RGS18 explained

Regulator of G-protein signaling 18 is a protein that in humans is encoded by the RGS18 gene.^{[1] [2]}

Function

This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved 120 amino acid motif called the RGS domain. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.

Clinical significance

Several RGS18 alleles that result in reduced RGS18 expression are associated with the development of atherosclerosis.^[3] Two single nucleotide polymorphisms in the RGS18 gene that interfere with binding of GATA1 and NFE2 transcription factors result in decreased expression of RGS18. RSG18 Knockout mice display an exaggerated platelet reactivity which in turn increases risk of developing atherosclerosis. A minor allele of RSG18 is associated with the appearance of thrombotic phenomena in a cohort of European-American and African-American patients.

Interactions

RGS18 has been shown to interact with GNAI3.^{[4] [5]}

Further reading

• Nagata Y, Oda M, Nakata H, Shozaki Y, Kozasa T, Todokoro K . A novel regulator of G-protein signaling bearing GAP activity for Galphai and Galphaq in megakaryocytes . Blood . 97 . 10 . 3051–3060 . May 2001 . 11342430 . 10.1182/blood.V97.10.3051 . free .
• Yowe D, Weich N, Prabhudas M, Poisson L, Errada P, Kapeller R, Yu K, Faron L, Shen M, Cleary J, Wilkie TM, Gutierrez-Ramos C, Hodge MR . 6 . RGS18 is a myeloerythroid lineage-specific regulator of G-protein-signalling molecule highly expressed in megakaryocytes . The Biochemical Journal . 359 . Pt 1 . 109–118 . October 2001 . 11563974 . 1222126 . 10.1042/bj3590109 .
• Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker SA, He W, Wensel TG, Otero G, Brown G, Copeland NG, Jenkins NA, Wilkie TM . 6 . Evolution of the regulators of G-protein signaling multigene family in mouse and human . Genomics . 79 . 2 . 177–185 . February 2002 . 11829488 . 10.1006/geno.2002.6693 . 16065132 .
• Gagnon AW, Murray DL, Leadley RJ . Cloning and characterization of a novel regulator of G protein signalling in human platelets . Cellular Signalling . 14 . 7 . 595–606 . July 2002 . 11955952 . 10.1016/S0898-6568(02)00012-8 .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nature Biotechnology . 21 . 5 . 566–569 . May 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, Garnier M . Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system . Brain Research. Molecular Brain Research . 122 . 1 . 24–34 . March 2004 . 14992813 . 10.1016/j.molbrainres.2003.11.014 .

Notes and References

1. Park IK, Klug CA, Li K, Jerabek L, Li L, Nanamori M, Neubig RR, Hood L, Weissman IL, Clarke MF . 6 . Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells . The Journal of Biological Chemistry . 276 . 2 . 915–923 . January 2001 . 11042171 . 10.1074/jbc.M005947200 . free .
2. Web site: Entrez Gene: RGS18 regulator of G-protein signalling 18.
3. Keramati AR, Chen MH, Rodriguez BA, Yanek LR, Bhan A, Gaynor BJ, Ryan K, Brody JA, Zhong X, Wei Q, Kammers K, Kanchan K, Iyer K, Kowalski MH, Pitsillides AN, Cupples LA, Li B, Schlaeger TM, Shuldiner AR, O'Connell JR, Ruczinski I, Mitchell BD, Faraday N, Taub MA, Becker LC, Lewis JP, Mathias RA, Johnson AD . 6 . NHLBI Trans-Omics for Precision (TOPMed) Consortium . Genome sequencing unveils a regulatory landscape of platelet reactivity . Nature Communications . 12 . 1 . 3626 . June 2021 . 34131117 . 8206369 . 10.1038/s41467-021-23470-9 . 2021NatCo..12.3626K .
4. Yowe D, Weich N, Prabhudas M, Poisson L, Errada P, Kapeller R, Yu K, Faron L, Shen M, Cleary J, Wilkie TM, Gutierrez-Ramos C, Hodge MR . 6 . RGS18 is a myeloerythroid lineage-specific regulator of G-protein-signalling molecule highly expressed in megakaryocytes . The Biochemical Journal . 359 . Pt 1 . 109–118 . October 2001 . 11563974 . 1222126 . 10.1042/bj3590109 .
5. Gagnon AW, Murray DL, Leadley RJ . Cloning and characterization of a novel regulator of G protein signalling in human platelets . Cellular Signalling . 14 . 7 . 595–606 . July 2002 . 11955952 . 10.1016/S0898-6568(02)00012-8 .