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UniProtKB - P05549 (AP2A_HUMAN)

Protein

Transcription factor AP-2-alpha

Gene

TFAP2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-3232118 SUMOylation of transcription factors
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
SIGNORiP05549

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor AP-2-alpha
Short 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000137203.10
HGNCiHGNC:11742 TFAP2A
MIMi107580 gene
neXtProtiNX_P05549

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Branchiooculofacial syndrome (BOFS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by growth retardation, bilateral branchial sinus defects with hemangiomatous, scarred skin, cleft lip with or without cleft palate, pseudocleft of the upper lip, nasolacrimal duct obstruction, low set ears with posterior rotation, a malformed, asymmetrical nose with a broad bridge and flattened tip, conductive or sensorineural deafness, ocular and renal anomalies.
See also OMIM:113620
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_045838249L → P in BOFS. 1 Publication1
Natural variantiVAR_045839254R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs151344528EnsemblClinVar.1
Natural variantiVAR_045840255R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909574Ensembl.1
Natural variantiVAR_045841262G → E in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909575Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi239S → A: No phosphorylation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7020
GeneReviewsiTFAP2A
MalaCardsiTFAP2A
MIMi113620 phenotype
OpenTargetsiENSG00000137203
Orphaneti1297 Branchio-oculo-facial syndrome
PharmGKBiPA36459

Polymorphism and mutation databases

BioMutaiTFAP2A
DMDMi135302

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001847961 – 437Transcription factor AP-2-alphaAdd BLAST437

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki10Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki10Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki184Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei239Phosphoserine; by PKA1 Publication1

Post-translational modificationi

Sumoylated on Lys-10; which inhibits transcriptional activity.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP05549
PaxDbiP05549
PeptideAtlasiP05549
PRIDEiP05549
ProteomicsDBi51847
51848 [P05549-2]
51849 [P05549-5]

PTM databases

iPTMnetiP05549
PhosphoSitePlusiP05549

Miscellaneous databases

PMAP-CutDBiP05549

Expressioni

Gene expression databases

BgeeiENSG00000137203 Expressed in 162 organ(s), highest expression level in placenta
CleanExiHS_TFAP2A
ExpressionAtlasiP05549 baseline and differential
GenevisibleiP05549 HS

Organism-specific databases

HPAiCAB000326
HPA028850
HPA056871

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 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112878, 63 interactors
CORUMiP05549
IntActiP05549, 91 interactors
MINTiP05549
STRINGi9606.ENSP00000368924

Structurei

3D structure databases

ProteinModelPortaliP05549
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni280 – 410H-S-H (helix-span-helix), dimerizationAdd BLAST131

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi57 – 62PPxY motif6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi29 – 117Gln/Pro-rich (transactivation domain)Add BLAST89

Domaini

The PPxY motif mediates interaction with WWOX.By similarity

Sequence similaritiesi

Belongs to the AP-2 family.Curated

Phylogenomic databases

eggNOGiKOG3811 Eukaryota
ENOG410XR9E LUCA
GeneTreeiENSGT00550000074577
HOGENOMiHOG000231737
HOVERGENiHBG002455
InParanoidiP05549
KOiK09176
PhylomeDBiP05549
TreeFamiTF313718

Family and domain databases

InterProiView protein in InterPro
IPR004979 TF_AP2
IPR008121 TF_AP2_alpha_N
IPR013854 TF_AP2_C
PANTHERiPTHR10812 PTHR10812, 1 hit
PfamiView protein in Pfam
PF03299 TF_AP-2, 1 hit
PRINTSiPR01749 AP2ATNSCPFCT
PR01748 AP2TNSCPFCT

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Experimental confirmation may be lacking for some isoforms.

This entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P05549-1) [UniParc]FASTAAdd to basket
Also known as: AP-2A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:437
Mass (Da):48,062
Last modified:July 1, 1989 - v1
Checksum:iFB8FA33C3AEED71F
GO
Isoform 2 (identifier: P05549-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MLWKLTDNIKYEDCE → MLVHSFSAM

Note: No experimental confirmation available.
Show »
Length:431
Mass (Da):47,183
Checksum:i17337CD2D317620F
GO
Isoform 4 (identifier: P05549-2) [UniParc]FASTAAdd to basket
Also known as: AP-2B

The sequence of this isoform differs from the canonical sequence as follows:
     296-437: EAVHLARDFG...SSDKEEKHRK → KRIHLLTRRN...SILLPSFPLP

Note: May be an aberrantly processed form with no significant distribution in vivo.
Show »
Length:365
Mass (Da):40,557
Checksum:iC0D74B07799B98A5
GO
Isoform 5 (identifier: P05549-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MLWKLTDNIKYEDCE → MSILAKMGDWQ

Note: Gene prediction based on EST data.
Show »
Length:433
Mass (Da):47,440
Checksum:i2521AB97F25AD8B1
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q96SH1Q96SH1_HUMAN
Transcription factor AP-2 alpha (Ac...
TFAP2A hCG_37170
439Annotation score:
C1K3N0C1K3N0_HUMAN
Transcription factor AP-2-alpha
TFAP2A
328Annotation score:
H7C5E5H7C5E5_HUMAN
Transcription factor AP-2-alpha
TFAP2A
218Annotation score:
C9J6N8C9J6N8_HUMAN
Transcription factor AP-2-alpha
TFAP2A
173Annotation score:
H7C4N4H7C4N4_HUMAN
Transcription factor AP-2-alpha
TFAP2A
81Annotation score:
C9JXZ2C9JXZ2_HUMAN
Transcription factor AP-2-alpha
TFAP2A
136Annotation score:
F8WEX2F8WEX2_HUMAN
Transcription factor AP-2-alpha
TFAP2A
121Annotation score:
F8WDC8F8WDC8_HUMAN
Transcription factor AP-2-alpha
TFAP2A
113Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_045838249L → P in BOFS. 1 Publication1
Natural variantiVAR_045839254R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs151344528EnsemblClinVar.1
Natural variantiVAR_045840255R → G in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909574Ensembl.1
Natural variantiVAR_045841262G → E in BOFS. 1 PublicationCorresponds to variant dbSNP:rs121909575Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0432681 – 15MLWKL…YEDCE → MLVHSFSAM in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_0470501 – 15MLWKL…YEDCE → MSILAKMGDWQ in isoform 5. CuratedAdd BLAST15
Alternative sequenceiVSP_006401296 – 437EAVHL…EKHRK → KRIHLLTRRNFLLGKWIIFS GQMFGRILCQLGSFIFAENI ARCEWNYFMAKRNICMYSYT SILLPSFPLP in isoform 4. 1 PublicationAdd BLAST142

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
CCDSiCCDS34337.1 [P05549-5]
CCDS43422.1 [P05549-6]
CCDS4510.1 [P05549-1]
PIRiA31752
RefSeqiNP_001027451.1, NM_001032280.2 [P05549-5]
NP_001035890.1, NM_001042425.1 [P05549-6]
NP_003211.1, NM_003220.2 [P05549-1]
UniGeneiHs.519880

Genome annotation databases

EnsembliENST00000319516; ENSP00000316516; ENSG00000137203 [P05549-6]
ENST00000379608; ENSP00000368928; ENSG00000137203 [P05549-5]
ENST00000482890; ENSP00000418541; ENSG00000137203 [P05549-1]
GeneIDi7020
KEGGihsa:7020
UCSCiuc003myq.4 human [P05549-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
CCDSiCCDS34337.1 [P05549-5]
CCDS43422.1 [P05549-6]
CCDS4510.1 [P05549-1]
PIRiA31752
RefSeqiNP_001027451.1, NM_001032280.2 [P05549-5]
NP_001035890.1, NM_001042425.1 [P05549-6]
NP_003211.1, NM_003220.2 [P05549-1]
UniGeneiHs.519880

3D structure databases

ProteinModelPortaliP05549
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112878, 63 interactors
CORUMiP05549
IntActiP05549, 91 interactors
MINTiP05549
STRINGi9606.ENSP00000368924

PTM databases

iPTMnetiP05549
PhosphoSitePlusiP05549

Polymorphism and mutation databases

BioMutaiTFAP2A
DMDMi135302

Proteomic databases

EPDiP05549
PaxDbiP05549
PeptideAtlasiP05549
PRIDEiP05549
ProteomicsDBi51847
51848 [P05549-2]
51849 [P05549-5]

Protocols and materials databases

DNASUi7020
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000319516; ENSP00000316516; ENSG00000137203 [P05549-6]
ENST00000379608; ENSP00000368928; ENSG00000137203 [P05549-5]
ENST00000482890; ENSP00000418541; ENSG00000137203 [P05549-1]
GeneIDi7020
KEGGihsa:7020
UCSCiuc003myq.4 human [P05549-1]

Organism-specific databases

CTDi7020
DisGeNETi7020
EuPathDBiHostDB:ENSG00000137203.10
GeneCardsiTFAP2A
GeneReviewsiTFAP2A
HGNCiHGNC:11742 TFAP2A
HPAiCAB000326
HPA028850
HPA056871
MalaCardsiTFAP2A
MIMi107580 gene
113620 phenotype
neXtProtiNX_P05549
OpenTargetsiENSG00000137203
Orphaneti1297 Branchio-oculo-facial syndrome
PharmGKBiPA36459
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3811 Eukaryota
ENOG410XR9E LUCA
GeneTreeiENSGT00550000074577
HOGENOMiHOG000231737
HOVERGENiHBG002455
InParanoidiP05549
KOiK09176
PhylomeDBiP05549
TreeFamiTF313718

Enzyme and pathway databases

ReactomeiR-HSA-3232118 SUMOylation of transcription factors
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
SIGNORiP05549

Miscellaneous databases

ChiTaRSiTFAP2A human
GeneWikiiTFAP2A
GenomeRNAii7020
PMAP-CutDBiP05549
PROiPR:P05549
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137203 Expressed in 162 organ(s), highest expression level in placenta
CleanExiHS_TFAP2A
ExpressionAtlasiP05549 baseline and differential
GenevisibleiP05549 HS

Family and domain databases

InterProiView protein in InterPro
IPR004979 TF_AP2
IPR008121 TF_AP2_alpha_N
IPR013854 TF_AP2_C
PANTHERiPTHR10812 PTHR10812, 1 hit
PfamiView protein in Pfam
PF03299 TF_AP-2, 1 hit
PRINTSiPR01749 AP2ATNSCPFCT
PR01748 AP2TNSCPFCT
ProtoNetiSearch...

Entry informationi

Entry nameiAP2A_HUMAN
AccessioniPrimary (citable) accession number: P05549
Secondary accession number(s): Q13777, Q5TAV5, Q8N1C6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 7, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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