regulator of G-protein signaling 20 | RZ family | IUPHAR/BPS Guide to PHARMACOLOGY

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regulator of G-protein signaling 20

Target not currently curated in GtoImmuPdb

Target id: 2803

Nomenclature: regulator of G-protein signaling 20

Abbreviated Name: RGS20

Family: RZ 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 - 388 8q11.23 RGS20 regulator of G protein signaling 20
Mouse - 372 1 A1 Rgs20 regulator of G-protein signaling 20 10
Rat - 242 5q12 Rgs20 regulator of G-protein signaling 20 11
Previous and Unofficial Names
RGSZ1 | ZGAP1
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
G Proteins
Name References
Gαi0, Gz 12-13
Interacting Proteins
Name Effect References
SCG10 (superior cervical ganglia, neural specific 10) RGS20 blocks SCG10-induced microtubule disassembly in a dose dependent manner in vitro. RGS20 does not block SCG10 mediated microtubule assembly. SCG10 has no effect on RGS20 GAP activity. 9
PKCI-1 (protein kinase C interacting protein) Exact consequences unknown, however cotransfection of PKCI-1 and RGS20 blocked DAMGO mediated inhibition of cAMP formation upon forskolin treatment. This result was of greater extent than either protein alone, perhaps indicating some scaffolding arrangement which promotes regulation of μ-opiod receptor signaling. 1
14-3-3 proteins Interaction was noted however not fully explored. Several theories were postulated. For example, 14-3-3-ζ inhibits PKCα phosphorylation of Gαz, so binding to RGS20 may serve as a scaffold to help regulate Gαz signaling. At the same time it was noted that 14-3-3 actually interferes with Gαi/o interactions in the case of RGS7. More work needs to be done. 1
GIPN (GAIP interacting protein N terminus) Identified in a yeast teo screen for GAIP, and confirmed to bind to all RZ family members including RGS20. Exact consequence of binding still needs to be determined, however GIPN was found to decrease the half-life of Gαi3 when overexpressed. Knockdown of RZ family members needs to be performed to determine if GIPN still regulates Gαi3 in the absence of RGS. 4
Associated Protein Comments
PKCI-1 and GIPN exclusilvely interact with the poly cysteine string region of RGS20. SGC10 primarily interacts with the poly cyteine string region but shows some pulldown with the RGS domain. 14-3-3 interacts with the RGS domain region and not the poly cysteine string.
Tissue Distribution
Brain
Species:  Human
Technique:  Northen blot
References:  6,12
Adult brain and lung, fetal brain
Species:  Human
Technique:  PCR
References:  6
Functional Assays
Increased rate of GTP hydrolysis for Gαz.
Species:  None
Tissue:  Biochemical assay, reconsituted into unilamellar phopholipid vesicles.
Response measured:  ncreased rate of GTP hydrolysis in the presence of RGS20
References:  12
Microtubule disassembly
Species:  None
Tissue:  Biochemical, purified proteins, turbididty or microscpy based assays
Response measured:  Presence of RGS20 inhibits SGC10 mediated microtuble disassembly
References:  9
Regulation of Gαi signaling
Species:  None
Tissue:  Cell based assays in PC12 and CHO-K1 cells
Response measured:  Decreased MAPK activity (PC12) and decreased SRE activation (CHO)
References:  13
Regulation of Gαi/o signaling
Species:  None
Tissue:  Cell based assays in HEK293 GT cells
Response measured:  Protects against DAMGO-mediated inhibition of cAMP formation. Effect is compounded when also expressed with PKC1-1
References:  1
Physiological Functions
Temporal regulation of Gαi/o and Gαz signaling
Species:  None
Tissue: 
References:  1,12-13
Regulation of microtubule disassemly
Species:  None
Tissue: 
References:  9
Physiological Consequences of Altering Gene Expression
Enhancement of μ-opioid induced analgesia, increased development of tolerance to morphine
Species:  Mouse
Tissue:  CNS
Technique:  Antisense oligodeoxynucleotide (ODN) gene knockdown
References:  5
Gene Expression and Pathophysiology Comments
RGS20 was identified as being upregulated comparing primary to metastatic melanomas [7]. RGS20 was also identified as a susceptibility gene for hypertension [8].
Biologically Significant Variants
Type:  Splice variant
Species:  Mouse
Description:  Ret RGS, retina specific RGS.
Amino acids:  374
References:  2-3

References

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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. Barker SA, Wang J, Sierra DA, Ross EM. (2001) RGSZ1 and Ret RGS: two of several splice variants from the gene RGS20. Genomics, 78 (3): 223-9. [PMID:11735229]

3. 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]

4. 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. U.S.A., 100 (14): 8270-5. [PMID:12826607]

5. Garzón J, Rodríguez-Muñoz M, López-Fando A, García-España A, Sánchez-Blázquez P. (2004) RGSZ1 and GAIP regulate mu- but not delta-opioid receptors in mouse CNS: role in tachyphylaxis and acute tolerance. Neuropsychopharmacology, 29 (6): 1091-104. [PMID:14997173]

6. Glick JL, Meigs TE, Miron A, Casey PJ. (1998) RGSZ1, a Gz-selective regulator of G protein signaling whose action is sensitive to the phosphorylation state of Gzalpha. J. Biol. Chem., 273 (40): 26008-13. [PMID:9748279]

7. Honda K, Satomura K, Hashida M, Sezaki H. (1985) [Topical application of mitomycin C conjugated with dextran (MMC-D): a high molecular weight derivative of mitomycin C]. Gan To Kagaku Ryoho, 12 (3 Pt 1): 530-5. [PMID:2408576]

8. Kohara K, Tabara Y, Nakura J, Imai Y, Ohkubo T, Hata A, Soma M, Nakayama T, Umemura S, Hirawa N et al.. (2008) Identification of hypertension-susceptibility genes and pathways by a systemic multiple candidate gene approach: the millennium genome project for hypertension. Hypertens. Res., 31 (2): 203-12. [PMID:18360038]

9. Nixon AB, Grenningloh G, Casey PJ. (2002) The interaction of RGSZ1 with SCG10 attenuates the ability of SCG10 to promote microtubule disassembly. J. Biol. Chem., 277 (20): 18127-33. [PMID:11882662]

10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T et al.. (2011) A conditional knockout resource for the genome-wide study of mouse gene function. Nature, 474 (7351): 337-42. [PMID:21677750]

11. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF et al.. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc. Natl. Acad. Sci. U.S.A., 99 (26): 16899-903. [PMID:12477932]

12. Wang J, Ducret A, Tu Y, Kozasa T, Aebersold R, Ross EM. (1998) RGSZ1, a Gz-selective RGS protein in brain. Structure, membrane association, regulation by Galphaz phosphorylation, and relationship to a Gz gtpase-activating protein subfamily. J. Biol. Chem., 273 (40): 26014-25. [PMID:9748280]

13. Wang Y, Ho G, Zhang JJ, Nieuwenhuijsen B, Edris W, Chanda PK, Young KH. (2002) Regulator of G protein signaling Z1 (RGSZ1) interacts with Galpha i subunits and regulates Galpha i-mediated cell signaling. J. Biol. Chem., 277 (50): 48325-32. [PMID:12379657]

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