Top ▲

regulator of G-protein signaling 1

Click here for help

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2804

Nomenclature: regulator of G-protein signaling 1

Abbreviated Name: RGS1

Family: R4 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 209 1q31.2 RGS1 regulator of G protein signaling 1
Mouse - 209 1 62.56 cM Rgs1 regulator of G-protein signaling 1
Rat - 209 13q21 Rgs1 regulator of G-protein signaling 1
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold Q08116 (Hs), Q9JL25 (Mm), P97844 (Rn)
CATH/Gene3D 1.10.196.10
Ensembl Gene ENSG00000090104 (Hs), ENSMUSG00000026358 (Mm), ENSRNOG00000003895 (Rn)
Entrez Gene 5996 (Hs), 50778 (Mm), 54289 (Rn)
Human Protein Atlas ENSG00000090104 (Hs)
KEGG Gene hsa:5996 (Hs), mmu:50778 (Mm), rno:54289 (Rn)
OMIM 600323 (Hs)
Pharos Q08116 (Hs)
RefSeq Nucleotide NM_002922 (Hs), NM_015811 (Mm), NM_019336 (Rn)
RefSeq Protein NP_002913 (Hs), NP_056626 (Mm), NP_062209 (Rn)
UniProtKB Q08116 (Hs), Q9JL25 (Mm), P97844 (Rn)
Wikipedia RGS1 (Hs)
Associated Proteins Click here for help
G Proteins
Name References
Gαi/0 38
Gαq/11 38
Gαs (non-GAP function) 13
Interacting Proteins
Name Effect References
Calmodulin Does not directly affect GAP activity 32
G-protein α subunit Increase in the intrinsic GTPase activity, acceleration of Gα-mediated GTP hydrolysis, and signaling attenuation 38,41
GTPase Increases the activity of a GTPase hence catalyzing the hydrolysis of GTP 6,25,38
Immunopharmacology Comments
RGS1 is expressed in lymphocytes and macrophages and plays a role in leukocyte trafficking and vascular inflammation [3,10,20,30], and has been associated with multiple immune-mediated diseases [2,4,15,37].
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:  30
Tissue Distribution Click here for help
Lymphocytes
Species:  Human
Technique:  RT-PCR
References:  19
Lung, intestine, placenta, kidney, testis
Species:  Human
Technique:  RT-PCR
References:  19
B cells
Species:  Human
Technique:  Northern blot, in situ hybridisation
References:  12,26
Spleen B cells
Species:  Mouse
Technique:  Northern blot
References:  21
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 Click here for help
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:  38
Physiological Functions Click here for help
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:  30
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:  5,20
Impairment of chemokine-induced cell migration in lymphocytes
Species:  Human
Tissue:  B lymphocytes
References:  3,22
Down regulation of B cell responses to lymphoid chemokine
Species:  Mouse
Tissue:  B lymphocytes
References:  33
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:  27
Reduced RGS1 gene expression levels in peripheral blood mononuclear cells from MS patients.
Species:  Human
Tissue:  PBMCs
References:  39
RGS1 promotes melanoma progression through regulation of Gαs‑mediated inactivation of AKT and ERK.
Species:  None
Tissue:  Cell culture
References:  39
Vascular wall Rgs1 is required for angiotensin II-mediated blood pressure control.
Species:  Mouse
Tissue: 
References:  29
Physiological Consequences of Altering Gene Expression Click here for help
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:  36
Leukocyte Rgs1 deficiency protects against aneurysm rupture.
Species:  Mouse
Tissue:  Bone marrow
Technique:  Gene knockout
References:  30
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:  33
Lack of Rgs1 results in aberrant responses to the chemokines CXCL12 and CXCL13.
Species:  Mouse
Tissue:  B cells
Technique:  Gene knockout
References:  21
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:  21
Immunization of Rgs1 knockout leads to abnormal trafficking of immunoglobulin-secreting cells.
Species:  Mouse
Tissue:  Plasma cells
Technique:  Gene knockout
References:  21
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:  21
RGS1 expression inhibits chemoattractant-induced migration and adhesion (to a lesser extent).
Species:  Human
Tissue:  Lymphoid cells
Technique:  Transient transfection
References:  3
Suppression of Rgs1 inhibits the inflammatory response and angiogenesis by inactivating the TLR signaling pathway in rats with collagen-induced arthritis.
Species:  Rat
Tissue: 
Technique:  shRNA
References:  13
High RGS1 expression correlates with poor prognosis in multiple myeloma.
Species:  Human
Tissue: 
Technique:  qPCR
References:  34
Xenobiotics Influencing Gene Expression Click here for help
RGS1 is strongly inducible by phorbol esters.
Species:  Human
Tissue:  B lymphocytes
Technique: 
References:  11-12,24
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:  12,24
RGS1 expression is upregulated following in vivo antigen exposure.
Species:  Mouse
Tissue:  B cells
Technique: 
References:  33
Clinically-Relevant Mutations and Pathophysiology Click here for help
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:  Vascular diseases: Atherosclerosis AND aortic aneurysms
References:  28,30
Disease:  Celiac disease
Disease Ontology: DOID:10608
References:  1,8-9,14-15,17,31,35,37
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:  Crohn's disease AND ulcerative colitis
References:  8
Disease:  Diabetes mellitus, insulin-dependent; IDDM
Synonyms: Type 1 diabetes mellitus [Disease Ontology: DOID:9744]
Disease Ontology: DOID:9744
OMIM: 222100
References:  37
Disease:  Multiple sclerosis
Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802
References:  16,18,23,40
Gene Expression and Pathophysiology Comments
RGS1 has been associated with multiple immune-mediated diseases [2,4,15,37].
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  RGS1 as novel multiple sclerosis susceptibility locus.
References:  15
Type:  Single nucleotide polymorphism
Species:  Human
Description:  RGS1 SNP rs2816316 is associated with celiac disease.
SNP accession:  rs2816316
References:  9
Type:  Polymorphism
Species:  Human
Description:  RGS1 polymorphism is associated with reduced attack severity of multiple sclerosis.
References:  23

References

Show »

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. Hu X, Tang J, Zeng G, Hu X, Bao P, Wu J, Liang Y, Deng W, Tang Y. (2019) RGS1 silencing inhibits the inflammatory response and angiogenesis in rheumatoid arthritis rats through the inactivation of Toll-like receptor signaling pathway. J Cell Physiol, 234 (11): 20432-20442. [PMID:31012109]

14. 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]

15. 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]

16. 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]

17. 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]

18. 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]

19. 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]

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

21. 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]

22. 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]

23. 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]

24. 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]

25. 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]

26. 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]

27. 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]

28. Patel J, Channon KM, McNeill E. (2013) The downstream regulation of chemokine receptor signalling: implications for atherosclerosis. Mediators Inflamm, 2013: 459520. [PMID:23690662]

29. Patel J, Chuaiphichai S, Douglas G, Gorvin CM, Channon KM. (2018) Vascular wall regulator of G-protein signalling-1 (RGS-1) is required for angiotensin II-mediated blood pressure control. Vascul Pharmacol, 108: 15-22. [PMID:29654907]

30. 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]

31. 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]

32. Popov SG, Krishna UM, Falck JR, Wilkie TM. (2000) Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity. J Biol Chem, 275 (25): 18962-8. [PMID:10747990]

33. 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]

34. Roh J, Shin SJ, Lee AN, Yoon DH, Suh C, Park CJ, Huh J, Park CS. (2017) RGS1 expression is associated with poor prognosis in multiple myeloma. J Clin Pathol, 70 (3): 202-207. [PMID:27445341]

35. 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]

36. 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]

37. 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]

38. 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 USA, 105 (17): 6457-62. [PMID:18434541]

39. Sun MY, Wang Y, Zhu J, Lv C, Wu K, Wang XW, Xue CY. (2018) Critical role for non‑GAP function of Gαs in RGS1‑mediated promotion of melanoma progression through AKT and ERK phosphorylation. Oncol Rep, 39 (6): 2673-2680. [PMID:29620236]

40. 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]

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

Contributors

Show »

How to cite this page