and cellular enhancer elements to regulate CC transcription of selected genes. AP-2 factors bind to the consensus CC sequence 5'-GCCNNNGGC-3' and activate genes involved in a large CC spectrum of important biological functions including proper eye, face, CC body wall, limb and neural tube development. They also suppress a CC number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha CC is the only AP-2 protein required for early morphogenesis of the lens CC vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 CC promoter transcription activation. Associates with chromatin to the CC PITX2 P1 promoter region. {ECO:0000269|PubMed:11694877, CC ECO:0000269|PubMed:12586840}. CC -!- SUBUNIT: Binds DNA as a dimer. Can form homodimers or heterodimers with CC other AP-2 family members. Interacts with WWOX. Interacts with CITED4. CC Interacts with UBE2I. Interacts with RALBP1 in a complex also CC containing EPN1 and NUMB during interphase and mitosis. Interacts with CC KCTD1; this interaction represses transcription activation. Interacts CC (via C-terminus) with CITED2 (via C-terminus); the interaction CC stimulates TFAP2A-transcriptional activation. Interacts (via N- CC terminus) with EP300 (via N-terminus); the interaction requires CITED2. CC Interacts with KCTD15; this interaction inhibits TFAP2A transcriptional CC activation. {ECO:0000269|PubMed:11694877, ECO:0000269|PubMed:11744733, CC ECO:0000269|PubMed:12072434, ECO:0000269|PubMed:12586840, CC ECO:0000269|PubMed:12775724, ECO:0000269|PubMed:15548692, CC ECO:0000269|PubMed:19115315, ECO:0000269|PubMed:1998122, CC ECO:0000269|PubMed:23382213}. CC -!- INTERACTION: CC P05549; Q09472: EP300; NbExp=7; IntAct=EBI-347351, EBI-447295; CC P05549; Q9H4Y5: GSTO2; NbExp=4; IntAct=EBI-347351, EBI-10194609; CC P05549; P61244: MAX; NbExp=2; IntAct=EBI-347351, EBI-751711; CC P05549; Q13064: MKRN3; NbExp=3; IntAct=EBI-347351, EBI-2340269; CC P05549; P06748: NPM1; NbExp=6; IntAct=EBI-347351, EBI-78579; CC P05549; P63279: UBE2I; NbExp=4; IntAct=EBI-347351, EBI-80168; CC P05549-5; Q9H4Y5: GSTO2; NbExp=6; IntAct=EBI-12194905, EBI-10194609; CC P05549-5; Q0VD86: INCA1; NbExp=3; IntAct=EBI-12194905, EBI-6509505; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12586840}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Experimental confirmation may be lacking for some isoforms.; CC Name=1; Synonyms=AP-2A; CC IsoId=P05549-1; Sequence=Displayed; CC Name=2; CC IsoId=P05549-5; Sequence=VSP_043268; CC Name=4; Synonyms=AP-2B; CC IsoId=P05549-2; Sequence=VSP_006401; CC Name=5; CC IsoId=P05549-6; Sequence=VSP_047050; CC -!- DOMAIN: The PPxY motif mediates interaction with WWOX. {ECO:0000250}. CC -!- PTM: Sumoylated on Lys-10; which inhibits transcriptional activity. CC {ECO:0000305|PubMed:12072434}. CC -!- DISEASE: Branchiooculofacial syndrome (BOFS) [MIM:113620]: A syndrome CC characterized by growth retardation, bilateral branchial sinus defects CC with hemangiomatous, scarred skin, cleft lip with or without cleft CC palate, pseudocleft of the upper lip, nasolacrimal duct obstruction, CC low set ears with posterior rotation, a malformed, asymmetrical nose CC with a broad bridge and flattened tip, conductive or sensorineural CC deafness, ocular and renal anomalies. {ECO:0000269|PubMed:18423521}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: [Isoform 4]: May be an aberrantly processed form with no CC significant distribution in vivo. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the AP-2 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Activating protein 2 entry; CC URL="https://en.wikipedia.org/wiki/Activating_protein_2"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42526/TFAP2A"; 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; M36711; AAA35539.1; -; mRNA. DR EMBL; M61156; AAA02487.1; -; mRNA. DR EMBL; X52611; CAA36842.1; -; mRNA. DR EMBL; X77343; CAB59735.1; -; Genomic_DNA. DR EMBL; AL138885; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471087; EAW55249.1; -; Genomic_DNA. DR EMBL; BC017754; AAH17754.1; -; mRNA. DR CCDS; CCDS34337.1; -. [P05549-5] DR CCDS; CCDS43422.1; -. [P05549-6] DR PIR; A31752; A31752. DR RefSeq; NP_001027451.1; NM_001032280.2. [P05549-5] DR RefSeq; NP_001035890.1; NM_001042425.1. [P05549-6] DR RefSeq; NP_003211.1; NM_003220.2. DR PDB; 8J0K; X-ray; 2.10 A; A/B=202-420. DR PDB; 8J0L; X-ray; 1.98 A; A/B=202-420. DR PDB; 8J0R; X-ray; 2.10 A; A/B=202-420. DR PDBsum; 8J0K; -. DR PDBsum; 8J0L; -. DR PDBsum; 8J0R; -. DR AlphaFoldDB; P05549; -. DR SMR; P05549; -. DR BioGRID; 112878; 108. DR CORUM; P05549; -. DR IntAct; P05549; 104. DR MINT; P05549; -. DR STRING; 9606.ENSP00000501092; -. DR iPTMnet; P05549; -. DR PhosphoSitePlus; P05549; -. DR BioMuta; TFAP2A; -. DR DMDM; 135302; -. DR EPD; P05549; -. DR jPOST; P05549; -. DR MassIVE; P05549; -. DR MaxQB; P05549; -. DR PaxDb; 9606-ENSP00000368924; -. DR PeptideAtlas; P05549; -. DR ProteomicsDB; 51847; -. [P05549-1] DR ProteomicsDB; 51848; -. [P05549-2] DR ProteomicsDB; 51849; -. [P05549-5] DR ProteomicsDB; 64874; -. DR Pumba; P05549; -. DR Antibodypedia; 3770; 599 antibodies from 37 providers. DR DNASU; 7020; -. DR Ensembl; ENST00000319516.8; ENSP00000316516.4; ENSG00000137203.15. [P05549-6] DR Ensembl; ENST00000379608.9; ENSP00000368928.3; ENSG00000137203.15. [P05549-5] DR GeneID; 7020; -. DR KEGG; hsa:7020; -. DR UCSC; uc003myq.4; human. [P05549-1] DR AGR; HGNC:11742; -. DR CTD; 7020; -. DR DisGeNET; 7020; -. DR GeneCards; TFAP2A; -. DR GeneReviews; TFAP2A; -. DR HGNC; HGNC:11742; TFAP2A. DR HPA; ENSG00000137203; Tissue enhanced (breast, skin). DR MalaCards; TFAP2A; -. DR MIM; 107580; gene. DR MIM; 113620; phenotype. DR neXtProt; NX_P05549; -. DR OpenTargets; ENSG00000137203; -. DR Orphanet; 1297; Branchio-oculo-facial syndrome. DR PharmGKB; PA36459; -. DR VEuPathDB; HostDB:ENSG00000137203; -. DR eggNOG; KOG3811; Eukaryota. DR GeneTree; ENSGT00950000182848; -. DR HOGENOM; CLU_035175_4_1_1; -. DR InParanoid; P05549; -. DR OrthoDB; 2883153at2759; -. DR PhylomeDB; P05549; -. DR TreeFam; TF313718; -. DR PathwayCommons; P05549; -. DR Reactome; R-HSA-3232118; SUMOylation of transcription factors. [P05549-1] DR Reactome; R-HSA-8864260; Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors. DR Reactome; R-HSA-8866904; Negative regulation of activity of TFAP2 (AP-2) family transcription factors. DR Reactome; R-HSA-8866906; TFAP2 (AP-2) family regulates transcription of other transcription factors. DR Reactome; R-HSA-8866907; Activation of the TFAP2 (AP-2) family of transcription factors. DR Reactome; R-HSA-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors. DR Reactome; R-HSA-8866911; TFAP2 (AP-2) family regulates transcription of cell cycle factors. DR Reactome; R-HSA-8869496; TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation. DR SignaLink; P05549; -. DR SIGNOR; P05549; -. DR BioGRID-ORCS; 7020; 46 hits in 1176 CRISPR screens. DR ChiTaRS; TFAP2A; human. DR GeneWiki; TFAP2A; -. DR GenomeRNAi; 7020; -. DR Pharos; P05549; Tbio. DR PRO; PR:P05549; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P05549; Protein. DR Bgee; ENSG00000137203; Expressed in upper leg skin and 158 other cell types or tissues. DR ExpressionAtlas; P05549; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; 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:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0140536; F:nuclear receptor corepressor activity; IMP:ARUK-UCL. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000977; F:RNA polymerase II transcription 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:0048856; P:anatomical structure development; IBA:GO_Central. DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB. DR GO; GO:0071281; P:cellular response to iron ion; IDA:UniProtKB. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:UniProtKB. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; ISS:UniProtKB. DR GO; GO:0061029; P:eyelid development in camera-type eye; ISS:UniProtKB. DR GO; GO:0042472; P:inner ear morphogenesis; IMP:UniProtKB. DR GO; GO:0001822; P:kidney development; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IDA:UniProtKB. DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0021623; P:oculomotor nerve formation; ISS:UniProtKB. DR GO; GO:0003409; P:optic cup structural organization; ISS:UniProtKB. DR GO; GO:0003404; P:optic vesicle morphogenesis; ISS:UniProtKB. DR GO; GO:0030501; P:positive regulation of bone mineralization; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:UniProtKB. DR GO; GO:0070172; P:positive regulation of tooth mineralization; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0045595; P:regulation of cell differentiation; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0010842; P:retina layer formation; IEP:UniProtKB. DR GO; GO:0060021; P:roof of mouth development; IMP:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB. DR GO; GO:0021559; P:trigeminal nerve development; ISS:UniProtKB. DR InterPro; IPR004979; TF_AP2. DR InterPro; IPR008121; TF_AP2_alpha_N. DR InterPro; IPR013854; TF_AP2_C. DR PANTHER; PTHR10812; TRANSCRIPTION FACTOR AP-2; 1. DR PANTHER; PTHR10812:SF8; TRANSCRIPTION FACTOR AP-2-ALPHA; 1. DR Pfam; PF03299; TF_AP-2; 1. DR PRINTS; PR01749; AP2ATNSCPFCT. DR PRINTS; PR01748; AP2TNSCPFCT. DR Genevisible; P05549; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing; KW Disease variant; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..437 FT /note="Transcription factor AP-2-alpha" FT /id="PRO_0000184796" FT REGION 14..107 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 280..410 FT /note="H-S-H (helix-span-helix), dimerization" FT /evidence="ECO:0000269|PubMed:1998122" FT REGION 414..437 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 57..62 FT /note="PPxY motif" FT COMPBIAS 23..48 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 49..67 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 68..107 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 239 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:10037142" FT CROSSLNK 10 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:12072434" FT CROSSLNK 10 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 177 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 184 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..15 FT /note="MLWKLTDNIKYEDCE -> MLVHSFSAM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043268" FT VAR_SEQ 1..15 FT /note="MLWKLTDNIKYEDCE -> MSILAKMGDWQ (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_047050" FT VAR_SEQ 296..437 FT /note="EAVHLARDFGYVCETEFPAKAVAEFLNRQHSDPNEQVTRKNMLLATKQICKE FT FTDLLAQDRSPLGNSRPNPILEPGIQSCLTHFNLISHGFGSPAVCAAVTALQNYLTEAL FT KAMDKMYLSNNPNSHTDNNAKSSDKEEKHRK -> KRIHLLTRRNFLLGKWIIFSGQMF FT GRILCQLGSFIFAENIARCEWNYFMAKRNICMYSYTSILLPSFPLP (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:8321221" FT /id="VSP_006401" FT VARIANT 249 FT /note="L -> P (in BOFS)" FT /evidence="ECO:0000269|PubMed:18423521" FT /id="VAR_045838" FT VARIANT 254 FT /note="R -> G (in BOFS; dbSNP:rs151344528)" FT /evidence="ECO:0000269|PubMed:18423521" FT /id="VAR_045839" FT VARIANT 255 FT /note="R -> G (in BOFS; dbSNP:rs121909574)" FT /evidence="ECO:0000269|PubMed:18423521" FT /id="VAR_045840" FT VARIANT 262 FT /note="G -> E (in BOFS; dbSNP:rs121909575)" FT /evidence="ECO:0000269|PubMed:18423521" FT /id="VAR_045841" FT MUTAGEN 239 FT /note="S->A: No phosphorylation." FT /evidence="ECO:0000269|PubMed:10037142" FT STRAND 209..215 FT /evidence="ECO:0007829|PDB:8J0L" FT STRAND 226..230 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 231..238 FT /evidence="ECO:0007829|PDB:8J0L" FT TURN 240..242 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 246..252 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 265..272 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 289..291 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 294..310 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 314..323 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 331..353 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 370..383 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 387..410 FT /evidence="ECO:0007829|PDB:8J0L" FT HELIX 412..415 FT /evidence="ECO:0007829|PDB:8J0K" SQ SEQUENCE 437 AA; 48062 MW; FB8FA33C3AEED71F CRC64; MLWKLTDNIK YEDCEDRHDG TSNGTARLPQ LGTVGQSPYT SAPPLSHTPN ADFQPPYFPP PYQPIYPQSQ DPYSHVNDPY SLNPLHAQPQ PQHPGWPGQR QSQESGLLHT HRGLPHQLSG LDPRRDYRRH EDLLHGPHAL SSGLGDLSIH SLPHAIEEVP HVEDPGINIP DQTVIKKGPV SLSKSNSNAV SAIPINKDNL FGGVVNPNEV FCSVPGRLSL LSSTSKYKVT VAEVQRRLSP PECLNASLLG GVLRRAKSKN GGRSLREKLD KIGLNLPAGR RKAANVTLLT SLVEGEAVHL ARDFGYVCET EFPAKAVAEF LNRQHSDPNE QVTRKNMLLA TKQICKEFTD LLAQDRSPLG NSRPNPILEP GIQSCLTHFN LISHGFGSPA VCAAVTALQN YLTEALKAMD KMYLSNNPNS HTDNNAKSSD KEEKHRK //