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Protein

Pituitary homeobox 3

Gene

PITX3

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

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

GO - Biological processi

  1. dopaminergic neuron differentiation Source: UniProtKB
  2. lens development in camera-type eye Source: UniProtKB
  3. lens fiber cell differentiation Source: Ensembl
  4. lens morphogenesis in camera-type eye Source: UniProtKB
  5. locomotory behavior Source: Ensembl
  6. midbrain development Source: UniProtKB
  7. neuron development Source: Ensembl
  8. organ morphogenesis Source: ProtInc
  9. positive regulation of transcription, DNA-templated Source: UniProtKB
  10. 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
Synonyms:PTX3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:9006. PITX3.

Subcellular locationi

  1. Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

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

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Anterior segment mesenchymal dysgenesis (ASMD)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:107250
Cataract 11, multiple types (CTRCT11)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn 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.

See also OMIM:610623
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131S → N in CTRCT11. 1 Publication
VAR_003767

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

MIMi107250. phenotype.
610623. phenotype.
Orphaneti162. Cataract-glaucoma.
88632. Familial ocular anterior segment mesenchymal dysgenesis.
98993. Posterior polar cataract.
PharmGKBiPA33340.

Polymorphism and mutation databases

BioMutaiPITX3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 302302Pituitary homeobox 3PRO_0000049229Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO75364.
PRIDEiO75364.

PTM databases

PhosphoSiteiO75364.

Expressioni

Tissue specificityi

Highly expressed in developing eye lens.

Gene expression databases

BgeeiO75364.
CleanExiHS_PITX3.
HS_PTX3.
GenevestigatoriO75364.

Organism-specific databases

HPAiHPA044639.

Interactioni

Subunit structurei

Interacts with SFPQ.By similarity

Protein-protein interaction databases

BioGridi111326. 4 interactions.
STRINGi9606.ENSP00000359019.

Structurei

3D structure databases

ProteinModelPortaliO75364.
SMRiO75364. 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.
InParanoidiO75364.
KOiK09357.
OMAiLCKGGFA.
OrthoDBiEOG7VTDNW.
PhylomeDBiO75364.
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.

O75364-1 [UniParc]FASTAAdd to basket

« Hide

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

PV
Length:302
Mass (Da):31,832
Last modified:November 1, 1998 - v1
Checksum:i1E5259206ABC2E87
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131S → N in CTRCT11. 1 Publication
VAR_003767

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041339 mRNA. Translation: AAC24502.1.
AL160011 Genomic DNA. Translation: CAH71624.1.
BC011642 mRNA. Translation: AAH11642.1.
CCDSiCCDS7532.1.
RefSeqiNP_005020.1. NM_005029.3.
UniGeneiHs.137568.

Genome annotation databases

EnsembliENST00000370002; ENSP00000359019; ENSG00000107859.
ENST00000539804; ENSP00000439383; ENSG00000107859.
GeneIDi5309.
KEGGihsa:5309.
UCSCiuc001kuu.1. human.

Polymorphism and mutation databases

BioMutaiPITX3.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041339 mRNA. Translation: AAC24502.1.
AL160011 Genomic DNA. Translation: CAH71624.1.
BC011642 mRNA. Translation: AAH11642.1.
CCDSiCCDS7532.1.
RefSeqiNP_005020.1. NM_005029.3.
UniGeneiHs.137568.

3D structure databases

ProteinModelPortaliO75364.
SMRiO75364. Positions 62-121.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111326. 4 interactions.
STRINGi9606.ENSP00000359019.

PTM databases

PhosphoSiteiO75364.

Polymorphism and mutation databases

BioMutaiPITX3.

Proteomic databases

PaxDbiO75364.
PRIDEiO75364.

Protocols and materials databases

DNASUi5309.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370002; ENSP00000359019; ENSG00000107859.
ENST00000539804; ENSP00000439383; ENSG00000107859.
GeneIDi5309.
KEGGihsa:5309.
UCSCiuc001kuu.1. human.

Organism-specific databases

CTDi5309.
GeneCardsiGC10M103979.
GeneReviewsiPITX3.
HGNCiHGNC:9006. PITX3.
HPAiHPA044639.
MIMi107250. phenotype.
602669. gene.
610623. phenotype.
neXtProtiNX_O75364.
Orphaneti162. Cataract-glaucoma.
88632. Familial ocular anterior segment mesenchymal dysgenesis.
98993. Posterior polar cataract.
PharmGKBiPA33340.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG249113.
GeneTreeiENSGT00760000118908.
HOGENOMiHOG000273886.
HOVERGENiHBG068770.
InParanoidiO75364.
KOiK09357.
OMAiLCKGGFA.
OrthoDBiEOG7VTDNW.
PhylomeDBiO75364.
TreeFamiTF351940.

Miscellaneous databases

GeneWikiiPITX3.
GenomeRNAii5309.
NextBioi20526.
PROiO75364.
SOURCEiSearch...

Gene expression databases

BgeeiO75364.
CleanExiHS_PITX3.
HS_PTX3.
GenevestigatoriO75364.

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. "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.
    , 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].

Entry informationi

Entry nameiPITX3_HUMAN
AccessioniPrimary (citable) accession number: O75364
Secondary accession number(s): Q5VZL2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1998
Last modified: April 29, 2015
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.