regulator of G-protein signaling 18 | R4 family | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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regulator of G-protein signaling 18

Target id: 2807

Nomenclature: regulator of G-protein signaling 18

Abbreviated Name: RGS18

Family: R4 family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 235 1q31.2 RGS18 regulator of G protein signaling 18 18
Mouse - 235 1 F Rgs18 regulator of G-protein signaling 18 18
Rat - 235 13q21 Rgs18 regulator of G-protein signaling 18
Previous and Unofficial Names
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
G Proteins
Name References
Interacting Proteins
Name Effect References
Gi, Gq alpha subunits GTP hydrolysis 15
Gnai-3 GTP hydrolysis 19
Gnai-1, i-2, i-3, Gnaq 2
Gnai, Gnaq GTP hydrolysis 14
14-3-3γ 14-3-3γ protein binds to phosphorylated serines 49 and 218 of RGS18, which blocks activity. 3
spinophilin (SPL), and the tyrosine phosphatase, SHP-1 bind Rgs18 Sequesters Rgs18 11-12
Tissue Distribution
RGS18 protein is upregulated in the plasma of patients with amyotrophic lateral sclerosis (ALS).
Species:  Human
Technique:  Western blot.
References:  6
Platelets, monocytes, lymphocytes, megakaryocytes, fetal liver.
Species:  Human
Technique:  RT-PCR, northern and western blots.
References:  2,9,17,19
Hematopoietic stem cells, fetal liver, spleen, and lung.
Species:  Human
Technique:  Northern blot and RT-PCR.
References:  15
Megakaryocytes, spleen, hematopoietic cells and monocytes.
Species:  Mouse
Technique:  Northern blot and RT-PCR.
References:  14,17
Hematopoietic stem cells, fetal liver, spleen, and lung. Megakaryocytes, platelets, fetal liver (qRT-PCR).
Species:  Mouse
Technique:  Western blot and quantitative RT-PCR.
References:  15,19
Natural killer (NK) cells.
Species:  Rat
Technique:  RT-PCR and western blot.
References:  8
Species:  None
Technique:  Microarray analysis.
References:  16
Functional Assays
GTP hydrolysis by Gαi-GTP and Gαq-GTP
Species:  None
Tissue:  Megakaryocytes, platelets, granulocytes/monocytes.
Response measured:  RGS18 GTPase-activating protein (GAP) activity for Gαi and Gαq.
References:  14-15,19
RGS18 inhibited mitogen-activated-protein kinase activation in HEK-293/chemokine receptor 2 cells treated with monocyte chemotactic protein-1.
Species:  None
Tissue:  HEK-293 cells.
Response measured:  Inhibition of MAPK activation.
References:  19
Physiological Functions
Activity dependent inhibition of TXA2 and thrombin.
Species:  Human
Tissue:  Platelets.
References:  12
Rgs18 can reduce cell migration evoked by CXC chemokine ligand (CXCL)12, CC chemokine ligand (CCL)19, or CCL21.
Species:  Mouse
Tissue:  Hematopoietic dendritic cells.
References:  17
Rgs18 inhibited osteoclastogenesis evoked by RANKL in RAW264.7, and primary osteoclast precursor monocytes derived from mouse bone marrow cultured with macrophage-colony stimulating factor (M-CSF).
Species:  Mouse
Tissue:  RAW264.7 cells and primary osteoclast precursor monocytes from mouse bone marrow.
References:  7
Physiological Consequences of Altering Gene Expression
RGS18-/- mice present a mild thrombocytopenia, accompanied with a marked deficit in megakaryocyte (MK) number in the bone marrow; defective megakaryopoiesis; lower bone marrow content of only the most committed MK precursors and defect of platelet recovery in vivo under acute conditions of thrombocytopenia.
Species:  Mouse
Tissue:  Bone marrow.
Technique:  Gene knockout.
References:  1,12
Lentiviral RGS18 overexpression during differentiation of mouse Sca1 hematopoietic stem cells induces increase of megakaryocyte proliferation. RGS18 depletion in zebrafish results in thrombocytopenia (embryos lack thrombocytes after injection of an ATG or splice-blocking morpholino); all RGS18 depleted embryos have curly tails and an almost absent response to acoustic stimuli. In situ hybridization in zebrafish, Xenopus, and mouse embryos shows RGS18 expression in thrombocytes and/or hematological tissues but also in brain and otic vesicles. RGS18 interferes with development of cilia in hair cells of the inner ear and neuromast cells.
Species:  Mouse
Tissue:  Hematopoietic stem cells.
Technique:  Viral gene transfer. Immunoblot and RT-PCR were also used. Zebrafish and Xenopus were also investigated.
References:  10
Xenobiotics Influencing Gene Expression
Thrombin, thromboxane A2, or ADP stimulate the interaction of RGS18 and 14-3-3γ protein by increasing the phosphorylation of serine residue S49 of RGS18. This is believed to integrate activating and inhibitory signaling in platelets.
Species:  Human
Tissue:  Platelets.
Technique:  Western blot.
References:  3-4
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cancer
Disease Ontology: DOID:162
References:  5,16
Disease:  Metabolic syndrome
Synonyms: Metabolic syndrome X [Disease Ontology: DOID:14221]
Disease Ontology: DOID:14221
References:  13


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1. Delesque-Touchard N, Pendaries C, Volle-Challier C, Millet L, Salel V, Hervé C, Pflieger AM, Berthou-Soulie L, Prades C, Sorg T et al.. (2014) Regulator of G-protein signaling 18 controls both platelet generation and function. PLoS ONE, 9 (11): e113215. [PMID:25405900]

2. Gagnon AW, Murray DL, Leadley RJ. (2002) Cloning and characterization of a novel regulator of G protein signalling in human platelets. Cell. Signal., 14 (7): 595-606. [PMID:11955952]

3. Gegenbauer K, Elia G, Blanco-Fernandez A, Smolenski A. (2012) Regulator of G-protein signaling 18 integrates activating and inhibitory signaling in platelets. Blood, 119 (16): 3799-807. [PMID:22234696]

4. Gegenbauer K, Nagy Z, Smolenski A. (2013) Cyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets. PLoS ONE, 8 (11): e80251. [PMID:24244663]

5. Hurst JH, Hooks SB. (2009) Regulator of G-protein signaling (RGS) proteins in cancer biology. Biochem. Pharmacol., 78 (10): 1289-97. [PMID:19559677]

6. Häggmark A, Mikus M, Mohsenchian A, Hong MG, Forsström B, Gajewska B, Barańczyk-Kuźma A, Uhlén M, Schwenk JM, Kuźma-Kozakiewicz M et al.. (2014) Plasma profiling reveals three proteins associated to amyotrophic lateral sclerosis. Ann Clin Transl Neurol, 1 (8): 544-53. [PMID:25356426]

7. Iwai K, Koike M, Ohshima S, Miyatake K, Uchiyama Y, Saeki Y, Ishii M. (2007) RGS18 acts as a negative regulator of osteoclastogenesis by modulating the acid-sensing OGR1/NFAT signaling pathway. J. Bone Miner. Res., 22 (10): 1612-20. [PMID:17576169]

8. Kveberg L, Ryan JC, Rolstad B, Inngjerdingen M. (2005) Expression of regulator of G protein signalling proteins in natural killer cells, and their modulation by Ly49A and Ly49D. Immunology, 115 (3): 358-65. [PMID:15946253]

9. Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, Garnier M. (2004) Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system. Brain Res. Mol. Brain Res., 122 (1): 24-34. [PMID:14992813]

10. Louwette S, Labarque V, Wittevrongel C, Thys C, Metz J, Gijsbers R, Debyser Z, Arnout J, Van Geet C, Freson K. (2012) Regulator of G-protein signaling 18 controls megakaryopoiesis and the cilia-mediated vertebrate mechanosensory system. FASEB J., 26 (5): 2125-36. [PMID:22308195]

11. Ma P, Cierniewska A, Signarvic R, Cieslak M, Kong H, Sinnamon AJ, Neubig RR, Newman DK, Stalker TJ, Brass LF. (2012) A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein-dependent signaling. Blood, 119 (8): 1935-45. [PMID:22210881]

12. Ma P, Foote DC, Sinnamon AJ, Brass LF. (2015) Dissociation of SHP-1 from spinophilin during platelet activation exposes an inhibitory binding site for protein phosphatase-1 (PP1). PLoS ONE, 10 (3): e0119496. [PMID:25785436]

13. Mao Y, Lei L, Su J, Yu Y, Liu Z, Huo Y. (2014) Regulators of G protein signaling are up-regulated in aspirin-resistant platelets from patients with metabolic syndrome. Pharmazie, 69 (5): 371-3. [PMID:24855830]

14. Nagata Y, Oda M, Nakata H, Shozaki Y, Kozasa T, Todokoro K. (2001) A novel regulator of G-protein signaling bearing GAP activity for Galphai and Galphaq in megakaryocytes. Blood, 97 (10): 3051-60. [PMID:11342430]

15. Park IK, Klug CA, Li K, Jerabek L, Li L, Nanamori M, Neubig RR, Hood L, Weissman IL, Clarke MF. (2001) Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. J. Biol. Chem., 276 (2): 915-23. [PMID:11042171]

16. Sethakorn N, Dulin NO. (2013) RGS expression in cancer: oncomining the cancer microarray data. J. Recept. Signal Transduct. Res., 33 (3): 166-71. [PMID:23464602]

17. Shi GX, Harrison K, Han SB, Moratz C, Kehrl JH. (2004) Toll-like receptor signaling alters the expression of regulator of G protein signaling proteins in dendritic cells: implications for G protein-coupled receptor signaling. J. Immunol., 172 (9): 5175-84. [PMID:15100254]

18. Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker SA, He W, Wensel TG, Otero G et al.. (2002) Evolution of the regulators of G-protein signaling multigene family in mouse and human. Genomics, 79 (2): 177-85. [PMID:11829488]

19. Yowe D, Weich N, Prabhudas M, Poisson L, Errada P, Kapeller R, Yu K, Faron L, Shen M, Cleary J et al.. (2001) RGS18 is a myeloerythroid lineage-specific regulator of G-protein-signalling molecule highly expressed in megakaryocytes. Biochem. J., 359 (Pt 1): 109-18. [PMID:11563974]


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