Top ▲

regulator of G-protein signaling 17

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2801

Nomenclature: regulator of G-protein signaling 17

Abbreviated Name: RGS17

Family: RZ family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 210 6q25.2 RGS17 regulator of G protein signaling 17
Mouse - 210 10 A1 Rgs17 regulator of G-protein signaling 17
Rat - 210 1p11 Rgs17 regulator of G-protein signaling 17
Database Links Click here for help
Alphafold Q9UGC6 (Hs), Q9QZB0 (Mm)
CATH/Gene3D 1.10.196.10
ChEMBL Target CHEMBL4295974 (Hs)
Ensembl Gene ENSG00000091844 (Hs), ENSMUSG00000019775 (Mm), ENSRNOG00000018690 (Rn)
Entrez Gene 26575 (Hs), 56533 (Mm), 308118 (Rn)
Human Protein Atlas ENSG00000091844 (Hs)
KEGG Gene hsa:26575 (Hs), mmu:56533 (Mm), rno:308118 (Rn)
OMIM 607191 (Hs)
Pharos Q9UGC6 (Hs)
RefSeq Nucleotide NM_012419 (Hs), NM_001161822 (Mm), NM_001107459 (Rn)
RefSeq Protein NP_036551 (Hs), NP_001155294 (Mm), NP_001100929 (Rn)
UniProtKB Q9UGC6 (Hs), Q9QZB0 (Mm)
Wikipedia RGS17 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the Regulator of G-Protein Signaling 17 (RGSZ2)
PDB Id:  1ZV4
Resolution:  2.4Å
Species:  Human
References:  23
Image of receptor 3D structure from RCSB PDB
Description:  Regulator of G protein signaling (RGS) 17 in complex with Ca2+
PDB Id:  6AM3
Ligand:  Ca2+
Resolution:  1.53Å
Species:  Human
References:  21
Associated Proteins Click here for help
G Proteins
Name References
Go, Gq, Gi, Gz 16
Interacting Proteins
Name Effect References
GPCRs: CB1R, A2AR, M4R, D2R, MOR, 5HT1AR, 5HT2AR and M2R Releases zinc ions. 25
GIPN (GAIP interacting protein N terminus) 6
protein kinase C gamma Acts as an adaptor that couples PKCγ to the MOR in a zinc-dependent manner to downregulate its signalling stamina. 19
μ receptor Recruits PKCγ to the MOR where they phosphorylate specific serine/threonine residues to regulate the signalling capacity of the receptor. 7,19,25
Neuronal NOS Negatively regulates nNOS activity. 8
Histidine triad nucleotide-binding protein 1 (HINT1)/ protein kinase C interacting protein (PKCI-1) Scaffold protein 1,20,25

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound I [PMID: 29351497] Small molecule or natural product Hs Inhibition 5.0 pIC50 3
⤷ pIC50 5.0 (IC50 9.5x10-6 M) [3]
celastrol Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.0 pIC50 2
⤷ pIC50 5.0 (IC50 1.05x10-5 M) [2]
compound III [PMID: 29351497] Small molecule or natural product Hs Inhibition 4.8 pIC50 3
⤷ pIC50 4.8 (IC50 1.44x10-5 M) [3]
compound V [PMID: 29351497] Small molecule or natural product Hs Inhibition 4.8 pIC50 3
⤷ pIC50 4.8 (IC50 1.43x10-5 M) [3]
compound II [PMID: 29351497] Small molecule or natural product Hs Inhibition 4.7 pIC50 3
⤷ pIC50 4.7 (IC50 1.92x10-5 M) [3]
compound IV [PMID: 29351497] Small molecule or natural product Hs Inhibition 4.5 pIC50 3
⤷ pIC50 4.5 (IC50 3.11x10-5 M) [3]
irigenol Small molecule or natural product Hs Inhibition 4.3 pIC50 2
⤷ pIC50 4.3 (IC50 4.72x10-5 M) [2]
pseudochelerythrine Small molecule or natural product Ligand has a PDB structure Hs Inhibition 4.1 pIC50 2
⤷ pIC50 4.1 (IC50 7.28x10-5 M) [2]
Tissue Distribution Click here for help
Brain and testis
Species:  Human
Technique:  RT-PCR, Northern blot
References:  12,16
RGS17 mRNA levels were expressed at higher levels in the cerebellum, striatum, parahippocampal gyrus and the putamen than other regions of the brain
Species:  Human
Technique:  RT-PCR
References:  12
Spleen, lung and blood leukocytes
Species:  Human
Technique:  Northern blot
References:  18
RGS17 (RGSZ2) mRNA was most readily detected in the hypothalamus, PAG, and pons-medulla; lower levels were observed in the thalamus, followed by the cortex and spinal cord; and the weakest signals were seen in the striatum and cerebellum. The abundance of the protein expressed correlated well with the mRNA levels.
Species:  Mouse
Technique:  RT-PCR and western blot
References:  7,9
Atrial myocytes
Species:  Rat
Technique:  RT-PCR
References:  5
Functional Assays Click here for help
Attenuation of Gi-mediated inhibition of cAMP
Species:  Human
Tissue:  HEK293 cells
Response measured:  cAMP level measured by radioimmunoassay
References:  16
Steady-state and single-turnover GTPase assay
Species:  None
Tissue:  Biochemical assay with purified proteins
Response measured:  Measuring GTPase activity using [γ-32P]GTP
References:  16
Attenuation of Gq-mediated calcium mobilization
Species:  Mouse
Tissue:  Ltk cells
Response measured:  Calcium concentration measured by Fura-2 AM fluorometric assay
References:  16
Malachite Green Assay (a viable HTS assay for measuring GAP function)
Species:  None
Tissue:  Biochemical assay with purified proteins
Response measured:  Free phosphate formation (reacting with molybdate and malachite green to produce a strong absorbance peak at 642 nm)
References:  17
Physiological Functions Click here for help
RGS17 regulates neuronal nitric oxide synthase (nNOS) signaling.
Species:  Mouse
Tissue:  Periaqueductal gray (PAG) neurons
References:  8
RGS17 regulates zinc release in response to nitric oxide donors.
Species:  Mouse
Tissue:  Brain
References:  25
RGS17 is involved in regulating μ-opioid receptor signaling.
Species:  Mouse
Tissue:  Brain
References:  7
Physiological Consequences of Altering Gene Expression Click here for help
Both protein level and mRNA level of RGS17 are highly expressed in human colorectal carcinoma tissues compared with the adjacent normal tissues. Overexpression of RGS17 increases cell proliferation, migration, and invasion; knockdown of RGS17 inhibits tumor growth.
Species:  Human
Tissue:  Colorectal carcinoma tissues, HCT116 (xenograft mouse model), HT-29 cells
Technique:  Transient overexpression, siRNA interference, shRNA
References:  11,13,27
RGS17 overexpression reversed miR-203-induced cell proliferation, migration, and invasion inhibition. Knockdown of RGS17 inhibits cell proliferation and tumorigenesis in xenograft mouse model.
Species:  Human
Tissue:  Lung cancer cell lines: A549 cells and Calu-1 cells; CRL-5889 cells and CRL5803 cells; H1299 cells
Technique:  Transient or stable overexpression, shRNA
References:  4,11,24,27
RGS17 is downregulated in nasopharyngreal carcinoma (NPC) cell lines. Overexpression of RGS17 inhibits cell proliferation in vitro and tumour growth in vivo.
Species:  Human
Tissue:  NPC cell lines (CNE2, CNE1 and HNE1)
Technique:  Transient overexpression
References:  28
Overexpression of RGS17 promotes hepatocellular carcinoma cell proliferation, migration and invasion. Knockdown of RGS17 inhibits cell proliferation, migration and invasion.
Species:  Human
Tissue:  Hepatocellular carcinoma HepG2 and HuH-7 cells
Technique:  Transient overexpression, shRNA
References:  22,32
Overexpression of RGS17 reverses miR-203-induced cell proliferation, migration and invasion in prostate cancer cells. Knockdown of RGS17 inhibits cancer cell growth.
Species:  Human
Tissue:  Prostate cancer cell lines DU145, 22RV1 and LnCap
Technique:  Transient overexpression, shRNA, siRNA
References:  11,27,30-31
Knockdown of RGS17 increases cell viability and reduces chemotherapy-induced cell toxicity.
Species:  Human
Tissue:  Ovarian cancer cell line SKOV-3
Technique:  siRNA
References:  10
Overexpression of RGS17 inhibits LPA-mediated activation of AKT
Species:  Human
Tissue:  Ovarian cancer cell line SKOV-3
Technique:  Transient overexpression
References:  10
Knockdown of RGS17 inhibits cell proliferation, migration, and invasion. Overexpression of RGS17 can rescue inhibited proliferation, migration and invasion caused by miR-32 overexpression.
Species:  Human
Tissue:  Breast cancer cell line ZR-75-30
Technique:  shRNA, transient overexpression
References:  14
Inhibition of RGS17 expression reduces cAMP levels in response to mastoparan M7.
Species:  Human
Tissue:  Hepatocellular carcinoma HuH-7 cells
Technique:  shRNA
References:  22
Loss of RGS17 leads to decreased expression of and decreased forskolin induction of CREB-responsive genes. Overexpression of RGS17 increases cAMP accumulation and CREB phosphorylation.
Species:  Human
Tissue:  H1299 lung cancer cells
Technique:  shRNA, transient overexpression
References:  11
Xenobiotics Influencing Gene Expression Click here for help
RGS17 protein level is increased after the treatment with proteasome inhibitors including epoxomicin and MG132.
Species:  Human
Tissue:  HuH-7 hepatocellular carcinoma cell line
Technique:  Western blot
References:  22
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Seven RGS17 SNPs showed a significant association with at least one of the four dependence traits (alcohol, cocaine, opioid or marijuana) in the population of African American or European American
SNP accession:  rs545323, rs516557, rs9371276, rs1933258, rs9397585, rs6931160, rs596359
References:  29
Type:  Single nucleotide polymorphism
Species:  Human
Description:  SNPs (rs9397585 and rs6931160) are associated with lower mRNA expression level in CEU (Northern Europeans from Utah) and YRI (Yoruba in Ibadan, Nigeria) subjects. SNPs (rs9371276 and rs596359) are associated with lower mRNA expression level only in YRI subjects.
SNP accession:  rs9397585, rs6931160, rs9371276, rs596359
References:  29
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A region-wide scan across 6q23-25 found significant association between lung cancer susceptibility and three single nucleotide polymorphisms in the first intron of the RGS17 gene.
SNP accession:  rs6901126, rs4083914, rs9479510
References:  15,27
Type:  Single nucleotide polymorphism
Species:  Human
Description:  SNP associated with RGS17 expression levels in LNCaP cells
SNP accession:  rs13215402
References:  31
Type:  Single nucleotide polymorphism
Species:  Human
Description:  SNPs associated with smoking initiation in populations of European-American and African American origin.
SNP accession:  rs7747583, rs2349433
References:  26

References

Show »

1. Ajit SK, Ramineni S, Edris W, Hunt RA, Hum WT, Hepler JR, Young KH. (2007) RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. Cell Signal, 19 (4): 723-30. [PMID:17126529]

2. Bodle CR, Mackie DI, Hayes MP, Schamp JH, Miller MR, Henry MD, Doorn JA, Houtman JCD, James MA, Roman DL. (2017) Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines. J Nat Prod, 80 (7): 1992-2000. [PMID:28621943]

3. Bodle CR, Schamp JH, O'Brien JB, Hayes MP, Wu M, Doorn JA, Roman DL. (2018) Screen Targeting Lung and Prostate Cancer Oncogene Identifies Novel Inhibitors of RGS17 and Problematic Chemical Substructures. SLAS Discov, 23 (4): 363-374. [PMID:29351497]

4. Chi Y, Jin Q, Liu X, Xu L, He X, Shen Y, Zhou Q, Zhang J, Jin M. (2017) miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17. Cancer Sci, 108 (12): 2366-2372. [PMID:28921827]

5. Doupnik CA, Xu T, Shinaman JM. (2001) Profile of RGS expression in single rat atrial myocytes. Biochim Biophys Acta, 1522 (2): 97-107. [PMID:11750060]

6. Fischer T, De Vries L, Meerloo T, Farquhar MG. (2003) Promotion of G alpha i3 subunit down-regulation by GIPN, a putative E3 ubiquitin ligase that interacts with RGS-GAIP. Proc Natl Acad Sci USA, 100 (14): 8270-5. [PMID:12826607]

7. Garzón J, Rodríguez-Muñoz M, López-Fando A, Sánchez-Blázquez P. (2005) The RGSZ2 protein exists in a complex with mu-opioid receptors and regulates the desensitizing capacity of Gz proteins. Neuropsychopharmacology, 30 (9): 1632-48. [PMID:15827571]

8. Garzón J, Rodríguez-Muñoz M, Vicente-Sánchez A, Bailón C, Martínez-Murillo R, Sánchez-Blázquez P. (2011) RGSZ2 binds to the neural nitric oxide synthase PDZ domain to regulate mu-opioid receptor-mediated potentiation of the N-methyl-D-aspartate receptor-calmodulin-dependent protein kinase II pathway. Antioxid Redox Signal, 15 (4): 873-87. [PMID:21348811]

9. Garzón J, Rodríguez-Muñoz M, Vicente-Sánchez A, García-López MÁ, Martínez-Murillo R, Fischer T, Sánchez-Blázquez P. (2011) SUMO-SIM interactions regulate the activity of RGSZ2 proteins. PLoS One, 6 (12): e28557. [PMID:22163035]

10. Hooks SB, Callihan P, Altman MK, Hurst JH, Ali MW, Murph MM. (2010) Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer, 9: 289. [PMID:21044322]

11. James MA, Lu Y, Liu Y, Vikis HG, You M. (2009) RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway. Cancer Res, 69 (5): 2108-16. [PMID:19244110]

12. 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]

13. Li L, Luo HS. (2018) G-Protein Signaling Protein-17 (RGS17) Is Upregulated and Promotes Tumor Growth and Migration in Human Colorectal Carcinoma. Oncol Res, 26 (1): 27-35. [PMID:28337960]

14. Li Y, Li L, Lin J, Hu X, Li B, Xue A, Shen Y, Jiang J, Zhang M, Xie J et al.. (2015) Deregulation of RGS17 Expression Promotes Breast Cancer Progression. J Cancer, 6 (8): 767-75. [PMID:26185539]

15. Liu P, Vikis HG, Lu Y, Wang Y, Schwartz AG, Pinney SM, Yang P, de Andrade M, Gazdar A, Gaba C et al.. (2010) Cumulative effect of multiple loci on genetic susceptibility to familial lung cancer. Cancer Epidemiol Biomarkers Prev, 19 (2): 517-24. [PMID:20142248]

16. Mao H, Zhao Q, Daigle M, Ghahremani MH, Chidiac P, Albert PR. (2004) RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling. J Biol Chem, 279 (25): 26314-22. [PMID:15096504]

17. Monroy CA, Mackie DI, Roman DL. (2013) A high throughput screen for RGS proteins using steady state monitoring of free phosphate formation. PLoS ONE, 8 (4): e62247. [PMID:23626793]

18. Nunn C, Mao H, Chidiac P, Albert PR. (2006) RGS17/RGSZ2 and the RZ/A family of regulators of G-protein signaling. Semin Cell Dev Biol, 17 (3): 390-9. [PMID:16765607]

19. Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P, Wang JB, Garzón J. (2008) NMDAR-nNOS generated zinc recruits PKCgamma to the HINT1-RGS17 complex bound to the C terminus of Mu-opioid receptors. Cell Signal, 20 (10): 1855-64. [PMID:18652891]

20. Rodríguez-Muñoz M, Sánchez-Blázquez P, Herrero-Labrador R, Martínez-Murillo R, Merlos M, Vela JM, Garzón J. (2015) The σ1 receptor engages the redox-regulated HINT1 protein to bring opioid analgesia under NMDA receptor negative control. Antioxid Redox Signal, 22 (10): 799-818. [PMID:25557043]

21. Sieng M, Hayes MP, O'Brien JB, Andrew Fowler C, Houtman JC, Roman DL, Lyon AM. (2019) High-resolution structure of RGS17 suggests a role for Ca2+ in promoting the GTPase-activating protein activity by RZ subfamily members. J Biol Chem, 294 (20): 8148-8160. [PMID:30940727]

22. Sokolov E, Iannitti DA, Schrum LW, McKillop IH. (2011) Altered expression and function of regulator of G-protein signaling-17 (RGS17) in hepatocellular carcinoma. Cell Signal, 23 (10): 1603-10. [PMID:21620966]

23. Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, Gileadi C, Fedorov OY, Dowler EF, Higman VA et al.. (2008) Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc Natl Acad Sci USA, 105 (17): 6457-62. [PMID:18434541]

24. Sun Y, Fang R, Li C, Li L, Li F, Ye X, Chen H. (2010) Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. Biochem Biophys Res Commun, 396 (2): 501-7. [PMID:20420807]

25. Sánchez-Blázquez P, Rodríguez-Muñoz M, Bailón C, Garzón J. (2012) GPCRs promote the release of zinc ions mediated by nNOS/NO and the redox transducer RGSZ2 protein. Antioxid Redox Signal, 17 (9): 1163-77. [PMID:22563771]

26. Yoon D, Kim YJ, Cui WY, Van der Vaart A, Cho YS, Lee JY, Ma JZ, Payne TJ, Li MD, Park T. (2012) Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence. Hum Genet, 131 (6): 1009-21. [PMID:22006218]

27. You M, Wang D, Liu P, Vikis H, James M, Lu Y, Wang Y, Wang M, Chen Q, Jia D et al.. (2009) Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene. Clin Cancer Res, 15 (8): 2666-74. [PMID:19351763]

28. Yu Q, Zhang N, Jiang Y, Huang Y, Lian YY, Liu T, Li N, Guan G. (2018) RGS17 inhibits tumorigenesis and improves 5-fluorouracil sensitivity in nasopharyngeal carcinoma. Onco Targets Ther, 11: 7591-7600. [PMID:30464507]

29. Zhang H, Wang F, Kranzler HR, Anton RF, Gelernter J. (2012) Variation in regulator of G-protein signaling 17 gene (RGS17) is associated with multiple substance dependence diagnoses. Behav Brain Funct, 8: 23. [PMID:22591552]

30. Zhang LS, Ma HG, Sun FH, Zhao WC, Li G. (2019) MiR-203 inhibits the malignant behavior of prostate cancer cells by targeting RGS17. Eur Rev Med Pharmacol Sci, 23 (13): 5667-5674. [PMID:31298318]

31. Zhang P, Xia JH, Zhu J, Gao P, Tian YJ, Du M, Guo YC, Suleman S, Zhang Q, Kohli M et al.. (2018) High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing. Nat Commun, 9 (1): 2022. [PMID:29789573]

32. Zhang W, Qian S, Yang G, Zhu L, Zhou B, Wang J, Liu R, Yan Z, Qu X. (2018) MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma. Gene, 659: 22-28. [PMID:29559347]

Contributors

Show »

How to cite this page