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regulator of G-protein signaling 20

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Target not currently curated in GtoImmuPdb

Target id: 2803

Nomenclature: regulator of G-protein signaling 20

Abbreviated Name: RGS20

Family: RZ family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 388 8q11.23 RGS20 regulator of G protein signaling 20
Mouse - 239 1 A1 Rgs20 regulator of G-protein signaling 20 21
Rat - 242 5q12 Rgs20 regulator of G-protein signaling 20 22
Previous and Unofficial Names Click here for help
RGSZ1 | ZGAP1
Database Links Click here for help
Alphafold O76081 (Hs), Q9QZB1 (Mm)
CATH/Gene3D 1.10.196.10
Ensembl Gene ENSG00000147509 (Hs), ENSMUSG00000002459 (Mm), ENSRNOG00000008100 (Rn)
Entrez Gene 8601 (Hs), 58175 (Mm), 362477 (Rn)
Human Protein Atlas ENSG00000147509 (Hs)
KEGG Gene hsa:8601 (Hs), mmu:58175 (Mm), rno:362477 (Rn)
OMIM 607193 (Hs)
Pharos O76081 (Hs)
RefSeq Nucleotide NM_170587 (Hs), NM_001177795 (Mm), NM_001127495 (Rn)
RefSeq Protein NP_733466 (Hs), NP_001171266 (Mm), NP_001120967 (Rn)
UniProtKB O76081 (Hs), Q9QZB1 (Mm)
Wikipedia RGS20 (Hs)
Associated Proteins Click here for help
G Proteins
Name References
Gαi0, Gz 23-24
Gi1 transient state 24
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. 20
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. 6
MT1 receptor 15-16
μ receptor 8
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.
Inhibitor Comments
WAY-243 inhibits RGS20-mediated acceleration of GTP hydrolysis by Gαz in a single turnover GTPase assay (IC50 50 μM) [26].
Tissue Distribution Click here for help
Brain
Species:  Human
Technique:  Northen blot
References:  10,23
Adult brain and lung, fetal brain
Species:  Human
Technique:  PCR
References:  10
Functional Assays Click here for help
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:  23
Microtubule disassembly
Species:  None
Tissue:  Biochemical, purified proteins, turbididty or microscpy based assays
Response measured:  Presence of RGS20 inhibits SGC10 mediated microtuble disassembly
References:  20
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:  24
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 Click here for help
Temporal regulation of Gαi/o and Gαz signaling
Species:  None
Tissue: 
References:  1,23-24
Regulation of microtubule disassemly
Species:  None
Tissue: 
References:  20
Physiological Consequences of Altering Gene Expression Click here for help
Enhancement of μ-opioid induced analgesia, increased development of tolerance to morphine
Species:  Mouse
Tissue:  CNS
Technique:  Antisense oligodeoxynucleotide (ODN) gene knockdown
References:  7
Overexpression of RGS20 promotes cell proliferation and invasion.
Species:  Human
Tissue:  Tongue (Cal-27 cells)
Technique:  Transient transfection
References:  12
Overexpression of RGS20 blocks MAPK activation by UK14304 in PC12 cells.
Species:  Rat
Tissue:  Adrenal gland
Technique:  Stable overexpression
References:  24
RGS20 knockout enhances the analgesic efficacy of MOPR agonists and delays morphine tolerance.
Species:  Mouse
Tissue:  gGlobal manipulations of expression
Technique:  Gene knockout
References:  9
RGS20 is significantly upregulated in bladder cancer. Overexpression of RGS20 promotes proliferation and migration of bladder cancer cells and knockdown of RGS20 inhibits these effects.
Species:  Human
Tissue:  Bladder
Technique:  Stable overexpression, shRNA
References:  14
Overexpression of RGS20 enhances cell aggregation, migration, invasion and adhesion. Conversely, shRNA-mediated knockdown of endogenous RGS20 impaired these responses.
Species:  Human
Tissue:  Cancer cell types, including cervical cancer HeLa, breast adenocarcinoma MDA-MB-231, and non-small cell lung carcinoma H1299 and A549 cells.
Technique:  Stable overexpression, shRNA
References:  25
Knockdown of RGS20 decreases the expression of vimentin (a mesenchymal cell marker) but increases the expression of E-cadherin, two indicators commonly associated with metastasis.
Species:  Human
Tissue:  Non-small cell lung carcinoma A547 cells
Technique:  shRNA
References:  25
Overexpression of RGS20 increases cell aggregation.
Species:  Mouse
Tissue:  NIH3T3 fibroblasts
Technique:  Stable overexpression
References:  25
RGS20 actions in the vlPAG promote the development of analgesic tolerance without impacting the development of physical dependence.
Species:  Mouse
Tissue:  Brain
Technique:  Conditional knockdown of RGS20 in neurons
References:  9
Overexpression of RGS20 markedly induces dispersal of the Golgi apparatus.
Species:  Human
Tissue:  HeLa cells
Technique:  Transient overexpression
References:  19
Xenobiotics Influencing Gene Expression Click here for help
RGS20 protein level in the PAG is upregulated by morphine treatment.
Species:  Mouse
Tissue:  Brain
Technique:  Western blot
References:  9
Stimulation of GPER1 with the selective agonist G-1 and non-selective stimulation of estrogen receptors with estradiol alter RGS20 isoforms’ expression in the hypothalamic paraventricular nucleus (PVN).
Species:  Rat
Tissue:  Brain
Technique:  Western blot, RT-PCR
References:  3-4,17-18
Gene Expression and Pathophysiology Comments
RGS20 was identified as being upregulated comparing primary to metastatic melanomas [11]. RGS20 was also identified as a susceptibility gene for hypertension [13].
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Mouse
Description:  Ret RGS, retina specific RGS.
Amino acids:  374
References:  2,5

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. Carrasco GA, Barker SA, Zhang Y, Damjanoska KJ, Sullivan NR, Garcia F, D'souza DN, Muma NA, van De Kar LD. (2004) Estrogen treatment increases the levels of regulator of G protein signaling-Z1 in the hypothalamic paraventricular nucleus: possible role in desensitization of 5-hydroxytryptamine1A receptors. Neuroscience, 127 (2): 261-7. [PMID:15262317]

4. Creech RD, Li Q, Carrasco GA, Van de Kar LD, Muma NA. (2012) Estradiol induces partial desensitization of serotonin 1A receptor signaling in the paraventricular nucleus of the hypothalamus and alters expression and interaction of RGSZ1 and Gαz. Neuropharmacology, 62 (5-6): 2040-9. [PMID:22251927]

5. 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 USA, 94 (7): 2945-50. [PMID:9096326]

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, 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]

8. 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]

9. Gaspari S, Purushothaman I, Cogliani V, Sakloth F, Neve RL, Howland D, Ring RH, Ross EM, Shen L, Zachariou V. (2018) Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway. Proc Natl Acad Sci U S A, 115 (9): E2085-E2094. [PMID:29440403]

10. 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]

11. 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]

12. Huang G, He X, Wei XL. (2018) lncRNA NEAT1 promotes cell proliferation and invasion by regulating miR‑365/RGS20 in oral squamous cell carcinoma. Oncol Rep, 39 (4): 1948-1956. [PMID:29484420]

13. 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]

14. Li G, Wang M, Ren L, Li H, Liu Q, Ouyang Y, He L, Li F. (2019) Regulator of G protein signaling 20 promotes proliferation and migration in bladder cancer via NF-κB signaling. Biomed Pharmacother, 117: 109112. [PMID:31212130]

15. Maurice P, Daulat AM, Broussard C, Mozo J, Clary G, Hotellier F, Chafey P, Guillaume JL, Ferry G, Boutin JA et al.. (2008) A generic approach for the purification of signaling complexes that specifically interact with the carboxyl-terminal domain of G protein-coupled receptors. Mol Cell Proteomics, 7 (8): 1556-69. [PMID:18448421]

16. Maurice P, Daulat AM, Turecek R, Ivankova-Susankova K, Zamponi F, Kamal M, Clement N, Guillaume JL, Bettler B, Galès C et al.. (2010) Molecular organization and dynamics of the melatonin MT₁ receptor/RGS20/G(i) protein complex reveal asymmetry of receptor dimers for RGS and G(i) coupling. EMBO J, 29 (21): 3646-59. [PMID:20859254]

17. McAllister CE, Creech RD, Kimball PA, Muma NA, Li Q. (2012) GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus. Psychoneuroendocrinology, 37 (8): 1248-60. [PMID:22265196]

18. McAllister CE, Mi Z, Mure M, Li Q, Muma NA. (2014) GPER1 stimulation alters posttranslational modification of RGSz1 and induces desensitization of 5-HT1A receptor signaling in the rat hypothalamus. Neuroendocrinology, 100 (2-3): 228-39. [PMID:25402859]

19. Nagahama M, Usui S, Shinohara T, Yamaguchi T, Tani K, Tagaya M. (2002) Inactivation of Galpha(z) causes disassembly of the Golgi apparatus. J Cell Sci, 115 (Pt 23): 4483-93. [PMID:12414994]

20. 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]

21. 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]

22. 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 USA, 99 (26): 16899-903. [PMID:12477932]

23. 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]

24. 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]

25. Yang L, Lee MM, Leung MM, Wong YH. (2016) Regulator of G protein signaling 20 enhances cancer cell aggregation, migration, invasion and adhesion. Cell Signal, 28 (11): 1663-72. [PMID:27495875]

26. Young KH, Wang Y, Bender C, Ajit S, Ramirez F, Gilbert A, Nieuwenhuijsen BW. (2004) Yeast-based screening for inhibitors of RGS proteins. Methods Enzymol, 389: 277-301. [PMID:15313572]

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