ID PITX2_MOUSE Reviewed; 317 AA. AC P97474; O08646; O70336; P97933; Q9JLA0; Q9QXB8; Q9R1V9; Q9Z141; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 02-NOV-2016, entry version 154. DE RecName: Full=Pituitary homeobox 2; DE AltName: Full=ALL1-responsive protein ARP1; DE AltName: Full=BRX1 homeoprotein; DE AltName: Full=Homeobox protein PITX2; DE AltName: Full=Orthodenticle-like homeobox 2; DE AltName: Full=Paired-like homeodomain transcription factor 2; DE AltName: Full=Paired-like homeodomain transcription factor Munc 30; DE AltName: Full=Solurshin; GN Name=Pitx2; Synonyms=Arp1, Brx1, Otlx2, Ptx2, Rgs; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PTX2A). RA Mucchielli M.L., Martinez S., Pattyn A., Goridis C., Brunet J.-F.; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2A AND PTX2B). RC TISSUE=Pituitary; RX PubMed=9147650; DOI=10.1093/hmg/6.3.457; RA Gage P.J., Camper S.A.; RT "Pituitary homeobox 2, a novel member of the bicoid-related family of RT homeobox genes, is a potential regulator of anterior structure RT formation."; RL Hum. Mol. Genet. 6:457-464(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2B AND PTX2C). RX PubMed=9347917; DOI=10.1016/S0925-4773(97)00110-X; RA Kitamura K., Miura H., Yanazawa M., Miyashita T., Kato K.; RT "Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1 RT and Arx during zona limitans intrathalamica and embryonic ventral RT lateral geniculate nuclear formation."; RL Mech. Dev. 67:83-96(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2A AND PTX2C). RX PubMed=9539779; DOI=10.1073/pnas.95.8.4573; RA Arakawa H., Nakamura T., Zhadanov A.B., Fidanza Y., Yano T., RA Bullrich F., Shimizu M., Blechman J., Mazo A., Canaani E., Croce C.M.; RT "Identification and characterization of the ARP1 gene, a target for RT the human acute leukemia ALL1 gene."; RL Proc. Natl. Acad. Sci. U.S.A. 95:4573-4578(1998). RN [5] RP PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM PTX2C). RX PubMed=10585561; DOI=10.1016/S0925-4773(99)00227-0; RA Schweickert A., Campione M., Steinbeisser H., Blum M.; RT "Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in RT vertebrate left-right asymmetry."; RL Mech. Dev. 90:41-51(2000). RN [6] RP PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM PTX2C). RX PubMed=11319841; DOI=10.1006/cbir.2000.0638; RA Nicholson L.F.B., Ma L., Goulding M.; RT "Cloning and expression of Munc 30: a member of the paired-like RT homeodomain gene family."; RL Cell Biol. Int. 25:351-365(2001). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 63-317. RC TISSUE=Embryonic carcinoma; RX PubMed=8944018; DOI=10.1038/ng1296-392; RA Semina E.V., Reiter R., Leysens N.J., Alward W.L.M., Small K.W., RA Datson N.A., Siegle-Bartelt J., Bierke-Nelson D., Bitoun P., RA Zabel B.U., Carey J.C., Murray J.C.; RT "Cloning and characterization of a novel bicoid-related homeobox RT transcription factor gene, RIEG, involved in Rieger syndrome."; RL Nat. Genet. 14:392-399(1996). RN [8] RP ALTERNATIVE SPLICING (ISOFORM PITX2CALPHA) AND ALTERNATIVE INITIATION RP (ISOFORM PITX2CBETA). RA Lamba P., Hjalt T.A., Bernard D.J.; RT "Novel forms of paired-like homeodomain transcription factor 2 RT (PITX2): generation by alternative translation initiation and mRNA RT splicing."; RL Unpublished observations (JAN-2008). RN [9] RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE. RX PubMed=15475956; DOI=10.1038/ng1446; RA Bamforth S.D., Braganca J., Farthing C.R., Schneider J.E., RA Broadbent C., Michell A.C., Clarke K., Neubauer S., Norris D., RA Brown N.A., Anderson R.H., Bhattacharya S.; RT "Cited2 controls left-right patterning and heart development through a RT Nodal-Pitx2c pathway."; RL Nat. Genet. 36:1189-1196(2004). RN [10] RP PHOSPHORYLATION AT THR-90, AND FUNCTION. RX PubMed=20019746; DOI=10.1038/cdd.2009.194; RA Gherzi R., Trabucchi M., Ponassi M., Gallouzi I.E., Rosenfeld M.G., RA Briata P.; RT "Akt2-mediated phosphorylation of Pitx2 controls Ccnd1 mRNA decay RT during muscle cell differentiation."; RL Cell Death Differ. 17:975-983(2010). CC -!- FUNCTION: Controls cell proliferation in a tissue-specific manner CC and is involved in morphogenesis. During embryonic development, CC exerts a role in the expansion of muscle progenitors. May play a CC role in the proper localization of asymmetric organs such as the CC heart and stomach. Isoform Ptx2c is involved in left-right CC asymmetry the developing embryo. {ECO:0000269|PubMed:20019746}. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=5; CC Name=Ptx2B; Synonyms=ARP1B, BRX1B; CC IsoId=P97474-1; Sequence=Displayed; CC Name=Ptx2C; Synonyms=ARP1C, BRX1A; CC IsoId=P97474-2; Sequence=VSP_002262; CC Name=Ptx2A; Synonyms=ARP1A; CC IsoId=P97474-3; Sequence=VSP_002263; CC Name=Pitx2Calpha; CC IsoId=P97474-4; Sequence=VSP_031522; CC Name=Pitx2Cbeta; CC IsoId=P97474-5; Sequence=VSP_031521; CC Note=Produced by alternative initiation at Met-35 of isoform CC Ptx2C.; CC -!- TISSUE SPECIFICITY: In day-11 embryos, expressed in the periocular CC mesenchyme, maxillary and mandibular epithelia, umbilicus, Rathke CC pouch, vitelline vessels and limb mesenchyme. In adult tissues, CC expressed in pituitary gland, brain, kidney, eye, lung, testis and CC tongue. CC -!- DEVELOPMENTAL STAGE: Expressed in the embryonic heart. Expressed CC in the left lateral plate mesoderm and symmetrically in the head CC mesoderm at 8.5 dpc. Isoform Ptx2c is expressed in the ventral CC outflow tract region (OFT), right ventricle (RV) and in the left CC atrium of the heart. {ECO:0000269|PubMed:15475956}. CC -!- PTM: Phosphorylation at Thr-90 impairs its association with the CC CCND1 mRNA-stabilizing complex thus shortening the half-life of CC CCND1. {ECO:0000269|PubMed:20019746}. CC -!- DISRUPTION PHENOTYPE: Mice embryos lacking isoform Ptx2c show CC left-right patterning defects and severe developmental CC abnormalities. {ECO:0000269|PubMed:15475956}. CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid CC subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF44618.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U80036; AAB38505.1; -; mRNA. DR EMBL; U80010; AAC53119.1; -; mRNA. DR EMBL; U80011; AAC53120.1; -; mRNA. DR EMBL; AB006320; BAA75247.1; -; mRNA. DR EMBL; AB006321; BAA75248.1; -; mRNA. DR EMBL; AF048723; AAC40086.1; -; mRNA. DR EMBL; AF048724; AAC40087.1; -; mRNA. DR EMBL; AJ243597; CAB65259.1; -; mRNA. DR EMBL; AF201091; AAF44618.1; ALT_INIT; mRNA. DR EMBL; U70132; AAB38864.1; -; mRNA. DR CCDS; CCDS17830.1; -. [P97474-1] DR CCDS; CCDS38630.1; -. [P97474-3] DR CCDS; CCDS38631.1; -. [P97474-2] DR CCDS; CCDS71316.1; -. [P97474-4] DR RefSeq; NP_001035967.1; NM_001042502.2. [P97474-2] DR RefSeq; NP_001035969.1; NM_001042504.2. [P97474-3] DR RefSeq; NP_035228.2; NM_011098.4. [P97474-1] DR RefSeq; XP_006501194.1; XM_006501131.3. [P97474-1] DR RefSeq; XP_006501195.1; XM_006501132.2. [P97474-3] DR RefSeq; XP_006501196.1; XM_006501133.1. [P97474-3] DR UniGene; Mm.246804; -. DR ProteinModelPortal; P97474; -. DR SMR; P97474; -. DR BioGrid; 202187; 3. DR DIP; DIP-37454N; -. DR IntAct; P97474; 1. DR STRING; 10090.ENSMUSP00000047359; -. DR iPTMnet; P97474; -. DR PhosphoSitePlus; P97474; -. DR PaxDb; P97474; -. DR PRIDE; P97474; -. DR Ensembl; ENSMUST00000042587; ENSMUSP00000047359; ENSMUSG00000028023. [P97474-2] DR Ensembl; ENSMUST00000106382; ENSMUSP00000101990; ENSMUSG00000028023. [P97474-3] DR Ensembl; ENSMUST00000172645; ENSMUSP00000134692; ENSMUSG00000028023. [P97474-4] DR Ensembl; ENSMUST00000174661; ENSMUSP00000133756; ENSMUSG00000028023. [P97474-1] DR GeneID; 18741; -. DR KEGG; mmu:18741; -. DR UCSC; uc008rhu.2; mouse. [P97474-1] DR UCSC; uc008rhv.2; mouse. [P97474-3] DR CTD; 5308; -. DR MGI; MGI:109340; Pitx2. DR eggNOG; KOG0486; Eukaryota. DR eggNOG; ENOG410ZZ6J; LUCA. DR GeneTree; ENSGT00820000126963; -. DR HOVERGEN; HBG068770; -. DR InParanoid; P97474; -. DR KO; K04686; -. DR OMA; PLNIDHH; -. DR PhylomeDB; P97474; -. DR TreeFam; TF351940; -. DR PRO; PR:P97474; -. DR Proteomes; UP000000589; Chromosome 3. DR Bgee; ENSMUSG00000028023; -. DR CleanEx; MM_PITX2; -. DR ExpressionAtlas; P97474; baseline and differential. DR Genevisible; P97474; MM. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0005667; C:transcription factor complex; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0001105; F:RNA polymerase II transcription coactivator activity; ISO:MGI. DR GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IDA:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:MGI. DR GO; GO:0008134; F:transcription factor binding; ISO:MGI. DR GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl. DR GO; GO:0009653; P:anatomical structure morphogenesis; IMP:MGI. DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI. DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IMP:MGI. DR GO; GO:0003171; P:atrioventricular valve development; IMP:MGI. DR GO; GO:0043010; P:camera-type eye development; ISO:MGI. DR GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:MGI. DR GO; GO:0048738; P:cardiac muscle tissue development; IMP:MGI. DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IMP:BHF-UCL. DR GO; GO:0061325; P:cell proliferation involved in outflow tract morphogenesis; IMP:BHF-UCL. DR GO; GO:0035993; P:deltoid tuberosity development; IMP:BHF-UCL. DR GO; GO:0007368; P:determination of left/right symmetry; IMP:BHF-UCL. DR GO; GO:0055123; P:digestive system development; IMP:MGI. DR GO; GO:0031076; P:embryonic camera-type eye development; IMP:MGI. DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IMP:MGI. DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IGI:MGI. DR GO; GO:0061031; P:endodermal digestive tract morphogenesis; IMP:MGI. DR GO; GO:0002074; P:extraocular skeletal muscle development; IMP:MGI. DR GO; GO:0008585; P:female gonad development; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IMP:MGI. DR GO; GO:0021855; P:hypothalamus cell migration; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0061072; P:iris morphogenesis; ISO:MGI. DR GO; GO:0060460; P:left lung morphogenesis; IMP:MGI. DR GO; GO:0070986; P:left/right axis specification; IMP:BHF-UCL. DR GO; GO:0030324; P:lung development; IMP:MGI. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0007520; P:myoblast fusion; IDA:MGI. DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IMP:MGI. DR GO; GO:0042476; P:odontogenesis; IMP:MGI. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0001569; P:patterning of blood vessels; IMP:MGI. DR GO; GO:0021983; P:pituitary gland development; IMP:MGI. DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:MGI. DR GO; GO:2000288; P:positive regulation of myoblast proliferation; IDA:MGI. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:MGI. DR GO; GO:0003350; P:pulmonary myocardium development; IMP:MGI. DR GO; GO:0060577; P:pulmonary vein morphogenesis; IMP:MGI. DR GO; GO:0030334; P:regulation of cell migration; IMP:MGI. DR GO; GO:0042127; P:regulation of cell proliferation; IMP:MGI. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IGI:MGI. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI. DR GO; GO:0009725; P:response to hormone; IEA:Ensembl. DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl. DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:MGI. DR GO; GO:0048536; P:spleen development; IMP:BHF-UCL. DR GO; GO:0021763; P:subthalamic nucleus development; IMP:MGI. DR GO; GO:0060578; P:superior vena cava morphogenesis; IMP:MGI. DR GO; GO:0035886; P:vascular smooth muscle cell differentiation; IMP:MGI. DR GO; GO:0001570; P:vasculogenesis; IMP:MGI. DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IMP:MGI. DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:MGI. DR GO; GO:0016055; P:Wnt signaling pathway; IDA:MGI. DR Gene3D; 1.10.10.60; -; 1. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR016233; Homeobox_Pitx/unc30. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR003654; OAR_dom. DR Pfam; PF00046; Homeobox; 1. DR Pfam; PF03826; OAR; 1. DR PIRSF; PIRSF000563; Homeobox_protein_Pitx/Unc30; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS50803; OAR; 1. PE 1: Evidence at protein level; KW Alternative initiation; Alternative splicing; Complete proteome; KW Developmental protein; DNA-binding; Homeobox; Nucleus; Phosphoprotein; KW Reference proteome. FT CHAIN 1 317 Pituitary homeobox 2. FT /FTId=PRO_0000049224. FT DNA_BIND 85 144 Homeobox. {ECO:0000255|PROSITE- FT ProRule:PRU00108}. FT MOTIF 279 292 OAR. {ECO:0000255|PROSITE- FT ProRule:PRU00138}. FT MOTIF 285 289 Nuclear localization signal. FT {ECO:0000255}. FT MOD_RES 90 90 Phosphothreonine; by PKB/AKT2. FT {ECO:0000250}. FT VAR_SEQ 1 61 METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSP FT KSRKESASSKLFPRQHPGAN -> MASVLAPGQPRSLDSSK FT HRLEVHTISDTSSPEVA (in isoform FT Pitx2Cbeta). {ECO:0000305}. FT /FTId=VSP_031521. FT VAR_SEQ 1 61 METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSP FT KSRKESASSKLFPRQHPGAN -> MNCMKGPLPLEHRAAGT FT KLSAASSPFCHHPQALAMASVLAPGQPRSLDSSKHRLEVHT FT ISDTSSPEVA (in isoform Ptx2C). FT {ECO:0000303|PubMed:9347917, FT ECO:0000303|PubMed:9539779}. FT /FTId=VSP_002262. FT VAR_SEQ 16 61 Missing (in isoform Ptx2A). FT {ECO:0000303|PubMed:9147650, FT ECO:0000303|PubMed:9539779, FT ECO:0000303|Ref.1}. FT /FTId=VSP_002263. FT VAR_SEQ 16 28 Missing (in isoform Pitx2Calpha). FT {ECO:0000305}. FT /FTId=VSP_031522. FT CONFLICT 187 187 A -> T (in Ref. 3; BAA75247/BAA75248). FT {ECO:0000305}. SQ SEQUENCE 317 AA; 35321 MW; 188315708E6BD95D CRC64; METNCRKLVS ACVQLGVQPA AVECLFSKDS EIKKVEFTDS PKSRKESASS KLFPRQHPGA NEKDKGQQGK NEDVGAEDPS KKKRQRRQRT HFTSQQLQEL EATFQRNRYP DMSTREEIAV WTNLTEARVR VWFKNRRAKW RKRERNQQAE LCKNGFGPQF NGLMQPYDDM YPGYSYNNWA AKGLTSASLS TKSFPFFNSM NVNPLSSQSM FSPPNSISSM SMSSSMVPSA VTGVPGSSLN SLNNLNNLSS PSLNSAVPTP ACPYAPPTPP YVYRDTCNSS LASLRLKAKQ HSSFGYASVQ NPASNLSACQ YAVDRPV //