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regulator of G-protein signaling 1

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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

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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]

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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]

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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]

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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]

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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]

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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]

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