regulator of G-protein signaling 16 | R4 family | IUPHAR/BPS Guide to PHARMACOLOGY

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regulator of G-protein signaling 16

Target not currently curated in GtoImmuPdb

Target id: 2806

Nomenclature: regulator of G-protein signaling 16

Abbreviated Name: RGS16

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 - 202 1q25-q31 RGS16 regulator of G protein signaling 16 32,34
Mouse - 201 1 G3 Rgs16 regulator of G-protein signaling 16 6,32
Rat - 199 13q21 Rgs16 regulator of G-protein signaling 16 6
Previous and Unofficial Names
A28-RGS14 | RGS-R | A24-RGS14p
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
G Proteins
Name References
Gαi/o, Gαq/11, Gα12/13 1,3,5,14,19,25,31,33
Interacting Proteins
Name Effect References
TP53 TP53 induces RGS16 transcription 3,41
Membrane interacting protein of RGS16 (MIR16: gene symbol GDE1)) 43-44
Transducin Accelerates GTPase activity and enhances recycling of transducin. 6,10
Calmodulin Ca2+ dependent binding of calmodulin can activate Rgs proteins by displaceing an inhibitor of GAP activity. 30
Spinophilin 40
Tissue Distribution
Megakaryocytes, platelets
Species:  Human
Technique:  RT-PCR, Western blot
References:  2
Breast tissue
Species:  Human
Technique: 
References:  38,41
Retinally abundant but not specific
Species:  Human
Technique:  Northern blot
References:  34
Retina
Species:  Mouse
Technique:  RT-PCR
References:  6,15,34
Pituitary
Species:  Mouse
Technique:  Northern blot
References:  5,15
Liver, endocrine pancreas, pancreatic ductal adenocarcinoma
Species:  Mouse
Technique:  Northern blot, in situ hybridization, qRT-PCR, GFP transgene reporter
References:  5,15,18,26-27,39
Suprachiasmatic nucleus and thalamus
Species:  Mouse
Technique:  Microarray analysis, In situ hybridization, Northern blot
References:  9,11,13,18,37
Cardiac myocytes
Species:  Rat
Technique:  Northern blot, Western blot
References:  20,28-29,35
Several regions in the brain
Species:  Rat
Technique:  In situ hybridization
References:  12
Functional Assays
Mediates cAMP signaling and expression of clock gene Per1
Species:  Mouse
Tissue:  Suprachiasmatic nucleus
Response measured:  Increased levels of cAMP and acclerated expression of Per1
References:  9
Inhibits Gα13 signaling via a GAP-independent mechanism. Rgs16 binds Gα13 and translocates it to detergent-resistant membranes and prevents effector interaction and thus inhibits Gα13 signaling.
Species:  None
Tissue: 
Response measured: 
References:  19
EGFR-mediated phosphorylation
Species:  Human
Tissue:  HEK 293T or COS-7 cells
Response measured:  EGFR-mediated phosphorylation depends on residue Y168 and phosphorylation enhances GAP activity. Y177 is important for regulated Gi-coupled M2 muscarinic receptor signaling.
References:  8
Physiological Functions
Determines the period of circadian rhytms in behavior.
Species:  Mouse
Tissue:  Dorsomedial cells of suprachiasmatic nucleus
References:  9
Negative regulation of SDF-1-CXCR4 signalling.
Species:  Human
Tissue:  Megakaryocytes
References:  2
Rgs16 regulates T lymphocyte migration induced by CXCR4, CCR3 and CCR5.
Species:  Mouse
Tissue:  T lymphocytes
References:  23
Inhibits fatty acid oxidation in the liver of fasted mice, suppresses Fgf21 expression in liver of fasted mice.
Species:  Mouse
Tissue:  Hepatocytes
References:  27
Physiological Consequences of Altering Gene Expression
Lenghtening of the circadian period of behavior.
Species:  Mouse
Tissue:  Brain
Technique:  Gene knockout
References:  9
RGS16 is strongly associated with early morning activity in humans.
Species:  Human
Tissue:  SCN, retina
Technique:  Genome-wide association (GWAS)
References:  17
Elevated fatty acid oxidation rate and elevated beta-ketone level. During caloric restriction, before feeding, increased abulatory activity. After feeding, increased rate of food consumption.
Species:  Mouse
Tissue:  Liver, hepatocytes
Technique:  Gene knockout
References:  27
Develops fatty liver during prolonged fast.
Species:  Mouse
Tissue:  Liver, Hepatocytes
Technique:  Gene over-expression
References:  27
Rgs16 inhibits migration and invasion of pancreatic cancer cells
Species:  Human
Tissue:  BxBP3, AsPC-1
Technique:  Gene over-expression
References:  4
RGS16 knockdown by RNAi upregulates IL-1b, IL-6 and TNFα. RGS16 enhances Pam3-mediated induction of the anti inflammatory cytokine IL-10.
Species:  Human
Tissue:  Monocytes (THP-1 cell line)
Technique:  RNA intererence (RNAi)
References:  36
RGS16 overexpression in THP-1 cells restricts the induction of pro-inflammatory response by TLR2 agonist Pam3.
Species:  Human
Tissue:  Monocytes (THP-1 cell line)
Technique:  Gene over-expression
References:  36
RGS16 Knockdown enhances breast cancer cell growth and cell cycle progression. It also negatively regulates growth of MCF7 cells induced by specific factors including EGF. It impairs EGF-induced growth of breast cancer cells specifically by binding p85 and suppressing activation of the PI3K-Akt signaling pathway.
Species:  Human
Tissue:  MCF7 cells
Technique:  RNA intererence (RNAi)
References:  22
Restriction of the pro-Inflammatory response of monocytes.
Species:  Human
Tissue:  Promonocytic cell line THP-1
Technique:  RNA intererence (RNAi), Gene knockouts were also used, with cells obtained from Rgs16-/- mice
References:  36
Elevated Rgs16 in B-cells reduces B-cell chemotaxis responses to chemokines, and promotes retention of B cells within germinal centers, thus provides optimal microenvironment for the production of pathogenic autoantibodies.
Species:  Mouse
Tissue:  B Cells
Technique: 
References:  16,42
Xenobiotics Influencing Gene Expression
Upregulation of Rgs16 gene expression by combined application of LSD1 inhibitor, pargyline and HDAC inhibitor, SAHA.
Species:  Human
Tissue:  Breast cancer cell lines
Technique:  Microarray analysis of gene expression, qRT-PCR
References:  38
Anti-cancer and DNA damaging agent doxorubicin leads to induction of RGS16 transcript.
Species:  Human
Tissue:  RKO colon carcinoma cells
Technique:  Northern blot
References:  3
Bacterial endotoxin (LPS) causes upregulation of Rgs16 expression by a IL-1b, TNFα mediated pathway.
Species:  Rat
Tissue:  Cardiac myocytes
Technique:  Western blot
References:  28-29
300-fold induction of Rgs16 mRNA in Zone 1, 2, 3 hepatocytes of sucrose fed mice provided 5% sucrose-water > 3 days, and no chow for the final 18 hours.
Species:  Mouse
Tissue:  Liver, hepatocytes
Technique:  qPCR, in situ hybridization
References:  27
The TNF-κB p65 (Ser276) inhibitory peptide inhibits interleukin 17 mediated expression of Rgs16.
Species:  Mouse
Tissue:  B-cells
Technique:  qRT-PCR
References:  42
Clinically-Relevant Mutations and Pathophysiology
Disease:  Alpha-1 antitrypsin deficiency (A1ATD)
Description: A1ATD is an autosomal recessive disorder, characterised by defective production of alpha 1-antitrypsin (protein product of the SERPINA1 gene). This leads to decreased A1AT activity in the blood and lungs, and deposition of excessive abnormal A1AT protein in liver cells. The form and severity of disease depends on whether the sufferer is homozygous or heterozygous for a deffective SERPINA1 allele.
OMIM: 613490
Orphanet: ORPHA60
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
References:  22,41
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human none A 104bp-1.4kb deletion of th 5'-regulatory site of RGS16 41
Disease:  Colorectal cancer
Disease Ontology: DOID:9256
OMIM: 114500
References:  24
Disease:  Fatty liver disease, nonalcoholic, susceptibility to, 1; NAFLD1
OMIM: 613282
References:  27
Disease:  Hematological malignancies
Description: Tumours of the hematopoietic and lymphoid tissues. Examples of hematologic cancer are acute and chronic leukemias, lymphomas, multiple myeloma and myelodysplastic syndromes.
References:  7
Disease:  Pancreatic cancer
Disease Ontology: DOID:1793
OMIM: 260350
Role: 
References:  21,26
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%)

References

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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. U.S.A., 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. U.S.A., 93 (23): 12885-9. [PMID:8917514]

7. 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]

8. 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]

9. 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]

10. 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. U.S.A., 94 (7): 2945-50. [PMID:9096326]

11. 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]

12. 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]

13. 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]

14. 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]

15. Hepler JR. (1999) Emerging roles for RGS proteins in cell signalling. Trends Pharmacol. Sci., 20 (9): 376-82. [PMID:10462761]

16. 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]

17. 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]

18. 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]

19. 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]

20. 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]

21. 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]

22. 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]

23. 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]

24. 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]

25. 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]

26. 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]

27. 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]

28. 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]

29. 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]

30. 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]

31. 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]

32. 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]

33. 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. U.S.A., 105 (17): 6243-8. [PMID:18434540]

34. 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]

35. 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]

36. 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]

37. 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]

38. 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]

39. 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]

40. 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]

41. 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]

42. 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]

43. 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. U.S.A., 100 (4): 1745-50. [PMID:12576545]

44. Zheng B, Chen D, Farquhar MG. (2000) MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16. Proc. Natl. Acad. Sci. U.S.A., 97 (8): 3999-4004. [PMID:10760272]

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