Gene Symbol: RGS14
Description: regulator of G protein signaling 14
Alias: regulator of G-protein signaling 14, regulator of G-protein signalling 14
Species: human
Products:     RGS14

Top Publications

  1. Traver S, Bidot C, Spassky N, Baltauss T, de Tand M, Thomas J, et al. RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao. Biochem J. 2000;350 Pt 1:19-29 pubmed
    ..This protein was identified as RGS14, a member of the recently discovered family of RGS ('regulators of G-protein signalling') proteins that stimulate ..
  2. Martin McCaffrey L, Willard F, Oliveira dos Santos A, Natale D, Snow B, Kimple R, et al. RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote. Dev Cell. 2004;7:763-9 pubmed
    ..elegans and D. melanogaster. Here we show that "regulator of G protein signaling-14" (RGS14) is expressed by the mouse embryonic genome immediately prior to the first mitosis, where it colocalizes with the ..
  3. Evans P, Gerber K, Dammer E, Duong D, Goswami D, Lustberg D, et al. Interactome Analysis Reveals Regulator of G Protein Signaling 14 (RGS14) is a Novel Calcium/Calmodulin (Ca2+/CaM) and CaM Kinase II (CaMKII) Binding Partner. J Proteome Res. 2018;17:1700-1711 pubmed publisher
    b>Regulator of G Protein Signaling 14 (RGS14) is a complex scaffolding protein that integrates G protein and MAPK signaling pathways...
  4. Agudelo L, Ferreira D, Cervenka I, Bryzgalova G, Dadvar S, Jannig P, et al. Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation. Cell Metab. 2018;27:378-392.e5 pubmed publisher
    ..Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling...
  5. Jia M, Li J, Zhu J, Wen W, Zhang M, Wang W. Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Gαi. J Biol Chem. 2012;287:36766-76 pubmed publisher
    ..features when compared with the only high resolution structure known with GL/Gα(i) interaction between RGS14 and Gα(i1...
  6. Evans P, Parra Bueno P, Smirnov M, Lustberg D, Dudek S, Hepler J, et al. RGS14 Restricts Plasticity in Hippocampal CA2 by Limiting Postsynaptic Calcium Signaling. Eneuro. 2018;5: pubmed publisher
    ..b>Regulator of G protein signaling 14 (RGS14) is a complex scaffolding protein enriched in CA2 dendritic spines that naturally blocks CA2 ..
  7. Lee S, Simons S, Heldt S, Zhao M, Schroeder J, Vellano C, et al. RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc Natl Acad Sci U S A. 2010;107:16994-8 pubmed publisher
    ..Here we demonstrate that the signaling protein RGS14 is highly enriched in CA2 pyramidal neurons and plays a role in suppression of both synaptic plasticity at these ..
  8. Gerber K, Squires K, Hepler J. 14-3-3γ binds regulator of G protein signaling 14 (RGS14) at distinct sites to inhibit the RGS14:Gαi-AlF4- signaling complex and RGS14 nuclear localization. J Biol Chem. 2018;293:14616-14631 pubmed publisher
    b>Regulator of G protein signaling 14 (RGS14) is a multifunctional brain scaffolding protein that integrates G protein and Ras/ERK signaling pathways. It is also a nucleocytoplasmic shuttling protein...
  9. Brown N, Blumer J, Hepler J. Bioluminescence resonance energy transfer to detect protein-protein interactions in live cells. Methods Mol Biol. 2015;1278:457-65 pubmed publisher
    ..Here we describe a protocol for detecting BRET from two known protein binding partners (Gαi1 and RGS14) in HEK 293 cells using Renilla luciferase and yellow fluorescent protein tags...

More Information


  1. Brown N, Goswami D, Branch M, Ramineni S, Ortlund E, Griffin P, et al. Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14). J Biol Chem. 2015;290:9037-49 pubmed publisher
    b>RGS14 contains distinct binding sites for both active (GTP-bound) and inactive (GDP-bound) forms of Gα subunits...
  2. Robinson Cohen C, Bartz T, Lai D, Ikizler T, Peacock M, Imel E, et al. Genetic Variants Associated with Circulating Fibroblast Growth Factor 23. J Am Soc Nephrol. 2018;29:2583-2592 pubmed publisher
    ..Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport)...
  3. Vellano C, Lee S, Dudek S, Hepler J. RGS14 at the interface of hippocampal signaling and synaptic plasticity. Trends Pharmacol Sci. 2011;32:666-74 pubmed publisher
    ..Recently, the signaling protein RGS14 (Regulator of G protein Signaling 14) was identified as a natural suppressor of hippocampal-based learning and memory as well as ..
  4. Asli A, Sadiya I, Avital Shacham M, Kosloff M. "Disruptor" residues in the regulator of G protein signaling (RGS) R12 subfamily attenuate the inactivation of G? subunits. Sci Signal. 2018;11: pubmed publisher
    ..We found that the R12 subfamily members RGS10 and RGS14 had lower activity than most R4 subfamily members toward the Gi subfamily member G?o Using ..
  5. Willard F, Willard M, Kimple A, Soundararajan M, Oestreich E, Li X, et al. Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector. PLoS ONE. 2009;4:e4884 pubmed publisher
    ..b>RGS14 contains tandem Ras-binding domains that have been reported to bind to Rap- but not Ras GTPases in vitro, leading ..
  6. Li Y, Tang X, Li X, Dai H, Miao R, Cai J, et al. Regulator of G protein signalling 14 attenuates cardiac remodelling through the MEK-ERK1/2 signalling pathway. Basic Res Cardiol. 2016;111:47 pubmed publisher
    ..As one of the multifunctional family members, RGS14 is involved in various biological processes, such as synaptic plasticity, cell division, and phagocytosis...
  7. Robinson Cohen C, Lutsey P, Kleber M, Nielson C, Mitchell B, Bis J, et al. Genetic Variants Associated with Circulating Parathyroid Hormone. J Am Soc Nephrol. 2017;28:1553-1565 pubmed publisher
    ..The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10-17), rs219779 adjacent to CLDN14 (P=3...
  8. Mahajan A, Rodan A, Le T, Gaulton K, Haessler J, Stilp A, et al. Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity. Am J Hum Genet. 2016;99:636-646 pubmed publisher
    ..DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues...
  9. Gerber K, Squires K, Hepler J. Roles for Regulator of G Protein Signaling Proteins in Synaptic Signaling and Plasticity. Mol Pharmacol. 2016;89:273-86 pubmed publisher
    ..Here, we review and highlight the current knowledge of specific RGS proteins (RGS2, RGS4, RGS7, RGS9-2, and RGS14) that have been clearly demonstrated to serve critical roles in modulating synaptic signaling and plasticity ..
  10. Evans P, Dudek S, Hepler J. Regulator of G Protein Signaling 14: A Molecular Brake on Synaptic Plasticity Linked to Learning and Memory. Prog Mol Biol Transl Sci. 2015;133:169-206 pubmed publisher
    ..In the brain, regulator of G protein signaling 14 (RGS14) is enriched in neurons in the hippocampus where the mRNA and protein are highly expressed...
  11. Jeong S, Kim I, Oh K, Han N, Joo K, Kim H, et al. Pharmacogenetic analysis of cinacalcet response in secondary hyperparathyroidism patients. Drug Des Devel Ther. 2016;10:2211-25 pubmed publisher
    ..Twenty-four single nucleotide polymorphisms of CASR, VDR, FGFR1, KL, ALPL, RGS14, NR4A2, and PTHLH genes were selected for the pharmacogenetic analysis...
  12. Kimple R, Kimple M, Betts L, Sondek J, Siderovski D. Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits. Nature. 2002;416:878-81 pubmed
    ..crystal structure of Galpha(i1) GDP bound to the GoLoco region of the 'regulator of G-protein signalling' protein RGS14. Key contacts are described between the GoLoco motif and Galpha protein, including the extension of GoLoco's ..
  13. Zhao P, Nunn C, Ramineni S, Hepler J, Chidiac P. The Ras-binding domain region of RGS14 regulates its functional interactions with heterotrimeric G proteins. J Cell Biochem. 2013;114:1414-23 pubmed publisher
    b>RGS14 is a 60 kDa protein that contains a regulator of G protein signaling (RGS) domain near its N-terminus, a central region containing a pair of tandem Ras-binding domains (RBD), and a GPSM (G protein signaling modulator) domain (a.k.a...
  14. Goh L, Manser E. The GTPase-deficient Rnd proteins are stabilized by their effectors. J Biol Chem. 2012;287:31311-20 pubmed publisher
    ..This effector feedback behavior is analogous to the ability of ACK1 and PAK1 to prolong the lifetime of the active GTP-bound state of Cdc42 and Rac1. ..
  15. Dowler E, Diehl A, Schmieder P, Brockmann C, Elkins J, Soundararajan M, et al. Backbone and sidechain 1H, 13C and 15N resonance assignments of the RGS domain from human RGS14. Biomol NMR Assign. 2007;1:95-7 pubmed publisher
    We have assigned 1H, 13C and 15N resonances of the RGS domain from the human RGS14 protein, a multi-domain member of the RGS (Regulators of G-protein signalling) family of proteins, important in the down-regulation of specific G-protein ..
  16. Hollinger S, Ramineni S, Hepler J. Phosphorylation of RGS14 by protein kinase A potentiates its activity toward G alpha i. Biochemistry. 2003;42:811-9 pubmed
    ..b>RGS14 and RGS12 are unique among RGS proteins in that they also regulate Galpha(i) signals because of the guanine ..
  17. Martin McCaffrey L, Willard F, Pajak A, Dagnino L, Siderovski D, D Souza S. RGS14 is a microtubule-associated protein. Cell Cycle. 2005;4:953-60 pubmed
    ..elegans, D. melanogaster and mammals. We recently demonstrated that RGS14 is required for completion of the first mitotic division of the mouse embryo, and that it regulates microtubule ..
  18. Kimple R, de Vries L, Tronchere H, Behe C, Morris R, Gist Farquhar M, et al. RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. J Biol Chem. 2001;276:29275-81 pubmed
    ..RGS12 and RGS14 contain not only the hallmark RGS box responsible for GTPase-accelerating activity but also a single G alpha(i/o)-..
  19. Hayes M, Bodle C, Roman D. Evaluation of the Selectivity and Cysteine Dependence of Inhibitors across the Regulator of G Protein-Signaling Family. Mol Pharmacol. 2018;93:25-35 pubmed publisher
    ..we found that several previously identified RGS4 inhibitors were active against other RGS members, such as RGS14, with comparable or greater potency...
  20. Branch M, Hepler J. Endogenous RGS14 is a cytoplasmic-nuclear shuttling protein that localizes to juxtanuclear membranes and chromatin-rich regions of the nucleus. PLoS ONE. 2017;12:e0184497 pubmed publisher
    b>Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and H-Ras/MAPkinase signaling pathways to regulate synaptic plasticity important for hippocampal learning and memory...
  21. Jeon J, Thakur D, Tian J, So I, Zhu M. Regulator of G-protein signalling and GoLoco proteins suppress TRPC4 channel function via acting at G?i/o. Biochem J. 2016;473:1379-90 pubmed publisher
    ..Using whole-cell patch-clamp recordings, we show that both RGS and GoLoco proteins [RGS4, RGS6, RGS12, RGS14, LGN or activator of G-protein signalling 3 (AGS3)] suppress receptor-mediated TRPC4 activation without causing ..
  22. Squires K, Gerber K, Pare J, Branch M, Smith Y, Hepler J. Regulator of G protein signaling 14 (RGS14) is expressed pre- and postsynaptically in neurons of hippocampus, basal ganglia, and amygdala of monkey and human brain. Brain Struct Funct. 2018;223:233-253 pubmed publisher
    b>Regulator of G protein signaling 14 (RGS14) is a multifunctional signaling protein primarily expressed in mouse pyramidal neurons of hippocampal area CA2 where it regulates synaptic plasticity important for learning and memory...
  23. Martín Montañez E, Acevedo M, Lopez Tellez J, Duncan R, Mateos A, Pavía J, et al. Regulator of G-protein signaling 14 protein modulates Ca²+ influx through Cav1 channels. Neuroreport. 2010;21:1034-9 pubmed publisher
    ..Thus, our results provide evidence supporting the idea that RGS-14 may facilitate the cognitive processing by modulating Cav1 channel-mediated intracellular Ca²+ transients. ..
  24. Cho H, Kehrl J. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007;178:245-55 pubmed
    ..Fluorescence resonance energy transfer analysis confirms a direct interaction between RGS14 and G(ialpha1) in centrosomes...
  25. Sammond D, Eletr Z, Purbeck C, Kuhlman B. Computational design of second-site suppressor mutations at protein-protein interfaces. Proteins. 2010;78:1055-65 pubmed publisher
    ..Computational predictions were tested with two separate protein complexes; the G-protein Galpha(i1) bound to the RGS14 GoLoco motif, and UbcH7 bound to the ubiquitin ligase E6AP. Eight designs were experimentally tested...
  26. Cho H, Kozasa T, Takekoshi K, de Gunzburg J, Kehrl J. RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha-mediated signaling pathways. Mol Pharmacol. 2000;58:569-76 pubmed
    ..Mouse RGS14 encodes a 547-amino-acid protein with an N-terminal RGS domain, which is highly expressed in lymphoid tissues...
  27. Sammond D, Eletr Z, Purbeck C, Kimple R, Siderovski D, Kuhlman B. Structure-based protocol for identifying mutations that enhance protein-protein binding affinities. J Mol Biol. 2007;371:1392-404 pubmed
    ..tested on two separate protein complexes; Galpha(i1) from the heterotrimeric G-protein system bound to the RGS14 GoLoco motif, and the E2, UbcH7, bound to the E3, E6AP from the ubiquitin pathway...
  28. Urabe Y, Tanikawa C, Takahashi A, Okada Y, Morizono T, Tsunoda T, et al. A genome-wide association study of nephrolithiasis in the Japanese population identifies novel susceptible Loci at 5q35.3, 7p14.3, and 13q14.1. PLoS Genet. 2012;8:e1002541 pubmed publisher
    ..Here we found three novel loci for nephrolithiasis: RGS14-SLC34A1-PFN3-F12 on 5q35.3 (rs11746443; P?=?8.51×10?¹², odds ratio (OR)?=?1.19), INMT-FAM188B-AQP1 on 7p14...
  29. O Seaghdha C, Wu H, Yang Q, Kapur K, Guessous I, Zuber A, et al. Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations. PLoS Genet. 2013;9:e1003796 pubmed publisher
    ..We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis. ..
  30. Wang J, Lippman S, Lee J, Yang H, Khuri F, Kim E, et al. Genetic variations in regulator of G-protein signaling genes as susceptibility loci for second primary tumor/recurrence in head and neck squamous cell carcinoma. Carcinogenesis. 2010;31:1755-61 pubmed publisher
    ..Our results stressed the importance of taking a polygenic approach to evaluate the cumulative and interaction effects of genetic variations in the prediction of cancer risk and prognosis. ..
  31. Shu F, Ramineni S, Hepler J. RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways. Cell Signal. 2010;22:366-76 pubmed publisher
    ..We report here that RGS14 is an integrator of G protein and MAPKinase signalling pathways...
  32. Snow B, Antonio L, Suggs S, Gutstein H, Siderovski D. Molecular cloning and expression analysis of rat Rgs12 and Rgs14. Biochem Biophys Res Commun. 1997;233:770-7 pubmed
    ..We have also identified conserved regions in RGS12 which are similar to protein domains found in mouse rhophilin and coiled-coil proteins suggesting possible interactions with ras-like G-proteins. ..
  33. Vellano C, Maher E, Hepler J, Blumer J. G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·G?i1 complex in live cells. J Biol Chem. 2011;286:38659-69 pubmed publisher
    b>Regulator of G protein Signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates both conventional and unconventional G protein signaling pathways...