UniProtKB - P05549 (AP2A_HUMAN)
Transcription factor AP-2-alpha
TFAP2A
Functioni
Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region.
2 PublicationsGO - Molecular functioni
- chromatin binding Source: UniProtKB
- DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: UniProtKB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: UniProtKB
- identical protein binding Source: UniProtKB
- nuclear receptor corepressor activity Source: ARUK-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific DNA binding Source: UniProtKB
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- anatomical structure development Source: GO_Central
- bone morphogenesis Source: UniProtKB
- cellular response to iron ion Source: UniProtKB
- embryonic cranial skeleton morphogenesis Source: UniProtKB
- embryonic forelimb morphogenesis Source: UniProtKB
- eyelid development in camera-type eye Source: UniProtKB
- inner ear morphogenesis Source: UniProtKB
- kidney development Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of reactive oxygen species metabolic process Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by competitive promoter binding Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- oculomotor nerve formation Source: UniProtKB
- optic cup structural organization Source: UniProtKB
- optic vesicle morphogenesis Source: UniProtKB
- positive regulation of bone mineralization Source: UniProtKB
- positive regulation of gene expression Source: UniProtKB
- positive regulation of neuron apoptotic process Source: UniProtKB
- positive regulation of tooth mineralization Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of cell differentiation Source: UniProtKB
- regulation of cell population proliferation Source: GO_Central
- regulation of transcription by RNA polymerase II Source: GO_Central
- retina layer formation Source: UniProtKB
- roof of mouth development Source: UniProtKB
- sensory perception of sound Source: UniProtKB
- trigeminal nerve development Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P05549 |
Reactomei | R-HSA-3232118, SUMOylation of transcription factors [P05549-1] R-HSA-8864260, Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors R-HSA-8866904, Negative regulation of activity of TFAP2 (AP-2) family transcription factors R-HSA-8866906, TFAP2 (AP-2) family regulates transcription of other transcription factors R-HSA-8866907, Activation of the TFAP2 (AP-2) family of transcription factors R-HSA-8866910, TFAP2 (AP-2) family regulates transcription of growth factors and their receptors R-HSA-8866911, TFAP2 (AP-2) family regulates transcription of cell cycle factors R-HSA-8869496, TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation |
SignaLinki | P05549 |
SIGNORi | P05549 |
Names & Taxonomyi
Protein namesi | Recommended name: Transcription factor AP-2-alphaShort name: AP2-alpha Alternative name(s): AP-2 transcription factor Activating enhancer-binding protein 2-alpha Activator protein 2 Short name: AP-2 |
Gene namesi | Name:TFAP2A Synonyms:AP2TF, TFAP2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11742, TFAP2A |
MIMi | 107580, gene |
neXtProti | NX_P05549 |
VEuPathDBi | HostDB:ENSG00000137203 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- chromatin Source: NTNU_SB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Branchiooculofacial syndrome (BOFS)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_045838 | 249 | L → P in BOFS. 1 Publication | 1 | |
Natural variantiVAR_045839 | 254 | R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs151344528Ensembl. | 1 | |
Natural variantiVAR_045840 | 255 | R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909574Ensembl. | 1 | |
Natural variantiVAR_045841 | 262 | G → E in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909575Ensembl. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 239 | S → A: No phosphorylation. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 7020 |
GeneReviewsi | TFAP2A |
MalaCardsi | TFAP2A |
MIMi | 113620, phenotype |
OpenTargetsi | ENSG00000137203 |
Orphaneti | 1297, Branchio-oculo-facial syndrome |
PharmGKBi | PA36459 |
Miscellaneous databases
Pharosi | P05549, Tbio |
Genetic variation databases
BioMutai | TFAP2A |
DMDMi | 135302 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000184796 | 1 – 437 | Transcription factor AP-2-alphaAdd BLAST | 437 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 10 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication | ||
Cross-linki | 10 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources | ||
Cross-linki | 177 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 184 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 239 | Phosphoserine; by PKA1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P05549 |
jPOSTi | P05549 |
MassIVEi | P05549 |
MaxQBi | P05549 |
PaxDbi | P05549 |
PeptideAtlasi | P05549 |
PRIDEi | P05549 |
ProteomicsDBi | 51847 [P05549-1] 51848 [P05549-2] 51849 [P05549-5] 64874 |
PTM databases
iPTMneti | P05549 |
PhosphoSitePlusi | P05549 |
Expressioni
Gene expression databases
Bgeei | ENSG00000137203, Expressed in placenta and 177 other tissues |
ExpressionAtlasi | P05549, baseline and differential |
Genevisiblei | P05549, HS |
Organism-specific databases
HPAi | ENSG00000137203, Tissue enhanced (breast, skin) |
Interactioni
Subunit structurei
Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members.
Interacts with WWOX.
Interacts with CITED4.
Interacts with UBE2I.
Interacts with RALBP1 in a complex also containing EPN1 and NUMB during interphase and mitosis.
Interacts with KCTD1; this interaction represses transcription activation.
Interacts (via C-terminus) with CITED2 (via C-terminus); the interaction stimulates TFAP2A-transcriptional activation.
Interacts (via N-terminus) with EP300 (via N-terminus); the interaction requires CITED2.
Interacts with KCTD15; this interaction inhibits TFAP2A transcriptional activation.
9 PublicationsBinary interactionsi
P05549
Isoform 2 [P05549-5]
With | #Exp. | IntAct |
---|---|---|
GSTO2 [Q9H4Y5] | 6 | EBI-12194905,EBI-10194609 |
INCA1 [Q0VD86] | 3 | EBI-12194905,EBI-6509505 |
GO - Molecular functioni
- identical protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 112878, 90 interactors |
CORUMi | P05549 |
IntActi | P05549, 103 interactors |
MINTi | P05549 |
STRINGi | 9606.ENSP00000368924 |
Miscellaneous databases
RNActi | P05549, protein |
Structurei
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 14 – 107 | DisorderedSequence analysisAdd BLAST | 94 | |
Regioni | 280 – 410 | H-S-H (helix-span-helix), dimerization1 PublicationAdd BLAST | 131 | |
Regioni | 414 – 437 | DisorderedSequence analysisAdd BLAST | 24 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 57 – 62 | PPxY motif | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 23 – 48 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 49 – 67 | Pro residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 68 – 107 | Polar residuesSequence analysisAdd BLAST | 40 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3811, Eukaryota |
GeneTreei | ENSGT00950000182848 |
HOGENOMi | CLU_035175_4_1_1 |
InParanoidi | P05549 |
OrthoDBi | 641707at2759 |
PhylomeDBi | P05549 |
TreeFami | TF313718 |
Family and domain databases
InterProi | View protein in InterPro IPR004979, TF_AP2 IPR008121, TF_AP2_alpha_N IPR013854, TF_AP2_C |
PANTHERi | PTHR10812, PTHR10812, 1 hit |
Pfami | View protein in Pfam PF03299, TF_AP-2, 1 hit |
PRINTSi | PR01749, AP2ATNSCPFCT PR01748, AP2TNSCPFCT |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLWKLTDNIK YEDCEDRHDG TSNGTARLPQ LGTVGQSPYT SAPPLSHTPN
60 70 80 90 100
ADFQPPYFPP PYQPIYPQSQ DPYSHVNDPY SLNPLHAQPQ PQHPGWPGQR
110 120 130 140 150
QSQESGLLHT HRGLPHQLSG LDPRRDYRRH EDLLHGPHAL SSGLGDLSIH
160 170 180 190 200
SLPHAIEEVP HVEDPGINIP DQTVIKKGPV SLSKSNSNAV SAIPINKDNL
210 220 230 240 250
FGGVVNPNEV FCSVPGRLSL LSSTSKYKVT VAEVQRRLSP PECLNASLLG
260 270 280 290 300
GVLRRAKSKN GGRSLREKLD KIGLNLPAGR RKAANVTLLT SLVEGEAVHL
310 320 330 340 350
ARDFGYVCET EFPAKAVAEF LNRQHSDPNE QVTRKNMLLA TKQICKEFTD
360 370 380 390 400
LLAQDRSPLG NSRPNPILEP GIQSCLTHFN LISHGFGSPA VCAAVTALQN
410 420 430
YLTEALKAMD KMYLSNNPNS HTDNNAKSSD KEEKHRK
The sequence of this isoform differs from the canonical sequence as follows:
296-437: EAVHLARDFG...SSDKEEKHRK → KRIHLLTRRN...SILLPSFPLP
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC1K3N0 | C1K3N0_HUMAN | AP-2 transcription factor | TFAP2A | 328 | Annotation score: | ||
A0A6E1XE14 | A0A6E1XE14_HUMAN | AP-2 transcription factor | TFAP2A hCG_37170 | 439 | Annotation score: | ||
H7C5E5 | H7C5E5_HUMAN | Transcription factor AP-2-alpha | TFAP2A | 218 | Annotation score: | ||
C9J6N8 | C9J6N8_HUMAN | Transcription factor AP-2-alpha | TFAP2A | 173 | Annotation score: | ||
C9JXZ2 | C9JXZ2_HUMAN | Transcription factor AP-2-alpha | TFAP2A | 136 | Annotation score: | ||
H7C4N4 | H7C4N4_HUMAN | Transcription factor AP-2-alpha | TFAP2A | 81 | Annotation score: | ||
F8WEX2 | F8WEX2_HUMAN | Transcription factor AP-2-alpha | TFAP2A | 121 | Annotation score: | ||
F8WDC8 | F8WDC8_HUMAN | Transcription factor AP-2-alpha | TFAP2A | 113 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_045838 | 249 | L → P in BOFS. 1 Publication | 1 | |
Natural variantiVAR_045839 | 254 | R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs151344528Ensembl. | 1 | |
Natural variantiVAR_045840 | 255 | R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909574Ensembl. | 1 | |
Natural variantiVAR_045841 | 262 | G → E in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909575Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043268 | 1 – 15 | MLWKL…YEDCE → MLVHSFSAM in isoform 2. 1 PublicationAdd BLAST | 15 | |
Alternative sequenceiVSP_047050 | 1 – 15 | MLWKL…YEDCE → MSILAKMGDWQ in isoform 5. CuratedAdd BLAST | 15 | |
Alternative sequenceiVSP_006401 | 296 – 437 | EAVHL…EKHRK → KRIHLLTRRNFLLGKWIIFS GQMFGRILCQLGSFIFAENI ARCEWNYFMAKRNICMYSYT SILLPSFPLP in isoform 4. 1 PublicationAdd BLAST | 142 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M36711 mRNA Translation: AAA35539.1 M61156 mRNA Translation: AAA02487.1 X52611 mRNA Translation: CAA36842.1 X77343 Genomic DNA Translation: CAB59735.1 AL138885 Genomic DNA No translation available. CH471087 Genomic DNA Translation: EAW55249.1 BC017754 mRNA Translation: AAH17754.1 |
CCDSi | CCDS34337.1 [P05549-5] CCDS43422.1 [P05549-6] |
PIRi | A31752 |
RefSeqi | NP_001027451.1, NM_001032280.2 [P05549-5] NP_001035890.1, NM_001042425.1 [P05549-6] NP_003211.1, NM_003220.2 |
Genome annotation databases
Ensembli | ENST00000319516; ENSP00000316516; ENSG00000137203 [P05549-6] ENST00000379608; ENSP00000368928; ENSG00000137203 [P05549-5] |
GeneIDi | 7020 |
KEGGi | hsa:7020 |
UCSCi | uc003myq.4, human [P05549-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Activating protein 2 entry |
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M36711 mRNA Translation: AAA35539.1 M61156 mRNA Translation: AAA02487.1 X52611 mRNA Translation: CAA36842.1 X77343 Genomic DNA Translation: CAB59735.1 AL138885 Genomic DNA No translation available. CH471087 Genomic DNA Translation: EAW55249.1 BC017754 mRNA Translation: AAH17754.1 |
CCDSi | CCDS34337.1 [P05549-5] CCDS43422.1 [P05549-6] |
PIRi | A31752 |
RefSeqi | NP_001027451.1, NM_001032280.2 [P05549-5] NP_001035890.1, NM_001042425.1 [P05549-6] NP_003211.1, NM_003220.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 112878, 90 interactors |
CORUMi | P05549 |
IntActi | P05549, 103 interactors |
MINTi | P05549 |
STRINGi | 9606.ENSP00000368924 |
PTM databases
iPTMneti | P05549 |
PhosphoSitePlusi | P05549 |
Genetic variation databases
BioMutai | TFAP2A |
DMDMi | 135302 |
Proteomic databases
EPDi | P05549 |
jPOSTi | P05549 |
MassIVEi | P05549 |
MaxQBi | P05549 |
PaxDbi | P05549 |
PeptideAtlasi | P05549 |
PRIDEi | P05549 |
ProteomicsDBi | 51847 [P05549-1] 51848 [P05549-2] 51849 [P05549-5] 64874 |
Protocols and materials databases
Antibodypediai | 3770, 548 antibodies from 37 providers |
DNASUi | 7020 |
Genome annotation databases
Ensembli | ENST00000319516; ENSP00000316516; ENSG00000137203 [P05549-6] ENST00000379608; ENSP00000368928; ENSG00000137203 [P05549-5] |
GeneIDi | 7020 |
KEGGi | hsa:7020 |
UCSCi | uc003myq.4, human [P05549-1] |
Organism-specific databases
CTDi | 7020 |
DisGeNETi | 7020 |
GeneCardsi | TFAP2A |
GeneReviewsi | TFAP2A |
HGNCi | HGNC:11742, TFAP2A |
HPAi | ENSG00000137203, Tissue enhanced (breast, skin) |
MalaCardsi | TFAP2A |
MIMi | 107580, gene 113620, phenotype |
neXtProti | NX_P05549 |
OpenTargetsi | ENSG00000137203 |
Orphaneti | 1297, Branchio-oculo-facial syndrome |
PharmGKBi | PA36459 |
VEuPathDBi | HostDB:ENSG00000137203 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3811, Eukaryota |
GeneTreei | ENSGT00950000182848 |
HOGENOMi | CLU_035175_4_1_1 |
InParanoidi | P05549 |
OrthoDBi | 641707at2759 |
PhylomeDBi | P05549 |
TreeFami | TF313718 |
Enzyme and pathway databases
PathwayCommonsi | P05549 |
Reactomei | R-HSA-3232118, SUMOylation of transcription factors [P05549-1] R-HSA-8864260, Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors R-HSA-8866904, Negative regulation of activity of TFAP2 (AP-2) family transcription factors R-HSA-8866906, TFAP2 (AP-2) family regulates transcription of other transcription factors R-HSA-8866907, Activation of the TFAP2 (AP-2) family of transcription factors R-HSA-8866910, TFAP2 (AP-2) family regulates transcription of growth factors and their receptors R-HSA-8866911, TFAP2 (AP-2) family regulates transcription of cell cycle factors R-HSA-8869496, TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation |
SignaLinki | P05549 |
SIGNORi | P05549 |
Miscellaneous databases
BioGRID-ORCSi | 7020, 37 hits in 1065 CRISPR screens |
ChiTaRSi | TFAP2A, human |
GeneWikii | TFAP2A |
GenomeRNAii | 7020 |
Pharosi | P05549, Tbio |
PROi | PR:P05549 |
RNActi | P05549, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000137203, Expressed in placenta and 177 other tissues |
ExpressionAtlasi | P05549, baseline and differential |
Genevisiblei | P05549, HS |
Family and domain databases
InterProi | View protein in InterPro IPR004979, TF_AP2 IPR008121, TF_AP2_alpha_N IPR013854, TF_AP2_C |
PANTHERi | PTHR10812, PTHR10812, 1 hit |
Pfami | View protein in Pfam PF03299, TF_AP-2, 1 hit |
PRINTSi | PR01749, AP2ATNSCPFCT PR01748, AP2TNSCPFCT |
MobiDBi | Search... |
Entry informationi
Entry namei | AP2A_HUMAN | |
Accessioni | P05549Primary (citable) accession number: P05549 Secondary accession number(s): Q13777, Q5TAV5, Q8N1C6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
Last sequence update: | July 1, 1989 | |
Last modified: | February 23, 2022 | |
This is version 210 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families