PITX2

Paired-like homeodomain 2
PDB rendering based on 1yz8.
Available structures PDB 1yz8
Identifiers
Symbols	PITX2; ARP1; Brx1; IDG2; IGDS; IGDS2; IHG2; IRID2; MGC111022; MGC20144; Otlx2; PTX2; RGS; RIEG; RIEG1; RS
External IDs	OMIM: 601542 MGI: 109340 HomoloGene: 55454 GeneCards: PITX2 Gene
Gene Ontology Molecular function • sequence-specific DNA binding transcription factor activity • protein binding • transcription factor binding • sequence-specific DNA binding Cellular component • nucleus • transcription factor complex Biological process • transcription, DNA-dependent • regulation of transcription, DNA-dependent • multicellular organismal development • determination of left/right symmetry • organ morphogenesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5308	18741
Ensembl	ENSG00000164093	ENSMUSG00000028023
UniProt	Q99697	P97474
RefSeq (mRNA)	NM_000325.5	NM_001042502
RefSeq (protein)	NP_000316.2	NP_001035967
Location (UCSC)	Chr 4: 111.54 – 111.56 Mb	Chr 3: 128.9 – 128.92 Mb
PubMed search	[1]	[2]

Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.

Function

This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. This protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein is involved in the development of the eye, tooth and abdominal organs. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Three transcript variants encoding distinct isoforms have been identified for this gene.

Clinical significance

Mutations in this gene are associated with Axenfeld-Rieger syndrome (ARS), iridogoniodysgenesis syndrome (IGDS), and sporadic cases of Peters anomaly. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes.

Further reading

• Franco D, Campione M (2003). "The role of Pitx2 during cardiac development. Linking left-right signaling and congenital heart diseases". Trends Cardiovasc. Med. 13 (4): 157–63. doi:10.1016/S1050-1738(03)00039-2. PMID 12732450. 
• Hjalt TA, Semina EV (2007). "Current molecular understanding of Axenfeld-Rieger syndrome". Expert reviews in molecular medicine 7 (25): 1–17. doi:10.1017/S1462399405010082. PMID 16274491. 
• Murray JC, Bennett SR, Kwitek AE, et al. (1993). "Linkage of Rieger syndrome to the region of the epidermal growth factor gene on chromosome 4". Nat. Genet. 2 (1): 46–9. doi:10.1038/ng0992-46. PMID 1303248. 
• Walter MA, Mirzayans F, Mears AJ, et al. (1996). "Autosomal-dominant iridogoniodysgenesis and Axenfeld-Rieger syndrome are genetically distinct". Ophthalmology 103 (11): 1907–15. PMID 8942889. 
• Semina EV, Reiter R, Leysens NJ, et al. (1997). "Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome". Nat. Genet. 14 (4): 392–9. doi:10.1038/ng1296-392. PMID 8944018. 
• Alward WL, Semina EV, Kalenak JW, et al. (1998). "Autosomal dominant iris hypoplasia is caused by a mutation in the Rieger syndrome (RIEG/PITX2) gene". Am. J. Ophthalmol. 125 (1): 98–100. doi:10.1016/S0002-9394(99)80242-6. PMID 9437321. 
• Kulak SC, Kozlowski K, Semina EV, et al. (1999). "Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome". Hum. Mol. Genet. 7 (7): 1113–7. doi:10.1093/hmg/7.7.1113. PMID 9618168. 
• Amendt BA, Sutherland LB, Semina EV, Russo AF (1998). "The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities". J. Biol. Chem. 273 (32): 20066–72. doi:10.1074/jbc.273.32.20066. PMID 9685346. 
• Yoshioka H, Meno C, Koshiba K, et al. (1998). "Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry". Cell 94 (3): 299–305. doi:10.1016/S0092-8674(00)81473-7. PMID 9708732. 
• Doward W, Perveen R, Lloyd IC, et al. (1999). "A mutation in the RIEG1 gene associated with Peters' anomaly". J. Med. Genet. 36 (2): 152–5. doi:10.1136/jmg.36.2.152. PMC 1734311. PMID 10051017. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1734311. 
• Pellegrini-Bouiller I, Manrique C, Gunz G, et al. (1999). "Expression of the members of the Ptx family of transcription factors in human pituitary adenomas". J. Clin. Endocrinol. Metab. 84 (6): 2212–20. doi:10.1210/jc.84.6.2212. PMID 10372733. 
• Hjalt TA, Amendt BA, Murray JC (2001). "Pitx2 Regulates Procollagen Lysyl Hydroxylase (Plod) Gene Expression: Implications for the Pathology of Rieger Syndrome". J. Cell Biol. 152 (3): 545–52. doi:10.1083/jcb.152.3.545. PMC 2196000. PMID 11157981. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2196000. 
• Priston M, Kozlowski K, Gill D, et al. (2001). "Functional analyses of two newly identified PITX2 mutants reveal a novel molecular mechanism for Axenfeld-Rieger syndrome". Hum. Mol. Genet. 10 (16): 1631–8. doi:10.1093/hmg/10.16.1631. PMID 11487566. 
• Green PD, Hjalt TA, Kirk DE, et al. (2002). "Antagonistic regulation of Dlx2 expression by PITX2 and Msx2: implications for tooth development". Gene Expr. 9 (6): 265–81. PMID 11763998. 
• Vincent AL, Billingsley G, Buys Y, et al. (2002). "Digenic Inheritance of Early-Onset Glaucoma: CYP1B1, a Potential Modifier Gene". Am. J. Hum. Genet. 70 (2): 448–60. doi:10.1086/338709. PMC 384919. PMID 11774072. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=384919. 
• Borges AS, Susanna R, Carani JC, et al. (2002). "Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil". J. Glaucoma 11 (1): 51–6. doi:10.1097/00061198-200202000-00010. PMID 11821690. 
• Cox CJ, Espinoza HM, McWilliams B, et al. (2002). "Differential regulation of gene expression by PITX2 isoforms". J. Biol. Chem. 277 (28): 25001–10. doi:10.1074/jbc.M201737200. PMID 11948188. 
• Quentien MH, Pitoia F, Gunz G, et al. (2002). "Regulation of prolactin, GH, and Pit-1 gene expression in anterior pituitary by Pitx2: An approach using Pitx2 mutants". Endocrinology 143 (8): 2839–51. doi:10.1210/en.143.8.2839. PMID 12130547. 

External links

• MeSH PITX2+protein,+human

This article incorporates text from the United States National Library of Medicine, which is in the public domain.