PREX1

PREX1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3QIK, 4YON, 5D3W, 5D3V, 5FI0, 5D27, 5D3Y, 5FI1, 5D3X
Identifiers
Aliases	PREX1 , P-REX1, phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1
External IDs	OMIM: 606905; MGI: 3040696; HomoloGene: 10821; GeneCards: PREX1; OMA:PREX1 - orthologs
Gene location (Human) Chr. Chromosome 20 (human) [1] Band 20q13.13 Start 48,624,252 bp [1] End 48,827,999 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 H3 Start 166,408,262 bp [2] End 166,555,752 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in inferior ganglion of vagus nerve blood corpus callosum C1 segment granulocyte ganglionic eminence right lung subthalamic nucleus external globus pallidus substantia nigra Top expressed in granulocyte decidua lymph node gastrula mesenteric lymph nodes thymus membranous bone trigeminal ganglion tail of embryo superior frontal gyrus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function GTPase activator activity protein binding enzyme binding phospholipid binding guanyl-nucleotide exchange factor activity Cellular component membrane growth cone plasma membrane dendritic shaft perinuclear region of cytoplasm cytoplasm cytosol Biological process intracellular signal transduction neutrophil activation regulation of dendrite development neutrophil chemotaxis reactive oxygen species metabolic process regulation of actin filament polymerization actin filament polymerization positive regulation of GTPase activity positive regulation of substrate adhesion-dependent cell spreading T cell differentiation regulation of Rho protein signal transduction superoxide metabolic process positive regulation of cell adhesion negative regulation of protein kinase activity positive regulation of cell migration negative regulation of TOR signaling positive regulation of apoptotic process regulation of small GTPase mediated signal transduction G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57580 277360 Ensembl ENSG00000124126 ENSMUSG00000039621 UniProt Q8TCU6 Q69ZK0 RefSeq (mRNA) NM_020820 NM_177782 RefSeq (protein) NP_065871 NP_808450 Location (UCSC) Chr 20: 48.62 – 48.83 Mb Chr 2: 166.41 – 166.56 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein is a protein that in humans is encoded by the PREX1 gene. ^{[5] [6] [7] [8]}

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. ^[8] 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. ^[9]

Clinical significance

The protein has been implicated in the spread of melanoma skin cancer. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000124126 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039621 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Welch HC, Coadwell WJ, Ellson CD, et al. (March 2002). "P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac". Cell. 108 (6): 809–21. doi: 10.1016/S0092-8674(02)00663-3 . PMID   11955434. S2CID   14185057.
6. Hill K, Krugmann S, Andrews SR, et al. (February 2005). "Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits". The Journal of Biological Chemistry. 280 (6): 4166–73. doi: 10.1074/jbc.M411262200 . PMID   15545267.
7. Mayeenuddin LH, Garrison JC (January 2006). "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". The Journal of Biological Chemistry. 281 (4): 1921–8. doi: 10.1074/jbc.M506035200 . PMID   16301320.
8. "Entrez Gene: PREX1 phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1".
9. Cervantes-Villagrana RD, Adame-García SR, García-Jiménez I, et al. (January 2019). "13 proteins". The Journal of Biological Chemistry. 294 (2): 531–546. doi: 10.1074/jbc.RA118.006254 . PMC   6333895 . PMID   30446620.
10. Lindsay CR, Lawn S, Campbell AD, et al. (November 2011). "P-Rex1 is required for efficient melanoblast migration and melanoma metastasis". Nature Communications. 2: 555. Bibcode:2011NatCo...2..555L. doi:10.1038/ncomms1560. PMC   3400057 . PMID   22109529.
    • "Protein linked to spread of skin cancer". Cancer Research UK. 22 November 2011. Archived from the original on 2011-11-25.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, et al. (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi: 10.1093/dnares/9.3.99 . PMID   12168954.
• Nagase T, Kikuno R, Ishikawa KI, et al. (February 2000). "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". DNA Research. 7 (1): 65–73. doi: 10.1093/dnares/7.1.65 . PMID   10718198.
• Wiemann S, Weil B, Wellenreuther R, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Fossey SC, Mychaleckyj JC, Pendleton JK, et al. (August 2001). "A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20". Genomics. 76 (1–3): 45–57. doi:10.1006/geno.2001.6584. PMID   11549316.
• Weiner OD (June 2002). "Rac activation: P-Rex1 - a convergence point for PIP(3) and Gbetagamma?". Current Biology. 12 (12): R429-31. doi:10.1016/S0960-9822(02)00917-X. PMC   2819105 . PMID   12123595.
• Zhao T, Nalbant P, Hoshino M, et al. (April 2007). "Signaling requirements for translocation of P-Rex1, a key Rac2 exchange factor involved in chemoattractant-stimulated human neutrophil function". Journal of Leukocyte Biology. 81 (4): 1127–36. doi:10.1189/jlb.0406251. PMID   17227822. S2CID   25318452.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.
• Hernández-Negrete I, Carretero-Ortega J, Rosenfeldt H, et al. (August 2007). "P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration". The Journal of Biological Chemistry. 282 (32): 23708–15. doi: 10.1074/jbc.M703771200 . PMID   17565979.
• Barber MA, Donald S, Thelen S, et al. (October 2007). "Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase". The Journal of Biological Chemistry. 282 (41): 29967–76. doi: 10.1074/jbc.M701877200 . PMID   17698854.