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target has curated data in GtoImmuPdb
Target id: 2806
Nomenclature: regulator of G-protein signaling 16
Abbreviated Name: RGS16
Family: R4 family
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 202 | 1q25.3 | RGS16 | regulator of G protein signaling 16 | 43,45 |
Mouse | - | 201 | 1 65.43 cM | Rgs16 | regulator of G-protein signaling 16 | 6,43 |
Rat | - | 199 | 13q21 | Rgs16 | regulator of G-protein signaling 16 | 6 |
Previous and Unofficial Names |
A28-RGS14 | RGS-R | A24-RGS14p |
Database Links | |
Alphafold | O15492 (Hs), P97428 (Mm), P56700 (Rn) |
CATH/Gene3D | 1.10.196.10 |
ChEMBL Target | CHEMBL3707469 (Hs) |
Ensembl Gene | ENSG00000143333 (Hs), ENSMUSG00000026475 (Mm), ENSRNOG00000027024 (Rn) |
Entrez Gene | 6004 (Hs), 19734 (Mm), 360857 (Rn) |
Human Protein Atlas | ENSG00000143333 (Hs) |
KEGG Gene | hsa:6004 (Hs), mmu:19734 (Mm), rno:360857 (Rn) |
OMIM | 602514 (Hs) |
Pharos | O15492 (Hs) |
RefSeq Nucleotide | NM_002928 (Hs), NM_011267 (Mm), NM_001077589 (Rn) |
RefSeq Protein | NP_002919 (Hs), NP_035397 (Mm), NP_001071057 (Rn) |
UniProtKB | O15492 (Hs), P97428 (Mm), P56700 (Rn) |
Wikipedia | RGS16 (Hs) |
Associated Proteins | ||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
RGS proteins, including RGS16, modulate Gαi2 signaling to facilitate thymocyte egress and T cell trafficking [24,32]. RGS protein/Gαi2 interactions are essential for normal thymocyte egress, T cell trafficking, and homeostasis. Mature thymocytes with a Gαi2 mutation that disables RGS protein binding accumulated in the perivascular channels of thymic corticomedullary venules. |
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Functional Assays | ||||||||||
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Physiological Functions | ||||||||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Xenobiotics Influencing Gene Expression | ||||||||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology Comments | ||||||||||||||||||||||||||
Cancer mutation overview, a summary of information held by the cBioPortal for Cancer Genomics and The Cancer Genome Atlas (TGCA database) for RGS16: A total of 58 mutations have been recorded (3 nonsense), distributed from amino acids 11-178, there are 47 single occurrences, missense mutation S174L has 3 independent occurrences in uterine cancer and melanoma, 4 residues appear with 2 independent occurrences (including S174L). RGS16 mutaions are reported in these cancers: Uterine carcinosarcoma/uterine malignant mixed müllerian tumor (>4%) Cutaneious melanoma (>4%) Lung Bladder Colorectal Pancreas Breast Bladder Stomach Prostate Liver Head and neck Breast (<0.5%) |
Gene Expression and Pathophysiology | ||||||||||||
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Biologically Significant Variant Comments |
Genome-wide association studies (GWAS) of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128, 266 white British individuals showed that sixteen variants were associated with chronotype, including variants near the known circadian rhythm gene RGS16 [26]. 6 out of the 41 alleles previously identified by GWAS to be chronotype loci in European participants (in the genes RGS16, PER2 and AK5 and between the genes APH1A and CA14) are absent from some non-European population groups [11]. |
1. Beadling C, Druey KM, Richter G, Kehrl JH, Smith KA. (1999) Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes. J Immunol, 162 (5): 2677-82. [PMID:10072511]
2. Berthebaud M, Rivière C, Jarrier P, Foudi A, Zhang Y, Compagno D, Galy A, Vainchenker W, Louache F. (2005) RGS16 is a negative regulator of SDF-1-CXCR4 signaling in megakaryocytes. Blood, 106 (9): 2962-8. [PMID:15998835]
3. Buckbinder L, Velasco-Miguel S, Chen Y, Xu N, Talbott R, Gelbert L, Gao J, Seizinger BR, Gutkind JS, Kley N. (1997) The p53 tumor suppressor targets a novel regulator of G protein signaling. Proc Natl Acad Sci USA, 94 (15): 7868-72. [PMID:9223279]
4. Carper MB, Denvir J, Boskovic G, Primerano DA, Claudio PP. (2014) RGS16, a novel p53 and pRb cross-talk candidate inhibits migration and invasion of pancreatic cancer cells. Genes Cancer, 5 (11-12): 420-35. [PMID:25568667]
5. Chen C, Zheng B, Han J, Lin SC. (1997) Characterization of a novel mammalian RGS protein that binds to Galpha proteins and inhibits pheromone signaling in yeast. J Biol Chem, 272 (13): 8679-85. [PMID:9079700]
6. Chen CK, Wieland T, Simon MI. (1996) RGS-r, a retinal specific RGS protein, binds an intermediate conformation of transducin and enhances recycling. Proc Natl Acad Sci USA, 93 (23): 12885-9. [PMID:8917514]
7. Dantoft W, Martínez-Vicente P, Jafali J, Pérez-Martínez L, Martin K, Kotzamanis K, Craigon M, Auer M, Young NT, Walsh P et al.. (2017) Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses. Front Immunol, 8: 1146. [PMID:28993767]
8. Davidsson J, Andersson A, Paulsson K, Heidenblad M, Isaksson M, Borg A, Heldrup J, Behrendtz M, Panagopoulos I, Fioretos T et al.. (2007) Tiling resolution array comparative genomic hybridization, expression and methylation analyses of dup(1q) in Burkitt lymphomas and pediatric high hyperdiploid acute lymphoblastic leukemias reveal clustered near-centromeric breakpoints and overexpression of genes in 1q22-32.3. Hum Mol Genet, 16 (18): 2215-25. [PMID:17613536]
9. Derrien A, Druey KM. (2001) RGS16 function is regulated by epidermal growth factor receptor-mediated tyrosine phosphorylation. J Biol Chem, 276 (51): 48532-8. [PMID:11602604]
10. Doi M, Ishida A, Miyake A, Sato M, Komatsu R, Yamazaki F, Kimura I, Tsuchiya S, Kori H, Seo K et al.. (2011) Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus. Nat Commun, 2: 327. [PMID:21610730]
11. Emmanuel P, von Schantz M. (2018) Absence of morningness alleles in non-European populations. Chronobiol Int, 35 (12): 1758-1761. [PMID:30084654]
12. Faurobert E, Hurley JB. (1997) The core domain of a new retina specific RGS protein stimulates the GTPase activity of transducin in vitro. Proc Natl Acad Sci USA, 94 (7): 2945-50. [PMID:9096326]
13. Gerstner JR, Vander Heyden WM, Lavaute TM, Landry CF. (2006) Profiles of novel diurnally regulated genes in mouse hypothalamus: expression analysis of the cysteine and histidine-rich domain-containing, zinc-binding protein 1, the fatty acid-binding protein 7 and the GTPase, ras-like family member 11b. Neuroscience, 139 (4): 1435-48. [PMID:16517089]
14. Goto K, Doi M, Wang T, Kunisue S, Murai I, Okamura H. (2017) G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in the center of the circadian clock [Review]. Endocr J, 64 (6): 571-579. [PMID:28502923]
15. Grafstein-Dunn E, Young KH, Cockett MI, Khawaja XZ. (2001) Regional distribution of regulators of G-protein signaling (RGS) 1, 2, 13, 14, 16, and GAIP messenger ribonucleic acids by in situ hybridization in rat brain. Brain Res Mol Brain Res, 88 (1-2): 113-23. [PMID:11295237]
16. Hayasaka N, Aoki K, Kinoshita S, Yamaguchi S, Wakefield JK, Tsuji-Kawahara S, Horikawa K, Ikegami H, Wakana S, Murakami T et al.. (2011) Attenuated food anticipatory activity and abnormal circadian locomotor rhythms in Rgs16 knockdown mice. PLoS ONE, 6 (3): e17655. [PMID:21408016]
17. Hendriks-Balk MC, Hajji N, van Loenen PB, Michel MC, Peters SL, Alewijnse AE. (2009) Sphingosine-1-phosphate regulates RGS2 and RGS16 mRNA expression in vascular smooth muscle cells. Eur J Pharmacol, 606 (1-3): 25-31. [PMID:19374869]
18. Hepler JR. (1999) Emerging roles for RGS proteins in cell signalling. Trends Pharmacol Sci, 20 (9): 376-82. [PMID:10462761]
19. Hoshi Y, Endo K, Shirakihara T, Fukagawa A, Miyazawa K, Saitoh M. (2016) The potential role of regulator of G-protein signaling 16 in cell motility mediated by δEF1 family proteins. FEBS Lett, 590 (2): 270-8. [PMID:26823172]
20. Hsu HC, Yang P, Wang J, Wu Q, Myers R, Chen J, Yi J, Guentert T, Tousson A, Stanus AL et al.. (2008) Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol, 9 (2): 166-75. [PMID:18157131]
21. Hu Y, Shmygelska A, Tran D, Eriksson N, Tung JY, Hinds DA. (2016) GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person. Nat Commun, 7: 10448. [PMID:26835600]
22. Huang J, Pashkov V, Kurrasch DM, Yu K, Gold SJ, Wilkie TM. (2006) Feeding and fasting controls liver expression of a regulator of G protein signaling (Rgs16) in periportal hepatocytes. Comp Hepatol, 5: 8. [PMID:17123436]
23. Huang R, Li G, Zhao Z, Zeng F, Zhang K, Liu Y, Wang K, Hu H. (2020) RGS16 promotes glioma progression and serves as a prognostic factor. CNS Neurosci Ther, 26 (8): 791-803. [PMID:32319728]
24. Hwang IY, Park C, Harrison K, Kehrl JH. (2017) Normal Thymocyte Egress, T Cell Trafficking, and CD4+ T Cell Homeostasis Require Interactions between RGS Proteins and Gαi2. J Immunol, 198 (7): 2721-2734. [PMID:28235863]
25. Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM. (2003) RGS16 inhibits signalling through the G alpha 13-Rho axis. Nat Cell Biol, 5 (12): 1095-103. [PMID:14634662]
26. Jones SE, Tyrrell J, Wood AR, Beaumont RN, Ruth KS, Tuke MA, Yaghootkar H, Hu Y, Teder-Laving M, Hayward C et al.. (2016) Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. PLoS Genet, 12 (8): e1006125. [PMID:27494321]
27. 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]
28. Karim ZA, Alshbool FZ, Vemana HP, Conlon C, Druey KM, Khasawneh FT. (2016) CXCL12 regulates platelet activation via the regulator of G-protein signaling 16. Biochim Biophys Acta, 1863 (2): 314-21. [PMID:26628381]
29. Kim JH, Lee JY, Lee KT, Lee JK, Lee KH, Jang KT, Heo JS, Choi SH, Rhee JC. (2010) RGS16 and FosB underexpressed in pancreatic cancer with lymph node metastasis promote tumor progression. Tumour Biol, 31 (5): 541-8. [PMID:20571966]
30. Kim K, Lee J, Ghil S. (2018) The regulators of G protein signaling RGS16 and RGS18 inhibit protease-activated receptor 2/Gi/o signaling through distinct interactions with Gα in live cells. FEBS Lett, 592 (18): 3126-3138. [PMID:30117167]
31. 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]
32. Lippert E, Yowe DL, Gonzalo JA, Justice JP, Webster JM, Fedyk ER, Hodge M, Miller C, Gutierrez-Ramos JC, Borrego F et al.. (2003) Role of regulator of G protein signaling 16 in inflammation-induced T lymphocyte migration and activation. J Immunol, 171 (3): 1542-55. [PMID:12874248]
33. Miyoshi N, Ishii H, Sekimoto M, Doki Y, Mori M. (2009) RGS16 is a marker for prognosis in colorectal cancer. Ann Surg Oncol, 16 (12): 3507-14. [PMID:19760045]
34. Natochin M, Lipkin VM, Artemyev NO. (1997) Interaction of human retinal RGS with G-protein alpha-subunits. FEBS Lett, 411 (2-3): 179-82. [PMID:9271201]
35. Ocal O, Pashkov V, Kollipara RK, Zolghadri Y, Cruz VH, Hale MA, Heath BR, Artyukhin AB, Christie AL, Tsoulfas P et al.. (2015) A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics. Dis Model Mech, 8 (10): 1201-11. [PMID:26438693]
36. Pashkov V, Huang J, Parameswara VK, Kedzierski W, Kurrasch DM, Tall GG, Esser V, Gerard RD, Uyeda K, Towle HC et al.. (2011) Regulator of G protein signaling (RGS16) inhibits hepatic fatty acid oxidation in a carbohydrate response element-binding protein (ChREBP)-dependent manner. J Biol Chem, 286 (17): 15116-25. [PMID:21357625]
37. Patten M, Krämer E, Bünemann J, Wenck C, Thoenes M, Wieland T, Long C. (2001) Endotoxin and cytokines alter contractile protein expression in cardiac myocytes in vivo. Pflugers Arch, 442 (6): 920-7. [PMID:11680626]
38. Patten M, Stübe S, Thoma B, Wieland T. (2003) Interleukin-1beta mediates endotoxin- and tumor necrosis factor alpha-induced RGS16 protein expression in cultured cardiac myocytes. Naunyn Schmiedebergs Arch Pharmacol, 368 (5): 360-5. [PMID:14566449]
39. Polidarová L, Houdek P, Sumová A. (2017) Chronic disruptions of circadian sleep regulation induce specific proinflammatory responses in the rat colon. Chronobiol Int, 34 (9): 1273-1287. [PMID:29039977]
40. 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]
41. Riddle EL, Schwartzman RA, Bond M, Insel PA. (2005) Multi-tasking RGS proteins in the heart: the next therapeutic target?. Circ Res, 96 (4): 401-11. [PMID:15746448]
42. Sae-Lee C, Moolsuwan K, Chan L, Poungvarin N. (2016) ChREBP Regulates Itself and Metabolic Genes Implicated in Lipid Accumulation in β-Cell Line. PLoS One, 11 (1): e0147411. [PMID:26808438]
43. Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker SA, He W, Wensel TG, Otero G et al.. (2002) Evolution of the regulators of G-protein signaling multigene family in mouse and human. Genomics, 79 (2): 177-85. [PMID:11829488]
44. Slep KC, Kercher MA, Wieland T, Chen CK, Simon MI, Sigler PB. (2008) Molecular architecture of Galphao and the structural basis for RGS16-mediated deactivation. Proc Natl Acad Sci USA, 105 (17): 6243-8. [PMID:18434540]
45. Snow BE, Antonio L, Suggs S, Siderovski DP. (1998) Cloning of a retinally abundant regulator of G-protein signaling (RGS-r/RGS16): genomic structure and chromosomal localization of the human gene. Gene, 206 (2): 247-53. [PMID:9469939]
46. Song D, Nishiyama M, Kimura S. (2016) Potent inhibition of angiotensin AT1 receptor signaling by RGS8: importance of the C-terminal third exon part of its RGS domain. J Recept Signal Transduct Res, 36 (5): 478-87. [PMID:26754208]
47. Stuebe S, Wieland T, Kraemer E, Stritzky Av, Schroeder D, Seekamp S, Vogt A, Chen CK, Patten M. (2008) Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein in cardiac myocytes by transcriptional activation of the rgs16 gene. Naunyn Schmiedebergs Arch Pharmacol, 376 (5): 363-73. [PMID:18046543]
48. Suurväli J, Pahtma M, Saar R, Paalme V, Nutt A, Tiivel T, Saaremäe M, Fitting C, Cavaillon JM, Rüütel Boudinot S. (2015) RGS16 restricts the pro-inflammatory response of monocytes. Scand J Immunol, 81 (1): 23-30. [PMID:25366993]
49. Ueda HR, Chen W, Adachi A, Wakamatsu H, Hayashi S, Takasugi T, Nagano M, Nakahama K, Suzuki Y, Sugano S et al.. (2002) A transcription factor response element for gene expression during circadian night. Nature, 418 (6897): 534-9. [PMID:12152080]
50. Vasilatos SN, Katz TA, Oesterreich S, Wan Y, Davidson NE, Huang Y. (2013) Crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells. Carcinogenesis, 34 (6): 1196-207. [PMID:23354309]
51. Villasenor A, Wang ZV, Rivera LB, Ocal O, Asterholm IW, Scherer PE, Brekken RA, Cleaver O, Wilkie TM. (2010) Rgs16 and Rgs8 in embryonic endocrine pancreas and mouse models of diabetes. Dis Model Mech, 3 (9-10): 567-80. [PMID:20616094]
52. Vivot K, Moullé VS, Zarrouki B, Tremblay C, Mancini AD, Maachi H, Ghislain J, Poitout V. (2016) The regulator of G-protein signaling RGS16 promotes insulin secretion and β-cell proliferation in rodent and human islets. Mol Metab, 5 (10): 988-996. [PMID:27689011]
53. Wang X, Zeng W, Soyombo AA, Tang W, Ross EM, Barnes AP, Milgram SL, Penninger JM, Allen PB, Greengard P et al.. (2005) Spinophilin regulates Ca2+ signalling by binding the N-terminal domain of RGS2 and the third intracellular loop of G-protein-coupled receptors. Nat Cell Biol, 7 (4): 405-11. [PMID:15793568]
54. Wiechec E, Overgaard J, Hansen LL. (2008) A fragile site within the HPC1 region at 1q25.3 affecting RGS16, RGSL1, and RGSL2 in human breast carcinomas. Genes Chromosomes Cancer, 47 (9): 766-80. [PMID:18521847]
55. Xie S, Li J, Wang JH, Wu Q, Yang P, Hsu HC, Smythies LE, Mountz JD. (2010) IL-17 activates the canonical NF-kappaB signaling pathway in autoimmune B cells of BXD2 mice to upregulate the expression of regulators of G-protein signaling 16. J Immunol, 184 (5): 2289-96. [PMID:20139273]
56. Xie Z, Chan EC, Druey KM. (2016) R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and Immunity. AAPS J, 18 (2): 294-304. [PMID:26597290]
57. Zheng B, Berrie CP, Corda D, Farquhar MG. (2003) GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors. Proc Natl Acad Sci USA, 100 (4): 1745-50. [PMID:12576545]
58. Zheng B, Chen D, Farquhar MG. (2000) MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16. Proc Natl Acad Sci USA, 97 (8): 3999-4004. [PMID:10760272]
59. Zolghadri Y, Pal Choudhuri S, Ocal O, Layeghi-Ghalehsoukhteh S, Berhe F, Hale MA, Wilkie TM. (2018) Malnutrition in Pancreatic Ductal Adenocarcinoma (PDA): Dietary Pancreatic Enzymes Improve Short-Term Health but Stimulate Tumor Growth. Am J Pathol, 188 (3): 616-626. [PMID:29248457]