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regulator of G-protein signaling 10

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Target not currently curated in GtoImmuPdb

Target id: 2818

Nomenclature: regulator of G-protein signaling 10

Abbreviated Name: RGS10

Family: R12 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 181 10q26.11 RGS10 regulator of G protein signaling 10
Mouse - 181 7 F3 Rgs10 regulator of G-protein signalling 10
Rat - 181 1q37 Rgs10 regulator of G-protein signaling 10
Gene and Protein Information Comments
Post-translational palmitoylation of a conserved cysteine residue (Cys66) within the RGS domain regulates GAP activity; determined by expression of palmitoylated protein in Sf9 cells [43]. PKA-mediated specific and inducible phosphorylation of Ser168 promotes nuclear translocation of RGS10 and reduces GIRK channel kinetics [6]. The S168A modification prevents phosphorylation and nuclear translocation.
Previous and Unofficial Names Click here for help
G0S8
Database Links Click here for help
Alphafold O43665 (Hs), Q9CQE5 (Mm), P49806 (Rn)
CATH/Gene3D 1.10.196.10
Ensembl Gene ENSG00000148908 (Hs), ENSMUSG00000030844 (Mm), ENSRNOG00000042592 (Rn)
Entrez Gene 6001 (Hs), 67865 (Mm), 54290 (Rn)
Human Protein Atlas ENSG00000148908 (Hs)
KEGG Gene hsa:6001 (Hs), mmu:67865 (Mm), rno:54290 (Rn)
OMIM 607191 (Hs)
Pharos O43665 (Hs)
RefSeq Nucleotide NM_001005339 (Hs), NM_026418 (Mm), NM_019337 (Rn)
RefSeq Protein NP_001005339 (Hs), NP_080694 (Mm), NP_062210 (Rn)
UniProtKB O43665 (Hs), Q9CQE5 (Mm), P49806 (Rn)
Wikipedia RGS10 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure of RGS10
PDB Id:  2I59
Resolution:  0.0Å
Species:  Human
References:  40
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the heterodimeric complex of human RGS10 and activated Gi alpha 3
PDB Id:  2IHB
Resolution:  2.71Å
Species:  Human
References:  40
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure of the RGS domain of human Regulator of G-protein Signaling 10
PDB Id:  2DLR
Resolution:  0.0Å
Species:  Human
References: 
Associated Proteins Click here for help
G Proteins
Name References
Gαi/0 9,22
Gαz 22
Interacting Proteins
Name Effect References
polyubiquitin-C 24,41,44
lysophosphatidic acid phosphatase type 6 10
spinophilin (SPL; Neurabin-2, PPP1R9B) Regulation of platelet activation through a time and context-dependent formation of SPL/RGS/SHP1 complex. 33
histone deacetlyase complex subunit SAP18 10
eukaryotic translation initiation factor 6 10
β2-adrenoceptor 25
Amyloid beta (A4) precursor protein 38
Calmodulin Regulation of RANKL-evoked Ca2+ oscillation in osteoclasts through competitive interaction with PIP3. 48
Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) Regulation of RANKL-evoked Ca2+ oscillation in osteoclast 48
Pleckstrin Homology and FYVE Domain Containing 2 32
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
References:  3-4,23,27-28,30,45
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
References:  47
Immuno Cell Type:  T cells
References:  12,23,29
Immuno Cell Type:  B cells
References:  16,23
Immuno Process Associations
Immuno Process:  Immune regulation
Comment:  Regulation of T cells, macrophages, platelets, osteoclasts, dendritic cells and microglia.
References:  3,8,17,27-30,33-35,47
Immuno Process:  Chemotaxis & migration
Comment:  T cells
References:  12,29
Immuno Process:  Cytokine production & signalling
Comment:  T cells, macrophages, osteoclasts and microglia.
References:  3-4,27-30,47
Immuno Disease Associations
Disease Name:  Multiple sclerosis
Disease Synonyms:  no synonynms
Disease X-refs:  Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802
References:  29
Disease Name:  Schizophrenia
Disease Synonyms:  no synonynms
Comment:  Possible link to schizophrenia and depression.
Disease X-refs:  Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
References:  15,18
Disease Name:  Parkinson Disease
Disease Synonyms:  no synonynms
Disease X-refs:  Disease Ontology: DOID:14330
OMIM: 168600
References:  28,30
Disease Name:  Periodontal disease
Disease Synonyms:  no synonynms
Disease Name:  Osteoporosis
Disease Synonyms:  no synonynms
Disease X-refs:  Disease Ontology: DOID:11476
OMIM: 166710
References:  47-48
Disease Name:  Vascular injury
Disease Synonyms:  no synonynms
Disease Name:  Ovarian cancer
Disease Synonyms:  no synonynms
Disease X-refs:  Disease Ontology: DOID:2394
OMIM: 167000
References:  5,7,20
Tissue Distribution Click here for help
Osteoclasts
Species:  Human
Technique: 
References:  46-48
Platelets
Species:  Human
Technique: 
References:  8,17,33-36
RGS10 is expressed in the forebrain interneurons, dentate gyrus and the striatum. Furthermore, microglia, enkephalin-expressing indirect pathway neuronal cells, and CA3 pyramidal cells expresses RGS10.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  45
Protein level expression of RGS10 is reported in various tissues including heart, lung, spleen, stomach, intestine and different region of the brain.
Species:  Mouse
Technique:  Immunoblot.
References:  2
RGS10 is expressed in the dentate gyrus granule cells; superficial layers of neocortex and the dorsal raphe.
Species:  Rat
Technique:  In situ hybridisation.
References:  14
RGS10 is expressed in the dentate gyrus granule cell layer, dorsal raphe nucleus, striatum, and the forebrain interneurons. Other cells that express RGS10 include: microglia, enkephalin-expressing indirect pathway neuronal cells, and CA3 pyramidal cells.
Species:  Rat
Technique:  Immunohistochemistry.
References:  45
Functional Assays Click here for help
RGS10 enhances GTPase activity, and accelerates the hydrolysis of the active GTP-bound Gαi.
Species:  Human
Tissue:  In vitro assays.
Response measured:  Inactivation of Gαi.
References:  22
RGS10 regulation of M2 muscarinic receptor-mediated GIRK 1/4 activity.
Species:  Human
Tissue:  Ectopic RGS10 expression in HEK293 cells.
Response measured:  GIRK channel activity by electrophysiology.
References:  6
RGS10 translocation from the plasma membrane to the nucleus.
Species:  Human
Tissue:  Ectopic RGS10 expression in HEK293 cells.
Response measured:  PKA phosphorylation by immunocytochemistry.
References:  6
RGS10 effect on RANKL-induced Calcium signaling.
Species:  Mouse
Tissue:  Primary BMMs.
Response measured:  Ca2+ oscillation in response to RANKL treatment.
References:  48
RGS10 effect on PKA/cAMP response-element (CREB) pro-survival pathway.
Species:  Mouse
Tissue:  Murine clonal hybrid MN9D cells.
Response measured:  CREB/p-CREB and caspase activity analysis via western blot.
References:  26
Physiological Functions Click here for help
RGS10 negatively regulates regulates microglial burden, NF-κB proinflammatory pathway and inflammation induced neurodegeneration.
Species:  Mouse
Tissue:  Brain.
References:  28
RGS10 regulates RANKL-induced osteoclast Ca2+ oscillation, differentiation and osteopetrosis.
Species:  Mouse
Tissue:  Murine BMMs
References:  48
RGS10 regulates cardiac remodeling by inhibiting MAPK-ERK 1/2 signaling (humand AND mouse).
Species:  Human
Tissue:  Failing human hearts, hypertrophic murine heart and isolated primary cardiomyocytes.
References:  37
RGS10 negatively regulates GPCR-induced platelet activation and thrombotic function.
Species:  Mouse
Tissue:  In vivo and in isolated platelets.
References:  17
RGS10 regulates Th1-mediated autoimmune and CNS inflammation, and exacerbates clinical symptoms of EAE.
Species:  Mouse
Tissue:  In vivo assay and isolated/differentiated T cells from spleen and lymph nodes.
References:  29
RGS10 limits high-fat diet-induced insulin resistance and inflammation.
Species:  Mouse
Tissue:  In vivo assay, liver and adipose tissue.
References:  11
Physiological Consequences of Altering Gene Expression Click here for help
RGS10 deficient T cells display impaired integrin-dependent cell adhesion.
Species:  Human
Tissue:  Molt-4, Jurkat T cells and peripheral blood T lymphocytes.
Technique:  RNA interference (RNAi).
References:  12
RGS10 knockdown in ovarian cancer cells enhances AKT activity and the survival of cells following chemotherapy treatment.
Species:  Human
Tissue:  SKOV-3 and MDR-HeyA8 cells
Technique:  RNA intererence (RNAi)
References:  19-20
RGS10 loss reduces immune cell infiltration in inflammatory lesion model and prevents osteoclast-mediated bone resorption.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout.
References:  47
RGS10 knockout mice display enhanced microglial activation and an increase in the production of pro-inflammatory cytokines. In contrast, over-expression of RGS10 prevents the activation of microglia and subsequent pro-inflammatory cytokine production.
Species:  Mouse
Tissue:  Brain tissue and primary microglia.
Technique:  Gene knockout and gene over-expression.
References:  28,30
RGS10 deficient mice exhibited dysregulated RANKL-evoked Ca2+ signaling that contributes to osteopetrosis and impaired osteoclast differentiation.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  48
RGS10 null mice displayed milder clinical symptoms of experimental autoimmune encephalomyelitis (EAE) with reduced demyelination and leukocyte infiltration.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout.
References:  29
RGS10 expression is reduced in hypertrophic hearts, and RGS10 null mice exhibit exacerbated cardiac hypertrophy and fibrosis.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout and tissue specific RGS10 overexpression.
References:  37
RGS10 gene transfer into the SNpc suppresses microgliosis and neurotoxin-induced hemiparkinsonism.
Species:  Rat
Tissue:  In vivo.
Technique:  Gene knockout and lentiviral-mediated restoration of RGS10.
References:  28
Loss of RGS10 alters platelet reactivity and alters the structure and stability of hemostatic thrombi.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout.
References:  35
RGS10 and RGS18 double knockout mice have dysreulated platelet activation, reduced platelet survival and increased hemostatic response to injury.
Species:  Mouse
Tissue:  In vivo.
Technique:  Double gene knockout using CRISPR-Cas9
References:  8
Dietary green tea extract ameliorates the exaggerated insulin resistance and inflammation phenotype of RGS10 deficient mice in response to high-fat diet.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout.
References:  11
RGS10 deficient mice have enhanced GPCR-induced platelet aggregation and activation and are susceptible to hyperagulation.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout.
References:  17
Loss of RGS10 is associated with age-dependent dysregulation of peripheral and immune cells.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout.
References:  23
Macrophages isolated from RGS10 deficient mice have enhanced M1/M2 polarization response.
Species:  Mouse
Tissue:  Isolated peritoneal macrophages.
Technique:  Gene knockout.
References:  27
RGS10 knockout enhances LPS-mediated induction of COX-2 and PGE2 production.
Species:  Mouse
Tissue:  BV2 microglia.
Technique:  CRISPR-Cas9 RGS10 knockout and RNAi.
References:  3
Xenobiotics Influencing Gene Expression Click here for help
Tumor necrosis factor (TNF) treatment (10 ng/ml) reduces RGS10 expression in BV-2 microglia cell line. The decrease in RGS10 expression is observed after 24 hours of TNF treatment.
Species:  Mouse
Tissue:  Murine BV2 microglial cell line.
Technique:  Immunoblot analysis.
References:  30
Lipopolysaccharide (10 ng/ml) treatment significantly down-regulates RGS10 expression in mouse primary microglia and murine BV-2 microglia cell line. The LPS-induced RGS10 suppression reaches its peak 48 hours after starting the treatment. LPS also induced RGS10 nuclear translocation.
Species:  Mouse
Tissue:  Mice primary microglia, murine BV2 microglial cell line.
Technique:  Immunofluorescence and immunoblot analysis.
References:  30
RGS10 mRNA expression is enhanced by 48h treatment with sphingosine 1-phosphate (S1P) (10 μM) treatment, while RGS10 transcript and protein expression is silenced by LPS (10ng/mL -10 μg/ml) for 4-72h and 4h, respectively.
Species:  Mouse
Tissue:  BV2 microglia.
Technique:  RT-PCR and immunoblot analysis.
References:  4
Cisplatin treatment (10 ng/ml) for 48h significantly reduces RGS10 mRNA expression in SKOV-3 cells.
Species:  Human
Tissue:  SKOV-3 ovarian tumor ‎cells.
Technique:  Quantitative real-time PCR.
References:  21
Histone deacetylase inhibitor trichostatin A (TSA) increases the mRNA expression of RGS10 in A2780-AD cells.
Species:  Human
Tissue:  A2780-AD human ovarian carcinoma cells.
Technique:  Quantitative real-time PCR.
References:  7
Synthetic lipoprotein FSL-1 (100nM) treatment for 6h and LPS (10ng/ml) treatment for 3h induces reduction in RGS10 mRNA levels in BMDM cells.
Species:  Mouse
Tissue:  Differentiated bone marrow-derived macrophages (BMDMs).
Technique:  Microarray analysis.
References:  39
Amphetamine administration suppresses mRNA levels of RGS10 in the ventral tagmental area (VTA) of the brain.
Species:  Mouse
Tissue:  VTA of brain.
Technique:  Quantitative real-time PCR.
References:  42
Acute (30 min) and prolonged (5 days) treatment of reserpine enhances and suppresses striatal RGS10 mRNA levels, respectively.
Species:  Rat
Tissue:  Striatum.
Technique:  Quantitative in situ hybridization.
References:  13
Black tea polyphenol theaflavin monogallate (TF-2) treatment (4h) induces upregulation of RGS10 mRNA level in Caco-2 cells.
Species:  Human
Tissue:  Human colon cancer Caco-2 cells.
Technique:  Northern blot and real-time PCR.
References:  31
Angiotensin II treatment (50 μM) upregulates RGS10 protein expression in neonatal rat cardiomyocytes following 24h and 48h stimulation.
Species:  Rat
Tissue:  Primary neonatal rat cardiomyocytes.
Technique:  Immunoblotting.
References:  37
RANKL induces RGS10 mRNA and protein expression in mouse osteoclasts derived from BMMs after >3h stimulation.
Species:  Mouse
Tissue:  Differentiated osteoclasts derived from bone-marrow derived monocytes.
Technique:  Northern blot and immunoblotting.
References:  48
Trimethylamine N-oxide (TMAO) injection in rats downregulates RGS10 protein expression in the paw and spinal cord tissues after 24h.
Species:  Rat
Tissue:  Paw and spinal cord tissue.
Technique:  ELISA.
References:  49
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Osteoporosis
Disease Ontology: DOID:11476
OMIM: 166710
References:  48
Disease:  Parkinson Disease
Synonyms: Parkinson's disease [Disease Ontology: DOID:14330]
Disease Ontology: DOID:14330
OMIM: 168600
References:  30
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human Glu52Lys (E52K) E52K mutant RGS10 has impaired Gαi3 binding and GAP activity; synthetically introduced mutation, expressed in HEK293 and SKOV3 cells. 3
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Polymorphism associated with schizophrenia.
Nucleotide change:  A>G
References:  15
Type:  Missense mutation
Species:  Human
Description:  Polymorphism associated with schizophrenia.
Amino acid change:  Val38Met
References:  18
Type:  Splice variant
Species:  Human
Description:  Splice variant lacking 14 amino acids in the N-terminus region has impaired GAP activity validated in yeast.
References:  1
Type:  Splice variant
Species:  Human
Description:  Loss of RGS10A variant alters RANKL-evoked signaling pathway which impairs osteoclast differentiation.
Amino acids:  181
Nucleotide accession:  NM_001005339
Protein accession:  NP_001005339
References:  46

References

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