RGS17

RGS17
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZV4
Identifiers
Aliases	RGS17 , RGS-17, RGSZ2, hregulator of G-protein signaling 17, regulator of G protein signaling 17
External IDs	OMIM: 607191; MGI: 1927469; HomoloGene: 8242; GeneCards: RGS17; OMA:RGS17 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6q25.2 Start 153,004,459 bp [1] End 153,131,282 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10|10 A1 Start 5,775,663 bp [2] End 5,872,400 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell tendon of biceps brachii cartilage tissue middle temporal gyrus islet of Langerhans ganglionic eminence Brodmann area 23 mucosa of paranasal sinus pancreatic ductal cell testicle Top expressed in superior colliculus dorsomedial hypothalamic nucleus zygote central gray substance of midbrain secondary oocyte ventral tegmental area inferior colliculi paraventricular nucleus of hypothalamus nucleus of stria terminalis pontine nuclei More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding GTPase activator activity GTPase activity Cellular component cytoplasm neuron projection cell junction synapse membrane nucleus plasma membrane cytoplasmic vesicle Biological process positive regulation of GTPase activity negative regulation of signal transduction response to amphetamine G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26575 56533 Ensembl ENSG00000091844 ENSMUSG00000019775 UniProt Q9UGC6 Q9QZB0 RefSeq (mRNA) NM_012419 NM_001161822 NM_019958 RefSeq (protein) NP_036551 NP_001155294 NP_064342 Location (UCSC) Chr 6: 153 – 153.13 Mb Chr 10: 5.78 – 5.87 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Regulator of G-protein signaling 17 is a protein that in humans is encoded by the RGS17 gene. ^{[5] [6]}

Function

This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif called the RGS domain and a cysteine-rich region. The protein attenuates the signaling activity of G-proteins by binding to activated, GTP-bound G alpha subunits and acting as a GTPase activating protein (GAP), increasing the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. ^[6] Along with RGS4, RGS9 and RGS14, ^{[7] [8]} RGS17 plays an important role in termination of signalling by mu opioid receptors and development of tolerance to opioid analgesic drugs. ^{[9] [10]}

Clinical significance

RGS17 is a putative lung cancer susceptibility gene in the lung cancer associated locus on chromosome 6q in humans. ^[11] RGS17 is overexpressed in lung and prostate cancers, induces cAMP production, CREB phosphorylation and CREB responsive gene expression[2]. Expression of RGS17 is required for maintenance of proliferation in lung tumor cell lines. ^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000091844 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019775 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Jordan JD, Carey KD, Stork PJ, Iyengar R (Jul 1999). "Modulation of rap activity by direct interaction of Galpha(o) with Rap1 GTPase-activating protein". The Journal of Biological Chemistry. 274 (31): 21507–10. doi: 10.1074/jbc.274.31.21507 . PMID   10419452.
6. "Entrez Gene: RGS17 regulator of G-protein signalling 17".
7. Garzón J, Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P (Jun 2005). "Effector antagonism by the regulators of G protein signalling (RGS) proteins causes desensitization of mu-opioid receptors in the CNS". Psychopharmacology. 180 (1): 1–11. doi:10.1007/s00213-005-2248-9. hdl: 10261/154655 . PMID   15830230. S2CID   21952312.
8. Rodríguez-Muñoz M, de la Torre-Madrid E, Gaitán G, Sánchez-Blázquez P, Garzón J (Dec 2007). "RGS14 prevents morphine from internalizing Mu-opioid receptors in periaqueductal gray neurons". Cellular Signalling. 19 (12): 2558–71. doi:10.1016/j.cellsig.2007.08.003. PMID   17825524.
9. Garzón J, Rodríguez-Muñoz M, López-Fando A, Sánchez-Blázquez P (Sep 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. doi: 10.1038/sj.npp.1300726 . PMID   15827571.
10. Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P, Garzón J (2007). "Morphine induces endocytosis of neuronal mu-opioid receptors through the sustained transfer of Galpha subunits to RGSZ2 proteins". Molecular Pain. 3: 1744-8069 –3-19. doi: 10.1186/1744-8069-3-19 . PMC   1947952 . PMID   17634133.
11. You M, Wang D, Liu P, Vikis H, James M, Lu Y, Wang Y, Wang M, Chen Q, Jia D, Liu Y, Wen W, Yang P, Sun Z, Pinney SM, Zheng W, Shu XO, Long J, Gao YT, Xiang YB, Chow WH, Rothman N, Petersen GM, de Andrade M, Wu Y, Cunningham JM, Wiest JS, Fain PR, Schwartz AG, Girard L, Gazdar A, Gaba C, Rothschild H, Mandal D, Coons T, Lee J, Kupert E, Seminara D, Minna J, Bailey-Wilson JE, Amos CI, Anderson MW (Apr 2009). "Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene". Clinical Cancer Research. 15 (8): 2666–74. doi:10.1158/1078-0432.ccr-08-2335. PMC   2746091 . PMID   19351763.
12. James MA, Lu Y, Liu Y, Vikis HG, You M (Mar 2009). "RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway". Cancer Research. 69 (5): 2108–16. doi:10.1158/0008-5472.can-08-3495. PMC   2746047 . PMID   19244110.

Further reading

• Mao H, Zhao Q, Daigle M, Ghahremani MH, Chidiac P, Albert PR (Jun 2004). "RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling". The Journal of Biological Chemistry. 279 (25): 26314–22. doi: 10.1074/jbc.M401800200 . PMID   15096504.
• Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, Garnier M (Mar 2004). "Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system". Brain Research. Molecular Brain Research. 122 (1): 24–34. doi:10.1016/j.molbrainres.2003.11.014. PMID   14992813.
• Fischer T, De Vries L, Meerloo T, Farquhar MG (Jul 2003). "Promotion of G alpha i3 subunit down-regulation by GIPN, a putative E3 ubiquitin ligase that interacts with RGS-GAIP". Proceedings of the National Academy of Sciences of the United States of America. 100 (14): 8270–5. Bibcode:2003PNAS..100.8270F. doi: 10.1073/pnas.1432965100 . PMC   166218 . PMID   12826607.
• Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker SA, He W, Wensel TG, Otero G, Brown G, Copeland NG, Jenkins NA, Wilkie TM (Feb 2002). "Evolution of the regulators of G-protein signaling multigene family in mouse and human". Genomics. 79 (2): 177–85. doi:10.1006/geno.2002.6693. PMID   11829488. S2CID   16065132.