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O75364 (PITX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

Clusters with 100%, 90%, 50% identity | Documents (5) | 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
Synonyms:PTX3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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 By similarity.

Subunit structure

Interacts with SFPQ By similarity.

Subcellular location

Nucleus By similarity.

Tissue specificity

Highly expressed in developing eye lens.

Involvement in disease

Anterior segment mesenchymal dysgenesis (ASMD) [MIM:107250]: A range of developmental defects in structures at the front of the eye, resulting from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to the cornea, iris, and other components of the anterior chamber during eye development. Different mature anterior segment anomalies may exist alone or in combination, and are associated with an increased risk of glaucoma and corneal opacity. Conditions falling within the phenotypic spectrum of anterior segment anomalies include aniridia, posterior embryotoxon, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Cataract 11, multiple types (CTRCT11) [MIM:610623]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT11 includes posterior polar cataract, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Some CTRCT11 patients can present a severe phenotype including microphthalmia and neurological dysfunction.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 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
   DiseaseCataract
Disease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdopaminergic neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

lens development in camera-type eye

Inferred from sequence or structural similarity. Source: UniProtKB

lens fiber cell differentiation

Inferred from electronic annotation. Source: Ensembl

lens morphogenesis in camera-type eye

Inferred from sequence or structural similarity. Source: UniProtKB

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

midbrain development

Inferred from sequence or structural similarity. Source: UniProtKB

neuron development

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Traceable author statement Ref.1. Source: ProtInc

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionsequence-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_0000049229

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

Natural variations

Natural variant131S → N in CTRCT11. Ref.1
VAR_003767

Sequences

Sequence LengthMass (Da)Tools
O75364 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 1E5259206ABC2E87

FASTA30231,832
        10         20         30         40         50         60 
MEFGLLSEAE ARSPALSLSD AGTPHPQLPE HGCKGQEHSD SEKASASLPG GSPEDGSLKK 

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

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

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

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


PV 

« Hide

References

« Hide 'large scale' references
[1]"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: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CTRCT11 ASN-13, INVOLVEMENT IN ASMD.
Tissue: Craniofacial.
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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: Muscle.
[4]"Recurrent 17 bp duplication in PITX3 is primarily associated with posterior polar cataract (CPP4)."
Berry V., Yang Z., Addison P.K., Francis P.J., Ionides A., Karan G., Jiang L., Lin W., Hu J., Yang R., Moore A., Zhang K., Bhattacharya S.S.
J. Med. Genet. 41:E109-E109(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CTRCT11.
[5]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF041339 mRNA. Translation: AAC24502.1.
AL160011 Genomic DNA. Translation: CAH71624.1.
BC011642 mRNA. Translation: AAH11642.1.
CCDSCCDS7532.1.
RefSeqNP_005020.1. NM_005029.3.
UniGeneHs.137568.

3D structure databases

ProteinModelPortalO75364.
SMRO75364. Positions 62-121.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111326. 4 interactions.
STRING9606.ENSP00000359019.

PTM databases

PhosphoSiteO75364.

Proteomic databases

PaxDbO75364.
PRIDEO75364.

Protocols and materials databases

DNASU5309.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370002; ENSP00000359019; ENSG00000107859.
ENST00000539804; ENSP00000439383; ENSG00000107859.
GeneID5309.
KEGGhsa:5309.
UCSCuc001kuu.1. human.

Organism-specific databases

CTD5309.
GeneCardsGC10M103979.
GeneReviewsPITX3.
HGNCHGNC:9006. PITX3.
HPAHPA044639.
MIM107250. phenotype.
602669. gene.
610623. phenotype.
neXtProtNX_O75364.
Orphanet162. Cataract-glaucoma.
88632. Familial ocular anterior segment mesenchymal dysgenesis.
98993. Posterior polar cataract.
PharmGKBPA33340.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249113.
HOGENOMHOG000273886.
HOVERGENHBG068770.
InParanoidO75364.
KOK09357.
OMALCKGGFA.
OrthoDBEOG7VTDNW.
PhylomeDBO75364.
TreeFamTF351940.

Gene expression databases

BgeeO75364.
CleanExHS_PITX3.
HS_PTX3.
GenevestigatorO75364.

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

GeneWikiPITX3.
GenomeRNAi5309.
NextBio20526.
PROO75364.
SOURCESearch...

Entry information

Entry namePITX3_HUMAN
AccessionPrimary (citable) accession number: O75364
Secondary accession number(s): Q5VZL2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: July 9, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM