PITX2

Protein identityUniProt · HPA

UniProt accession

Q99697

Gene

PITX2

Ensembl

ENSG00000164093

Chromosome

4

Canonical length

317 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

317 residues, UniProt reviewed canonical sequence.

>Q99697|PITX2
     1  METNCRKLVS ACVQLGVQPA AVECLFSKDS EIKKVEFTDS PESRKEAASS KFFPRQHPGA
    61  NEKDKSQQGK NEDVGAEDPS KKKRQRRQRT HFTSQQLQEL EATFQRNRYP DMSTREEIAV
   121  WTNLTEARVR VWFKNRRAKW RKRERNQQAE LCKNGFGPQF NGLMQPYDDM YPGYSYNNWA
   181  AKGLTSASLS TKSFPFFNSM NVNPLSSQSM FSPPNSISSM SMSSSMVPSA VTGVPGSSLN
   241  SLNNLNNLSS PSLNSAVPTP ACPYAPPTPP YVYRDTCNSS LASLRLKAKQ HSSFGYASVQ
   301  NPASNLSACQ YAVDRPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PITX2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.62

Highest tissue expression

40 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PITX2.

Disease | AllUniProt

Conditions PITX2 is implicated in, by any mechanism.

• Axenfeld-Rieger syndrome 1 (RIEG1) MIM:180500
• Anterior segment dysgenesis 4 (ASGD4) MIM:137600
• Ring dermoid of cornea (RDC) MIM:180550

Disease | GeneticClinVar

80 pathogenic / likely-pathogenic of 257 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Axenfeld-Rieger syndrome type 1
• Anterior segment dysgenesis 4
• Inborn genetic diseases
• Anterior segment dysgenesis
• PITX2-related disorder

ReferencesPubMed · IEDB

Publications for PITX2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.26

gnomAD pLI

0.98

gnomAD missense Z

1.55

DepMap mean gene effect

0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anatomical structure morphogenesis
• atrial cardiac muscle tissue morphogenesis
• atrioventricular valve development
• branching involved in blood vessel morphogenesis
• camera-type eye development
• cardiac neural crest cell migration involved in outflow tract morphogenesis
• cell proliferation involved in outflow tract morphogenesis
• deltoid tuberosity development
• determination of left/right symmetry
• embryonic camera-type eye development
• embryonic digestive tract morphogenesis
• embryonic heart tube left/right pattern formation
• embryonic hindlimb morphogenesis
• endodermal digestive tract morphogenesis
• extraocular skeletal muscle development
• hair cell differentiation
• hypothalamus cell migration
• in utero embryonic development
• iris morphogenesis
• left lung morphogenesis
• left/right axis specification
• negative regulation of transcription by RNA polymerase II
• neuron migration
• odontogenesis
• outflow tract morphogenesis
• positive regulation of cell population proliferation
• positive regulation of transcription by RNA polymerase II
• prolactin secreting cell differentiation
• pulmonary myocardium development
• pulmonary vein morphogenesis
• regulation of cell migration
• regulation of DNA-templated transcription
• regulation of transcription by RNA polymerase II
• somatotropin secreting cell differentiation
• spleen development
• vascular associated smooth muscle cell differentiation
• vasculogenesis
• ventricular cardiac muscle cell development
• ventricular septum morphogenesis
• Wnt signaling pathway
• subthalamic nucleus development
• superior vena cava morphogenesis

Molecular functions

• chromatin DNA binding
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription factor binding
• DNA-binding transcription repressor activity, RNA polymerase II-specific
• identical protein binding
• phosphoprotein binding
• protein homodimerization activity
• ribonucleoprotein complex binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• sequence-specific double-stranded DNA binding
• transcription cis-regulatory region binding

Cellular components

• chromatin
• cytoplasm
• nucleoplasm
• nucleus
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• OAR domain
• Homedomain-like superfamily
• Homeobox protein Pitx/unc30
• Homeobox, conserved site
• Homeodomain
• OAR motif

KeywordsUniProt

• Cytoplasm
• Developmental protein
• DNA-binding
• Homeobox
• Nucleus
• Peters anomaly
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of PITX2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EFEMP2