PREX1

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=3}} {{Infobox_gene}} '''Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein''' is a protein that in humans is encoded by the ''PREX1'' gene.<ref name="pmid11955434">{{cite journal | vauthors = Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, Tempst P, Hawkins PT, Stephens LR | s2cid = 14185057 | title = P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac | journal = Cell | volume = 108 | issue = 6 | pages = 809–21 | date = March 2002 | pmid = 11955434 | doi = 10.1016/S0092-8674(02)00663-3 | doi-access = free }}</ref><ref name="pmid15545267">{{cite journal | vauthors = Hill K, Krugmann S, Andrews SR, Coadwell WJ, Finan P, Welch HC, Hawkins PT, Stephens LR | title = Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits | journal = The Journal of Biological Chemistry | volume = 280 | issue = 6 | pages = 4166–73 | date = February 2005 | pmid = 15545267 | doi = 10.1074/jbc.M411262200 | doi-access = free }}</ref><ref name="pmid16301320">{{cite journal | vauthors = Mayeenuddin LH, Garrison JC | title = Phosphorylation of P-Rex1 by the cyclic AMP-dependent protein kinase inhibits the phosphatidylinositiol (3,4,5)-trisphosphate and Gbetagamma-mediated regulation of its activity | journal = The Journal of Biological Chemistry | volume = 281 | issue = 4 | pages = 1921–8 | date = January 2006 | pmid = 16301320 | doi = 10.1074/jbc.M506035200 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PREX1 phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=57580}}</ref>

== Function ==

The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins.<ref name="entrez"/> The activation of P-REX1 is efficient when chemotactic receptors coupled to Gi proteins are activated, as a consequence of a better release of the Gβɣ heterodimer.<ref>{{cite journal | vauthors = Cervantes-Villagrana RD, Adame-García SR, García-Jiménez I, Color-Aparicio VM, Beltrán-Navarro YM, König GM, Kostenis E, Reyes-Cruz G, Gutkind JS, Vázquez-Prado J | title = 13 proteins | journal = The Journal of Biological Chemistry | volume = 294 | issue = 2 | pages = 531–546 | date = January 2019 | pmid = 30446620 | pmc = 6333895 | doi = 10.1074/jbc.RA118.006254 | doi-access = free }}</ref>

== Clinical significance ==

The protein has been implicated in the spread of melanoma skin cancer.<ref name=Lindsay_2011>{{cite journal | vauthors = Lindsay CR, Lawn S, Campbell AD, Faller WJ, Rambow F, Mort RL, Timpson P, Li A, Cammareri P, Ridgway RA, Morton JP, Doyle B, Hegarty S, Rafferty M, Murphy IG, McDermott EW, Sheahan K, Pedone K, Finn AJ, Groben PA, Thomas NE, Hao H, Carson C, Norman JC, Machesky LM, Gallagher WM, Jackson IJ, Van Kempen L, Beermann F, Der C, Larue L, Welch HC, Ozanne BW, Sansom OJ | title = P-Rex1 is required for efficient melanoblast migration and melanoma metastasis | journal = Nature Communications | volume = 2 | pages = 555 | date = November 2011 | pmid = 22109529 | pmc = 3400057 | doi = 10.1038/ncomms1560 | bibcode = 2011NatCo...2..555L}} * {{cite web |date=22 November 2011 |title=Protein linked to spread of skin cancer |website=Cancer Research UK |url=http://info.cancerresearchuk.org/news/archive/cancernews/2011-11-22-Protein-linked-to-spread-of-skin-cancer |archive-url=https://web.archive.org/web/20111125004834/http://info.cancerresearchuk.org/news/archive/cancernews/2011-11-22-Protein-linked-to-spread-of-skin-cancer |archive-date=2011-11-25}}</ref>

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T | title = Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones | journal = DNA Research | volume = 9 | issue = 3 | pages = 99–106 | date = June 2002 | pmid = 12168954 | doi = 10.1093/dnares/9.3.99 | doi-access = free }} * {{cite journal | vauthors = Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 7 | issue = 1 | pages = 65–73 | date = February 2000 | pmid = 10718198 | doi = 10.1093/dnares/7.1.65 | doi-access = free }} * {{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = March 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }} * {{cite journal | vauthors = Fossey SC, Mychaleckyj JC, Pendleton JK, Snyder JR, Bensen JT, Hirakawa S, Rich SS, Freedman BI, Bowden DW | title = A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20 | journal = Genomics | volume = 76 | issue = 1–3 | pages = 45–57 | date = August 2001 | pmid = 11549316 | doi = 10.1006/geno.2001.6584 | url = https://cdr.lib.unc.edu/downloads/6w924p34v }} * {{cite journal | vauthors = Weiner OD | title = Rac activation: P-Rex1 - a convergence point for PIP(3) and Gbetagamma? | journal = Current Biology | volume = 12 | issue = 12 | pages = R429-31 | date = June 2002 | pmid = 12123595 | pmc = 2819105 | doi = 10.1016/S0960-9822(02)00917-X }} * {{cite journal | vauthors = Zhao T, Nalbant P, Hoshino M, Dong X, Wu D, Bokoch GM | title = Signaling requirements for translocation of P-Rex1, a key Rac2 exchange factor involved in chemoattractant-stimulated human neutrophil function | journal = Journal of Leukocyte Biology | volume = 81 | issue = 4 | pages = 1127–36 | date = April 2007 | pmid = 17227822 | doi = 10.1189/jlb.0406251 | s2cid = 25318452 }} * {{cite journal | vauthors = Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }} * {{cite journal | vauthors = Hernández-Negrete I, Carretero-Ortega J, Rosenfeldt H, Hernández-García R, Calderón-Salinas JV, Reyes-Cruz G, Gutkind JS, Vázquez-Prado J | title = P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration | journal = The Journal of Biological Chemistry | volume = 282 | issue = 32 | pages = 23708–15 | date = August 2007 | pmid = 17565979 | doi = 10.1074/jbc.M703771200 | doi-access = free }} * {{cite journal | vauthors = Barber MA, Donald S, Thelen S, Anderson KE, Thelen M, Welch HC | title = Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase | journal = The Journal of Biological Chemistry | volume = 282 | issue = 41 | pages = 29967–76 | date = October 2007 | pmid = 17698854 | doi = 10.1074/jbc.M701877200 | doi-access = free }} {{refend}}