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Pituitary homeobox 2 (ALL1-responsive protein ARP1) (BRX1 homeoprotein) (Homeobox protein PITX2) (Orthodenticle-like homeobox 2) (Paired-like homeodomain transcription factor 2) (Paired-like homeodomain transcription factor Munc 30) (Solurshin)

 PITX2_MOUSE             Reviewed;         317 AA.
P97474; O08646; O70336; P97933; Q9JLA0; Q9QXB8; Q9R1V9; Q9Z141;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
15-JUL-1999, sequence version 2.
22-NOV-2017, entry version 159.
RecName: Full=Pituitary homeobox 2;
AltName: Full=ALL1-responsive protein ARP1;
AltName: Full=BRX1 homeoprotein;
AltName: Full=Homeobox protein PITX2;
AltName: Full=Orthodenticle-like homeobox 2;
AltName: Full=Paired-like homeodomain transcription factor 2;
AltName: Full=Paired-like homeodomain transcription factor Munc 30;
AltName: Full=Solurshin;
Name=Pitx2; Synonyms=Arp1, Brx1, Otlx2, Ptx2, Rgs;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PTX2A).
Mucchielli M.L., Martinez S., Pattyn A., Goridis C., Brunet J.-F.;
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2A AND PTX2B).
TISSUE=Pituitary;
PubMed=9147650; DOI=10.1093/hmg/6.3.457;
Gage P.J., Camper S.A.;
"Pituitary homeobox 2, a novel member of the bicoid-related family of
homeobox genes, is a potential regulator of anterior structure
formation.";
Hum. Mol. Genet. 6:457-464(1997).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2B AND PTX2C).
PubMed=9347917; DOI=10.1016/S0925-4773(97)00110-X;
Kitamura K., Miura H., Yanazawa M., Miyashita T., Kato K.;
"Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1
and Arx during zona limitans intrathalamica and embryonic ventral
lateral geniculate nuclear formation.";
Mech. Dev. 67:83-96(1997).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2A AND PTX2C).
PubMed=9539779; DOI=10.1073/pnas.95.8.4573;
Arakawa H., Nakamura T., Zhadanov A.B., Fidanza Y., Yano T.,
Bullrich F., Shimizu M., Blechman J., Mazo A., Canaani E., Croce C.M.;
"Identification and characterization of the ARP1 gene, a target for
the human acute leukemia ALL1 gene.";
Proc. Natl. Acad. Sci. U.S.A. 95:4573-4578(1998).
[5]
PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM PTX2C).
PubMed=10585561; DOI=10.1016/S0925-4773(99)00227-0;
Schweickert A., Campione M., Steinbeisser H., Blum M.;
"Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in
vertebrate left-right asymmetry.";
Mech. Dev. 90:41-51(2000).
[6]
PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM PTX2C).
PubMed=11319841; DOI=10.1006/cbir.2000.0638;
Nicholson L.F.B., Ma L., Goulding M.;
"Cloning and expression of Munc 30: a member of the paired-like
homeodomain gene family.";
Cell Biol. Int. 25:351-365(2001).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 63-317.
TISSUE=Embryonic carcinoma;
PubMed=8944018; DOI=10.1038/ng1296-392;
Semina E.V., Reiter R., Leysens N.J., Alward W.L.M., Small K.W.,
Datson N.A., Siegle-Bartelt J., Bierke-Nelson D., Bitoun P.,
Zabel B.U., Carey J.C., Murray J.C.;
"Cloning and characterization of a novel bicoid-related homeobox
transcription factor gene, RIEG, involved in Rieger syndrome.";
Nat. Genet. 14:392-399(1996).
[8]
ALTERNATIVE SPLICING (ISOFORM PITX2CALPHA) AND ALTERNATIVE INITIATION
(ISOFORM PITX2CBETA).
Lamba P., Hjalt T.A., Bernard D.J.;
"Novel forms of paired-like homeodomain transcription factor 2
(PITX2): generation by alternative translation initiation and mRNA
splicing.";
Unpublished observations (JAN-2008).
[9]
DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
PubMed=15475956; DOI=10.1038/ng1446;
Bamforth S.D., Braganca J., Farthing C.R., Schneider J.E.,
Broadbent C., Michell A.C., Clarke K., Neubauer S., Norris D.,
Brown N.A., Anderson R.H., Bhattacharya S.;
"Cited2 controls left-right patterning and heart development through a
Nodal-Pitx2c pathway.";
Nat. Genet. 36:1189-1196(2004).
[10]
PHOSPHORYLATION AT THR-90, AND FUNCTION.
PubMed=20019746; DOI=10.1038/cdd.2009.194;
Gherzi R., Trabucchi M., Ponassi M., Gallouzi I.E., Rosenfeld M.G.,
Briata P.;
"Akt2-mediated phosphorylation of Pitx2 controls Ccnd1 mRNA decay
during muscle cell differentiation.";
Cell Death Differ. 17:975-983(2010).
-!- FUNCTION: Controls cell proliferation in a tissue-specific manner
and is involved in morphogenesis. During embryonic development,
exerts a role in the expansion of muscle progenitors. May play a
role in the proper localization of asymmetric organs such as the
heart and stomach. Isoform Ptx2c is involved in left-right
asymmetry the developing embryo. {ECO:0000269|PubMed:20019746}.
-!- INTERACTION:
Q60795:Nfe2l2; NbExp=2; IntAct=EBI-1175125, EBI-642563;
P46938:Yap1; NbExp=2; IntAct=EBI-1175125, EBI-1211949;
-!- SUBCELLULAR LOCATION: Nucleus.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing, Alternative initiation; Named isoforms=5;
Name=Ptx2B; Synonyms=ARP1B, BRX1B;
IsoId=P97474-1; Sequence=Displayed;
Name=Ptx2C; Synonyms=ARP1C, BRX1A;
IsoId=P97474-2; Sequence=VSP_002262;
Name=Ptx2A; Synonyms=ARP1A;
IsoId=P97474-3; Sequence=VSP_002263;
Name=Pitx2Calpha;
IsoId=P97474-4; Sequence=VSP_031522;
Name=Pitx2Cbeta;
IsoId=P97474-5; Sequence=VSP_031521;
Note=Produced by alternative initiation at Met-35 of isoform
Ptx2C.;
-!- TISSUE SPECIFICITY: In day-11 embryos, expressed in the periocular
mesenchyme, maxillary and mandibular epithelia, umbilicus, Rathke
pouch, vitelline vessels and limb mesenchyme. In adult tissues,
expressed in pituitary gland, brain, kidney, eye, lung, testis and
tongue.
-!- DEVELOPMENTAL STAGE: Expressed in the embryonic heart. Expressed
in the left lateral plate mesoderm and symmetrically in the head
mesoderm at 8.5 dpc. Isoform Ptx2c is expressed in the ventral
outflow tract region (OFT), right ventricle (RV) and in the left
atrium of the heart. {ECO:0000269|PubMed:15475956}.
-!- PTM: Phosphorylation at Thr-90 impairs its association with the
CCND1 mRNA-stabilizing complex thus shortening the half-life of
CCND1. {ECO:0000269|PubMed:20019746}.
-!- DISRUPTION PHENOTYPE: Mice embryos lacking isoform Ptx2c show
left-right patterning defects and severe developmental
abnormalities. {ECO:0000269|PubMed:15475956}.
-!- SIMILARITY: Belongs to the paired homeobox family. Bicoid
subfamily. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAF44618.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; U80036; AAB38505.1; -; mRNA.
EMBL; U80010; AAC53119.1; -; mRNA.
EMBL; U80011; AAC53120.1; -; mRNA.
EMBL; AB006320; BAA75247.1; -; mRNA.
EMBL; AB006321; BAA75248.1; -; mRNA.
EMBL; AF048723; AAC40086.1; -; mRNA.
EMBL; AF048724; AAC40087.1; -; mRNA.
EMBL; AJ243597; CAB65259.1; -; mRNA.
EMBL; AF201091; AAF44618.1; ALT_INIT; mRNA.
EMBL; U70132; AAB38864.1; -; mRNA.
CCDS; CCDS17830.1; -. [P97474-1]
CCDS; CCDS38630.1; -. [P97474-3]
CCDS; CCDS38631.1; -. [P97474-2]
CCDS; CCDS71316.1; -. [P97474-4]
RefSeq; NP_001035967.1; NM_001042502.2. [P97474-2]
RefSeq; NP_001035969.1; NM_001042504.2. [P97474-3]
RefSeq; NP_035228.2; NM_011098.4. [P97474-1]
RefSeq; XP_006501194.1; XM_006501131.3. [P97474-1]
RefSeq; XP_006501195.1; XM_006501132.2. [P97474-3]
RefSeq; XP_006501196.1; XM_006501133.1. [P97474-3]
UniGene; Mm.246804; -.
ProteinModelPortal; P97474; -.
SMR; P97474; -.
BioGrid; 202187; 3.
DIP; DIP-37454N; -.
IntAct; P97474; 3.
STRING; 10090.ENSMUSP00000047359; -.
iPTMnet; P97474; -.
PhosphoSitePlus; P97474; -.
PaxDb; P97474; -.
PRIDE; P97474; -.
Ensembl; ENSMUST00000042587; ENSMUSP00000047359; ENSMUSG00000028023. [P97474-2]
Ensembl; ENSMUST00000106382; ENSMUSP00000101990; ENSMUSG00000028023. [P97474-3]
Ensembl; ENSMUST00000172645; ENSMUSP00000134692; ENSMUSG00000028023. [P97474-4]
Ensembl; ENSMUST00000174661; ENSMUSP00000133756; ENSMUSG00000028023. [P97474-1]
GeneID; 18741; -.
KEGG; mmu:18741; -.
UCSC; uc008rhu.2; mouse. [P97474-1]
UCSC; uc008rhv.2; mouse. [P97474-3]
CTD; 5308; -.
MGI; MGI:109340; Pitx2.
eggNOG; KOG0486; Eukaryota.
eggNOG; ENOG410ZZ6J; LUCA.
GeneTree; ENSGT00900000140776; -.
HOVERGEN; HBG068770; -.
InParanoid; P97474; -.
KO; K04686; -.
OMA; PLNIDHH; -.
PhylomeDB; P97474; -.
TreeFam; TF351940; -.
PRO; PR:P97474; -.
Proteomes; UP000000589; Chromosome 3.
Bgee; ENSMUSG00000028023; -.
CleanEx; MM_PITX2; -.
ExpressionAtlas; P97474; baseline and differential.
Genevisible; P97474; MM.
GO; GO:0005737; C:cytoplasm; IDA:MGI.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0005667; C:transcription factor complex; IDA:MGI.
GO; GO:0003682; F:chromatin binding; IDA:MGI.
GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0042802; F:identical protein binding; ISO:MGI.
GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; ISO:MGI.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0001105; F:RNA polymerase II transcription coactivator activity; ISO:MGI.
GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IDA:MGI.
GO; GO:0001085; F:RNA polymerase II transcription factor binding; ISO:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:MGI.
GO; GO:0008134; F:transcription factor binding; ISO:MGI.
GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; ISO:MGI.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISO:MGI.
GO; GO:0001191; F:transcriptional repressor activity, RNA polymerase II transcription factor binding; ISO:MGI.
GO; GO:0009653; P:anatomical structure morphogenesis; IMP:MGI.
GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IMP:MGI.
GO; GO:0003171; P:atrioventricular valve development; IMP:MGI.
GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:MGI.
GO; GO:0043010; P:camera-type eye development; ISO:MGI.
GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:MGI.
GO; GO:0048738; P:cardiac muscle tissue development; IMP:MGI.
GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IMP:BHF-UCL.
GO; GO:0061325; P:cell proliferation involved in outflow tract morphogenesis; IMP:BHF-UCL.
GO; GO:0035993; P:deltoid tuberosity development; IMP:BHF-UCL.
GO; GO:0007368; P:determination of left/right symmetry; IMP:BHF-UCL.
GO; GO:0055123; P:digestive system development; IMP:MGI.
GO; GO:0031076; P:embryonic camera-type eye development; IMP:MGI.
GO; GO:0048557; P:embryonic digestive tract morphogenesis; IMP:MGI.
GO; GO:0035116; P:embryonic hindlimb morphogenesis; IGI:MGI.
GO; GO:0061031; P:endodermal digestive tract morphogenesis; IMP:MGI.
GO; GO:0002074; P:extraocular skeletal muscle development; IMP:MGI.
GO; GO:0008585; P:female gonad development; IEA:Ensembl.
GO; GO:0007507; P:heart development; IMP:MGI.
GO; GO:0021855; P:hypothalamus cell migration; IMP:MGI.
GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
GO; GO:0061072; P:iris morphogenesis; ISO:MGI.
GO; GO:0060460; P:left lung morphogenesis; IMP:MGI.
GO; GO:0070986; P:left/right axis specification; IMP:BHF-UCL.
GO; GO:0030324; P:lung development; IMP:MGI.
GO; GO:0008584; P:male gonad development; IEA:Ensembl.
GO; GO:0007520; P:myoblast fusion; IDA:MGI.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISO:MGI.
GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
GO; GO:0001764; P:neuron migration; IMP:MGI.
GO; GO:0042476; P:odontogenesis; IMP:MGI.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
GO; GO:0021983; P:pituitary gland development; IMP:MGI.
GO; GO:0043388; P:positive regulation of DNA binding; IDA:MGI.
GO; GO:2000288; P:positive regulation of myoblast proliferation; IDA:MGI.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:MGI.
GO; GO:0003350; P:pulmonary myocardium development; IMP:MGI.
GO; GO:0060577; P:pulmonary vein morphogenesis; IMP:MGI.
GO; GO:0030334; P:regulation of cell migration; IMP:MGI.
GO; GO:0042127; P:regulation of cell proliferation; IMP:MGI.
GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IGI:MGI.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
GO; GO:0009725; P:response to hormone; IEA:Ensembl.
GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
GO; GO:0007519; P:skeletal muscle tissue development; IMP:MGI.
GO; GO:0048536; P:spleen development; IMP:BHF-UCL.
GO; GO:0021763; P:subthalamic nucleus development; IMP:MGI.
GO; GO:0060578; P:superior vena cava morphogenesis; IMP:MGI.
GO; GO:0035886; P:vascular smooth muscle cell differentiation; IMP:MGI.
GO; GO:0001570; P:vasculogenesis; IMP:MGI.
GO; GO:0055015; P:ventricular cardiac muscle cell development; IMP:MGI.
GO; GO:0060412; P:ventricular septum morphogenesis; IMP:MGI.
GO; GO:0016055; P:Wnt signaling pathway; IDA:MGI.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR016233; Homeobox_Pitx/unc30.
InterPro; IPR003654; OAR_dom.
Pfam; PF00046; Homeobox; 1.
Pfam; PF03826; OAR; 1.
PIRSF; PIRSF000563; Homeobox_protein_Pitx/Unc30; 1.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
PROSITE; PS50803; OAR; 1.
1: Evidence at protein level;
Alternative initiation; Alternative splicing; Complete proteome;
Developmental protein; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
Reference proteome.
CHAIN 1 317 Pituitary homeobox 2.
/FTId=PRO_0000049224.
DNA_BIND 85 144 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
MOTIF 279 292 OAR. {ECO:0000255|PROSITE-
ProRule:PRU00138}.
MOTIF 285 289 Nuclear localization signal.
{ECO:0000255}.
MOD_RES 90 90 Phosphothreonine; by PKB/AKT2.
{ECO:0000250}.
VAR_SEQ 1 61 METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSP
KSRKESASSKLFPRQHPGAN -> MASVLAPGQPRSLDSSK
HRLEVHTISDTSSPEVA (in isoform
Pitx2Cbeta). {ECO:0000305}.
/FTId=VSP_031521.
VAR_SEQ 1 61 METNCRKLVSACVQLGVQPAAVECLFSKDSEIKKVEFTDSP
KSRKESASSKLFPRQHPGAN -> MNCMKGPLPLEHRAAGT
KLSAASSPFCHHPQALAMASVLAPGQPRSLDSSKHRLEVHT
ISDTSSPEVA (in isoform Ptx2C).
{ECO:0000303|PubMed:9347917,
ECO:0000303|PubMed:9539779}.
/FTId=VSP_002262.
VAR_SEQ 16 61 Missing (in isoform Ptx2A).
{ECO:0000303|PubMed:9147650,
ECO:0000303|PubMed:9539779,
ECO:0000303|Ref.1}.
/FTId=VSP_002263.
VAR_SEQ 16 28 Missing (in isoform Pitx2Calpha).
{ECO:0000305}.
/FTId=VSP_031522.
CONFLICT 187 187 A -> T (in Ref. 3; BAA75247/BAA75248).
{ECO:0000305}.
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


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