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O35160

- PITX3_MOUSE

UniProt

O35160 - PITX3_MOUSE

Protein

Pituitary homeobox 3

Gene

Pitx3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. In addition to its importance during development, it also has roles in the long-term survival and maintenance of the mdDA neurons. Activates NR4A2/NURR1-mediated transcription of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons. Acts by decreasing the interaction of NR4A2/NURR1 with the corepressor NCOR2/SMRT which acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state. Essential for the normal lens development and differentiation. Plays a critical role in the maintenance of mitotic activity of lens epithelial cells, fiber cell differentiation and in the control of the temporal and spatial activation of fiber cell-specific crystallins. Positively regulates FOXE3 expression and negatively regulates PROX1 in the anterior lens epithelium, preventing activation of CDKN1B/P27Kip1 and CDKN1C/P57Kip2 and thus maintains lens epithelial cells in cell cycle.5 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi62 – 12160HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB

    GO - Biological processi

    1. dopaminergic neuron differentiation Source: UniProtKB
    2. lens development in camera-type eye Source: UniProtKB
    3. lens fiber cell differentiation Source: UniProtKB
    4. lens morphogenesis in camera-type eye Source: UniProtKB
    5. locomotory behavior Source: MGI
    6. midbrain development Source: UniProtKB
    7. neuron development Source: MGI
    8. positive regulation of transcription, DNA-templated Source: UniProtKB
    9. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
    10. regulation of gene expression Source: MGI
    11. regulation of transcription, DNA-templated Source: UniProtKB

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pituitary homeobox 3
    Alternative name(s):
    Homeobox protein PITX3
    Paired-like homeodomain transcription factor 3
    Gene namesi
    Name:Pitx3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 19

    Organism-specific databases

    MGIiMGI:1100498. Pitx3.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Mutations in Pitx3 appear to be the cause of the aphakia (ak) phenotype, a recessive homozygous disease characterized by small eyes and closed eyelids.1 Publication

    Disruption phenotypei

    Mice show loss of nascent substantia nigra dopaminergic neurons at the beginning of their final differentiation and a loss of tyrosine hydroxylase (TH) expression specifically in the substantia nigra neurons.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 302302Pituitary homeobox 3PRO_0000049230Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei52 – 521PhosphoserineBy similarity
    Modified residuei57 – 571PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiO35160.

    PTM databases

    PhosphoSiteiO35160.

    Expressioni

    Tissue specificityi

    Highly expressed in developing eye lens. Expression is restricted to the substantia nigra and ventral tegmental area in the midbrain.2 Publications

    Developmental stagei

    First visible in E10.5 embryos where expression is confined to the lens vesicles. Between E11.5 and E12.5, expressed in both the lens epithelium and differentiating primary fiber cells. In the late fetal stage after the lens is formed, primarily found in the lens epithelium and the lens equator region where lens epithelial cells exit from the cell cycle and differentiate into fiber cells (at protein level). First expressed in the eye at 10 dpc embryos. Throughout eye development, expressed in the lens placode and forming lens pit. From 12 dpc, also detected in the midbrain region, tongue, incisor primordia, condensing mesenchyme around the sternum and vertebrae and in the head muscles.2 Publications

    Gene expression databases

    ArrayExpressiO35160.
    BgeeiO35160.
    CleanExiMM_PITX3.
    GenevestigatoriO35160.

    Interactioni

    Subunit structurei

    Interacts with SFPQ.1 Publication

    Protein-protein interaction databases

    BioGridi202188. 1 interaction.
    STRINGi10090.ENSMUSP00000026259.

    Structurei

    3D structure databases

    ProteinModelPortaliO35160.
    SMRiO35160. Positions 62-121.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi262 – 27514OARAdd
    BLAST
    Motifi268 – 2725Nuclear localization signalSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi240 – 25011Poly-AlaAdd
    BLAST

    Sequence similaritiesi

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

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG249113.
    GeneTreeiENSGT00740000115425.
    HOGENOMiHOG000273886.
    HOVERGENiHBG068770.
    InParanoidiQ0VB03.
    KOiK09357.
    OMAiLCKGGFA.
    OrthoDBiEOG7VTDNW.
    PhylomeDBiO35160.
    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]

    Sequencei

    Sequence statusi: Complete.

    O35160-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEFGLLGEAE ARSPALSLSD AGTPHPPLPE HGCKGQEHSD SEKASASLPG    50
    GSPEDGSLKK KQRRQRTHFT SQQLQELEAT FQRNRYPDMS TREEIAVWTN 100
    LTEARVRVWF KNRRAKWRKR ERSQQAELCK GGFAAPLGGL VPPYEEVYPG 150
    YSYGNWPPKA LAPPLAAKTF PFAFNSVNVG PLASQPVFSP PSSIAASMVP 200
    SAAAAPGTVP GPGALQGLGG APPGLAPAAV SSGAVSCPYA SAAAAAAAAA 250
    SSPYVYRDPC NSSLASLRLK AKQHASFSYP AVPGPPPAAN LSPCQYAVER 300
    PV 302
    Length:302
    Mass (Da):31,715
    Last modified:January 1, 1998 - v1
    Checksum:iEB6EF6863B349264
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF005772 mRNA. Translation: AAB87380.1.
    BC120844 mRNA. Translation: AAI20845.1.
    BC137810 mRNA. Translation: AAI37811.1.
    CCDSiCCDS29872.1.
    RefSeqiNP_032878.1. NM_008852.4.
    UniGeneiMm.6255.

    Genome annotation databases

    EnsembliENSMUST00000026259; ENSMUSP00000026259; ENSMUSG00000025229.
    GeneIDi18742.
    KEGGimmu:18742.
    UCSCiuc008hsl.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF005772 mRNA. Translation: AAB87380.1 .
    BC120844 mRNA. Translation: AAI20845.1 .
    BC137810 mRNA. Translation: AAI37811.1 .
    CCDSi CCDS29872.1.
    RefSeqi NP_032878.1. NM_008852.4.
    UniGenei Mm.6255.

    3D structure databases

    ProteinModelPortali O35160.
    SMRi O35160. Positions 62-121.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202188. 1 interaction.
    STRINGi 10090.ENSMUSP00000026259.

    PTM databases

    PhosphoSitei O35160.

    Proteomic databases

    PRIDEi O35160.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000026259 ; ENSMUSP00000026259 ; ENSMUSG00000025229 .
    GeneIDi 18742.
    KEGGi mmu:18742.
    UCSCi uc008hsl.1. mouse.

    Organism-specific databases

    CTDi 5309.
    MGIi MGI:1100498. Pitx3.

    Phylogenomic databases

    eggNOGi NOG249113.
    GeneTreei ENSGT00740000115425.
    HOGENOMi HOG000273886.
    HOVERGENi HBG068770.
    InParanoidi Q0VB03.
    KOi K09357.
    OMAi LCKGGFA.
    OrthoDBi EOG7VTDNW.
    PhylomeDBi O35160.
    TreeFami TF351940.

    Miscellaneous databases

    ChiTaRSi PITX3. mouse.
    NextBioi 294893.
    PROi O35160.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O35160.
    Bgeei O35160.
    CleanExi MM_PITX3.
    Genevestigatori O35160.

    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. "Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19."
      Semina E.V., Reiter R.S., Murray J.C.
      Hum. Mol. Genet. 6:2109-2116(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Embryo and Embryonic carcinoma.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain and Testis.
    3. "A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD."
      Semina E.V., Ferrell R.E., Mintz-Hittner H.A., Bitoun P., Alward W.L.M., Reiter R.S., Funkhauser C., Daack-Hirsch S., Murray J.C.
      Nat. Genet. 19:167-170(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE.
    4. "Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development."
      Maxwell S.L., Ho H.Y., Kuehner E., Zhao S., Li M.
      Dev. Biol. 282:467-479(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
    5. "Induction of tyrosine hydroxylase expression by the transcription factor Pitx3."
      Messmer K., Remington M.P., Skidmore F., Fishman P.S.
      Int. J. Dev. Neurosci. 25:29-37(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    6. "Pitx3 controls multiple aspects of lens development."
      Medina-Martinez O., Shah R., Jamrich M.
      Dev. Dyn. 238:2193-2201(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISEASE.
    7. "Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression."
      Jacobs F.M., van Erp S., van der Linden A.J., von Oerthel L., Burbach J.P., Smidt M.P.
      Development 136:531-540(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SFPQ.
    8. "Homeodomain protein Pitx3 maintains the mitotic activity of lens epithelial cells."
      Ho H.Y., Chang K.H., Nichols J., Li M.
      Mech. Dev. 126:18-29(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.

    Entry informationi

    Entry nameiPITX3_MOUSE
    AccessioniPrimary (citable) accession number: O35160
    Secondary accession number(s): Q0VB03
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 117 of the entry and version 1 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