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P97474

- PITX2_MOUSE

UniProt

P97474 - PITX2_MOUSE

Protein

Pituitary homeobox 2

Gene

Pitx2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 2 (15 Jul 1999)
      Previous versions | rss
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    Functioni

    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.1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi85 – 14460HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: MGI
    2. chromatin DNA binding Source: MGI
    3. DNA binding Source: MGI
    4. protein binding Source: MGI
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
    6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: Ensembl
    7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
    8. RNA polymerase II transcription coactivator activity Source: Ensembl
    9. RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Source: Ensembl
    10. sequence-specific DNA binding Source: MGI
    11. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: MGI
    12. sequence-specific DNA binding transcription factor activity Source: MGI

    GO - Biological processi

    1. anatomical structure morphogenesis Source: MGI
    2. atrial cardiac muscle tissue morphogenesis Source: MGI
    3. atrioventricular valve development Source: MGI
    4. cardiac muscle cell differentiation Source: MGI
    5. cardiac muscle tissue development Source: MGI
    6. cardiac neural crest cell migration involved in outflow tract morphogenesis Source: BHF-UCL
    7. cell proliferation involved in outflow tract morphogenesis Source: BHF-UCL
    8. deltoid tuberosity development Source: BHF-UCL
    9. determination of left/right symmetry Source: BHF-UCL
    10. digestive system development Source: MGI
    11. embryonic camera-type eye development Source: MGI
    12. embryonic digestive tract morphogenesis Source: MGI
    13. embryonic hindlimb morphogenesis Source: MGI
    14. endodermal digestive tract morphogenesis Source: MGI
    15. extraocular skeletal muscle development Source: MGI
    16. female gonad development Source: Ensembl
    17. heart development Source: MGI
    18. hypothalamus cell migration Source: MGI
    19. in utero embryonic development Source: MGI
    20. iris morphogenesis Source: Ensembl
    21. left/right axis specification Source: BHF-UCL
    22. left lung morphogenesis Source: MGI
    23. lung development Source: MGI
    24. male gonad development Source: Ensembl
    25. myoblast fusion Source: MGI
    26. neuron differentiation Source: Ensembl
    27. neuron migration Source: MGI
    28. odontogenesis Source: MGI
    29. odontogenesis of dentin-containing tooth Source: Ensembl
    30. organ morphogenesis Source: MGI
    31. patterning of blood vessels Source: MGI
    32. pituitary gland development Source: MGI
    33. positive regulation of DNA binding Source: MGI
    34. positive regulation of myoblast proliferation Source: MGI
    35. positive regulation of transcription, DNA-templated Source: MGI
    36. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    37. pulmonary myocardium development Source: MGI
    38. pulmonary vein morphogenesis Source: MGI
    39. regulation of cell migration Source: MGI
    40. regulation of cell proliferation Source: MGI
    41. regulation of transcription, DNA-templated Source: MGI
    42. regulation of transcription from RNA polymerase II promoter Source: MGI
    43. response to hormone Source: Ensembl
    44. response to vitamin A Source: Ensembl
    45. skeletal muscle tissue development Source: MGI
    46. spleen development Source: BHF-UCL
    47. subthalamic nucleus development Source: MGI
    48. superior vena cava morphogenesis Source: MGI
    49. transcription from RNA polymerase II promoter Source: GOC
    50. vascular smooth muscle cell differentiation Source: MGI
    51. vasculogenesis Source: MGI
    52. ventricular cardiac muscle cell development Source: MGI
    53. ventricular septum morphogenesis Source: MGI
    54. Wnt signaling pathway Source: MGI

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:Pitx2
    Synonyms:Arp1, Brx1, Otlx2, Ptx2, Rgs
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:109340. Pitx2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. nucleus Source: MGI
    3. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice embryos lacking isoform Ptx2c show left-right patterning defects and severe developmental abnormalities.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 317317Pituitary homeobox 2PRO_0000049224Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei90 – 901Phosphothreonine; by PKB/AKT2By similarity

    Post-translational modificationi

    Phosphorylation at Thr-90 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiP97474.

    Expressioni

    Tissue specificityi

    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 stagei

    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.1 Publication

    Gene expression databases

    ArrayExpressiP97474.
    BgeeiP97474.
    CleanExiMM_PITX2.
    GenevestigatoriP97474.

    Interactioni

    Protein-protein interaction databases

    BioGridi202187. 3 interactions.
    IntActiP97474. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliP97474.
    SMRiP97474. Positions 14-144.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi279 – 29214OARAdd
    BLAST
    Motifi285 – 2895Nuclear localization signalSequence Analysis

    Sequence similaritiesi

    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG249113.
    GeneTreeiENSGT00740000115425.
    HOVERGENiHBG068770.
    KOiK04686.
    OMAiRINHSAR.
    PhylomeDBiP97474.
    TreeFamiTF351940.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR016233. Homeobox_Pitx/unc30.
    IPR009057. Homeodomain-like.
    IPR003654. OAR_dom.
    [Graphical view]
    PfamiPF00046. Homeobox. 1 hit.
    PF03826. OAR. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000563. Homeobox_protein_Pitx/Unc30. 1 hit.
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    PS50803. OAR. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing and alternative initiation. Align

    Isoform Ptx2B (identifier: P97474-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    METNCRKLVS ACVQLGVQPA AVECLFSKDS EIKKVEFTDS PKSRKESASS    50
    KLFPRQHPGA NEKDKGQQGK NEDVGAEDPS KKKRQRRQRT HFTSQQLQEL 100
    EATFQRNRYP DMSTREEIAV WTNLTEARVR VWFKNRRAKW RKRERNQQAE 150
    LCKNGFGPQF NGLMQPYDDM YPGYSYNNWA AKGLTSASLS TKSFPFFNSM 200
    NVNPLSSQSM FSPPNSISSM SMSSSMVPSA VTGVPGSSLN SLNNLNNLSS 250
    PSLNSAVPTP ACPYAPPTPP YVYRDTCNSS LASLRLKAKQ HSSFGYASVQ 300
    NPASNLSACQ YAVDRPV 317
    Length:317
    Mass (Da):35,321
    Last modified:July 15, 1999 - v2
    Checksum:i188315708E6BD95D
    GO
    Isoform Ptx2C (identifier: P97474-2) [UniParc]FASTAAdd to Basket

    Also known as: ARP1C, BRX1A

    The sequence of this isoform differs from the canonical sequence as follows:
         1-61: METNCRKLVS...LFPRQHPGAN → MNCMKGPLPL...ISDTSSPEVA

    Show »
    Length:324
    Mass (Da):35,770
    Checksum:i3D574CE3136A2159
    GO
    Isoform Ptx2A (identifier: P97474-3) [UniParc]FASTAAdd to Basket

    Also known as: ARP1A

    The sequence of this isoform differs from the canonical sequence as follows:
         16-61: Missing.

    Show »
    Length:271
    Mass (Da):30,306
    Checksum:iF1D2ADA39B03FF6C
    GO
    Isoform Pitx2Calpha (identifier: P97474-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         16-28: Missing.

    Show »
    Length:304
    Mass (Da):33,990
    Checksum:iDFEA0CDF492CF8B4
    GO
    Isoform Pitx2Cbeta (identifier: P97474-5) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:290
    Mass (Da):32,215
    Checksum:i997DC30E88513A48
    GO

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti187 – 1871A → T in BAA75247. (PubMed:9347917)Curated
    Sequence conflicti187 – 1871A → T in BAA75248. (PubMed:9347917)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6161METNC…HPGAN → MASVLAPGQPRSLDSSKHRL EVHTISDTSSPEVA in isoform Pitx2Cbeta. CuratedVSP_031521Add
    BLAST
    Alternative sequencei1 – 6161METNC…HPGAN → MNCMKGPLPLEHRAAGTKLS AASSPFCHHPQALAMASVLA PGQPRSLDSSKHRLEVHTIS DTSSPEVA in isoform Ptx2C. 2 PublicationsVSP_002262Add
    BLAST
    Alternative sequencei16 – 6146Missing in isoform Ptx2A. 3 PublicationsVSP_002263Add
    BLAST
    Alternative sequencei16 – 2813Missing in isoform Pitx2Calpha. CuratedVSP_031522Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS17830.1. [P97474-1]
    CCDS38630.1. [P97474-3]
    CCDS38631.1. [P97474-2]
    CCDS71316.1. [P97474-4]
    RefSeqiNP_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]
    UniGeneiMm.246804.

    Genome annotation databases

    EnsembliENSMUST00000042587; ENSMUSP00000047359; ENSMUSG00000028023. [P97474-2]
    ENSMUST00000106382; ENSMUSP00000101990; ENSMUSG00000028023. [P97474-3]
    ENSMUST00000172645; ENSMUSP00000134692; ENSMUSG00000028023. [P97474-4]
    ENSMUST00000174661; ENSMUSP00000133756; ENSMUSG00000028023. [P97474-1]
    GeneIDi18741.
    KEGGimmu:18741.
    UCSCiuc008rhu.1. mouse. [P97474-1]
    uc008rhv.1. mouse. [P97474-3]

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS17830.1. [P97474-1 ]
    CCDS38630.1. [P97474-3 ]
    CCDS38631.1. [P97474-2 ]
    CCDS71316.1. [P97474-4 ]
    RefSeqi NP_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 ]
    UniGenei Mm.246804.

    3D structure databases

    ProteinModelPortali P97474.
    SMRi P97474. Positions 14-144.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202187. 3 interactions.
    IntActi P97474. 1 interaction.

    Proteomic databases

    PRIDEi P97474.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000042587 ; ENSMUSP00000047359 ; ENSMUSG00000028023 . [P97474-2 ]
    ENSMUST00000106382 ; ENSMUSP00000101990 ; ENSMUSG00000028023 . [P97474-3 ]
    ENSMUST00000172645 ; ENSMUSP00000134692 ; ENSMUSG00000028023 . [P97474-4 ]
    ENSMUST00000174661 ; ENSMUSP00000133756 ; ENSMUSG00000028023 . [P97474-1 ]
    GeneIDi 18741.
    KEGGi mmu:18741.
    UCSCi uc008rhu.1. mouse. [P97474-1 ]
    uc008rhv.1. mouse. [P97474-3 ]

    Organism-specific databases

    CTDi 5308.
    MGIi MGI:109340. Pitx2.

    Phylogenomic databases

    eggNOGi NOG249113.
    GeneTreei ENSGT00740000115425.
    HOVERGENi HBG068770.
    KOi K04686.
    OMAi RINHSAR.
    PhylomeDBi P97474.
    TreeFami TF351940.

    Miscellaneous databases

    NextBioi 294885.
    PROi P97474.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P97474.
    Bgeei P97474.
    CleanExi MM_PITX2.
    Genevestigatori P97474.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR016233. Homeobox_Pitx/unc30.
    IPR009057. Homeodomain-like.
    IPR003654. OAR_dom.
    [Graphical view ]
    Pfami PF00046. Homeobox. 1 hit.
    PF03826. OAR. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000563. Homeobox_protein_Pitx/Unc30. 1 hit.
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    PS50803. OAR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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.

    Entry informationi

    Entry nameiPITX2_MOUSE
    AccessioniPrimary (citable) accession number: P97474
    Secondary accession number(s): O08646
    , O70336, P97933, Q9JLA0, Q9QXB8, Q9R1V9, Q9Z141
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: July 15, 1999
    Last modified: October 1, 2014
    This is version 136 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3