PITX2_MOUSE
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 03-AUG-2022, entry version 187.
DE RecName: Full=Pituitary homeobox 2 {ECO:0000305};
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 {ECO:0000312|MGI:MGI:109340};
GN Synonyms=Arp1, Brx1, Otlx2, Ptx2, Rgs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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 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 and
RT Arx during zona limitans intrathalamica and embryonic ventral lateral
RT 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., Bullrich F.,
RA Shimizu M., Blechman J., Mazo A., Canaani E., Croce C.M.;
RT "Identification and characterization of the ARP1 gene, a target for the
RT 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 homeodomain
RT 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., Zabel B.U.,
RA 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 (PITX2):
RT generation by alternative translation initiation and mRNA 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., Broadbent C.,
RA Michell A.C., Clarke K., Neubauer S., Norris D., Brown N.A., Anderson R.H.,
RA 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 during
RT muscle cell differentiation.";
RL Cell Death Differ. 17:975-983(2010).
CC -!- FUNCTION: Controls cell proliferation in a tissue-specific manner and
CC is involved in morphogenesis. During embryonic development, exerts a
CC role in the expansion of muscle progenitors. May play a role in the
CC proper localization of asymmetric organs such as the heart and stomach.
CC Isoform Ptx2c is involved in left-right asymmetry the developing
CC embryo. {ECO:0000269|PubMed:20019746}.
CC -!- SUBUNIT: Interacts with PITX2. {ECO:0000250|UniProtKB:Q99697}.
CC -!- INTERACTION:
CC P97474; Q60795: Nfe2l2; NbExp=2; IntAct=EBI-1175125, EBI-642563;
CC P97474; P46938: Yap1; NbExp=2; IntAct=EBI-1175125, EBI-1211949;
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 -!- 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 in the
CC left lateral plate mesoderm and symmetrically in the head mesoderm at
CC 8.5 dpc. Isoform Ptx2c is expressed in the ventral outflow tract region
CC (OFT), right ventricle (RV) and in the left atrium of the heart.
CC {ECO:0000269|PubMed:15475956}.
CC -!- PTM: Phosphorylation at Thr-90 impairs its association with the CCND1
CC mRNA-stabilizing complex thus shortening the half-life of CCND1.
CC {ECO:0000269|PubMed:20019746}.
CC -!- DISRUPTION PHENOTYPE: Mice embryos lacking isoform Ptx2c show left-
CC right patterning defects and severe developmental abnormalities.
CC {ECO:0000269|PubMed:15475956}.
CC -!- MISCELLANEOUS: [Isoform Pitx2Cbeta]: Produced by alternative initiation
CC at Met-35 of isoform Ptx2C. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF44618.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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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 AlphaFoldDB; P97474; -.
DR BMRB; P97474; -.
DR BioGRID; 202187; 3.
DR DIP; DIP-37454N; -.
DR IntAct; P97474; 3.
DR STRING; 10090.ENSMUSP00000047359; -.
DR iPTMnet; P97474; -.
DR PhosphoSitePlus; P97474; -.
DR PaxDb; P97474; -.
DR PRIDE; P97474; -.
DR ProteomicsDB; 289582; -. [P97474-1]
DR ProteomicsDB; 289583; -. [P97474-2]
DR ProteomicsDB; 289584; -. [P97474-3]
DR ProteomicsDB; 289585; -. [P97474-4]
DR ProteomicsDB; 289586; -. [P97474-5]
DR DNASU; 18741; -.
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 VEuPathDB; HostDB:ENSMUSG00000028023; -.
DR eggNOG; KOG0486; Eukaryota.
DR GeneTree; ENSGT00940000154518; -.
DR HOGENOM; CLU_030301_0_0_1; -.
DR InParanoid; P97474; -.
DR OMA; NSMRNPL; -.
DR PhylomeDB; P97474; -.
DR TreeFam; TF351940; -.
DR BioGRID-ORCS; 18741; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Pitx2; mouse.
DR PRO; PR:P97474; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P97474; protein.
DR Bgee; ENSMUSG00000028023; Expressed in calcareous tooth and 278 other tissues.
DR ExpressionAtlas; P97474; baseline and differential.
DR Genevisible; P97474; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator 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:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
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:0001569; P:branching involved in blood vessel morphogenesis; 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:0060971; P:embryonic heart tube left/right pattern formation; IMP:BHF-UCL.
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:0000122; P:negative regulation of transcription by RNA polymerase II; ISO: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:0021983; P:pituitary gland development; IMP:MGI.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; 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 population proliferation; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO: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 associated 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 CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR016233; Homeobox_Pitx/unc30.
DR InterPro; IPR003654; OAR_dom.
DR Pfam; PF00046; Homeodomain; 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; Developmental protein;
KW DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..317
FT /note="Pituitary homeobox 2"
FT /id="PRO_0000049224"
FT DNA_BIND 85..144
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 35..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 279..292
FT /note="OAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT MOTIF 285..289
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 35..83
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 90
FT /note="Phosphothreonine; by PKB/AKT2"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..61
FT /note="METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSPKSRKESASSKL
FT FPRQHPGAN -> MASVLAPGQPRSLDSSKHRLEVHTISDTSSPEVA (in isoform
FT Pitx2Cbeta)"
FT /evidence="ECO:0000305"
FT /id="VSP_031521"
FT VAR_SEQ 1..61
FT /note="METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSPKSRKESASSKL
FT FPRQHPGAN -> MNCMKGPLPLEHRAAGTKLSAASSPFCHHPQALAMASVLAPGQPRS
FT LDSSKHRLEVHTISDTSSPEVA (in isoform Ptx2C)"
FT /evidence="ECO:0000303|PubMed:9347917,
FT ECO:0000303|PubMed:9539779"
FT /id="VSP_002262"
FT VAR_SEQ 16..61
FT /note="Missing (in isoform Ptx2A)"
FT /evidence="ECO:0000303|PubMed:9147650,
FT ECO:0000303|PubMed:9539779, ECO:0000303|Ref.1"
FT /id="VSP_002263"
FT VAR_SEQ 16..28
FT /note="Missing (in isoform Pitx2Calpha)"
FT /evidence="ECO:0000305"
FT /id="VSP_031522"
FT CONFLICT 187
FT /note="A -> T (in Ref. 3; BAA75247/BAA75248)"
FT /evidence="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
