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Protein

Pituitary homeobox 3

Gene

Pitx3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  2. 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
Complete GO annotation...

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 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1100498. Pitx3.

Subcellular locationi

  1. Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  1. nucleus Source: UniProtKB
Complete GO annotation...

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.

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

BgeeiO35160.
CleanExiMM_PITX3.
ExpressionAtlasiO35160. baseline and differential.
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.
GeneTreeiENSGT00760000118908.
HOGENOMiHOG000273886.
HOVERGENiHBG068770.
InParanoidiO35160.
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

        10         20         30         40         50
MEFGLLGEAE ARSPALSLSD AGTPHPPLPE HGCKGQEHSD SEKASASLPG
60 70 80 90 100
GSPEDGSLKK KQRRQRTHFT SQQLQELEAT FQRNRYPDMS TREEIAVWTN
110 120 130 140 150
LTEARVRVWF KNRRAKWRKR ERSQQAELCK GGFAAPLGGL VPPYEEVYPG
160 170 180 190 200
YSYGNWPPKA LAPPLAAKTF PFAFNSVNVG PLASQPVFSP PSSIAASMVP
210 220 230 240 250
SAAAAPGTVP GPGALQGLGG APPGLAPAAV SSGAVSCPYA SAAAAAAAAA
260 270 280 290 300
SSPYVYRDPC NSSLASLRLK AKQHASFSYP AVPGPPPAAN LSPCQYAVER

PV
Length:302
Mass (Da):31,715
Last modified:January 1, 1998 - v1
Checksum:iEB6EF6863B349264
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi202188. 1 interaction.
STRINGi10090.ENSMUSP00000026259.

PTM databases

PhosphoSiteiO35160.

Proteomic databases

PRIDEiO35160.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5309.
MGIiMGI:1100498. Pitx3.

Phylogenomic databases

eggNOGiNOG249113.
GeneTreeiENSGT00760000118908.
HOGENOMiHOG000273886.
HOVERGENiHBG068770.
InParanoidiO35160.
KOiK09357.
OMAiLCKGGFA.
OrthoDBiEOG7VTDNW.
PhylomeDBiO35160.
TreeFamiTF351940.

Miscellaneous databases

NextBioi294893.
PROiO35160.
SOURCEiSearch...

Gene expression databases

BgeeiO35160.
CleanExiMM_PITX3.
ExpressionAtlasiO35160. baseline and differential.
GenevestigatoriO35160.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: March 4, 2015
This is version 121 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.