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.[6]
Clinical signficance[]
Several RGS18alleles that result in reduced RGS18 expression are associated with the development of atherosclerosis.[7] Two single nucleotide polymorphisms in the RGS18 gene that interfer 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.[7]
Interactions[]
RGS18 has been shown to interact with GNAI3.[8][9]
^Gagnon AW, Murray DL, Leadley RJ (July 2002). "Cloning and characterization of a novel regulator of G protein signalling in human platelets". Cellular Signalling. 14 (7): 595–606. doi:10.1016/S0898-6568(02)00012-8. PMID11955952.
Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, et al. (February 2002). "Evolution of the regulators of G-protein signaling multigene family in mouse and human". Genomics. 79 (2): 177–185. doi:10.1006/geno.2002.6693. PMID11829488.
Gagnon AW, Murray DL, Leadley RJ (July 2002). "Cloning and characterization of a novel regulator of G protein signalling in human platelets". Cellular Signalling. 14 (7): 595–606. doi:10.1016/S0898-6568(02)00012-8. PMID11955952.
Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–569. doi:10.1038/nbt810. PMID12665801. S2CID23783563.
Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, Garnier M (March 2004). "Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system". Brain Research. Molecular Brain Research. 122 (1): 24–34. doi:10.1016/j.molbrainres.2003.11.014. PMID14992813.
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PDB gallery
2dlv: Solution structure of the RGS domain of human regulator of G-protein signaling 18
2jm5: Solution Structure of the RGS domain from human RGS18
2owi: Solution structure of the RGS domain from human RGS18
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