RGS17

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RGS17
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRGS17, RGS-17, RGSZ2, hregulator of G-protein signaling 17, regulator of G protein signaling 17
External IDsOMIM: 607191 MGI: 1927469 HomoloGene: 8242 GeneCards: RGS17
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_012419

NM_001161822
NM_019958

RefSeq (protein)

NP_036551

NP_001155294
NP_064342

Location (UCSC)Chr 6: 153 – 153.13 MbChr 10: 5.78 – 5.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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. ^ a b c GRCh38: Ensembl release 89: ENSG00000091844 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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