RGS2

RGS2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2AF0, 2V4Z, 4EKC, 4EKD
Identifiers
Aliases	RGS2, G0S8, regulator of G-protein signaling 2, regulator of G protein signaling 2
External IDs	OMIM: 600861; MGI: 1098271; HomoloGene: 2192; GeneCards: RGS2; OMA:RGS2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q31.2 Start 192,809,039 bp[1] End 192,812,275 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 F|1 62.56 cM Start 143,875,076 bp[2] End 143,879,899 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte periodontal fiber monocyte tail of epididymis gastric mucosa granulocyte seminal vesicula mucosa of urinary bladder bone marrow jejunal mucosa Top expressed in cumulus cell gastrula zygote secondary oocyte primary oocyte median eminence left lung lobe dorsal striatum nucleus accumbens lobe of prostate More reference expression data BioGPS More reference expression data
Gene ontology Molecular function GTPase activator activity calmodulin binding protein binding G-protein alpha-subunit binding beta-tubulin binding GTPase activity Cellular component membrane nucleolus mitochondrion neuron projection cytoplasmic side of plasma membrane nucleus cytoplasm plasma membrane cytosol Biological process negative regulation of cAMP-mediated signaling regulation of G protein-coupled receptor signaling pathway negative regulation of cardiac muscle hypertrophy positive regulation of GTPase activity negative regulation of MAP kinase activity positive regulation of cardiac muscle contraction spermatogenesis brown fat cell differentiation positive regulation of microtubule polymerization relaxation of vascular associated smooth muscle cell cycle negative regulation of signal transduction negative regulation of G protein-coupled receptor signaling pathway relaxation of cardiac muscle regulation of translation negative regulation of phospholipase activity negative regulation of adenylate cyclase-inhibiting adrenergic receptor signaling pathway involved in heart process response to amphetamine brain development positive regulation of neuron projection development negative regulation of translation ovulation response to ethanol maternal process involved in female pregnancy negative regulation of cell growth involved in cardiac muscle cell development negative regulation of glycine import across plasma membrane G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5997 19735 Ensembl ENSG00000116741 ENSMUSG00000026360 UniProt P41220 O08849 RefSeq (mRNA) NM_002923 NM_009061 RefSeq (protein) NP_002914 NP_002914.1 NP_033087 Location (UCSC) Chr 1: 192.81 – 192.81 Mb Chr 1: 143.88 – 143.88 Mb PubMed search [3] [4]
Wikidata
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Regulator of G-protein signaling 2 is a protein that in humans is encoded by the RGS2 gene.^[5][6] It is part of a larger family of RGS proteins that control signalling through G-protein coupled receptors (GPCR).

RGS2 is thought to have protective effects against myocardial hypertrophy as well as atrial arrhythmias.^[7][8] Increased stimulation of Gs coupled β1-adrenergic receptors and Gq coupled α1-adrenergic receptors in the heart can result in cardiac hypertrophy.^[7] In the case of Gq protein coupled receptor (GqPCR) mediated hypertrophy, Gαq will activate the intracellular affectors phospholipase Cβ and rho guanine nucleotide exchange factor to stimulate cell processes which lead to cardiomyocyte hypertrophy.^[7][9] RGS2 functions as a GTPase Activating Protein (GAP) which acts to increase the natural GTPase activity of the Gα subunit.^[7][9] By increasing the GTPase activity of the Gα subunit, RGS2 promotes GTP hydrolysis back to GDP, thus converting the Gα subunit back to its inactive state and reducing its signalling ability.^[9] Both GsPCR and GqPCR activation can contribute to cardiac hypertrophy via activation of MAP Kinases as well. RGS2 has been shown to decrease phosphorylation of those MAP kinases and therefore decrease their activation in response to Gαs signalling.^[7]

In the case of GsPCR mediated hypertrophy, the main mechanism by which signalling contributes to hypertrophy is through the Gβγ subunit; Gαs signalling by itself is not sufficient.^[10] Nevertheless, RGS2 has been shown to inhibit Gs mediated hypertrophy. The mechanism of how RGS2 regulates increased Gβγ signalling is not well understood, apart from the fact that it is unrelated to RGS2's GAP function.^[10] A deficiency in RGS2 has been linked with increased cardiac hypertrophy in mice.^[7] RGS2 deficient hearts appear normal until confronted with an increased workload, to which they respond readily with increased Gαq signalling and hypertrophy.^[7][10]

Gαs subunits increase adenyl cyclase activity, which in turn leads to cAMP accumulation in the myocyte nucleus to trigger hypertrophy. RGS2 regulates the effects of increased Gαs signalling through its GAP function.^[7] Stimulation of GsPCRs not only leads to hypertrophy but it has also been shown to selectively induce higher expression levels of RGS2 which in turn, protects against hypertrophy, providing a mechanism for maintaining homeostatic conditions.^[7]

There has also been some evidence of a role of RGS2 in atrial arrhythmias where RGS2 deficient mice exhibited prolonged and greater susceptibility to electrically induced atrial fibrillation.^[8] This was attributed to a decrease in RGS2's inhibitory effects on Gq coupled M3 muscarinic receptor signalling, resulting in increased Gαq activity.^[8] The M3 muscarinic receptor normally activates delayed rectifier potassium channels in the atria, thus increased Gαq activity is thought to result in an altered potassium flux, a decreased refractory period, increased chance of current re-entry and inappropriate contraction.^[8]

^{[11] [12]}

RGS2 has been shown to interact with PRKG1^[13] and ADCY5.^[14]