regulator of G-protein signaling 3 | R4 family | IUPHAR/BPS Guide to PHARMACOLOGY

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regulator of G-protein signaling 3

Target not currently curated in GtoImmuPdb

Target id: 2810

Nomenclature: regulator of G-protein signaling 3

Abbreviated Name: RGS3

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 - 1198 9q32 RGS3 regulator of G protein signaling 3 2
Mouse - 966 4 B3 Rgs3 regulator of G-protein signaling 3
Rat - 967 5q24 Rgs3 regulator of G-protein signaling 3
Previous and Unofficial Names
C2PA | PDZ-RGS3  | RGP3
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
Gαq/11
Gαs
Interacting Proteins
Name Effect References
14-3-3 protein Inhibits GAP activity of RGS3. 24,30
GluA2 Regulates glutamatergic synapses. 19
EPH receptor B2 Inhibits heterotremeric G protein signal. 17,35
Phospholipid scramblase 1 (PLSCR1) 1,31
Guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 7
Polyubiquitin-C 13
Amyloid beta (A4) precursor protein 25
Arrestin, beta 1 38
Interferon, alpha-inducible protein 36
Tissue Distribution
Brain, heart, kindey, liver and pancreas, digestive tract, urinary bladder, male reproductive system, breast and female reproductive system, skin, blood and immune system, respiratory system.
Species:  Human
Technique:  Immunohistochemistry.
References:  5,10,15,20
Heart, brain, kindey, blood and immune system.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  10,16,23,29,37
Heart, spleen, brain, testis, intestine, uterus, ovary, lung.
Species:  Rat
Technique:  Western blot and immunohistochemistry.
References:  11,14,40
Functional Assays
Positive regulation of GTPase activity.
Species:  Human
Tissue:  HEK293 cells and mouse NIH 3T3 fibroblasts.
Response measured:  Increase in GTPase activation.
References:  8
Impairs signal transduction through the muscarinic M1 receptor and beta-adrenergic receptor.
Species:  Human
Tissue:  HEK 293T cells.
Response measured:  Inhibition of IP3 production.
References:  32
Attenuation of Gqαα protein activation of phospholipase C.
Species:  Unknown
Tissue:  COS1 cels.
Response measured:  Inhibition of IP3 production.
References:  21
Inactivation of MAPK activity.
Species:  Human
Tissue:  Mammalian cells.
Response measured:  Inactivation of MAPK activity.
References:  6
Translocation to the membrane.
Species:  Human
Tissue:  HEK293 cells and mouse NIH 3T3 fibroblasts.
Response measured:  Regulation of G-protein coupled receptor protein signaling pathway.
References:  8
RGS3T (a truncated variant comprising amino acids 314–519) is localized to the nucleus and induces apoptosis.
Species:  Human
Tissue:  Chinese hamster ovary (CHO) cells.
Response measured:  Apoptosis assay.
References:  7
Physiological Functions
Inhibition of MEK-ERK1/2 signaling.
Species:  Mouse
Tissue:  Heart.
References:  16
Modulating the LH secretory responsiveness of the pituitary gonadotrope to GnRH.
Species:  Human
Tissue:  Gonadotropic alpha T3-1 cells.
References:  21
Shaping the magnitude and kinetics of physiological events.
Species:  Human
Tissue:  HEK293 cells.
References:  18
Promotes epithelial mesenchymal transition.
Species:  Human
Tissue:  HEK 293 cells.
References:  34
Physiological Consequences of Altering Gene Expression
Overexpression of RGS3 protects against cardiac hypertrophy.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  16
Transformation of HL-60 cells to overexpress RGS3 promotes apoptosis in association with the downregulation of the extracellular signal-regulated kinase signal, and vice versa in the RGS3 knocked-down cells.
Species:  Mouse
Tissue:  HL-60 cells, fate of Q137N-HL-60 cells.
Technique:  RNA interference (RNAi).
References:  22
RGS3 deficiency causes early cell cycle exit and precocious differentiation in neural progenitor cells of the developing cerebral cortex, leading to a loss of cortical neural progenitor cells.
Species:  Mouse
Tissue:  Embryonic brain cells.
Technique:  Gene knock-out.
References:  27
Physiological Consequences of Altering Gene Expression Comments
RGS3 is upregulated in p53-mutated breast tumors, and may be a useful predictor of response to docetaxel [26].
RGS3 deficient C. elegans fail to respond to intense sensory stimuli [9].
Xenobiotics Influencing Gene Expression
Rgs3 gene expression is repressed by high-fat feeding.
Species:  Mouse
Tissue:  Hepatic cells.
Technique:  Misroarray.
References:  28
Gene Expression and Pathophysiology Comments
Experiments in rats suggests that modulation of Rgs3 gene expression (and/or other genes involved in the control of G-protein signalling) may play a role the pathology of hypertension-associated bladder dysfunction [39].
Biologically Significant Variants
Type:  mRNA transcript variant.
Species:  Human
Amino acids:  917
Nucleotide accession: 
Protein accession: 
References:  4,12,34
Type:  mRNA transcript variant.
Species:  Human
Description:  This RGS3 variant enhances canonical Wnt signaling and promotes epithelial mesenchymal transition via inhibition of G-protein-mediated MAP kinase activation
Amino acids:  93
Nucleotide accession: 
Protein accession: 
References:  6,34
Type:  mRNA transcript variant.
Species:  Human
Description:  This RGS3 variant enhances canonical Wnt signaling and promotes epithelial mesenchymal transition.
Amino acids:  311
Nucleotide accession: 
Protein accession: 
References:  3-4,12
Type:  mRNA transcript variant.
Species:  Human
Description:  This RGS3 variant leads to inhibition of G-protein-mediated MAP kinase activation.
Amino acids:  519
Nucleotide accession: 
Protein accession: 
References:  2,4,6
Type:  mRNA transcript variant.
Species:  Human
Description:  This variant localizes RGS3 to the nucleus and induces apoptosis.
Amino acids:  519
Nucleotide accession: 
Protein accession: 
References:  2
Type:  mRNA transcript variant.
Species:  Human
Description:  This RGS3 variant inhibits G-protein-mediated signal transduction.
Amino acids:  1198
Nucleotide accession: 
Protein accession: 
References:  4,33

References

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1. BioGRID3.4. PLSCR1. Accessed on 14/09/2015. Modified on 14/09/2015. BioGRID3.4http://thebiogrid.org/111373/summary/homo-sapiens/plscr1.html

2. Chatterjee TK, Eapen A, Kanis AB, Fisher RA. (1997) Genomic organization, 5'-flanking region, and chromosomal localization of the human RGS3 gene. Genomics, 45 (2): 429-33. [PMID:9344672]

3. Chatterjee TK, Eapen AK, Fisher RA. (1997) A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C. J. Biol. Chem., 272 (24): 15481-7. [PMID:9182581]

4. Chen B, Siderovski DP, Neubig RR, Lawson MA, Trejo J. (2014) Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins. J. Biol. Chem., 289 (3): 1580-91. [PMID:24297163]

5. Cho H, Harrison K, Schwartz O, Kehrl JH. (2003) The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling. Biochem. J., 371 (Pt 3): 973-80. [PMID:12564955]

6. Druey KM, Blumer KJ, Kang VH, Kehrl JH. (1996) Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature, 379 (6567): 742-6. [PMID:8602223]

7. Dulin NO, Pratt P, Tiruppathi C, Niu J, Voyno-Yasenetskaya T, Dunn MJ. (2000) Regulator of G protein signaling RGS3T is localized to the nucleus and induces apoptosis. J. Biol. Chem., 275 (28): 21317-23. [PMID:10749886]

8. Dulin NO, Sorokin A, Reed E, Elliott S, Kehrl JH, Dunn MJ. (1999) RGS3 inhibits G protein-mediated signaling via translocation to the membrane and binding to Galpha11. Mol. Cell. Biol., 19 (1): 714-23. [PMID:9858594]

9. Ferkey DM, Hyde R, Haspel G, Dionne HM, Hess HA, Suzuki H, Schafer WR, Koelle MR, Hart AC. (2007) C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli. Neuron, 53 (1): 39-52. [PMID:17196529]

10. Grüning W, Arnould T, Jochimsen F, Sellin L, Ananth S, Kim E, Walz G. (1999) Modulation of renal tubular cell function by RGS3. Am. J. Physiol., 276 (4 Pt 2): F535-43. [PMID:10198412]

11. Ikeda M, Hirokawa M, Satani N, Kinoshita T, Watanabe Y, Inoue H, Tone S, Ishikawa T, Minatogawa Y. (2001) Molecular cloning and characterization of a steroid receptor-binding regulator of G-protein signaling protein cDNA. Gene, 273 (2): 207-14. [PMID:11595167]

12. Kehrl JH, Srikumar D, Harrison K, Wilson GL, Shi CS. (2002) Additional 5' exons in the RGS3 locus generate multiple mRNA transcripts, one of which accounts for the origin of human PDZ-RGS3. Genomics, 79 (6): 860-8. [PMID:12036301]

13. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ et al.. (2011) Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell, 44 (2): 325-40. [PMID:21906983]

14. Koelle MR, Horvitz HR. (1996) EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins. Cell, 84 (1): 115-25. [PMID:8548815]

15. 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]

16. Liu Y, Huang H, Zhang Y, Zhu XY, Zhang R, Guan LH, Tang Q, Jiang H, Huang C. (2014) Regulator of G protein signaling 3 protects against cardiac hypertrophy in mice. J. Cell. Biochem., 115 (5): 977-86. [PMID:24375609]

17. Lu Q, Sun EE, Flanagan JG. (2004) Analysis of PDZ-RGS3 function in ephrin-B reverse signaling. Meth. Enzymol., 390: 120-8. [PMID:15488174]

18. Melliti K, Meza U, Fisher R, Adams B. (1999) Regulators of G protein signaling attenuate the G protein-mediated inhibition of N-type Ca channels. J. Gen. Physiol., 113 (1): 97-110. [PMID:9874691]

19. Meyer G, Varoqueaux F, Neeb A, Oschlies M, Brose N. (2004) The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a case study on neuroligin. Neuropharmacology, 47 (5): 724-33. [PMID:15458844]

20. Mittmann C, Schüler C, Chung CH, Höppner G, Nose M, Kehrl JH, Wieland T. (2001) Evidence for a short form of RGS3 preferentially expressed in the human heart. Naunyn Schmiedebergs Arch. Pharmacol., 363 (4): 456-63. [PMID:11330340]

21. Neill JD, Duck LW, Sellers JC, Musgrove LC, Scheschonka A, Druey KM, Kehrl JH. (1997) Potential role for a regulator of G protein signaling (RGS3) in gonadotropin-releasing hormone (GnRH) stimulated desensitization. Endocrinology, 138 (2): 843-6. [PMID:9003025]

22. Nishiura H, Nonaka H, Revollo IS, Semba U, Li Y, Ota Y, Irie A, Harada K, Kehrl JH, Yamamoto T. (2009) Pro- and anti-apoptotic dual functions of the C5a receptor: involvement of regulator of G protein signaling 3 and extracellular signal-regulated kinase. Lab. Invest., 89 (6): 676-94. [PMID:19333232]

23. Norlin EM, Berghard A. (2001) Spatially restricted expression of regulators of G-protein signaling in primary olfactory neurons. Mol. Cell. Neurosci., 17 (5): 872-82. [PMID:11358484]

24. Obsilova V, Kopecka M, Kosek D, Kacirova M, Kylarova S, Rezabkova L, Obsil T. (2014) Mechanisms of the 14-3-3 protein function: regulation of protein function through conformational modulation. Physiol Res, 63 Suppl 1: S155-64. [PMID:24564655]

25. Oláh J, Vincze O, Virók D, Simon D, Bozsó Z, Tõkési N, Horváth I, Hlavanda E, Kovács J, Magyar A et al.. (2011) Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. J. Biol. Chem., 286 (39): 34088-100. [PMID:21832049]

26. Ooe A, Kato K, Noguchi S. (2007) Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers. Breast Cancer Res. Treat., 101 (3): 305-15. [PMID:16821082]

27. Qiu R, Wang J, Tsark W, Lu Q. (2010) Essential role of PDZ-RGS3 in the maintenance of neural progenitor cells. Stem Cells, 28 (9): 1602-10. [PMID:20629178]

28. Raab RM, Bullen J, Kelleher J, Mantzoros C, Stephanopoulos G. (2005) Regulation of mouse hepatic genes in response to diet induced obesity, insulin resistance and fasting induced weight reduction. Nutr Metab (Lond), 2: 15. [PMID:15985155]

29. 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]

30. Rezabkova L, Boura E, Herman P, Vecer J, Bourova L, Sulc M, Svoboda P, Obsilova V, Obsil T. (2010) 14-3-3 protein interacts with and affects the structure of RGS domain of regulator of G protein signaling 3 (RGS3). J. Struct. Biol., 170 (3): 451-61. [PMID:20347994]

31. Rolland T, Taşan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, Yi S, Lemmens I, Fontanillo C, Mosca R et al.. (2014) A proteome-scale map of the human interactome network. Cell, 159 (5): 1212-26. [PMID:25416956]

32. Scheschonka A, Dessauer CW, Sinnarajah S, Chidiac P, Shi CS, Kehrl JH. (2000) RGS3 is a GTPase-activating protein for g(ialpha) and g(qalpha) and a potent inhibitor of signaling by GTPase-deficient forms of g(qalpha) and g(11alpha). Mol. Pharmacol., 58 (4): 719-28. [PMID:10999941]

33. 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]

34. Shi CS, Huang NN, Kehrl JH. (2012) Regulator of G-protein signaling 3 isoform 1 (PDZ-RGS3) enhances canonical Wnt signaling and promotes epithelial mesenchymal transition. J. Biol. Chem., 287 (40): 33480-7. [PMID:22859293]

35. Su Z, Xu P, Ni F. (2004) Single phosphorylation of Tyr304 in the cytoplasmic tail of ephrin B2 confers high-affinity and bifunctional binding to both the SH2 domain of Grb4 and the PDZ domain of the PDZ-RGS3 protein. Eur. J. Biochem., 271 (9): 1725-36. [PMID:15096211]

36. Takeuchi T, Inoue S, Yokosawa H. (2006) Identification and Herc5-mediated ISGylation of novel target proteins. Biochem. Biophys. Res. Commun., 348 (2): 473-7. [PMID:16884686]

37. Williams JW, Yau D, Sethakorn N, Kach J, Reed EB, Moore TV, Cannon J, Jin X, Xing H, Muslin AJ et al.. (2013) RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation. Am. J. Physiol. Lung Cell Mol. Physiol., 305 (10): L693-701. [PMID:24077945]

38. Xiao K, McClatchy DB, Shukla AK, Zhao Y, Chen M, Shenoy SK, Yates 3rd JR, Lefkowitz RJ. (2007) Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proc. Natl. Acad. Sci. U.S.A., 104 (29): 12011-6. [PMID:17620599]

39. Yono M, Yoshida M, Yamamoto Y, Imanishi A, Fukagawa A, Latifpour J, Eto M. (2010) Identification of potential therapeutic targets in hypertension-associated bladder dysfunction. BJU Int., 105 (6): 877-83. [PMID:19689474]

40. Zhang S, Watson N, Zahner J, Rottman JN, Blumer KJ, Muslin AJ. (1998) RGS3 and RGS4 are GTPase activating proteins in the heart. J. Mol. Cell. Cardiol., 30 (2): 269-76. [PMID:9515003]

Contributors

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How to cite this page

Rory A. Fisher, Zili Luo.
R4 family: regulator of G-protein signaling 3. Last modified on 08/05/2017. Accessed on 27/05/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2810.