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P97474 (PITX2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pituitary homeobox 2
Alternative name(s):
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
Gene names
Name:Pitx2
Synonyms:Arp1, Brx1, Otlx2, Ptx2, Rgs
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length317 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 Ptx2cis involved in left-right asymmetry the developing embryo. Ref.10

Subcellular location

Nucleus.

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 Ptx2cis expressed in the ventral outflow tract region (OFT), right ventricle (RV) and in the left atrium of the heart. Ref.9

Post-translational modification

Phosphorylation at Thr-90 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1.

Disruption phenotype

Mice embryos lacking isoform Ptx2cshow left-right patterning defects and severe developmental abnormalities. Ref.9

Sequence similarities

Belongs to the paired homeobox family. Bicoid subfamily.

Contains 1 homeobox DNA-binding domain.

Sequence caution

The sequence AAF44618.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityAlternative initiation
Alternative splicing
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from direct assay PubMed 12464179. Source: MGI

anatomical structure morphogenesis

Inferred from mutant phenotype PubMed 10499585. Source: MGI

atrial cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 11493526. Source: MGI

atrioventricular valve development

Inferred from mutant phenotype PubMed 18292603. Source: MGI

cardiac muscle cell differentiation

Inferred from mutant phenotype PubMed 12397115PubMed 17234970. Source: MGI

cardiac muscle tissue development

Inferred from mutant phenotype PubMed 16836994. Source: MGI

cardiac neural crest cell migration involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 12464179. Source: BHF-UCL

cell proliferation involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 12464179. Source: BHF-UCL

deltoid tuberosity development

Inferred from mutant phenotype PubMed 18312615. Source: BHF-UCL

determination of left/right symmetry

Inferred from mutant phenotype PubMed 9708732. Source: BHF-UCL

digestive system development

Inferred from mutant phenotype PubMed 11493526. Source: MGI

embryonic camera-type eye development

Inferred from mutant phenotype PubMed 10498698PubMed 10572050. Source: MGI

embryonic digestive tract morphogenesis

Inferred from mutant phenotype PubMed 21550054. Source: MGI

embryonic hindlimb morphogenesis

Inferred from genetic interaction PubMed 18231602. Source: MGI

endodermal digestive tract morphogenesis

Inferred from mutant phenotype PubMed 21550054. Source: MGI

extraocular skeletal muscle development

Inferred from mutant phenotype PubMed 16638982PubMed 21035439. Source: MGI

female gonad development

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from mutant phenotype PubMed 10498698PubMed 10499585PubMed 10572050PubMed 11493526PubMed 12397115PubMed 12464179. Source: MGI

hypothalamus cell migration

Inferred from mutant phenotype PubMed 18206388. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 11493526. Source: MGI

iris morphogenesis

Inferred from electronic annotation. Source: Ensembl

left lung morphogenesis

Inferred from mutant phenotype PubMed 11493526. Source: MGI

left/right axis specification

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

lung development

Inferred from mutant phenotype PubMed 10498698PubMed 10499586PubMed 10572050PubMed 18231602. Source: MGI

male gonad development

Inferred from electronic annotation. Source: Ensembl

myoblast fusion

Inferred from direct assay PubMed 16958127. Source: MGI

neuron differentiation

Inferred from electronic annotation. Source: Ensembl

neuron migration

Inferred from mutant phenotype PubMed 18206388. Source: MGI

odontogenesis

Inferred from mutant phenotype PubMed 10498698PubMed 10499586. Source: MGI

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Inferred from mutant phenotype PubMed 10572050. Source: MGI

patterning of blood vessels

Inferred from mutant phenotype PubMed 12397115. Source: MGI

pituitary gland development

Inferred from mutant phenotype PubMed 10498698PubMed 10499586. Source: MGI

positive regulation of DNA binding

Inferred from direct assay PubMed 18458156PubMed 21035439. Source: MGI

positive regulation of myoblast proliferation

Inferred from direct assay PubMed 16958127. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 11157981PubMed 18458156. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 17767158. Source: MGI

pulmonary myocardium development

Inferred from mutant phenotype PubMed 17823370. Source: MGI

pulmonary vein morphogenesis

Inferred from mutant phenotype PubMed 11493526. Source: MGI

regulation of cell migration

Inferred from mutant phenotype PubMed 12397115. Source: MGI

regulation of cell proliferation

Inferred from mutant phenotype PubMed 12464179. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 20816801. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12464179. Source: MGI

response to hormone

Inferred from electronic annotation. Source: Ensembl

response to vitamin A

Inferred from electronic annotation. Source: Ensembl

skeletal muscle tissue development

Inferred from mutant phenotype PubMed 10572050. Source: MGI

spleen development

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

subthalamic nucleus development

Inferred from mutant phenotype PubMed 18206388. Source: MGI

superior vena cava morphogenesis

Inferred from mutant phenotype PubMed 11493526. Source: MGI

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 18458156PubMed 21035439. Source: GOC

vascular smooth muscle cell differentiation

Inferred from mutant phenotype PubMed 18458156. Source: MGI

vasculogenesis

Inferred from mutant phenotype PubMed 18231602. Source: MGI

ventricular cardiac muscle cell development

Inferred from mutant phenotype PubMed 18292603. Source: MGI

ventricular septum morphogenesis

Inferred from mutant phenotype PubMed 18292603. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 19531352. Source: MGI

nucleus

Inferred from direct assay PubMed 10822271PubMed 18458156PubMed 19531352. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 12464179. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 18458156. Source: MGI

RNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription coactivator activity

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription

Inferred from electronic annotation. Source: Ensembl

chromatin DNA binding

Inferred from direct assay PubMed 21035439. Source: MGI

chromatin binding

Inferred from direct assay PubMed 11157981PubMed 17767158. Source: MGI

protein binding

Inferred from physical interaction PubMed 12464179PubMed 18458156PubMed 20816801. Source: MGI

sequence-specific DNA binding

Inferred from direct assay PubMed 20816801. Source: MGI

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay PubMed 18458156PubMed 21035439. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 11157981PubMed 12464179. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform Ptx2B (identifier: P97474-1)

Also known as: ARP1B; BRX1B;

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.
Isoform Ptx2C (identifier: P97474-2)

Also known as: ARP1C; BRX1A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: METNCRKLVS...LFPRQHPGAN → MNCMKGPLPL...ISDTSSPEVA
Isoform Ptx2A (identifier: P97474-3)

Also known as: ARP1A;

The sequence of this isoform differs from the canonical sequence as follows:
     16-61: Missing.
Isoform Pitx2Calpha (identifier: P97474-4)

The sequence of this isoform differs from the canonical sequence as follows:
     16-28: Missing.
Isoform Pitx2Cbeta (identifier: P97474-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: METNCRKLVS...LFPRQHPGAN → MASVLAPGQPRSLDSSKHRLEVHTISDTSSPEVA
Note: Produced by alternative initiation at Met-35 of isoform Ptx2C.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 317317Pituitary homeobox 2
PRO_0000049224

Regions

DNA binding85 – 14460Homeobox
Motif279 – 29214OAR
Motif285 – 2895Nuclear localization signal Potential

Amino acid modifications

Modified residue901Phosphothreonine; by PKB/AKT2 By similarity

Natural variations

Alternative sequence1 – 6161METNC…HPGAN → MASVLAPGQPRSLDSSKHRL EVHTISDTSSPEVA in isoform Pitx2Cbeta.
VSP_031521
Alternative sequence1 – 6161METNC…HPGAN → MNCMKGPLPLEHRAAGTKLS AASSPFCHHPQALAMASVLA PGQPRSLDSSKHRLEVHTIS DTSSPEVA in isoform Ptx2C.
VSP_002262
Alternative sequence16 – 6146Missing in isoform Ptx2A.
VSP_002263
Alternative sequence16 – 2813Missing in isoform Pitx2Calpha.
VSP_031522

Experimental info

Sequence conflict1871A → T in BAA75247. Ref.3
Sequence conflict1871A → T in BAA75248. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform Ptx2B (ARP1B) (BRX1B) [UniParc].

Last modified July 15, 1999. Version 2.
Checksum: 188315708E6BD95D

FASTA31735,321
        10         20         30         40         50         60 
METNCRKLVS ACVQLGVQPA AVECLFSKDS EIKKVEFTDS PKSRKESASS KLFPRQHPGA 

        70         80         90        100        110        120 
NEKDKGQQGK NEDVGAEDPS KKKRQRRQRT HFTSQQLQEL EATFQRNRYP DMSTREEIAV 

       130        140        150        160        170        180 
WTNLTEARVR VWFKNRRAKW RKRERNQQAE LCKNGFGPQF NGLMQPYDDM YPGYSYNNWA 

       190        200        210        220        230        240 
AKGLTSASLS TKSFPFFNSM NVNPLSSQSM FSPPNSISSM SMSSSMVPSA VTGVPGSSLN 

       250        260        270        280        290        300 
SLNNLNNLSS PSLNSAVPTP ACPYAPPTPP YVYRDTCNSS LASLRLKAKQ HSSFGYASVQ 

       310 
NPASNLSACQ YAVDRPV 

« Hide

Isoform Ptx2C (ARP1C) (BRX1A) [UniParc].

Checksum: 3D574CE3136A2159
Show »

FASTA32435,770
Isoform Ptx2A (ARP1A) [UniParc].

Checksum: F1D2ADA39B03FF6C
Show »

FASTA27130,306
Isoform Pitx2Calpha [UniParc].

Checksum: DFEA0CDF492CF8B4
Show »

FASTA30433,990
Isoform Pitx2Cbeta [UniParc].

Checksum: 997DC30E88513A48
Show »

FASTA29032,215

References

[1]Mucchielli M.L., Martinez S., Pattyn A., Goridis C., Brunet J.-F.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PTX2A).
[2]"Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation."
Gage P.J., Camper S.A.
Hum. Mol. Genet. 6:457-464(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2A AND PTX2B).
Tissue: Pituitary.
[3]"Expression patterns of Brx1 (Rieg gene), Sonic hedgehog, Nkx2.2, Dlx1 and Arx during zona limitans intrathalamica and embryonic ventral lateral geniculate nuclear formation."
Kitamura K., Miura H., Yanazawa M., Miyashita T., Kato K.
Mech. Dev. 67:83-96(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2B AND PTX2C).
[4]"Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene."
Arakawa H., Nakamura T., Zhadanov A.B., Fidanza Y., Yano T., Bullrich F., Shimizu M., Blechman J., Mazo A., Canaani E., Croce C.M.
Proc. Natl. Acad. Sci. U.S.A. 95:4573-4578(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PTX2A AND PTX2C).
[5]"Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in vertebrate left-right asymmetry."
Schweickert A., Campione M., Steinbeisser H., Blum M.
Mech. Dev. 90:41-51(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM PTX2C).
[6]"Cloning and expression of Munc 30: a member of the paired-like homeodomain gene family."
Nicholson L.F.B., Ma L., Goulding M.
Cell Biol. Int. 25:351-365(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM PTX2C).
[7]"Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome."
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.
Nat. Genet. 14:392-399(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 63-317.
Tissue: Embryonic carcinoma.
[8]"Novel forms of paired-like homeodomain transcription factor 2 (PITX2): generation by alternative translation initiation and mRNA splicing."
Lamba P., Hjalt T.A., Bernard D.J.
Unpublished observations (JAN-2008)
Cited for: ALTERNATIVE SPLICING (ISOFORM PITX2CALPHA) AND ALTERNATIVE INITIATION (ISOFORM PITX2CBETA).
[9]"Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway."
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.
Nat. Genet. 36:1189-1196(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
[10]"Akt2-mediated phosphorylation of Pitx2 controls Ccnd1 mRNA decay during muscle cell differentiation."
Gherzi R., Trabucchi M., Ponassi M., Gallouzi I.E., Rosenfeld M.G., Briata P.
Cell Death Differ. 17:975-983(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-90, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U80036 mRNA. Translation: AAB38505.1.
U80010 mRNA. Translation: AAC53119.1.
U80011 mRNA. Translation: AAC53120.1.
AB006320 mRNA. Translation: BAA75247.1.
AB006321 mRNA. Translation: BAA75248.1.
AF048723 mRNA. Translation: AAC40086.1.
AF048724 mRNA. Translation: AAC40087.1.
AJ243597 mRNA. Translation: CAB65259.1.
AF201091 mRNA. Translation: AAF44618.1. Different initiation.
U70132 mRNA. Translation: AAB38864.1.
CCDSCCDS17830.1. [P97474-1]
CCDS38630.1. [P97474-3]
CCDS38631.1. [P97474-2]
CCDS71316.1. [P97474-4]
RefSeqNP_001035967.1. NM_001042502.2. [P97474-2]
NP_001035969.1. NM_001042504.2. [P97474-3]
NP_035228.2. NM_011098.4. [P97474-1]
XP_006501194.1. XM_006501131.1. [P97474-1]
XP_006501195.1. XM_006501132.1. [P97474-3]
XP_006501196.1. XM_006501133.1. [P97474-3]
UniGeneMm.246804.

3D structure databases

ProteinModelPortalP97474.
SMRP97474. Positions 14-144.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202187. 3 interactions.
IntActP97474. 1 interaction.

Proteomic databases

PRIDEP97474.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000042587; ENSMUSP00000047359; ENSMUSG00000028023. [P97474-2]
ENSMUST00000106382; ENSMUSP00000101990; ENSMUSG00000028023. [P97474-3]
ENSMUST00000172645; ENSMUSP00000134692; ENSMUSG00000028023. [P97474-4]
ENSMUST00000174661; ENSMUSP00000133756; ENSMUSG00000028023. [P97474-1]
GeneID18741.
KEGGmmu:18741.
UCSCuc008rhu.1. mouse. [P97474-1]
uc008rhv.1. mouse. [P97474-3]

Organism-specific databases

CTD5308.
MGIMGI:109340. Pitx2.

Phylogenomic databases

eggNOGNOG249113.
GeneTreeENSGT00740000115425.
HOVERGENHBG068770.
KOK04686.
OMARINHSAR.
PhylomeDBP97474.
TreeFamTF351940.

Gene expression databases

ArrayExpressP97474.
BgeeP97474.
CleanExMM_PITX2.
GenevestigatorP97474.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR016233. Homeobox_Pitx/unc30.
IPR009057. Homeodomain-like.
IPR003654. OAR_dom.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
PF03826. OAR. 1 hit.
[Graphical view]
PIRSFPIRSF000563. Homeobox_protein_Pitx/Unc30. 1 hit.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS50803. OAR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294885.
PROP97474.
SOURCESearch...

Entry information

Entry namePITX2_MOUSE
AccessionPrimary (citable) accession number: P97474
Secondary accession number(s): O08646 expand/collapse secondary AC list , O70336, P97933, Q9JLA0, Q9QXB8, Q9R1V9, Q9Z141
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1999
Last modified: July 9, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot