RGS14

Regulator of G-protein signaling 14 (RGS14) is a protein that in humans is encoded by the RGS14 gene.[5]

RGS14
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JNU, 2OM2, 2XNS, 3ONW, 3QI2
Identifiers
Aliases	RGS14, regulator of G protein signaling 14
External IDs	OMIM: 602513 MGI: 1859709 HomoloGene: 4735 GeneCards: RGS14
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q35.3 Start 177,357,924 bp[1] End 177,372,596 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 B1|13 29.8 cM Start 55,369,732 bp[2] End 55,384,687 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GTPase activating protein binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity • GO:0005083 GTPase regulator activity • microtubule binding • GO:0001948 protein binding • GDP-dissociation inhibitor activity • G-protein alpha-subunit binding • receptor signaling complex scaffold activity • protein kinase binding • GTPase activity Cellular component • cytoplasm • PML body • centrosome • postsynaptic membrane • cell projection • spindle pole • nuclear body • membrane • GO:0097483, GO:0097481 postsynaptic density • cell membrane • spindle • dendritic spine • synapse • microtubule organizing center • cell junction • dendrite • microtubule • cytoskeleton • cell nucleus • glutamatergic synapse Biological process • visual learning • GO:0007243 intracellular signal transduction • regulation of G-protein coupled receptor protein signaling pathway • chromosome segregation • learning • response to oxidative stress • cell division • positive regulation of neurogenesis • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • GO:0043146 spindle organization • long-term memory • negative regulation of MAP kinase activity • nucleocytoplasmic transport • zygote asymmetric cell division • negative regulation of ERK1 and ERK2 cascade • cell cycle • platelet-derived growth factor receptor signaling pathway • negative regulation of signal transduction • regulation of DNA-templated transcription in response to stress • negative regulation of synaptic plasticity • signal transduction • long-term synaptic potentiation • GO:0007067 mitotic cell cycle • negative regulation of G-protein coupled receptor protein signaling pathway • modulation of chemical synaptic transmission • G-protein coupled receptor signaling pathway • positive regulation of signal transduction Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10636	51791
Ensembl	ENSG00000169220	ENSMUSG00000052087
UniProt	O43566	P97492
RefSeq (mRNA)	NM_006480 NM_001366617 NM_001366618	NM_016758 NM_001360714
RefSeq (protein)	NP_006471 NP_001353546 NP_001353547	NP_058038 NP_001347643
Location (UCSC)	Chr 5: 177.36 – 177.37 Mb	Chr 13: 55.37 – 55.38 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

RGS14 is a member of the regulator of G protein signalling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco motif. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.[5]

Increasing the expression of the RGS14 protein in the V2 secondary visual cortex of mice promotes the conversion of short-term to long-term object-recognition memory.[6] Conversely RGS14 is enriched in CA2 pyramidal neurons and suppresses synaptic plasticity of these synapses and hippocampal-based learning and memory.[7]

Interactions

RGS14 has been shown to interact with:

• GNAI1[8][9][10][11] and
• GNAI3.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000169220 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000052087 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: RGS14 regulator of G-protein signalling 14".
6. López-Aranda MF, López-Téllez JF, Navarro-Lobato I, Masmudi-Martín M, Gutiérrez A, Khan ZU (July 2009). "Role of layer 6 of V2 visual cortex in object-recognition memory". Science. 325 (5936): 87–9. doi:10.1126/science.1170869. PMID 19574389. Lay summary – Mad Science.
7. Lee SE, Simons SB, Heldt SA, Zhao M, Schroeder JP, Vellano CP, Cowan DP, Ramineni S, Yates CK, Feng Y, Smith Y, Sweatt JD, Weinshenker D, Ressler KJ, Dudek SM, Hepler JR (September 2010). "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. 107 (39): 16994–8. doi:10.1073/pnas.1005362107. PMC 2947872. PMID 20837545. Lay summary – MedicalDaily.
8. Kimple RJ, De Vries L, Tronchère H, Behe CI, Morris RA, Gist Farquhar M, Siderovski DP (August 2001). "RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity". J. Biol. Chem. 276 (31): 29275–81. doi:10.1074/jbc.M103208200. PMID 11387333.
9. Hollinger S, Taylor JB, Goldman EH, Hepler JR (December 2001). "RGS14 is a bifunctional regulator of Galphai/o activity that exists in multiple populations in brain". J. Neurochem. 79 (5): 941–9. doi:10.1046/j.1471-4159.2001.00629.x. PMID 11739605.
10. Kimple RJ, Kimple ME, Betts L, Sondek J, Siderovski DP (April 2002). "Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits". Nature. 416 (6883): 878–81. doi:10.1038/416878a. PMID 11976690.
11. Shu FJ, Ramineni S, Amyot W, Hepler JR (January 2007). "Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization". Cell. Signal. 19 (1): 163–76. doi:10.1016/j.cellsig.2006.06.002. PMID 16870394.

Further reading

• Snow BE, Antonio L, Suggs S, et al. (1997). "Molecular cloning and expression analysis of rat Rgs12 and Rgs14". Biochem. Biophys. Res. Commun. 233 (3): 770–7. doi:10.1006/bbrc.1997.6537. PMID 9168931.
• Traver S, Bidot C, Spassky N, et al. (2001). "RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao". Biochem. J. 350 (1): 19–29. doi:10.1042/0264-6021:3500019. PMC 1221220. PMID 10926822.
• Cho H, Kozasa T, Takekoshi K, et al. (2000). "RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha-mediated signaling pathways". Mol. Pharmacol. 58 (3): 569–76. doi:10.1124/mol.58.3.569. PMID 10953050.
• Hollinger S, Taylor JB, Goldman EH, Hepler JR (2001). "RGS14 is a bifunctional regulator of Gi/oalpha activity that exists in multiple populations in brain". Journal of Neurochemistry. 79 (5): 941–49. doi:10.1046/j.1471-4159.2001.00629.x. PMID 11739605.
• Kimple RJ, De Vries L, Tronchère H, et al. (2001). "RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity". J. Biol. Chem. 276 (31): 29275–81. doi:10.1074/jbc.M103208200. PMID 11387333.
• Sierra DA, Gilbert DJ, Householder D, et al. (2002). "Evolution of the regulators of G-protein signaling multigene family in mouse and human". Genomics. 79 (2): 177–85. doi:10.1006/geno.2002.6693. PMID 11829488.
• Kimple RJ, Kimple ME, Betts L, et al. (2002). "Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits". Nature. 416 (6883): 878–81. doi:10.1038/416878a. PMID 11976690.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Hollinger S, Ramineni S, Hepler JR (2003). "Phosphorylation of RGS14 by protein kinase A potentiates its activity toward G alpha i.". Biochemistry. 42 (3): 811–9. doi:10.1021/bi026664y. PMID 12534294.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Martin-McCaffrey L, Willard FS, Oliveira-dos-Santos AJ, et al. (2004). "RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote". Dev. Cell. 7 (5): 763–9. doi:10.1016/j.devcel.2004.10.004. PMID 15525537.
• Martin-McCaffrey L, Willard FS, Pajak A, et al. (2006). "RGS14 is a microtubule-associated protein". Cell Cycle. 4 (7): 953–60. doi:10.4161/cc.4.7.1787. PMID 15917656.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Shu FJ, Ramineni S, Amyot W, Hepler JR (2007). "Selective interactions between Gialpha1 and Gialpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization". Cellular Signalling. 19 (1): 941–49. doi:10.1016/j.cellsig.2006.06.002. PMID 16870394.
• Shu FJ, Ramineni S, Hepler JR (2009). "RGS14 is multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signaling pathways". Cellular Signalling: in press.

External links

• Overview of all the structural information available in the PDB for UniProt: O43566 (Regulator of G-protein signaling 14) at the PDBe-KB.