Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transcription factor AP-2-alpha

Gene

Tfap2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.1 Publication

GO - Molecular functioni

GO - Biological processi

  • anterior neuropore closure Source: MGI
  • basement membrane organization Source: MGI
  • bone morphogenesis Source: UniProtKB
  • cellular response to iron ion Source: UniProtKB
  • cornea development in camera-type eye Source: MGI
  • embryonic body morphogenesis Source: MGI
  • embryonic camera-type eye morphogenesis Source: MGI
  • embryonic cranial skeleton morphogenesis Source: UniProtKB
  • embryonic forelimb morphogenesis Source: UniProtKB
  • embryonic pattern specification Source: MGI
  • epidermis morphogenesis Source: MGI
  • eyelid development in camera-type eye Source: UniProtKB
  • face morphogenesis Source: MGI
  • forebrain neuron development Source: MGI
  • forelimb morphogenesis Source: MGI
  • inner ear morphogenesis Source: UniProtKB
  • keratinocyte development Source: MGI
  • kidney development Source: UniProtKB
  • lens induction in camera-type eye Source: MGI
  • lens morphogenesis in camera-type eye Source: MGI
  • metanephric nephron development Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of epidermal growth factor receptor signaling pathway Source: MGI
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of reactive oxygen species metabolic process Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of transcription by competitive promoter binding Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • nervous system development Source: UniProtKB
  • neural crest cell development Source: MGI
  • neural tube closure Source: MGI
  • oculomotor nerve formation Source: UniProtKB
  • optic cup structural organization Source: UniProtKB
  • optic vesicle morphogenesis Source: UniProtKB
  • outflow tract morphogenesis Source: MGI
  • palate development Source: UniProtKB
  • positive regulation of bone mineralization Source: UniProtKB
  • positive regulation of cell migration Source: MGI
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of neuron apoptotic process Source: MGI
  • positive regulation of tooth mineralization Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of cell differentiation Source: MGI
  • regulation of neuron differentiation Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • retina layer formation Source: Ensembl
  • sensory organ development Source: UniProtKB
  • sensory perception of sound Source: UniProtKB
  • skeletal system morphogenesis Source: MGI
  • skin development Source: UniProtKB
  • sympathetic nervous system development Source: MGI
  • transcription from RNA polymerase II promoter Source: MGI
  • trigeminal nerve development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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, Tcfap2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:104671. Tfap2a.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: MGI
  • cytoplasm Source: MGI
  • Golgi apparatus Source: MGI
  • intracellular membrane-bounded organelle Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 437437Transcription factor AP-2-alphaPRO_0000184797Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki10 – 10Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei239 – 2391Phosphoserine; by PKABy similarity

Post-translational modificationi

Sumoylated on Lys-10; which inhibits transcriptional activity.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP34056.
PRIDEiP34056.

PTM databases

PhosphoSiteiP34056.

Expressioni

Developmental stagei

Expressed in the embryonic heart. Expressed from embryo day 9.5 to birth. At day 12.5, expressed in the midbrain, hindbrain, spinal cord, sensory ganglia, epidermis, nephric system and limbs. At mid-embryogenesis, isoform 3 is the most abundant form in the nervous system and total embryo, but the least abundant form in the epidermis. In adults, AP-2A is expressed in the eye, skin, kidney, prostate, thymus, skeletal muscle and very weakly, in the brain. Highest expression found in skin and eye.1 Publication

Inductioni

All isoforms are induced during retinoic acid-mediated differentiation and by cAMP stimulation of primary astrocytes. Isoform 3 is most strongly induced in the former case, isoform 1 in the latter case.

Gene expression databases

BgeeiP34056.
CleanExiMM_TCFAP2A.
ExpressionAtlasiP34056. baseline and differential.
GenevisibleiP34056. MM.

Interactioni

Subunit structurei

Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members. Interacts with WWOX. Interacts with UBE2I. Interacts with RALBP1 in a complex also containing EPN1 and NUMB during interphase and mitosis (By similarity). Interacts with CITED4. 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 (By similarity). Interacts with KCTD15; this interaction inhibits TFAP2A transcriptional activation (By similarity).By similarity

Protein-protein interaction databases

BioGridi204011. 7 interactions.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni280 – 410131H-S-H (helix-span-helix), dimerizationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi57 – 626WW-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi29 – 11789Gln/Pro-rich (transactivation domain)Add
BLAST

Domaini

The WW-binding motif mediates interaction with WWOX.By similarity

Sequence similaritiesi

Belongs to the AP-2 family.Curated

Phylogenomic databases

eggNOGiNOG300693.
HOVERGENiHBG002455.
InParanoidiP34056.
KOiK09176.
OrthoDBiEOG7HHWS1.
PhylomeDBiP34056.
TreeFamiTF313718.

Family and domain databases

InterProiIPR004979. TF_AP2.
IPR008121. TF_AP2_alpha_N.
IPR013854. TF_AP2_C.
[Graphical view]
PANTHERiPTHR10812. PTHR10812. 1 hit.
PfamiPF03299. TF_AP-2. 1 hit.
[Graphical view]
PRINTSiPR01749. AP2ATNSCPFCT.
PR01748. AP2TNSCPFCT.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P34056-1) [UniParc]FASTAAdd to basket

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 GSGLGDLPIH
160 170 180 190 200
SLPHAIEDVP 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 QVARKNMLLA TKQICKEFTD
360 370 380 390 400
LLAQDRSPLG NSRPNPILEP GIQSCLTHFN LISHGFGSPA VCAAVTALQN
410 420 430
YLTEALKAMD KMYLSNNPNS HTDNSAKSSD KEEKHRK
Length:437
Mass (Da):47,971
Last modified:November 1, 1995 - v2
Checksum:i901F456EE07AE69C
GO
Isoform 2 (identifier: P34056-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     16-160: Missing.

Show »
Length:292
Mass (Da):31,960
Checksum:i6E9B01E97186E4E1
GO
Isoform 3 (identifier: P34056-3) [UniParc]FASTAAdd to basket

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

Show »
Length:431
Mass (Da):47,092
Checksum:i7CA39A800983538C
GO
Isoform 4 (identifier: P34056-4) [UniParc]FASTAAdd to basket

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

Show »
Length:466
Mass (Da):50,900
Checksum:i49A69CBE5826B8BB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti38 – 381P → S in AAH07471 (PubMed:15489334).Curated
Sequence conflicti139 – 1391A → G (PubMed:15489334).Curated
Sequence conflicti139 – 1391A → G (PubMed:7750631).Curated
Sequence conflicti158 – 1592DV → RL (PubMed:16141072).Curated
Sequence conflicti390 – 3901Missing (PubMed:1989904).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1515MLWKL…YEDCE → MLVHSFSAM in isoform 3. CuratedVSP_006402Add
BLAST
Alternative sequencei1 – 1515MLWKL…YEDCE → MNSVVVDTPYFGGLPTLGLW NGFSRVVEALRLISSSPSRL AFFQ in isoform 4. CuratedVSP_006403Add
BLAST
Alternative sequencei16 – 160145Missing in isoform 2. CuratedVSP_006404Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74216 mRNA. Translation: CAA52292.1.
BC018226 mRNA. Translation: AAH18226.1.
BC007471 mRNA. Translation: AAH07471.1.
U17285 mRNA. Translation: AAA85681.1.
U17291, U17289 Genomic DNA. Translation: AAA85678.1.
U17286 mRNA. Translation: AAA85682.1.
U17287 mRNA. Translation: AAA85683.1.
U17291, U17290 Genomic DNA. Translation: AAA85679.1.
U17288 mRNA. Translation: AAA85684.1.
U17291 Genomic DNA. Translation: AAA85680.1.
AK013900 mRNA. Translation: BAB29047.1.
X57012 mRNA. Translation: CAA40331.1.
CCDSiCCDS26467.1. [P34056-1]
CCDS49243.1. [P34056-3]
PIRiS42111.
RefSeqiNP_001288603.1. NM_001301674.1.
NP_035677.2. NM_011547.4.
UniGeneiMm.487150.
Mm.85544.

Genome annotation databases

GeneIDi21418.
KEGGimmu:21418.
UCSCiuc007qei.1. mouse. [P34056-4]
uc011yyq.1. mouse. [P34056-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74216 mRNA. Translation: CAA52292.1.
BC018226 mRNA. Translation: AAH18226.1.
BC007471 mRNA. Translation: AAH07471.1.
U17285 mRNA. Translation: AAA85681.1.
U17291, U17289 Genomic DNA. Translation: AAA85678.1.
U17286 mRNA. Translation: AAA85682.1.
U17287 mRNA. Translation: AAA85683.1.
U17291, U17290 Genomic DNA. Translation: AAA85679.1.
U17288 mRNA. Translation: AAA85684.1.
U17291 Genomic DNA. Translation: AAA85680.1.
AK013900 mRNA. Translation: BAB29047.1.
X57012 mRNA. Translation: CAA40331.1.
CCDSiCCDS26467.1. [P34056-1]
CCDS49243.1. [P34056-3]
PIRiS42111.
RefSeqiNP_001288603.1. NM_001301674.1.
NP_035677.2. NM_011547.4.
UniGeneiMm.487150.
Mm.85544.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204011. 7 interactions.

PTM databases

PhosphoSiteiP34056.

Proteomic databases

MaxQBiP34056.
PRIDEiP34056.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi21418.
KEGGimmu:21418.
UCSCiuc007qei.1. mouse. [P34056-4]
uc011yyq.1. mouse. [P34056-2]

Organism-specific databases

CTDi7020.
MGIiMGI:104671. Tfap2a.

Phylogenomic databases

eggNOGiNOG300693.
HOVERGENiHBG002455.
InParanoidiP34056.
KOiK09176.
OrthoDBiEOG7HHWS1.
PhylomeDBiP34056.
TreeFamiTF313718.

Miscellaneous databases

NextBioi300724.
PROiP34056.
SOURCEiSearch...

Gene expression databases

BgeeiP34056.
CleanExiMM_TCFAP2A.
ExpressionAtlasiP34056. baseline and differential.
GenevisibleiP34056. MM.

Family and domain databases

InterProiIPR004979. TF_AP2.
IPR008121. TF_AP2_alpha_N.
IPR013854. TF_AP2_C.
[Graphical view]
PANTHERiPTHR10812. PTHR10812. 1 hit.
PfamiPF03299. TF_AP-2. 1 hit.
[Graphical view]
PRINTSiPR01749. AP2ATNSCPFCT.
PR01748. AP2TNSCPFCT.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The complete murine cDNA sequence of the transcription factor AP-2."
    Moser M., Pscherer A., Bauer R., Imhof A., Seegers S., Kerscher M., Buettner R.
    Nucleic Acids Res. 21:4844-4844(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: NIH Swiss.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "Alternative mRNAs encode multiple isoforms of transcription factor AP-2 during murine embryogenesis."
    Meier P., Koedood M., Philipp J., Fontana A., Mitchell P.J.
    Dev. Biol. 169:1-14(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-279, ALTERNATIVE SPLICING.
    Strain: 129/4 and ICR.
    Tissue: Embryo.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 158-437.
    Strain: C57BL/6J.
    Tissue: Embryonic head.
  5. "Transcription factor AP-2 is expressed in neural crest cell lineages during mouse embryogenesis."
    Mitchell P.J., Timmons P.M., Hebert J.M., Rigby P.W.J., Tjian R.
    Genes Dev. 5:105-119(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 259-437.
  6. "Cloning of mouse Cited4, a member of the CITED family p300/CBP-binding transcriptional coactivators: induced expression in mammary epithelial cells."
    Yahata T., Takedatsu H., Dunwoodie S.L., Braganca J., Swingler T., Withington S.L., Hur J., Coser K.R., Isselbacher K.J., Bhattacharya S., Shioda T.
    Genomics 80:601-613(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CITED4.
  7. Cited for: FUNCTION, ASSOCIATION WITH CHROMATIN, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiAP2A_MOUSE
AccessioniPrimary (citable) accession number: P34056
Secondary accession number(s): Q60740
, Q60741, Q60742, Q60743, Q62067, Q62068, Q62069, Q91VX0, Q9CRY4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: November 1, 1995
Last modified: June 24, 2015
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.