RGS17 (regulator of G-protein signaling 17)

2011-10-01   Chenguang Li , Lei Wang , Yihua Sun , Haiquan Chen 

Department of Thoracic Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

Identity

HGNC
LOCATION
6q25.2
LOCUSID
ALIAS
RGS-17,RGSZ2,hRGS17
FUSION GENES

DNA/RNA

Description

The RGS17 gene spans over a region of 120 kbp DNA including 4 coding exons and 1 non-coding exon (exon 1).

Transcription

The RGS17 gene mRNA consists of about 1472 nucleotides with an open reading frame (ORF) of 633 bases.

Pseudogene

RGS17P1 regulator of G-protein signaling 17 pseudogene 1.

Proteins

Note

210 amino acids; 24 kDa.
Atlas Image
Diagram of the RGS17 protein in scale. The numbers represent specific residues. The regions are RGS_RZ-like (Regulator of G protein signaling (RGS) domain found in the RZ protein), putative G-alpha interaction site. C: Carboxyl-terminal; N: Amino-terminal.

Description

The RGS17 protein consists of 210 amino acid residues. 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.

Expression

Widely expressed in human organs.

Localisation

Its cellular localization has not been formally monitored to date.

Function

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. RGS proteins are GTPase-activating proteins for Gi and Gq class G-alpha proteins. They accelerate transit through the cycle of GTP binding and hydrolysis and thereby accelerate signaling kinetics and termination. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal.

Homology

The RGS17 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, and zebrafish.

Mutations

Germinal

No germline mutations in this gene have been reported.

Somatic

A synonymous-coding somatic mutations of this gene is reported in pancreas cancer at codon 166, P166P (COSMIC).

Implicated in

Entity name
Various cancer
Note
Lung cancer, prostate cancer.
Disease
RSG17 is overexpressed in lung and prostate cancer (James et al., 2009). Expression of RGS17 is up-regulated in 80% of lung tumors, and also up-regulated in prostate tumors. Overexpression of RGS17 induce and maintain cell proliferation.
Entity name
Lung cancer
Disease
hsa-mir-182 is involved in the down regulation of RGS17 expression through two conserved sites located in its 3 UTR region (Sun et al., 2010).
Two SNPs in the first intron of RGS17 (rs4083914 and rs9479510) were found associated with familial lung cancer susceptibility (You et al., 2009).
Entity name
Ovarian cancer
Disease
RGS2, RGS5, RGS10 and RGS17 transcripts are expressed at significantly lower levels in cells resistant to chemotherapy compared with parental, chemo-sensitive cells in ovarian cancer cells (Hooks et al., 2010).
Prognosis
RGS17 loss of expression contributes to the development of chemoresistance in ovarian cancer cells.

Bibliography

Pubmed IDLast YearTitleAuthors
210443222010Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells.Hooks SB et al
192441102009RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.James MA et al
204208072010Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro.Sun Y et al
193517632009Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene.You M et al

Other Information

Locus ID:

NCBI: 26575
MIM: 607191
HGNC: 14088
Ensembl: ENSG00000091844

Variants:

dbSNP: 26575
ClinVar: 26575
TCGA: ENSG00000091844
COSMIC: RGS17

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000091844ENST00000206262Q9UGC6
ENSG00000091844ENST00000367225Q9UGC6

Expression (GTEx)

0
1
2
3
4
5
6
7
8
9
10

Pathways

PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (z) signalling eventsREACTOMER-HSA-418597

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA447321Depressive Disorder, MajorDiseaseClinicalAnnotationassociatedPD
PA452229antidepressantsChemicalClinicalAnnotationassociatedPD

References

Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
204208072010Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro.48
192441102009RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.37
203062912010A three-stage genome-wide association study of general cognitive ability: hunting the small effects.36
220062182012Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence.36
150965042004RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling.34
193517632009Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene.33
193517632009Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene.33
186766802008Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.32
196921682010Genetic susceptibility to distinct bladder cancer subphenotypes.25

Citation

Chenguang Li ; Lei Wang ; Yihua Sun ; Haiquan Chen

RGS17 (regulator of G-protein signaling 17)

Atlas Genet Cytogenet Oncol Haematol. 2011-10-01

Online version: http://atlasgeneticsoncology.org/gene/47522/rgs17