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regulator of G-protein signaling 5

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Target not currently curated in GtoImmuPdb

Target id: 2812

Nomenclature: regulator of G-protein signaling 5

Abbreviated Name: RGS5

Family: R4 family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 181 1q23.3 RGS5 regulator of G protein signaling 5 45
Mouse - 181 1 76.84 cM Rgs5 regulator of G-protein signaling 5 47
Rat - 181 13q24 Rgs5 regulator of G-protein signaling 5
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins Click here for help
G Proteins
Name References
Interacting Proteins
Name Effect References
regulator of G-protein signaling 5 Homo dimerization confers protein stabilization. 54
14-3-3 epsilon, 14-3-3 beta Uncertain 1
phosphoinositide-3-kinase regulatory subunit 1 Uncertain 34
G-protein-signaling modulator 3 (GPSM3) Augments RGS5 GAP activity 60
SMO Represses Hedgehog (Hh) signaling. 38
Tissue Distribution Click here for help
Normal parathyroid tissue, with increased expression in parathyroid tumors.
Species:  Human
Technique:  Immunohistochemistry.
References:  29
Heart, lung, skeletal muscle, and small intestine, and at low levels in brain, placenta, liver, colon, and leukocytes.
Species:  Human
Technique:  Northern blot and RT-PCR.
References:  31,40,45
Species:  Human
Technique:  RT-PCR.
References:  35
Airway smooth muscle.
Species:  Human
Technique:  RT-PCR.
References:  7,52-53
Pericytes, vascular smooth muscle.
Species:  Mouse
Technique:  In situ hybridisation and RT-PCR.
References:  2,8-9,11-12,16,19,27,33,36-37,39,41,56,58
Species:  Mouse
Technique:  RT-PCR.
References:  5
Brain endothelium, tumor endothelium, dermal endothelial cells.
Species:  Rat
Technique:  In situ hybridisation and immunofluorescence.
References:  28,48-49
Species:  Rat
Technique:  In situ hybridisation.
References:  15
Cardiac myocytes.
Species:  Rat
Technique:  Northern blot and RT-PCR.
References:  13,18,24,26,42,59
Functional Assays Click here for help
Accelerate GTP hydrolysis by Gαi.
Species:  Human
Tissue:  Recombinant proteins.
Response measured:  Increased GTP hydrolysis.
References:  60
Physiological Functions Click here for help
Inhibits hedgehog signaling by Smo and osteogenesis in vitro.
Species:  Mouse
Tissue:  C3H10T1/2 cells.
References:  38
Regulation of endothelial cell apoptosis, p38 MAPK activation in vitro.
Species:  Human
Tissue:  HUVEC cells.
References:  25
Regulation of S1P-induced inhibition of cAMP.
Species:  Human
Tissue:  Vascular sommth muscle cells (VSMCs).
References:  19
Regulates angiotension 1 mediated IP3 production, MAP kinase activation.
Species:  Rat
Tissue:  Aortic smooth muscle cells.
References:  50
Supresses angiotensin II- and endothelin (ET)-1-induced intracellular Ca2+ transients.
Species:  Human
Tissue:  HEK-293T cells.
References:  61
Physiological Consequences of Altering Gene Expression Click here for help
Overexpression in human lung cancer cells induces apoptosis.
Species:  Human
Tissue:  A549, Calu-3 tumor cells.
Technique:  Gene over-expression.
References:  51
Acceleration of disease in atherosclerosis-prone ApoE-/- mice.
Species:  Mouse
Tissue:  Endothelium.
Technique:  Gene knockout.
References:  10
RGS5-null mice suffer enhanced carbon tetrachloride (CCl4)-induced liver injury, leading to liver fibrosis.
Species:  Human
Tissue:  Liver.
Technique:  Gene knockout.
References:  10
RGS5 knockout mice have spontaneous airway constriction in the absence of inflammation.
Species:  Mouse
Tissue:  Lung (bronchial smooth muscle).
Technique:  Gene knockout.
References:  7,53
Knockdown of RGS5 impairs growth and activation of vascular smooth muscle cells (VSMCs).
Species:  Human
Tissue:  Vascular smooth muscle cells (VSMCs).
Technique:  Antisense/siRNA.
References:  6
RGS-null mice are hypertensive and have impaired collateral arteriogenesis following arterial occlusion.
Species:  Mouse
Tissue:  Arteries.
Technique:  Gene knockout.
References:  6
Knockdown of RGS5 inhibits liver cancer cell migration and invasion; over-expression of RGS5 induces epithelial-mesenchymal transition in epithelial liver cancer cells and promotes tumor metastasis.
Species:  Human
Tissue:  Liver cancer cell lines.
Technique:  Antisense/siRNA, overexpression.
References:  22
RGS5-null mice have hypertension correlating with arterial hyper-responsiveness to vasoconstrictors and vascular stiffening.
Species:  Mouse
Technique:  Gene knockout.
References:  21
RGS5 knockout mice have enhanced susceptibility to atrial and ventricular tachyarrhythmias.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knockout.
References:  43-44
Xenograft tumors in Rgs5-deficient mice display vascular normalization which enhances immune destruction of tumour cells. This effect enhances survival.
Species:  Mouse
Tissue:  Insulinomas, ovarian cancer xenograft.
Technique:  Gene knockout.
References:  3,17
Knockout mice are more susceptible to pressure overload induced cardiac hypertrophy and fibrosis. Overexpressing transgenic mice are protected from this response.
Species:  Mouse
Tissue:  Haert.
Technique:  Gene knockout or overexpression.
References:  32
Xenobiotics Influencing Gene Expression Click here for help
The Notch 2/3 neutralizing antibody, tarextumab, downregulates RGS5 expression in xenograft solid tumors.
Species:  Human
Tissue:  Xenograft solid tumors.
Technique:  Quantitative RT-PCR.
References:  55
The hypoxia mimics, dimethyloxalylglycine (DMOG), cobalt chloride (CoCl2) and 3,4-dihydroxybenzoate (3,4-DHB) upregulate RGS5 expression.
Species:  Human
Tissue:  HUVEC cells.
Technique:  Western blot, northern blot.
References:  25
Statins downregulate RGS5 expression.
Species:  Human
Tissue:  Stenotic aortic valves.
Technique:  Quantitative RT-PCR and immunohistochemistry.
References:  4
Korean ginseng water extract increases RGS5 expression in LPS-activated macrophages.
Species:  Human
Tissue:  RAW264.7 macrophages.
Technique:  Quantitative RT-PCR.
References:  23
The PPARβ /δ agonist GW0742 upregulates RGS5 expression (in rat and mouse experiments)
Species:  Rat
Tissue:  Aorta.
Technique:  Quantitative RT-PCR.
References:  56-57
Dacarbazine and IFNα downregulate RGS5 expression in B16 (melanoma) tumor bearing mice.
Species:  Mouse
Tissue:  Tumor vessels.
Technique:  Quantitative RT-PCR, western blot, immunofluorescence.
References:  36
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Lymphoma, non-hodgkin, familial
Description: A lymphoma that is characterized as any kind of lymphoma except Hodgkin's lymphoma. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and lethargy.
Synonyms: Non-Hodgkin lymphoma [Disease Ontology: DOID:0060060]
Disease Ontology: DOID:0060060
OMIM: 605027
References:  46
Disease:  Preeclampsia
Description: Pregnancy-induced hypertension presenting after 20 weeks' gestation with clinically relevant proteinuria.
Synonyms: eclampsia 1
OMIM: 189800
References:  20
Biologically Significant Variants Click here for help
Type:  Naturally occurring SNP
Species:  Human
Description:  The SNP rs10917, in the first intron of RGS5 is associated with a poor bronchodiltor response in children with asthma.
Nucleotide change:  C696T
SNP accession: 
References:  30
Type:  Naturally occurring SNP
Species:  Human
Description:  The intronic SNP, rs2815272 is associated with hypertension in African-Americans.
SNP accession: 
References:  14


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1. Abramow-Newerly M, Ming H, Chidiac P. (2006) Modulation of subfamily B/R4 RGS protein function by 14-3-3 proteins. Cell. Signal., 18 (12): 2209-22. [PMID:16839744]

2. Adams LD, Geary RL, Li J, Rossini A, Schwartz SM. (2006) Expression profiling identifies smooth muscle cell diversity within human intima and plaque fibrous cap: loss of RGS5 distinguishes the cap. Arterioscler. Thromb. Vasc. Biol., 26 (2): 319-25. [PMID:16293795]

3. Altman MK, Nguyen DT, Patel SB, Fambrough JM, Beedle AM, Hardman WJ, Murph MM. (2012) Regulator of G-Protein Signaling 5 Reduces HeyA8 Ovarian Cancer Cell Proliferation and Extends Survival in a Murine Tumor Model. Biochem Res Int, 2012: 518437. [PMID:22792465]

4. Anger T, El-Chafchak J, Habib A, Stumpf C, Weyand M, Daniel WG, Hombach V, Hoeher M, Garlichs CD. (2008) Statins stimulate RGS-regulated ERK 1/2 activation in human calcified and stenotic aortic valves. Exp. Mol. Pathol., 85 (2): 101-11. [PMID:18671964]

5. Appleton CT, James CG, Beier F. (2006) Regulator of G-protein signaling (RGS) proteins differentially control chondrocyte differentiation. J. Cell. Physiol., 207 (3): 735-45. [PMID:16489565]

6. Arnold C, Feldner A, Pfisterer L, Hödebeck M, Troidl K, Genové G, Wieland T, Hecker M, Korff T. (2014) RGS5 promotes arterial growth during arteriogenesis. EMBO Mol Med, 6 (8): 1075-89. [PMID:24972930]

7. Balenga NA, Jester W, Jiang M, Panettieri Jr RA, Druey KM. (2014) Loss of regulator of G protein signaling 5 promotes airway hyperresponsiveness in the absence of allergic inflammation. J. Allergy Clin. Immunol., 134 (2): 451-9. [PMID:24666695]

8. Berger M, Bergers G, Arnold B, Hämmerling GJ, Ganss R. (2005) Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization. Blood, 105 (3): 1094-101. [PMID:15459006]

9. Bondjers C, Kalén M, Hellström M, Scheidl SJ, Abramsson A, Renner O, Lindahl P, Cho H, Kehrl J, Betsholtz C. (2003) Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells. Am. J. Pathol., 162 (3): 721-9. [PMID:12598306]

10. Cheng WL, Wang PX, Wang T, Zhang Y, Du C, Li H, Ji Y. (2015) Regulator of G-protein signalling 5 protects against atherosclerosis in apolipoprotein E-deficient mice. Br. J. Pharmacol., 172 (23): 5676-89. [PMID:25363362]

11. Cho H, Kozasa T, Bondjers C, Betsholtz C, Kehrl JH. (2003) Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation. FASEB J., 17 (3): 440-2. [PMID:12514120]

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14. Faruque MU, Chen G, Doumatey A, Huang H, Zhou J, Dunston GM, Rotimi CN, Adeyemo AA. (2011) Association of ATP1B1, RGS5 and SELE polymorphisms with hypertension and blood pressure in African-Americans. J. Hypertens., 29 (10): 1906-12. [PMID:21881522]

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17. Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti HH, Rabie T, Kaden S, Gröne HJ, Hämmerling GJ et al.. (2008) Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature, 453 (7193): 410-4. [PMID:18418378]

18. Hao J, Michalek C, Zhang W, Zhu M, Xu X, Mende U. (2006) Regulation of cardiomyocyte signaling by RGS proteins: differential selectivity towards G proteins and susceptibility to regulation. J. Mol. Cell. Cardiol., 41 (1): 51-61. [PMID:16756988]

19. Hendriks-Balk MC, van Loenen PB, Hajji N, Michel MC, Peters SL, Alewijnse AE. (2008) S1P receptor signalling and RGS proteins; expression and function in vascular smooth muscle cells and transfected CHO cells. Eur. J. Pharmacol., 600 (1-3): 1-9. [PMID:18854184]

20. Holobotovskyy V, Chong YS, Burchell J, He B, Phillips M, Leader L, Murphy TV, Sandow SL, McKitrick DJ, Charles AK et al.. (2015) Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia. Sci Transl Med, 7 (290): 290ra88. [PMID:26041705]

21. Holobotovskyy V, Manzur M, Tare M, Burchell J, Bolitho E, Viola H, Hool LC, Arnolda LF, McKitrick DJ, Ganss R. (2013) Regulator of G-protein signaling 5 controls blood pressure homeostasis and vessel wall remodeling. Circ. Res., 112 (5): 781-91. [PMID:23303165]

22. Hu M, Chen X, Zhang J, Wang D, Fang X, Wang X, Wang G, Chen G, Jiang X, Xia H et al.. (2013) Over-expression of regulator of G protein signaling 5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells. J Surg Oncol, 108 (3): 192-6. [PMID:23868206]

23. Im EJ, Yayeh T, Park SJ, Kim SH, Goo YK, Hong SB, Son YM, Kim SD, Rhee MH. (2014) Antiatherosclerotic effect of korean red ginseng extract involves regulator of g-protein signaling 5. Evid Based Complement Alternat Med, 2014: 985174. [PMID:25610490]

24. Jean-Baptiste G, Li X, Yang Z, Heubach J, Gaudio S, Khoury C, Ravens U, Greenwood MT. (2005) Beta adrenergic receptor-mediated atrial specific up-regulation of RGS5. Life Sci., 76 (13): 1533-45. [PMID:15680317]

25. Jin Y, An X, Ye Z, Cully B, Wu J, Li J. (2009) RGS5, a hypoxia-inducible apoptotic stimulator in endothelial cells. J. Biol. Chem., 284 (35): 23436-43. [PMID:19564336]

26. Kardestuncer T, Wu H, Lim AL, Neer EJ. (1998) Cardiac myocytes express mRNA for ten RGS proteins: changes in RGS mRNA expression in ventricular myocytes and cultured atria. FEBS Lett., 438 (3): 285-8. [PMID:9827562]

27. Ketsawatsomkron P, Lorca RA, Keen HL, Weatherford ET, Liu X, Pelham CJ, Grobe JL, Faraci FM, England SK, Sigmund CD. (2012) PPARγ regulates resistance vessel tone through a mechanism involving RGS5-mediated control of protein kinase C and BKCa channel activity. Circ. Res., 111 (11): 1446-58. [PMID:22962432]

28. Kirsch T, Wellner M, Luft FC, Haller H, Lippoldt A. (2001) Altered gene expression in cerebral capillaries of stroke-prone spontaneously hypertensive rats. Brain Res., 910 (1-2): 106-15. [PMID:11489260]

29. Koh J, Dar M, Untch BR, Dixit D, Shi Y, Yang Z, Adam MA, Dressman H, Wang X, Gesty-Palmer D et al.. (2011) Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor. Mol. Endocrinol., 25 (5): 867-76. [PMID:21393447]

30. Labuda M, Laberge S, Brière J, Bérubé D, Krajinovic M. (2013) RGS5 gene and therapeutic response to short acting bronchodilators in paediatric asthma patients. Pediatr. Pulmonol., 48 (10): 970-5. [PMID:23193110]

31. 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]

32. Li H, He C, Feng J, Zhang Y, Tang Q, Bian Z, Bai X, Zhou H, Jiang H, Heximer SP et al.. (2010) Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload. Proc. Natl. Acad. Sci. U.S.A., 107 (31): 13818-23. [PMID:20643937]

33. Li J, Adams LD, Wang X, Pabon L, Schwartz SM, Sane DC, Geary RL. (2004) Regulator of G protein signaling 5 marks peripheral arterial smooth muscle cells and is downregulated in atherosclerotic plaque. J. Vasc. Surg., 40 (3): 519-28. [PMID:15337883]

34. Liang G, Bansal G, Xie Z, Druey KM. (2009) RGS16 inhibits breast cancer cell growth by mitigating phosphatidylinositol 3-kinase signaling. J. Biol. Chem., 284 (32): 21719-27. [PMID:19509421]

35. Liang Y, Li C, Guzman VM, Chang WW, Evinger 3rd AJ, Sao D, Woodward DF. (2005) Identification of a novel alternative splicing variant of RGS5 mRNA in human ocular tissues. FEBS J., 272 (3): 791-9. [PMID:15670159]

36. Liu P, Zhang C, Chen J, Zhang R, Ren J, Huang Y, Zhu F, Li Z, Wu G. (2011) Combinational therapy of interferon-α and chemotherapy normalizes tumor vasculature by regulating pericytes including the novel marker RGS5 in melanoma. J. Immunother., 34 (3): 320-6. [PMID:21389866]

37. Lovschall H, Mitsiadis TA, Poulsen K, Jensen KH, Kjeldsen AL. (2007) Coexpression of Notch3 and Rgs5 in the pericyte-vascular smooth muscle cell axis in response to pulp injury. Int. J. Dev. Biol., 51 (8): 715-21. [PMID:17939118]

38. Mahoney Jr WM, Gunaje J, Daum G, Dong XR, Majesky MW. (2013) Regulator of G-protein signaling - 5 (RGS5) is a novel repressor of hedgehog signaling. PLoS ONE, 8 (4): e61421. [PMID:23637832]

39. Mitchell TS, Bradley J, Robinson GS, Shima DT, Ng YS. (2008) RGS5 expression is a quantitative measure of pericyte coverage of blood vessels. Angiogenesis, 11 (2): 141-51. [PMID:18038251]

40. Mittmann C, Chung CH, Höppner G, Michalek C, Nose M, Schüler C, Schuh A, Eschenhagen T, Weil J, Pieske B et al.. (2002) Expression of ten RGS proteins in human myocardium: functional characterization of an upregulation of RGS4 in heart failure. Cardiovasc. Res., 55 (4): 778-86. [PMID:12176127]

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43. Qin M, Huang H, Wang T, Hu H, Liu Y, Cao H, Li H, Huang C. (2012) Absence of Rgs5 prolongs cardiac repolarization and predisposes to ventricular tachyarrhythmia in mice. J. Mol. Cell. Cardiol., 53 (6): 880-90. [PMID:23079193]

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48. Silini A, Ghilardi C, Figini S, Sangalli F, Fruscio R, Dahse R, Pedley RB, Giavazzi R, Bani M. (2012) Regulator of G-protein signaling 5 (RGS5) protein: a novel marker of cancer vasculature elicited and sustained by the tumor's proangiogenic microenvironment. Cell. Mol. Life Sci., 69 (7): 1167-78. [PMID:22130514]

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51. Xu Z, Zuo Y, Wang J, Yu Z, Peng F, Chen Y, Dong Y, Hu X, Zhou Q, Ma H et al.. (2015) Overexpression of the regulator of G-protein signaling 5 reduces the survival rate and enhances the radiation response of human lung cancer cells. Oncol. Rep., 33 (6): 2899-907. [PMID:25891540]

52. Yang Z, Balenga N, Cooper PR, Damera G, Edwards R, Brightling CE, Panettieri Jr RA, Druey KM. (2012) Regulator of G-protein signaling-5 inhibits bronchial smooth muscle contraction in severe asthma. Am. J. Respir. Cell Mol. Biol., 46 (6): 823-32. [PMID:22281988]

53. Yang Z, Cooper PR, Damera G, Mukhopadhyay I, Cho H, Kehrl JH, Panettieri Jr RA, Druey KM. (2011) Beta-agonist-associated reduction in RGS5 expression promotes airway smooth muscle hyper-responsiveness. J. Biol. Chem., 286 (13): 11444-55. [PMID:21278382]

54. Yang Z, Gaudio S, Song W, Greenwood M, Jean-Baptiste G, Greenwood MT. (2007) Evidence for the dimerization of human regulator of G-protein signalling 5 (RGS5). Cell. Physiol. Biochem., 20 (5): 303-10. [PMID:17762159]

55. Yen WC, Fischer MM, Axelrod F, Bond C, Cain J, Cancilla B, Henner WR, Meisner R, Sato A, Shah J et al.. (2015) Targeting Notch signaling with a Notch2/Notch3 antagonist (tarextumab) inhibits tumor growth and decreases tumor-initiating cell frequency. Clin. Cancer Res., 21 (9): 2084-95. [PMID:25934888]

56. Zarzuelo MJ, Gómez-Guzmán M, Jiménez R, Quintela AM, Romero M, Sánchez M, Zarzuelo A, Tamargo J, Pérez-Vizcaíno F, Duarte J. (2013) Effects of peroxisome proliferator-activated receptor-β activation in endothelin-dependent hypertension. Cardiovasc. Res., 99 (4): 622-31. [PMID:23752977]

57. Zarzuelo MJ, Jiménez R, Galindo P, Sánchez M, Nieto A, Romero M, Quintela AM, López-Sepúlveda R, Gómez-Guzmán M, Bailón E et al.. (2011) Antihypertensive effects of peroxisome proliferator-activated receptor-β activation in spontaneously hypertensive rats. Hypertension, 58 (4): 733-43. [PMID:21825230]

58. Zhang H, Gu S, Al-Sabeq B, Wang S, He J, Tam A, Cifelli C, Mathalone N, Tirgari S, Boyd S et al.. (2012) Origin-specific epigenetic program correlates with vascular bed-specific differences in Rgs5 expression. FASEB J., 26 (1): 181-91. [PMID:21965603]

59. Zhang W, Anger T, Su J, Hao J, Xu X, Zhu M, Gach A, Cui L, Liao R, Mende U. (2006) Selective loss of fine tuning of Gq/11 signaling by RGS2 protein exacerbates cardiomyocyte hypertrophy. J. Biol. Chem., 281 (9): 5811-20. [PMID:16380388]

60. Zhao P, Chidiac P. (2015) Regulation of RGS5 GAP activity by GPSM3. Mol. Cell. Biochem., 405 (1-2): 33-40. [PMID:25842189]

61. Zhou J, Moroi K, Nishiyama M, Usui H, Seki N, Ishida J, Fukamizu A, Kimura S. (2001) Characterization of RGS5 in regulation of G protein-coupled receptor signaling. Life Sci., 68 (13): 1457-69. [PMID:11253162]


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