regulator of G-protein signaling 1 | R4 family | IUPHAR/BPS Guide to PHARMACOLOGY

regulator of G-protein signaling 1

Target id: 2804

Nomenclature: regulator of G-protein signaling 1

Abbreviated Name: RGS1

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

   GtoImmuPdb view: OFF :     regulator of G-protein signaling 1 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 209 1q31 RGS1 regulator of G protein signaling 1
Mouse - 209 1 F Rgs1 regulator of G-protein signaling 1
Rat - 162 13q21 Rgs1 regulator of G-protein signaling 1
Previous and Unofficial Names
BL34 | IER1 | IR20 | B-cell activation protein BL34 | Early response protein 1R20 | Immediate-Early Response 1, B-Cell Specific | Epididymis Secretory Protein Li 87 | HEL-S-87 | HELS87
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
G Proteins
Name References
Gαi/0 35
Gαq/11 35
Interacting Proteins
Name Effect References
Calmodulin Does not directly affect GAP activity 30
G-protein α subunit Increase in the intrinsic GTPase activity, acceleration of Gα-mediated GTP hydrolysis, and signaling attenuation 35,37
GTPase Increases the activity of a GTPase hence catalyzing the hydrolysis of GTP 6,24,35
Immunopharmacology Comments
RGS1 is expressed in lymphocytes and macrophages and plays a role in leukocyte trafficking and vascular inflammation [3,10,19,28], and has been associated with multiple immune-mediated diseases [2,4,14,34].
Cell Type Associations
Immuno Cell Type:  B cells
Immuno Cell Type:  T cells
Cell Ontology Term:   T follicular helper cell (CL:0002038)
References:  5
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
References:  28
Tissue Distribution
Lymphocytes
Species:  Human
Technique:  RT-PCR
References:  18
Lung, intestine, placenta, kidney, testis
Species:  Human
Technique:  RT-PCR
References:  18
B cells
Species:  Human
Technique:  Northern blot, in situ hybridisation
References:  12,25
Spleen B cells
Species:  Mouse
Technique:  Northern blot
References:  20
Tissue Distribution Comments
Lymphocytes and lungs: high levels of RGS1 (++++)
Intestine, kidney, placenta, and testis: moderate levels of RGS1 (+++)
Heart: low levels of RGS1 (+)
Functional Assays
Regulation of G protein-coupled receptor (GPCR) signaling cascades/signal transduction
Species:  Human
Tissue:  Monocytes
Response measured:  Desensitization of a variety of chemotactic receptors including signaling downstream of the N-formylpeptide chemoattractant receptors and leukotriene receptors.
References:  6
Regulator of G protein signaling
Species:  Human
Tissue: 
Response measured:  Inhibits signal transduction by increasing the GTPase activity of G protein α subunits thereby driving them into their inactive GDP-bound form.
References:  35
Physiological Functions
Role in Leukocyte trafficking and vascular inflammation: RGS1 reduces macrophage chemotaxis and desensitization and modulates macrophage trafficking into the aortic wall.
Species:  Mouse
Tissue:  Macrophage
References:  28
Trafficking of B lymphoctes into lymph nodes and within lymph node follicles
Species:  Mouse
Tissue:  Lymph nodes/ lymph node follicles
References:  10
Rgs1 is an essential regulator of T-cell migration within lymphoid tissue, by modulating chemokine receptor activation.
Species:  Mouse
Tissue:  T cells
References:  5,19
Impairment of chemokine-induced cell migration in lymphocytes
Species:  Human
Tissue:  B lymphocytes
References:  3,21
Down regulation of B cell responses to lymphoid chemokine
Species:  Mouse
Tissue:  B lymphocytes
References:  31
Rgs1 participates in the development and function of T follicular helper (TFH) cells.
Species:  Mouse
Tissue:  T cells
References:  5
Suppression of chemotactic (CXCL12-mediated) migration and AKT activation in cultured RPMI 8226 human plasmacytoma cells and plasmablasts
Species:  Human
Tissue:  Plasmocytoma cells and plasmabalsts
References:  26
Physiological Consequences of Altering Gene Expression
Immunization of Rgs1 knockout leads to abnormal trafficking of immunoglobulin-secreting cells.
Species:  Mouse
Tissue:  Plasma cells
Technique:  Gene knockout
References:  20
Gene is overexpressed in acute lymphocytic leukemia
Species:  Human
Tissue:  B lymphocytes
Technique: 
References:  12
Rgs1 knockout B lymphocytes show better adherence to lymph node high endothelial venules, better homing to lymph nodes, and more rapid movement within lymph node follicles than do wild-type B lymphocytes.
Species:  Mouse
Tissue:  Lymph nodes/lymph nodes follicles
Technique:  Gene knockout
References:  10
Rgs1 knockout mice show heightened dendritic cell migratory response to chemokines CXCL12 and CCL19.
Species:  Mouse
Tissue:  Bone marrow derived dendritic cells
Technique:  Gene knockout
References:  33
Leukocyte Rgs1 deficiency protects against aneurysm rupture.
Species:  Mouse
Tissue:  Bone marrow
Technique:  Gene knockout
References:  28
Rgs1 inhibits chemotaxis of mature B lymphocytes toward the lymphoid tissue chemokines: B lymphocyte chemoattractant (BLC) , EBV-induced molecule 1 ligand chemokine (ELC), and stromal cell-derived factor-1 (SDF-1). Regulating cell positioning in lymphoid orgas during immune response
Species:  Mouse
Tissue:  Mature B lymphocytes
Technique:  Transient transfection
References:  31
Lack of Rgs1 results in aberrant responses to the chemokines CXCL12 and CXCL13.
Species:  Mouse
Tissue:  B cells
Technique:  Gene knockout
References:  20
In Rgs1 knockouts, many of the B-cell follicles in the spleen have germinal centers even in the absence of immune stimulation, and show exagerated germinal center formation after immunization.
Species:  Mouse
Tissue:  B cell follicles in the spleen
Technique:  Gene knockout
References:  20
Immunization of Rgs1 knockout mice leads to a distorted immune architechture of the spleen and Peyer's patches.
Species:  Mouse
Tissue:  Spleen and Peyer's patches
Technique:  Gene knockout
References:  20
RGS1 expression inhibits chemoattractant-induced migration and adhesion (to a lesser extent).
Species:  Human
Tissue:  Lymphoid cells
Technique:  Transient transfection
References:  3
Xenobiotics Influencing Gene Expression
RGS1 is strongly inducible by phorbol esters.
Species:  Human
Tissue:  B lymphocytes
Technique: 
References:  11-12,23
RGS1 expression induced by Interferon B-1b (IFN-B)
Species:  Human
Tissue:  peripheral blood mononuclear cells (PBMCs)
Technique:  Immunoblotting and immunoprecpitation
References:  7
B cell treatment with anti-IgM, IL-4, cAMP, or platelet-activating factor induces the expression of RGS1.
Species:  Human
Tissue:  B lymphocytes
Technique: 
References:  12,23
RGS1 expression is upregulated following in vivo antigen exposure.
Species:  Mouse
Tissue:  B cells
Technique: 
References:  31
Clinically-Relevant Mutations and Pathophysiology
Disease:  Acute lymphocytic leukemia (ALL)
Description: ALL is a subtype of acute leukemia
Synonyms: Acute lymphoblastic leukemia
OMIM: 613065
References:  12
Disease:  Atherosclerosis susceptibility
Disease Ontology: DOID:1936
OMIM: 108725
Comments: 
References:  27-28
Disease:  Celiac disease
Disease Ontology: DOID:10608
References:  1,8-9,13-14,16,29,32,34
Disease:  Crohn's disease
Synonyms: Crohn disease [Disease Ontology: DOID:8778]
Inflammatory bowel disease 1; IBD1 [OMIM: 266600]
Disease Ontology: DOID:8778
OMIM: 266600
Orphanet: ORPHA206
Comments: 
References:  8
Disease:  Diabetes mellitus, insulin-dependent; IDDM
Synonyms: Type 1 diabetes mellitus [Disease Ontology: DOID:9744]
Disease Ontology: DOID:9744
OMIM: 222100
References:  34
Disease:  Multiple sclerosis
Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802
References:  15,17,22,36
Gene Expression and Pathophysiology Comments
RGS1 has been associated with multiple immune-mediated diseases [2,4,14,34].
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  RGS1 as novel multiple sclerosis susceptibility locus
References:  14
Type:  Polymorphism
Species:  Human
Description:  RGS 1 polymorphism associated with reduced attack severity of multiple sclerosis
References:  22

References

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1. Amundsen SS, Rundberg J, Adamovic S, Gudjónsdóttir AH, Ascher H, Ek J, Nilsson S, Lie BA, Naluai AT, Sollid LM. (2010) Four novel coeliac disease regions replicated in an association study of a Swedish-Norwegian family cohort. Genes Immun., 11 (1): 79-86. [PMID:19693089]

2. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C et al.. (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet., 41 (6): 703-7. [PMID:19430480]

3. Bowman EP, Campbell JJ, Druey KM, Scheschonka A, Kehrl JH, Butcher EC. (1998) Regulation of chemotactic and proadhesive responses to chemoattractant receptors by RGS (regulator of G-protein signaling) family members. J. Biol. Chem., 273 (43): 28040-8. [PMID:9774420]

4. Bradfield JP, Qu HQ, Wang K, Zhang H, Sleiman PM, Kim CE, Mentch FD, Qiu H, Glessner JT, Thomas KA et al.. (2011) A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. PLoS Genet., 7 (9): e1002293. [PMID:21980299]

5. Caballero-Franco C, Kissler S. (2016) The autoimmunity-associated gene RGS1 affects the frequency of T follicular helper cells. Genes Immun., 17 (4): 228-38. [PMID:27029527]

6. Denecke B, Meyerdierks A, Böttger EC. (1999) RGS1 is expressed in monocytes and acts as a GTPase-activating protein for G-protein-coupled chemoattractant receptors. J. Biol. Chem., 274 (38): 26860-8. [PMID:10480894]

7. Desai BB, Albright JW, Albright JF. (1987) Cooperative action of complement component C3 and phagocytic effector cells in innate murine resistance to Trypanosoma lewisi. Infect. Immun., 55 (2): 358-63. [PMID:3026965]

8. Gibbons DL, Abeler-Dörner L, Raine T, Hwang IY, Jandke A, Wencker M, Deban L, Rudd CE, Irving PM, Kehrl JH et al.. (2011) Cutting Edge: Regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential. J. Immunol., 187 (5): 2067-71. [PMID:21795595]

9. Guo CC, Wang M, Cao FD, Huang WH, Xiao D, Ye XG, Ou ML, Zhang N, Zhang BH, Liu Y et al.. (2016) Meta-Analysis on Associations of RGS1 and IL12A Polymorphisms with Celiac Disease Risk. Int J Mol Sci, 17 (4). [PMID:27043536]

10. Han SB, Moratz C, Huang NN, Kelsall B, Cho H, Shi CS, Schwartz O, Kehrl JH. (2005) Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles. Immunity, 22 (3): 343-54. [PMID:15780991]

11. Heximer SP, Cristillo AD, Forsdyke DR. (1997) Comparison of mRNA expression of two regulators of G-protein signaling, RGS1/BL34/1R20 and RGS2/G0S8, in cultured human blood mononuclear cells. DNA Cell Biol., 16 (5): 589-98. [PMID:9174164]

12. Hong JX, Wilson GL, Fox CH, Kehrl JH. (1993) Isolation and characterization of a novel B cell activation gene. J. Immunol., 150 (9): 3895-904. [PMID:8473738]

13. Hunt KA, Zhernakova A, Turner G, Heap GA, Franke L, Bruinenberg M, Romanos J, Dinesen LC, Ryan AW, Panesar D et al.. (2008) Newly identified genetic risk variants for celiac disease related to the immune response. Nat. Genet., 40 (4): 395-402. [PMID:18311140]

14. International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z et al.. (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature, 476 (7359): 214-9. [PMID:21833088]

15. International Multiple Sclerosis Genetics Conssortium (IMSGC). (2010) IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci. Genes Immun., 11 (5): 397-405. [PMID:20555355]

16. Izzo V, Pinelli M, Tinto N, Esposito MV, Cola A, Sperandeo MP, Tucci F, Cocozza S, Greco L, Sacchetti L. (2011) Improving the estimation of celiac disease sibling risk by non-HLA genes. PLoS ONE, 6 (11): e26920. [PMID:22087237]

17. Johnson BA, Wang J, Taylor EM, Caillier SJ, Herbert J, Khan OA, Cross AH, De Jager PL, Gourraud PA, Cree BC et al.. (2010) Multiple sclerosis susceptibility alleles in African Americans. Genes Immun., 11 (4): 343-50. [PMID:19865102]

18. 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]

19. Moratz C, Harrison K, Kehrl JH. (2004) Regulation of chemokine-induced lymphocyte migration by RGS proteins. Meth. Enzymol., 389: 15-32. [PMID:15313557]

20. Moratz C, Hayman JR, Gu H, Kehrl JH. (2004) Abnormal B-cell responses to chemokines, disturbed plasma cell localization, and distorted immune tissue architecture in Rgs1-/- mice. Mol. Cell. Biol., 24 (13): 5767-75. [PMID:15199133]

21. Moratz C, Kang VH, Druey KM, Shi CS, Scheschonka A, Murphy PM, Kozasa T, Kehrl JH. (2000) Regulator of G protein signaling 1 (RGS1) markedly impairs Gi alpha signaling responses of B lymphocytes. J. Immunol., 164 (4): 1829-38. [PMID:10657631]

22. Mowry EM, Carey RF, Blasco MR, Pelletier J, Duquette P, Villoslada P, Malikova I, Roger E, Kinkel RP, McDonald J et al.. (2013) Multiple sclerosis susceptibility genes: associations with relapse severity and recovery. PLoS ONE, 8 (10): e75416. [PMID:24130709]

23. Murphy JJ, Norton JD. (1993) Multiple signaling pathways mediate anti-Ig and IL-4-induced early response gene expression in human tonsillar B cells. Eur. J. Immunol., 23 (11): 2876-81. [PMID:7693480]

24. 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]

25. Newton JS, Deed RW, Mitchell EL, Murphy JJ, Norton JD. (1993) A B cell specific immediate early human gene is located on chromosome band 1q31 and encodes an alpha helical basic phosphoprotein. Biochim. Biophys. Acta, 1216 (2): 314-6. [PMID:8241276]

26. Pak HK, Gil M, Lee Y, Lee H, Lee AN, Roh J, Park CS. (2015) Regulator of G protein signaling 1 suppresses CXCL12-mediated migration and AKT activation in RPMI 8226 human plasmacytoma cells and plasmablasts. PLoS ONE, 10 (4): e0124793. [PMID:25897806]

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28. Patel J, McNeill E, Douglas G, Hale AB, de Bono J, Lee R, Iqbal AJ, Regan-Komito D, Stylianou E, Greaves DR et al.. (2015) RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling. Nat Commun, 6: 6614. [PMID:25782711]

29. Plaza-Izurieta L, Castellanos-Rubio A, Irastorza I, Fernández-Jimenez N, Gutierrez G, CEGEC, Bilbao JR. (2011) Revisiting genome wide association studies (GWAS) in coeliac disease: replication study in Spanish population and expression analysis of candidate genes. J. Med. Genet., 48 (7): 493-6. [PMID:21490378]

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31. Reif K, Cyster JG. (2000) RGS molecule expression in murine B lymphocytes and ability to down-regulate chemotaxis to lymphoid chemokines. J. Immunol., 164 (9): 4720-9. [PMID:10779778]

32. Romanos J, Barisani D, Trynka G, Zhernakova A, Bardella MT, Wijmenga C. (2009) Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease. J. Med. Genet., 46 (1): 60-3. [PMID:18805825]

33. 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]

34. Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, Howson JM, Stevens H, McManus R, Wijmenga C et al.. (2008) Shared and distinct genetic variants in type 1 diabetes and celiac disease. N. Engl. J. Med., 359 (26): 2767-77. [PMID:19073967]

35. Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA et al.. (2008) Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc. Natl. Acad. Sci. U.S.A., 105 (17): 6457-62. [PMID:18434541]

36. Tran T, Paz P, Velichko S, Cifrese J, Belur P, Yamaguchi KD, Ku K, Mirshahpanah P, Reder AT, Croze E. (2010) Interferonβ-1b Induces the Expression of RGS1 a Negative Regulator of G-Protein Signaling. Int J Cell Biol, 2010: 529376. [PMID:21274427]

37. Willars GB. (2006) Mammalian RGS proteins: multifunctional regulators of cellular signalling. Semin. Cell Dev. Biol., 17 (3): 363-76. [PMID:16687250]

Contributors

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How to cite this page

Josephine Bou Dagher, Jae-Kyung Lee.
R4 family: regulator of G-protein signaling 1. Last modified on 03/10/2017. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2804.