View source for Biology:PITX1

{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
'''Paired-like homeodomain 1''' is a [[Biology:Protein|protein]] that in humans is encoded by the ''PITX1'' [[Biology:Gene|gene]].<ref name="pmid9337397">{{cite journal | vauthors = Crawford MJ, Lanctôt C, Tremblay JJ, Jenkins N, Gilbert D, Copeland N, Beatty B, Drouin J | title = Human and murine PTX1/Ptx1 gene maps to the region for Treacher Collins syndrome | journal = Mammalian Genome | volume = 8 | issue = 11 | pages = 841–5 | year = 1997 | pmid = 9337397 | doi = 10.1007/s003359900589 | citeseerx = 10.1.1.326.9619 | s2cid = 8557603 }}</ref><ref name="pmid9070926">{{cite journal | vauthors = Shang J, Li X, Ring HZ, Clayton DA, Francke U | title = Backfoot, a novel homeobox gene, maps to human chromosome 5 (BFT) and mouse chromosome 13 (Bft) | journal = Genomics | volume = 40 | issue = 1 | pages = 108–13 | date = February 1997 | pmid = 9070926 | doi = 10.1006/geno.1996.4558 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PITX1 paired-like homeodomain transcription factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5307}}</ref>

== Function ==

This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin.<ref name="entrez"/>

== Clinical relevance ==

Mutations in this gene have been associated with [[Medicine:Autism|autism]],<ref>{{cite journal | vauthors = Philippi A, Tores F, Carayol J, Rousseau F, Letexier M, Roschmann E, Lindenbaum P, Benajjou A, Fontaine K, Vazart C, Gesnouin P, Brooks P, Hager J | display-authors = 6 | title = Association of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis | journal = BMC Medical Genetics | volume = 8 | pages = 74 | date = December 2007 | pmid = 18053270 | pmc = 2222245 | doi = 10.1186/1471-2350-8-74 | doi-access = free }}</ref> club foot<ref name = "Alvarado_2011">{{cite journal | vauthors = Alvarado DM, McCall K, Aferol H, Silva MJ, Garbow JR, Spees WM, Patel T, Siegel M, Dobbs MB, Gurnett CA | display-authors = 6 | title = Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice | journal = Human Molecular Genetics | volume = 20 | issue = 20 | pages = 3943–52 | date = October 2011 | pmid = 21775501 | pmc = 3177645 | doi = 10.1093/hmg/ddr313 }}</ref> and polydactyly<ref name="pmid.222585222">{{cite journal | vauthors = Klopocki E, Kähler C, Foulds N, Shah H, Joseph B, Vogel H, Lüttgen S, Bald R, Besoke R, Held K, Mundlos S, Kurth I | display-authors = 6 | title = Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly | journal = European Journal of Human Genetics | volume = 20 | issue = 6 | pages = 705–8 | date = June 2012 | pmid = 22258522 | pmc = 3355260 | doi = 10.1038/ejhg.2011.264 }}</ref> in humans.

== Genetic basis of pathologies ==
Genomic rearrangements at the PITX1 locus are associated with [[Medicine:Liebenberg syndrome|Liebenberg syndrome]].<ref name="Spielmann_2012">{{cite journal | vauthors = Spielmann M, Brancati F, Krawitz PM, Robinson PN, Ibrahim DM, Franke M, Hecht J, Lohan S, Dathe K, Nardone AM, Ferrari P, Landi A, Wittler L, Timmermann B, Chan D, Mennen U, Klopocki E, Mundlos S | display-authors = 6 | title = Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus | journal = American Journal of Human Genetics | volume = 91 | issue = 4 | pages = 629–35 | date = October 2012 | pmid = 23022097 | pmc = 3484647 | doi = 10.1016/j.ajhg.2012.08.014 }}</ref> In PITX1 Liebenberg is associated with a [[Biology:Chromosomal translocation|translocation]] or [[Biology:Deletion (genetics)|deletions]], which cause insert promoter groups into the PITX1 locus.<ref name="Spielmann_2012" />  A [[Biology:Missense mutation|missense]] mutation within the PITX1 locus is associated with the development of autosomal dominant clubfoot.<ref name = "Alvarado_2011" />

== Interactions ==

PITX1 has been shown to interact with [[Biology:Pituitary-specific positive transcription factor 1|pituitary-specific positive transcription factor 1]].<ref name=pmid8755540>{{cite journal | vauthors = Szeto DP, Ryan AK, O'Connell SM, Rosenfeld MG | title = P-OTX: a PIT-1-interacting homeodomain factor expressed during anterior pituitary gland development | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 15 | pages = 7706–10 | date = July 1996 | pmid = 8755540 | pmc = 38811 | doi = 10.1073/pnas.93.15.7706 | bibcode = 1996PNAS...93.7706S | doi-access = free }}</ref>

== References ==
{{Reflist|32em}}

== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Shang J, Luo Y, Clayton DA | title = Backfoot is a novel homeobox gene expressed in the mesenchyme of developing hind limb | journal = Developmental Dynamics | volume = 209 | issue = 2 | pages = 242–53 | date = June 1997 | pmid = 9186059 | doi = 10.1002/(SICI)1097-0177(199706)209:2<242::AID-AJA10>3.0.CO;2-0 | s2cid = 46565338 | doi-access =  }}
* {{cite journal | vauthors = Poulin G, Turgeon B, Drouin J | title = NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene | journal = Molecular and Cellular Biology | volume = 17 | issue = 11 | pages = 6673–82 | date = November 1997 | pmid = 9343431 | pmc = 232521 | doi = 10.1128/mcb.17.11.6673 }}
* {{cite journal | vauthors = Tremblay JJ, Drouin J | title = Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription | journal = Molecular and Cellular Biology | volume = 19 | issue = 4 | pages = 2567–76 | date = April 1999 | pmid = 10082522 | pmc = 84049 | doi = 10.1128/mcb.19.4.2567 }}
* {{cite journal | vauthors = Tremblay JJ, Marcil A, Gauthier Y, Drouin J | title = Ptx1 regulates SF-1 activity by an interaction that mimics the role of the ligand-binding domain | journal = The EMBO Journal | volume = 18 | issue = 12 | pages = 3431–41 | date = June 1999 | pmid = 10369682 | pmc = 1171422 | doi = 10.1093/emboj/18.12.3431 }}
* {{cite journal | vauthors = Pellegrini-Bouiller I, Manrique C, Gunz G, Grino M, Zamora AJ, Figarella-Branger D, Grisoli F, Jaquet P, Enjalbert A | title = Expression of the members of the Ptx family of transcription factors in human pituitary adenomas | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 84 | issue = 6 | pages = 2212–20 | date = June 1999 | doi = 10.1210/jcem.84.6.5760 | pmid = 10372733 | doi-access = free }}
* {{cite journal | vauthors = Tahara S, Kurotani R, Sanno N, Takumi I, Yoshimura S, Osamura RY, Teramoto A | title = Expression of pituitary homeo box 1 (Ptx1) in human non-neoplastic pituitaries and pituitary adenomas | journal = Modern Pathology | volume = 13 | issue = 10 | pages = 1097–108 | date = October 2000 | pmid = 11048804 | doi = 10.1038/modpathol.3880204 | doi-access = free }}
* {{cite journal | vauthors = Quentien MH, Manfroid I, Moncet D, Gunz G, Muller M, Grino M, Enjalbert A, Pellegrini I | title = Pitx factors are involved in basal and hormone-regulated activity of the human prolactin promoter | journal = The Journal of Biological Chemistry | volume = 277 | issue = 46 | pages = 44408–16 | date = November 2002 | pmid = 12223489 | doi = 10.1074/jbc.M207824200 | doi-access = free }}
* {{cite journal | vauthors = Ghosh AK, Majumder M, Steele R, Ray R, Ray RB | title = Modulation of interferon expression by hepatitis C virus NS5A protein and human homeodomain protein PTX1 | journal = Virology | volume = 306 | issue = 1 | pages = 51–9 | date = February 2003 | pmid = 12620797 | doi = 10.1016/S0042-6822(02)00029-6 | doi-access = free }}
* {{cite journal | vauthors = Hiroi N, Kino T, Bassett M, Rainey WE, Phung M, Abu-Asab M, Fojo T, Briata P, Chrousos GP, Bornstein SR | title = Pituitary homeobox factor 1, a novel transcription factor in the adrenal regulating steroid 11beta-hydroxylase | journal = Hormone and Metabolic Research | volume = 35 | issue = 5 | pages = 273–8 | date = May 2003 | pmid = 12915995 | doi = 10.1055/s-2003-41301 | s2cid = 260168691 }}
* {{cite journal | vauthors = Kolfschoten IG, van Leeuwen B, Berns K, Mullenders J, Beijersbergen RL, Bernards R, Voorhoeve PM, Agami R | title = A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity | journal = Cell | volume = 121 | issue = 6 | pages = 849–58 | date = June 2005 | pmid = 15960973 | doi = 10.1016/j.cell.2005.04.017 | hdl = 1874/17813 | s2cid = 18065721 | hdl-access = free }}
* {{cite journal | vauthors = Lord RV, Brabender J, Wickramasinghe K, DeMeester SR, Holscher A, Schneider PM, Danenberg PV, DeMeester TR | title = Increased CDX2 and decreased PITX1 homeobox gene expression in Barrett's esophagus and Barrett's-associated adenocarcinoma | journal = Surgery | volume = 138 | issue = 5 | pages = 924–31 | date = November 2005 | pmid = 16291394 | doi = 10.1016/j.surg.2005.05.007 }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = November 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}
* {{cite journal | vauthors = Picard C, Azeddine B, Moldovan F, Martel-Pelletier J, Moreau A | title = New emerging role of pitx1 transcription factor in osteoarthritis pathogenesis | journal = Clinical Orthopaedics and Related Research | volume = 462 | pages = 59–66 | date = September 2007 | pmid = 17549029 | doi = 10.1097/BLO.0b013e3180d09d9c | s2cid = 8232057 }}
* {{cite journal | vauthors = Qi DL, Ohhira T, Fujisaki C, Inoue T, Ohta T, Osaki M, Ohshiro E, Seko T, Aoki S, Oshimura M, Kugoh H | title = Identification of PITX1 as a TERT suppressor gene located on human chromosome 5 | journal = Molecular and Cellular Biology | volume = 31 | issue = 8 | pages = 1624–36 | date = April 2011 | pmid = 21300782 | pmc = 3126332 | doi = 10.1128/MCB.00470-10 }}

{{refend}}

== External links ==

** {{MeshName|PITX1+protein,+human}}
** http://omim.org/entry/602149 at OMIM, holds the most up to date information on PITX1.
** https://ghr.nlm.nih.gov/gene/PITX1 at the NIH, has a summary on the effects of PITX1 mutations.

{{NLM content}}
{{PDB Gallery|geneid=5307}}
{{Transcription factors|g3}}

[[Category:Transcription factors]]



{{Sourceattribution|PITX1}}