Reviewed, UniProtKB/Swiss-Prot P05549 (AP2A_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor AP-2 alpha
      Short name=AP2-alpha
Alternative name(s):
    Activating enhancer-binding protein 2 alpha
    AP-2 transcription factor
    Activator protein 2
      Short name=AP-2

Gene names

Name:	TFAP2A
Synonyms:	AP2TF, TFAP2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	437 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 By similarity.
Subunit structure	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. Ref.4 Ref.7 Ref.8 Ref.9 Ref.10
Subcellular location	Nucleus.
Domain	The WW-binding motif mediates interaction with WWOX By similarity. Ref.10
Post-translational modification	Sumoylated on Lys-10; which inhibits transcriptional activity Probable. Ref.8
Involvement in disease	Defects in TFAP2A are the cause of branchiooculofacial syndrome (BOFS) [MIM:113620]; also known as branchial clefts with characteristic facies, growth retardation, imperforate nasolacrimal duct, and premature aging or lip pseudocleft-hemangiomatous branchial cyst syndrome. BOFS is a rare autosomal dominant cleft palate craniofacial disorder with variable expressivity. The major features include cutaneous anomalies, ocular anomalies, characteristic facial appearance (malformed pinnae, oral clefts), and, less commonly, renal and ectodermal (dental and hair) anomalies. Ref.12
Sequence similarities	Belongs to the AP-2 family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	ectoderm development Traceable author statement. Source: ProtInc regulation of transcription from RNA polymerase II promoter Ref.2 Traceable author statement. Source: ProtInc transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.2 Inferred from mutant phenotype. Source: UniProtKB
Molecular function	protein dimerization activity Ref.8 Inferred from direct assay. Source: UniProtKB transcription coactivator activity Ref.2 Traceable author statement. Source: ProtInc transcription factor activity Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CITED2	Q99967	1	EBI-347351,EBI-937732
EP300	Q09472	1	EBI-347351,EBI-447295

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: P05549-1)

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.

Isoform 2 (identifier: P05549-3)

The sequence of this isoform is not available.

Isoform 3 (identifier: P05549-4)

The sequence of this isoform is not available.

Isoform 4 (identifier: P05549-2)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 437	437	Transcription factor AP-2 alpha		PRO_0000184796
Regions
	Region	280 – 410	131	H-S-H (helix-span-helix), dimerization
	Motif	57 – 62	6	WW-binding
	Compositional bias	29 – 117	89	Gln/Pro-rich (transactivation domain)
Amino acid modifications
	Modified residue	225	1	Phosphoserine Ref.11
	Modified residue	239	1	Phosphoserine; by PKA Ref.11
	Cross-link	10		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
Natural variations
	Alternative sequence	296 – 437	142	EAVHL…EKHRK → KRIHLLTRRNFLLGKWIIFS GQMFGRILCQLGSFIFAENI ARCEWNYFMAKRNICMYSYT SILLPSFPLP in isoform 4.		VSP_006401
	Natural variant	249	1	L → P in BOFS. Ref.12		VAR_045838
	Natural variant	254	1	R → G in BOFS. Ref.12		VAR_045839
	Natural variant	255	1	R → G in BOFS. Ref.12		VAR_045840
	Natural variant	262	1	G → E in BOFS. Ref.12		VAR_045841
Experimental info
	Mutagenesis	239	1	S → A: No phosphorylation. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (AP-2A) [UniParc]. Last modified July 1, 1989. Version 1. Checksum: FB8FA33C3AEED71F	FASTA	437	48,062
	10 20 30 40 50 60 MLWKLTDNIK YEDCEDRHDG TSNGTARLPQ LGTVGQSPYT SAPPLSHTPN ADFQPPYFPP 70 80 90 100 110 120 PYQPIYPQSQ DPYSHVNDPY SLNPLHAQPQ PQHPGWPGQR QSQESGLLHT HRGLPHQLSG 130 140 150 160 170 180 LDPRRDYRRH EDLLHGPHAL SSGLGDLSIH SLPHAIEEVP HVEDPGINIP DQTVIKKGPV 190 200 210 220 230 240 SLSKSNSNAV SAIPINKDNL FGGVVNPNEV FCSVPGRLSL LSSTSKYKVT VAEVQRRLSP 250 260 270 280 290 300 PECLNASLLG GVLRRAKSKN GGRSLREKLD KIGLNLPAGR RKAANVTLLT SLVEGEAVHL 310 320 330 340 350 360 ARDFGYVCET EFPAKAVAEF LNRQHSDPNE QVTRKNMLLA TKQICKEFTD LLAQDRSPLG 370 380 390 400 410 420 NSRPNPILEP GIQSCLTHFN LISHGFGSPA VCAAVTALQN YLTEALKAMD KMYLSNNPNS 430 HTDNNAKSSD KEEKHRK
	Isoform 2 (Sequence not available).	FASTA	–	–
	Isoform 3 (Sequence not available).	FASTA	–	–
	Isoform 4 (AP-2B). Checksum: C0D74B07799B98A5	FASTA	365	40,557
	10 20 30 40 50 60 MLWKLTDNIK YEDCEDRHDG TSNGTARLPQ LGTVGQSPYT SAPPLSHTPN ADFQPPYFPP 70 80 90 100 110 120 PYQPIYPQSQ DPYSHVNDPY SLNPLHAQPQ PQHPGWPGQR QSQESGLLHT HRGLPHQLSG 130 140 150 160 170 180 LDPRRDYRRH EDLLHGPHAL SSGLGDLSIH SLPHAIEEVP HVEDPGINIP DQTVIKKGPV 190 200 210 220 230 240 SLSKSNSNAV SAIPINKDNL FGGVVNPNEV FCSVPGRLSL LSSTSKYKVT VAEVQRRLSP 250 260 270 280 290 300 PECLNASLLG GVLRRAKSKN GGRSLREKLD KIGLNLPAGR RKAANVTLLT SLVEGKRIHL 310 320 330 340 350 360 LTRRNFLLGK WIIFSGQMFG RILCQLGSFI FAENIARCEW NYFMAKRNIC MYSYTSILLP SFPLP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements." Williams T., Admon A., Luescher B., Tjian R. Genes Dev. 2:1557-1569(1988) [PubMed: 3063603] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2." Buettner R., Kannan P., Imhof A., Bauer R., Yim S.O., Glockshuber R., Van Dyke M.W., Tainsky M.A. Mol. Cell. Biol. 13:4174-4185(1993) [PubMed: 8321221] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4). Tissue: Teratocarcinoma.
[3]	"The genomic structure of the human AP-2 transcription factor." Bauer R., Imhof A., Pscherer A., Kopp H., Moser M., Seegers S., Kerscher M., Tainsky M.A., Hofstaedter F., Buettner R. Nucleic Acids Res. 22:1413-1420(1994) [PubMed: 8190633] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Characterization of a dimerization motif in AP-2 and its function in heterologous DNA-binding proteins." Williams T., Tjian R. Science 251:1067-1071(1991) [PubMed: 1998122] [Abstract] Cited for: SUBUNIT.
[5]	"Analysis of the DNA-binding and activation properties of the human transcription factor AP-2." Williams T., Tjian R. Genes Dev. 5:670-682(1991) [PubMed: 2010091] [Abstract] Cited for: DNA-BINDING.
[6]	"Transcription factor AP-2 activity is modulated by protein kinase A-mediated phosphorylation." Garcia M.A., Campillos M., Marina A., Valdivieso F., Vazquez J. FEBS Lett. 444:27-31(1999) [PubMed: 10037142] [Abstract] Cited for: MUTAGENESIS OF SER-239, PHOSPHORYLATION.
[7]	"Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2." Braganca J., Swingler T., Marques F.I.R., Jones T., Eloranta J.J., Hurst H.C., Shioda T., Bhattacharya S. J. Biol. Chem. 277:8559-8565(2002) [PubMed: 11744733] [Abstract] Cited for: INTERACTION WITH CITED4.
[8]	"Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo." Eloranta J.J., Hurst H.C. J. Biol. Chem. 277:30798-30804(2002) [PubMed: 12072434] [Abstract] Cited for: INTERACTION WITH UBE2I, SUMOYLATION AT LYS-10.
[9]	"RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to phosphorylate epsin during the switch off of endocytosis in mitosis." Rosse C., L'Hoste S., Offner N., Picard A., Camonis J. J. Biol. Chem. 278:30597-30604(2003) [PubMed: 12775724] [Abstract] Cited for: INTERACTION WITH RALBP1.
[10]	"Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor." Aqeilan R.I., Palamarchuk A., Weigel R.J., Herrero J.J., Pekarsky Y., Croce C.M. Cancer Res. 64:8256-8261(2004) [PubMed: 15548692] [Abstract] Cited for: INTERACTION WITH WWOX, DOMAIN.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225 AND SER-239, MASS SPECTROMETRY.
[12]	"TFAP2A mutations result in branchio-oculo-facial syndrome." Milunsky J.M., Maher T.A., Zhao G., Roberts A.E., Stalker H.J., Zori R.T., Burch M.N., Clemens M., Mulliken J.B., Smith R., Lin A.E. Am. J. Hum. Genet. 82:1171-1177(2008) [PubMed: 18423521] [Abstract] Cited for: VARIANTS BOFS PRO-249; GLY-254; GLY-255 AND GLU-262.
+	Additional computationally mapped references.

Web resources

Wikipedia

Activatin protein 2 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	M36711 mRNA. Translation: AAA35539.1. M61156 mRNA. Translation: AAA02487.1. X52611 mRNA. Translation: CAA36842.1. X77343 Genomic DNA. Translation: CAB59735.1.
IPI	IPI00472844. IPI00844409.
PIR	A31752.
RefSeq	NP_001027451.1. NP_001035890.1. NP_003211.1.
UniGene	Hs.519880
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P05549. 4 interactions.
STRING	P05549.
PTM databases
PhosphoSite	P05549.
Genome annotation databases
Ensembl	ENST00000379604; ENSP00000368924; ENSG00000137203; Homo sapiens. [Genome view] ENST00000379613; ENSP00000368933; ENSG00000137203; Homo sapiens. [Genome view] ENST00000482890; ENSP00000418541; ENSG00000137203; Homo sapiens. [Genome view]
GeneID	7020.
KEGG	hsa:7020.
UCSC	uc003myr.1. human. uc003myu.1. human.
Organism-specific databases
CTD	7020.
GeneCards	GC06M010503.
H-InvDB	HIX0025068.
HGNC	HGNC:11742. TFAP2A.
HPA	CAB000326.
MIM	107580. gene. 113620. phenotype.
Orphanet	1297. Branchio-oculo-facial syndrome.
PharmGKB	PA36459.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15671.
HOVERGEN	P05549.
InParanoid	P05549.
PhylomeDB	P05549.
Enzyme and pathway databases
Pathway_Interaction_DB	caspase_pathway. Caspase cascade in apoptosis.
Gene expression databases
ArrayExpress	P05549.
Bgee	P05549.
CleanEx	HS_TFAP2A.
Genevestigator	P05549.
GermOnline	ENSG00000137203. Homo sapiens.
Family and domain databases
InterPro	IPR004979. TF_AP2. IPR008121. TF_AP2_alpha_N. IPR013854. TF_AP2_C. [Graphical view]
PANTHER	PTHR10812. TF_AP2. 1 hit. PTHR10812:SF8. TF_AP2_alpha_N. 1 hit.
Pfam	PF03299. TF_AP-2. 1 hit. [Graphical view]
PRINTS	PR01749. AP2ATNSCPFCT. PR01748. AP2TNSCPFCT.
ProtoNet	Search...
Other Resources
NextBio	27423.
PMAP-CutDB	P05549.
SOURCE	Search...

Entry information

Entry name

AP2A_HUMAN

Accession

Primary (citable) accession number: P05549
Secondary accession number(s): Q13777

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	January 19, 2010
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.