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O35160 (PITX3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pituitary homeobox 3
Alternative name(s):
Homeobox protein PITX3
Paired-like homeodomain transcription factor 3
Gene names
Name:Pitx3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length302 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8

Subunit structure

Interacts with SFPQ. Ref.7

Subcellular location

Nucleus Ref.5.

Tissue specificity

Highly expressed in developing eye lens. Expression is restricted to the substantia nigra and ventral tegmental area in the midbrain. Ref.4 Ref.8

Developmental stage

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. Ref.3 Ref.8

Involvement in disease

Mutations in Pitx3 appear to be the cause of the aphakia (ak) phenotype, a recessive homozygous disease characterized by small eyes and closed eyelids. Ref.6

Disruption phenotype

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. Ref.4

Sequence similarities

Belongs to the paired homeobox family. Bicoid subfamily.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdopaminergic neuron differentiation

Inferred from direct assay Ref.7. Source: UniProtKB

lens development in camera-type eye

Inferred from mutant phenotype Ref.8Ref.6. Source: UniProtKB

lens fiber cell differentiation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

lens morphogenesis in camera-type eye

Inferred from mutant phenotype Ref.6. Source: UniProtKB

locomotory behavior

Inferred from mutant phenotype PubMed 17919745. Source: MGI

midbrain development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

neuron development

Inferred from mutant phenotype PubMed 14973278. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.7. Source: UniProtKB

regulation of gene expression

Inferred from direct assay PubMed 17761882. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 302302Pituitary homeobox 3
PRO_0000049230

Regions

DNA binding62 – 12160Homeobox
Motif262 – 27514OAR
Motif268 – 2725Nuclear localization signal Potential
Compositional bias240 – 25011Poly-Ala

Amino acid modifications

Modified residue521Phosphoserine By similarity
Modified residue571Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
O35160 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: EB6EF6863B349264

FASTA30231,715
        10         20         30         40         50         60 
MEFGLLGEAE ARSPALSLSD AGTPHPPLPE HGCKGQEHSD SEKASASLPG GSPEDGSLKK 

        70         80         90        100        110        120 
KQRRQRTHFT SQQLQELEAT FQRNRYPDMS TREEIAVWTN LTEARVRVWF KNRRAKWRKR 

       130        140        150        160        170        180 
ERSQQAELCK GGFAAPLGGL VPPYEEVYPG YSYGNWPPKA LAPPLAAKTF PFAFNSVNVG 

       190        200        210        220        230        240 
PLASQPVFSP PSSIAASMVP SAAAAPGTVP GPGALQGLGG APPGLAPAAV SSGAVSCPYA 

       250        260        270        280        290        300 
SAAAAAAAAA SSPYVYRDPC NSSLASLRLK AKQHASFSYP AVPGPPPAAN LSPCQYAVER 


PV 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF005772 mRNA. Translation: AAB87380.1.
BC120844 mRNA. Translation: AAI20845.1.
BC137810 mRNA. Translation: AAI37811.1.
CCDSCCDS29872.1.
RefSeqNP_032878.1. NM_008852.4.
UniGeneMm.6255.

3D structure databases

ProteinModelPortalO35160.
SMRO35160. Positions 62-121.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202188. 1 interaction.
STRING10090.ENSMUSP00000026259.

PTM databases

PhosphoSiteO35160.

Proteomic databases

PRIDEO35160.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026259; ENSMUSP00000026259; ENSMUSG00000025229.
GeneID18742.
KEGGmmu:18742.
UCSCuc008hsl.1. mouse.

Organism-specific databases

CTD5309.
MGIMGI:1100498. Pitx3.

Phylogenomic databases

eggNOGNOG249113.
GeneTreeENSGT00740000115425.
HOGENOMHOG000273886.
HOVERGENHBG068770.
InParanoidQ0VB03.
KOK09357.
OMALCKGGFA.
OrthoDBEOG7VTDNW.
PhylomeDBO35160.
TreeFamTF351940.

Gene expression databases

ArrayExpressO35160.
BgeeO35160.
CleanExMM_PITX3.
GenevestigatorO35160.

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

ChiTaRSPITX3. mouse.
NextBio294893.
PROO35160.
SOURCESearch...

Entry information

Entry namePITX3_MOUSE
AccessionPrimary (citable) accession number: O35160
Secondary accession number(s): Q0VB03
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 116 of the entry and version 1 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