HGNC Approved Gene Symbol: RGS18
Cytogenetic location: 1q31.2 Genomic coordinates (GRCh38): 1:192,158,462-192,185,815 (from NCBI)
Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins are GTPase-activating proteins for Gi (see GNAI1; 139310) and Gq (see GNAQ; 600998) class G-alpha proteins. They accelerate transit through the cycle of GTP binding and hydrolysis and thereby accelerate signaling kinetics and termination.
Park et al. (2001) identified an EST clone for RGS18 expressed in fetal lung using the mouse sequence as query. The deduced mouse and human RGS18 proteins contain 234 amino acids with a central RGS box and share 82% sequence identity. The human sequence has 2 polyadenylation signal sequences and 3 ATTTA or ATTTTA sequences in its 3-prime untranslated region. Both human and mouse proteins contain putative phosphorylation sites for casein kinase II (see 115440), protein kinase C (see 176960), and protein kinase A (see 176911). Northern blot analysis revealed high expression in human peripheral leukocytes followed by bone marrow, spleen, and fetal liver. No expression was detected in any other tissue tested, including thymus and lymph nodes. Within cell lines, RGS18 was expressed only in a monocytic cell line and not in lymphoblastic T cells, chronic myelogenous leukemic cells, or B lymphocytes. In mouse hematopoietic stem cells (HSCs), Rgs18 expression was highest in long- and short-term HSCs and was lower in cells differentiated to more committed lineages.
By in vitro binding assays, Park et al. (2001) found that RGS18 purified from transfected HEK293T cells bound endogenous G-alpha(i) and G-alpha(q) in Jurkat T-cell extracts. In vitro GTPase single-turnover assays indicated that RGS18 accelerates the intrinsic GTPase activity of G-alpha(i). Transient overexpression of RGS18 attenuated inositol phosphate production via G-alpha(q) in response to stimulating the angiotensin receptor (106165). Overexpression also attenuated G-alpha(q)-transduced transcriptional activation through the cAMP-responsive element following activation of the M1 muscarinic receptor (CHRM1; 118510).
Sierra et al. (2002) determined that RGS18 contains 5 exons and spans more than 27 kb.
By genomic sequence analysis, Sierra et al. (2002) mapped the RGS18 gene to chromosome 1q31.2, where it is in tandem with 3 other RGS subfamily R4 genes. They mapped the mouse Rgs18 gene to chromosome 1 by interspecific backcross mapping.
Park, I.-K., Klug, C. A., Li, K., Jerabek, L., Li, L., Nanamori, M., Neubig, R. R., Hood, L., Weissman, I. L., Clarke, M. F. Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. J. Biol. Chem. 276: 915-923, 2001. [PubMed: 11042171] [Full Text: https://doi.org/10.1074/jbc.M005947200]
Sierra, D. A., Gilbert, D. J., Householder, D., Grishin, N. V., Yu, K., Ukidwe, P., Barker, S. A., He, W., Wensel, T. G., Otero, G., Brown, G., Copeland, N. G., Jenkins, N. A., Wilkie, T. M. Evolution of the regulators of G-protein signaling multigene family in mouse and human. Genomics 79: 177-185, 2002. [PubMed: 11829488] [Full Text: https://doi.org/10.1006/geno.2002.6693]