ID AP2A_RAT Reviewed; 437 AA.
AC P58197;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2001, sequence version 1.
DT 24-JAN-2024, entry version 136.
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=Tcfap2a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=10847586; DOI=10.1210/mend.14.6.0468;
RA Li B.-S., Kramer P.R., Zhao W., Ma W., Stenger D.A., Zhang L.;
RT "Molecular cloning, expression, and characterization of rat homolog of
RT human AP-2alpha that stimulates neuropeptide Y transcription activity in
RT response to nerve growth factor.";
RL Mol. Endocrinol. 14:837-847(2000).
RN [2]
RP EFFECT OF ANTIDEPRESSANTS.
RX PubMed=11205881; DOI=10.1016/s0024-3205(00)00969-3;
RA Damberg M., Ekblom J., Oreland L.;
RT "Chronic pharmacological treatment with certain antidepressants alters the
RT expression and DNA-binding activity of transcription factor AP-2.";
RL Life Sci. 68:669-678(2000).
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 c-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 (By similarity). {ECO:0000250}.
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 (By similarity). Interacts with KCTD15; this interaction inhibits
CC TFAP2A transcriptional activation (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P58197; P49418: AMPH; Xeno; NbExp=2; IntAct=EBI-7069641, EBI-7121510;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: In the brain, highly expressed in the hippocampus,
CC hypothalamus and cerebral cortex.
CC -!- INDUCTION: During retinoic acid-mediated differentiation and by nerve
CC growth factor (NGF). Inhibited by the antidepressants, citalopram and
CC imipramin.
CC -!- DOMAIN: The PPxY motif mediates interaction with WWOX. {ECO:0000250}.
CC -!- PTM: Sumoylated on Lys-10; which inhibits transcriptional activity.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: The antidepressants, citalopram, imipramin and lithium-
CC chloride decrease the DNA-binding activity.
CC -!- SIMILARITY: Belongs to the AP-2 family. {ECO:0000305}.
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DR AlphaFoldDB; P58197; -.
DR SMR; P58197; -.
DR IntAct; P58197; 2.
DR MINT; P58197; -.
DR STRING; 10116.ENSRNOP00000040925; -.
DR PhosphoSitePlus; P58197; -.
DR PaxDb; 10116-ENSRNOP00000040925; -.
DR AGR; RGD:1310267; -.
DR RGD; 1310267; Tfap2a.
DR eggNOG; KOG3811; Eukaryota.
DR InParanoid; P58197; -.
DR PhylomeDB; P58197; -.
DR Reactome; R-RNO-8864260; Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors.
DR Reactome; R-RNO-8866904; Negative regulation of activity of TFAP2 (AP-2) family transcription factors.
DR Reactome; R-RNO-8866907; Activation of the TFAP2 (AP-2) family of transcription factors.
DR Reactome; R-RNO-8869496; TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation.
DR PRO; PR:P58197; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005905; C:clathrin-coated pit; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0140536; F:nuclear receptor corepressor activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0021506; P:anterior neuropore closure; ISO:RGD.
DR GO; GO:0071711; P:basement membrane organization; ISO:RGD.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071281; P:cellular response to iron ion; ISS:UniProtKB.
DR GO; GO:0061303; P:cornea development in camera-type eye; ISO:RGD.
DR GO; GO:0010172; P:embryonic body morphogenesis; ISO:RGD.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; ISO:RGD.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:UniProtKB.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; ISS:UniProtKB.
DR GO; GO:0009880; P:embryonic pattern specification; ISO:RGD.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0048730; P:epidermis morphogenesis; ISO:RGD.
DR GO; GO:0061029; P:eyelid development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0060325; P:face morphogenesis; ISO:RGD.
DR GO; GO:0010761; P:fibroblast migration; ISO:RGD.
DR GO; GO:0021884; P:forebrain neuron development; ISO:RGD.
DR GO; GO:0035136; P:forelimb morphogenesis; ISO:RGD.
DR GO; GO:0042472; P:inner ear morphogenesis; ISS:UniProtKB.
DR GO; GO:0003334; P:keratinocyte development; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0060235; P:lens induction in camera-type eye; ISO:RGD.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; ISO:RGD.
DR GO; GO:0072210; P:metanephric nephron development; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISS:UniProtKB.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0014032; P:neural crest cell development; ISO:RGD.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
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:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0070172; P:positive regulation of tooth mineralization; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045595; P:regulation of cell differentiation; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:0045664; P:regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:RGD.
DR GO; GO:0010842; P:retina layer formation; ISO:RGD.
DR GO; GO:0060021; P:roof of mouth development; ISS:UniProtKB.
DR GO; GO:0014044; P:Schwann cell development; IEP:RGD.
DR GO; GO:0007423; P:sensory organ development; ISO:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0048705; P:skeletal system morphogenesis; ISO:RGD.
DR GO; GO:0043588; P:skin development; ISO:RGD.
DR GO; GO:0048485; P:sympathetic nervous system development; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:RGD.
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.
PE 1: Evidence at protein level;
KW Activator; 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_0000184798"
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:0000250|UniProtKB:P05549"
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:0000250|UniProtKB:P05549"
FT CROSSLNK 10
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 10
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P05549"
FT CROSSLNK 177
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P05549"
FT CROSSLNK 184
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P05549"
SQ SEQUENCE 437 AA; 47947 MW; EB8C53D07DCCFE3C CRC64;
MLWKLTDNIK YEDCEDRHDG TSNGTARLPQ LGTVGQSPYT SAPPLSHTPN ADFQPPYFPP
PYQPIYPQSQ DPYSHVNDPY SLNPLHAQPQ PQHPGWPGQR QSQESGLLHT HRGLPHQLSG
LDPRRDYRRH EDLLHGPHGL GSGLGDLPIH SLPHAIEDVP HVEDPGINIP DQTVIKKGPV
SLSKSNSNAV SAIPINKDNL FGGVVNPNEV FCSVPGRLSL LSSTSKYKVT VAEVQRRLSS
PECLNASLLG GVLRRAKSKN GGRSLREKLD KIGLNLPAGR RKAANVTLLT SLVEGEAVHL
ARDFGYVCET EFPAKAVAEF LNRQHSDPNE QVARKNMLLA TKQICKEFTD LLAQDRSPLG
NSRPNPILEP GIQSCLTHFN LISHGFGSPA VCAAVTALQN YLTEALKAMD KMYLSNNPNS
HTDNSAKSSD KEEKHRK
//
