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regulator of G-protein signaling 7

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Target not currently curated in GtoImmuPdb

Target id: 2816

Nomenclature: regulator of G-protein signaling 7

Abbreviated Name: RGS7

Family: R7 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 495 1q43 RGS7 regulator of G protein signaling 7
Mouse - 469 1 81.11 cM Rgs7 regulator of G protein signaling 7
Rat - 477 13q24-q25 Rgs7 regulator of G-protein signaling 7
Database Links Click here for help
Alphafold P49802 (Hs), O54829 (Mm), P49803 (Rn)
CATH/Gene3D 1.10.10.10, 1.10.196.10
Ensembl Gene ENSG00000182901 (Hs), ENSMUSG00000026527 (Mm), ENSRNOG00000021984 (Rn)
Entrez Gene 6000 (Hs), 24012 (Mm), 54296 (Rn)
Human Protein Atlas ENSG00000182901 (Hs)
KEGG Gene hsa:6000 (Hs), mmu:24012 (Mm), rno:54296 (Rn)
OMIM 602517 (Hs)
Pharos P49802 (Hs)
RefSeq Nucleotide NM_002924 (Hs), NM_001199003 (Mm), NM_011880 (Mm), NM_019343 (Rn)
RefSeq Protein NP_002915 (Hs), NP_036010 (Mm), NP_001185932 (Mm), NP_062216 (Rn)
UniProtKB P49802 (Hs), O54829 (Mm), P49803 (Rn)
Wikipedia RGS7 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of RGS7-Gbeta5 dimer
PDB Id:  6N9G
Resolution:  2.13Å
Species:  Bovine
References:  28
Associated Proteins Click here for help
G Proteins
Name References
Gαi/0 14,19,29
Interacting Proteins
Name Effect References
Gβ5 Proteolytic stabilization. 6
Regulator of G-protein signaling 7-binding protein (R7BP) Membrane or nuclear recruitment. 9,18
GPR179 Recruitment to postsynaptic specializations. 24
GPR158 Proteolytic stabilization, membrane recruitment. 24
GIRK channels Facilitaiton of channel regulaiton. 10,37
14-3-3 proteins 5
SNARE-associated protein SNAPIN 15
Tissue Distribution Click here for help
Retina (bipolar cells).
Species:  Mouse
Technique:  Western blot.
References:  6,36
Pituitary and purified pancreatic islets.
Species:  Mouse
Technique:  Western blot.
References:  22
Brain (cerebellum, brainstem, hypothalamus, thalamus, neocortex, hippocampus, amygdala, striatum).
Species:  Rat
Technique:  In situ hybridisation.
References:  13
Brain (cerebellum > cortex, thalamus > caudate-putamen > hippocampus).
Species:  Rat
Technique:  Western blot.
References:  17
Brain (low/absence of expression in heart, lung, stomach, spleen, liver, kidney, testis, and back muscle).
Species:  Rat
Technique:  Northern blot.
References: 
Functional Assays Click here for help
Bioluminescence resonance energy transfer-based assay shows that RGS7/Gβ5 displays a strong preference for Go over Gi.
Species:  Human
Tissue:  HEK293T/17 cells.
Response measured:  GTPase-accelerating protein (GAP) activity.
References:  19
Cells expressing RGS7 showed faster GIRK current deactivation kinetics activated by GABAB receptor.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Measurement of G protein-mediated modulation of K+ (GIRK) currents.
References:  10
RGS7-Gβ5 complex can inhibit Ca2+ signaling elicited by muscarinic acetylcholine receptor type 3 (M3 receptor) but not M1, M5, histamine H1, and GnRH receptors.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Measurement of Ca2+-mobilization.
References:  16,33
Accelerates G protein-mediated modulation of GIRK upon stimulation of the M2 muscarinic receptor.
Species:  Rat
Tissue:  Proetin expression in Xenopus oocytes.
Response measured:  Measurement of G protein-mediated modulation of K+ (GIRK) currents.
References:  32
Complex of 14-3-3 and RGS7 modulates of GIRK deactivation kinetics.
Species:  Human
Tissue:  Protein expression in Xenopus oocytes.
Response measured:  Measurement of G protein-mediated modulation of K+ (GIRK) currents.
References:  4
Speeds up the rate of GTP hydrolysis by Gai, Go, Gt in purified recombinant system.
Species:  Human
Tissue:  In vitro assays with recombinant proteins.
Response measured:  Acceleration of GTP hydrolysis rate by Ga subunits.
References:  14,31
TR-FRET assay to determine the extent of RGS7 complex formation with its partner R7BP in vitro.
Species:  Mouse
Tissue:  In vitro, using recombinat proteins.
Response measured:  Change in fluorescence intensity.
References:  21
Functional Assay Comments
The 14-3-3 proteins are evolutionarily conserved regulatory molecules which can bind a diverse range of signaling proteins, such as kinases, phosphatases, and transmembrane receptors [3,20,23].
Physiological Consequences of Altering Gene Expression Click here for help
Knockdown of RGS7 in the striatum potentiates locomotor sensitization to cocaine.
Species:  Mouse
Tissue:  Striatum.
Technique:  Viral gene transfer.
References:  2
Mice lacking RGS7 exhibit deficits in spatial learning and memory, observed as deficits in contextual fear conditioning and in the Morris water maze.
Species:  Mouse
Tissue:  In vivo.
Technique:  Gene knockout.
References:  26
RGS7-knockout mice display normal light responses but double RGS7/RGS11 knockout mice show an absence of the b-wave as measured by electroretinograms.
Species:  Mouse
Tissue:  In vivo (retina).
Technique:  Gene knockout
References:  7,34,38
RGS7 dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics, observed as decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene knockout
References:  26
Knockdown of RGS7 enhances the potency of antinociception promoted by mu opioid receptor agonists, and abrogates morphine tolerance.
Species:  Mouse
Tissue:  Brain.
Technique:  Antisense oligodeoxynucleotide knockdown.
References:  12
Mice lacking RGS7 display anti-depressant phenotype and are stress resilient.
Species:  Mouse
Tissue:  in vivo.
Technique:  Gene knockout.
References:  25
Elimination of RGS7 leads to increase in basal cAMP indicating that RGS7 inhibits cAMP formation.
Species:  Mouse
Tissue:  Brain PFC.
Technique:  Gene knockout.
References:  25
Potentiates Kv4.2 activity through PKA-dependent mechanism.
Species:  Mouse
Tissue:  Brain PFC.
Technique:  Gene knockout.
References:  35
Inhibits GABAB signaling to CaV2 channels.
Species:  Mouse
Tissue:  Hippocampus.
Technique:  Gene knockout.
References:  27
Biologically Significant Variants Click here for help
Type:  Naturally occurring SNPs
Species:  Human
Description:  RGS7 SNPs affect tumor growth of uterine fibroids.
References:  1
Type:  Naturally occurring SNP
Species:  Human
Description:  This SNP has been associated with survival time in late-stage non-small cell lung cancer.
Nucleotide change:  A>G
SNP accession:  rs6689169
References:  8
Type:  Naturally occurring SNP
Species:  Human
Description:  Genetic anaylsis suggests that RGS7 may be associatied with autosomal recessive cognitive disorder effects on intelligence.
References:  11
Biologically Significant Variant Comments
RGS7R44C and RGS7E384K (resulting from naturally occurring SNPs in the human gene) promote proliferation and invasion in melanoma [30].

References

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1. Aissani B, Wiener H, Zhang K. (2013) Multiple hits for the association of uterine fibroids on human chromosome 1q43. PLoS ONE, 8 (3): e58399. [PMID:23555580]

2. Anderson GR, Cao Y, Davidson S, Truong HV, Pravetoni M, Thomas MJ, Wickman K, Giesler Jr GJ, Martemyanov KA. (2010) R7BP complexes with RGS9-2 and RGS7 in the striatum differentially control motor learning and locomotor responses to cocaine. Neuropsychopharmacology, 35 (4): 1040-50. [PMID:20043004]

3. Bartel M, Schäfer A, Stevers LM, Ottmann C. (2014) Small molecules, peptides and natural products: getting a grip on 14-3-3 protein-protein modulation. Future Med Chem, 6 (8): 903-21. [PMID:24962282]

4. Benzing T, Köttgen M, Johnson M, Schermer B, Zentgraf H, Walz G, Kim E. (2002) Interaction of 14-3-3 protein with regulator of G protein signaling 7 is dynamically regulated by tumor necrosis factor-alpha. J Biol Chem, 277 (36): 32954-62. [PMID:12077120]

5. Benzing T, Yaffe MB, Arnould T, Sellin L, Schermer B, Schilling B, Schreiber R, Kunzelmann K, Leparc GG, Kim E et al.. (2000) 14-3-3 interacts with regulator of G protein signaling proteins and modulates their activity. J Biol Chem, 275 (36): 28167-72. [PMID:10862767]

6. Cabrera JL, de Freitas F, Satpaev DK, Slepak VZ. (1998) Identification of the Gbeta5-RGS7 protein complex in the retina. Biochem Biophys Res Commun, 249 (3): 898-902. [PMID:9731233]

7. Cao Y, Pahlberg J, Sarria I, Kamasawa N, Sampath AP, Martemyanov KA. (2012) Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons. Proc Natl Acad Sci USA, 109 (20): 7905-10. [PMID:22547806]

8. Dai J, Gu J, Lu C, Lin J, Stewart D, Chang D, Roth JA, Wu X. (2011) Genetic variations in the regulator of G-protein signaling genes are associated with survival in late-stage non-small cell lung cancer. PLoS ONE, 6 (6): e21120. [PMID:21698121]

9. Drenan RM, Doupnik CA, Boyle MP, Muglia LJ, Huettner JE, Linder ME, Blumer KJ. (2005) Palmitoylation regulates plasma membrane-nuclear shuttling of R7BP, a novel membrane anchor for the RGS7 family. J Cell Biol, 169 (4): 623-33. [PMID:15897264]

10. Fajardo-Serrano A, Wydeven N, Young D, Watanabe M, Shigemoto R, Martemyanov KA, Wickman K, Luján R. (2013) Association of Rgs7/Gβ5 complexes with Girk channels and GABAB receptors in hippocampal CA1 pyramidal neurons. Hippocampus, 23 (12): 1231-45. [PMID:23804514]

11. Franić S, Groen-Blokhuis MM, Dolan CV, Kattenberg MV, Pool R, Xiao X, Scheet PA, Ehli EA, Davies GE, van der Sluis S et al.. (2015) Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait. Eur J Hum Genet, 23 (10): 1378-83. [PMID:25712083]

12. Garzón J, López-Fando A, Sánchez-Blázquez P. (2003) The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors. Neuropsychopharmacology, 28 (11): 1983-90. [PMID:12902995]

13. Gold SJ, Ni YG, Dohlman HG, Nestler EJ. (1997) Regulators of G-protein signaling (RGS) proteins: region-specific expression of nine subtypes in rat brain. J Neurosci, 17 (20): 8024-37. [PMID:9315921]

14. Hooks SB, Waldo GL, Corbitt J, Bodor ET, Krumins AM, Harden TK. (2003) RGS6, RGS7, RGS9, and RGS11 stimulate GTPase activity of Gi family G-proteins with differential selectivity and maximal activity. J Biol Chem, 278 (12): 10087-93. [PMID:12531899]

15. Hunt RA, Edris W, Chanda PK, Nieuwenhuijsen B, Young KH. (2003) Snapin interacts with the N-terminus of regulator of G protein signaling 7. Biochem Biophys Res Commun, 303 (2): 594-9. [PMID:12659861]

16. Karpinsky-Semper D, Volmar CH, Brothers SP, Slepak VZ. (2014) Differential effects of the Gβ5-RGS7 complex on muscarinic M3 receptor-induced Ca2+ influx and release. Mol Pharmacol, 85 (5): 758-68. [PMID:24586057]

17. Krumins AM, Barker SA, Huang C, Sunahara RK, Yu K, Wilkie TM, Gold SJ, Mumby SM. (2004) Differentially regulated expression of endogenous RGS4 and RGS7. J Biol Chem, 279 (4): 2593-9. [PMID:14604980]

18. Martemyanov KA, Yoo PJ, Skiba NP, Arshavsky VY. (2005) R7BP, a novel neuronal protein interacting with RGS proteins of the R7 family. J Biol Chem, 280 (7): 5133-6. [PMID:15632198]

19. Masuho I, Xie K, Martemyanov KA. (2013) Macromolecular composition dictates receptor and G protein selectivity of regulator of G protein signaling (RGS) 7 and 9-2 protein complexes in living cells. J Biol Chem, 288 (35): 25129-42. [PMID:23857581]

20. Mhawech P. (2005) 14-3-3 proteins--an update. Cell Res, 15 (4): 228-36. [PMID:15857577]

21. Muntean BS, Patil DN, Madoux F, Fossetta J, Scampavia L, Spicer TP, Martemyanov KA. (2018) A High-Throughput Time-Resolved Fluorescence Energy Transfer Assay to Screen for Modulators of RGS7/Gβ5/R7BP Complex. Assay Drug Dev Technol, 16 (3): 150-161. [PMID:29658790]

22. Nini L, Zhang JH, Pandey M, Panicker LM, Simonds WF. (2012) Expression of the Gβ5/R7-RGS protein complex in pituitary and pancreatic islet cells. Endocrine, 42 (1): 214-7. [PMID:22322946]

23. Obsilova V, Kopecka M, Kosek D, Kacirova M, Kylarova S, Rezabkova L, Obsil T. (2014) Mechanisms of the 14-3-3 protein function: regulation of protein function through conformational modulation. Physiol Res, 63 Suppl 1: S155-64. [PMID:24564655]

24. Orlandi C, Posokhova E, Masuho I, Ray TA, Hasan N, Gregg RG, Martemyanov KA. (2012) GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes. J Cell Biol, 197 (6): 711-9. [PMID:22689652]

25. Orlandi C, Sutton LP, Muntean BS, Song C, Martemyanov KA. (2019) Homeostatic cAMP regulation by the RGS7 complex controls depression-related behaviors. Neuropsychopharmacology, 44 (3): 642-653. [PMID:30546127]

26. Ostrovskaya O, Xie K, Masuho I, Fajardo-Serrano A, Lujan R, Wickman K, Martemyanov KA. (2014) RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling. Elife, 3: e02053. [PMID:24755289]

27. Ostrovskaya OI, Orlandi C, Fajardo-Serrano A, Young Jr SM, Lujan R, Martemyanov KA. (2018) Inhibitory Signaling to Ion Channels in Hippocampal Neurons Is Differentially Regulated by Alternative Macromolecular Complexes of RGS7. J Neurosci, 38 (46): 10002-10015. [PMID:30315127]

28. Patil DN, Rangarajan ES, Novick SJ, Pascal BD, Kojetin DJ, Griffin PR, Izard T, Martemyanov KA. (2018) Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex. Elife, 7: e42150. DOI: 10.7554/eLife.42150 [PMID:30540250]

29. Posner BA, Gilman AG, Harris BA. (1999) Regulators of G protein signaling 6 and 7. Purification of complexes with gbeta5 and assessment of their effects on g protein-mediated signaling pathways. J Biol Chem, 274 (43): 31087-93. [PMID:10521509]

30. Qutob N, Masuho I, Alon M, Emmanuel R, Cohen I, Di Pizio A, Madore J, Elkahloun A, Ziv T, Levy R et al.. (2018) RGS7 is recurrently mutated in melanoma and promotes migration and invasion of human cancer cells. Sci Rep, 8 (1): 653. [PMID:29330521]

31. Rose JJ, Taylor JB, Shi J, Cockett MI, Jones PG, Hepler JR. (2000) RGS7 is palmitoylated and exists as biochemically distinct forms. J Neurochem, 75 (5): 2103-12. [PMID:11032900]

32. Saitoh O, Kubo Y, Odagiri M, Ichikawa M, Yamagata K, Sekine T. (1999) RGS7 and RGS8 differentially accelerate G protein-mediated modulation of K+ currents. J Biol Chem, 274 (14): 9899-904. [PMID:10092682]

33. Sandiford SL, Slepak VZ. (2009) The Gbeta5-RGS7 complex selectively inhibits muscarinic M3 receptor signaling via the interaction between the third intracellular loop of the receptor and the DEP domain of RGS7. Biochemistry, 48 (10): 2282-9. [PMID:19182865]

34. Shim H, Wang CT, Chen YL, Chau VQ, Fu KG, Yang J, McQuiston AR, Fisher RA, Chen CK. (2012) Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice. J Biol Chem, 287 (18): 14873-9. [PMID:22371490]

35. Song C, Orlandi C, Sutton LP, Martemyanov KA. (2019) The signaling proteins GPR158 and RGS7 modulate excitability of L2/3 pyramidal neurons and control A-type potassium channel in the prelimbic cortex. J Biol Chem, 294 (35): 13145-13157. [PMID:31311860]

36. Song JH, Song H, Wensel TG, Sokolov M, Martemyanov KA. (2007) Localization and differential interaction of R7 RGS proteins with their membrane anchors R7BP and R9AP in neurons of vertebrate retina. Mol Cell Neurosci, 35 (2): 311-9. [PMID:17442586]

37. Xie K, Allen KL, Kourrich S, Colón-Saez J, Thomas MJ, Wickman K, Martemyanov KA. (2010) Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling. Nat Neurosci, 13 (6): 661-3. [PMID:20453851]

38. Zhang J, Jeffrey BG, Morgans CW, Burke NS, Haley TL, Duvoisin RM, Brown RL. (2010) RGS7 and -11 complexes accelerate the ON-bipolar cell light response. Invest Ophthalmol Vis Sci, 51 (2): 1121-9. [PMID:19797214]

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