ID RGS2_HUMAN Reviewed; 211 AA. AC P41220; Q6I9U5; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 24-JAN-2024, entry version 208. DE RecName: Full=Regulator of G-protein signaling 2; DE Short=RGS2; DE AltName: Full=Cell growth-inhibiting gene 31 protein; DE AltName: Full=G0/G1 switch regulatory protein 8; GN Name=RGS2; Synonyms=G0S8; ORFNames=GIG31; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=8179820; DOI=10.1089/dna.1994.13.125; RA Siderovski D.P., Heximer S.P., Forsdyke D.R.; RT "A human gene encoding a putative basic helix-loop-helix phosphoprotein RT whose mRNA increases rapidly in cycloheximide-treated blood mononuclear RT cells."; RL DNA Cell Biol. 13:125-147(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF LEU-37; LEU-38; TRP-41; LEU-45; PHE-48 AND LEU-49. RX PubMed=11278586; DOI=10.1074/jbc.m009942200; RA Heximer S.P., Lim H., Bernard J.L., Blumer K.J.; RT "Mechanisms governing subcellular localization and function of human RT RGS2."; RL J. Biol. Chem. 276:14195-14203(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, SUBCELLULAR RP LOCATION, ALTERNATIVE INITIATION, AND MUTAGENESIS OF MET-1; MET-5; MET-16 RP AND MET-33. RX PubMed=17901199; DOI=10.1124/mol.107.036285; RA Gu S., Anton A., Salim S., Blumer K.J., Dessauer C.W., Heximer S.P.; RT "Alternative translation initiation of human regulators of G-protein RT signaling-2 yields a set of functionally distinct proteins."; RL Mol. Pharmacol. 73:1-11(2008). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kim J.W., Kim H.K., Shin S.M.; RT "Identification of a human cell growth-inhibiting gene."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP TISSUE SPECIFICITY. RX PubMed=7643615; RA Wu H.-K., Heng H.H.Q., Shi X.-M., Forsdyke D.R., Tsui L.-C., Mak T.W., RA Minden M.D., Siderovski D.P.; RT "Differential expression of a basic helix-loop-helix phosphoprotein gene, RT G0S8, in acute leukemia and localization to human chromosome 1q31."; RL Leukemia 9:1291-1298(1995). RN [13] RP PHOSPHORYLATION, AND FUNCTION. RX PubMed=11063746; DOI=10.1074/jbc.m007699200; RA Cunningham M.L., Waldo G.L., Hollinger S., Hepler J.R., Harden T.K.; RT "Protein kinase C phosphorylates RGS2 and modulates its capacity for RT negative regulation of Galpha 11 signaling."; RL J. Biol. Chem. 276:5438-5444(2001). RN [14] RP PHOSPHORYLATION BY PRKG1, AND INTERACTION WITH PRKG1. RX PubMed=14608379; DOI=10.1038/nm958; RA Tang K.M., Wang G.R., Lu P., Karas R.H., Aronovitz M., Heximer S.P., RA Kaltenbronn K.M., Blumer K.J., Siderovski D.P., Zhu Y., Mendelsohn M.E.; RT "Regulator of G-protein signaling-2 mediates vascular smooth muscle RT relaxation and blood pressure."; RL Nat. Med. 9:1506-1512(2003). RN [15] RP FUNCTION, INTERACTION WITH EIF2B5, AND MUTAGENESIS OF LEU-79; GLU-86; RP LEU-87; SER-90; LYS-102; PHE-105; ILE-110; GLU-111; LEU-114 AND ASN-149. RX PubMed=19736320; DOI=10.1083/jcb.200811058; RA Nguyen C.H., Ming H., Zhao P., Hugendubler L., Gros R., Kimball S.R., RA Chidiac P.; RT "Translational control by RGS2."; RL J. Cell Biol. 186:755-765(2009). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GNAQ, AND CHARACTERIZATION RP OF VARIANTS ARG-2; LEU-2; GLY-3; VAL-4; VAL-5; ASN-18; ASP-23; TYR-40; RP HIS-44; LYS-50; LEU-55; HIS-78; GLY-99; VAL-110; HIS-188 AND ARG-196. RX PubMed=28784619; DOI=10.1124/mol.117.109215; RA Phan H.T.N., Sjoegren B., Neubig R.R.; RT "Human missense mutations in regulator of G protein signaling 2 affect the RT protein function through multiple mechanisms."; RL Mol. Pharmacol. 92:451-458(2017). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 71-203, INTERACTION WITH GNAQ, RP LACK OF INTERACTION WITH GNAI1, AND MUTAGENESIS OF CYS-106 AND ASN-184. RX PubMed=18434541; DOI=10.1073/pnas.0801508105; RA Soundararajan M., Willard F.S., Kimple A.J., Turnbull A.P., Ball L.J., RA Schoch G.A., Gileadi C., Fedorov O.Y., Dowler E.F., Higman V.A., RA Hutsell S.Q., Sundstroem M., Doyle D.A., Siderovski D.P.; RT "Structural diversity in the RGS domain and its interaction with RT heterotrimeric G protein alpha-subunits."; RL Proc. Natl. Acad. Sci. U.S.A. 105:6457-6462(2008). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 71-209 IN COMPLEXES WITH GNAQ AND RP GNAI3, FUNCTION, INTERACTION WITH GNAQ, LACK OF INTERACTION WITH GNAI1 AND RP GNAI3, AND MUTAGENESIS OF CYS-106; ASN-184 AND GLU-191. RX PubMed=19478087; DOI=10.1074/jbc.m109.024711; RA Kimple A.J., Soundararajan M., Hutsell S.Q., Roos A.K., Urban D.J., RA Setola V., Temple B.R., Roth B.L., Knapp S., Willard F.S., Siderovski D.P.; RT "Structural determinants of G-protein alpha subunit selectivity by RT regulator of G-protein signaling 2 (RGS2)."; RL J. Biol. Chem. 284:19402-19411(2009). RN [19] RP VARIANTS ARG-2; LEU-2; VAL-5; HIS-44 AND HIS-78. RX PubMed=16003176; DOI=10.1097/01.hjh.0000174606.41651.ae; RA Yang J., Kamide K., Kokubo Y., Takiuchi S., Tanaka C., Banno M., Miwa Y., RA Yoshii M., Horio T., Okayama A., Tomoike H., Kawano Y., Miyata T.; RT "Genetic variations of regulator of G-protein signaling 2 in hypertensive RT patients and in the general population."; RL J. Hypertens. 23:1497-1505(2005). RN [20] RP VARIANTS ARG-2; LEU-2; GLY-3; VAL-4; VAL-5; ASN-18; ASP-23; TYR-40; HIS-44; RP LYS-50; LEU-55; GLY-99; VAL-110; HIS-188 AND ARG-196. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). CC -!- FUNCTION: Regulates G protein-coupled receptor signaling cascades. CC Inhibits signal transduction by increasing the GTPase activity of G CC protein alpha subunits, thereby driving them into their inactive GDP- CC bound form (PubMed:11063746, PubMed:19478087). It is involved in the CC negative regulation of the angiotensin-activated signaling pathway CC (PubMed:28784619). Plays a role in the regulation of blood pressure in CC response to signaling via G protein-coupled receptors and GNAQ. Plays a CC role in regulating the constriction and relaxation of vascular smooth CC muscle (By similarity). Binds EIF2B5 and blocks its activity, thereby CC inhibiting the translation of mRNA into protein (PubMed:19736320). CC {ECO:0000250|UniProtKB:O08849, ECO:0000269|PubMed:11063746, CC ECO:0000269|PubMed:11278586, ECO:0000269|PubMed:17901199, CC ECO:0000269|PubMed:19736320, ECO:0000269|PubMed:28784619, CC ECO:0000305|PubMed:7643615}. CC -!- SUBUNIT: Interacts with GNAQ (PubMed:18434541, PubMed:19478087, CC PubMed:28784619). Does not interact with GNAI1 and GNAI3 CC (PubMed:18434541, PubMed:19478087). Interacts with EIF2B5 CC (PubMed:19736320). Interacts with PRKG1 (isoform alpha) CC (PubMed:14608379). {ECO:0000269|PubMed:14608379, CC ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:19478087, CC ECO:0000269|PubMed:19736320, ECO:0000269|PubMed:28784619}. CC -!- INTERACTION: CC P41220; O76071: CIAO1; NbExp=3; IntAct=EBI-712388, EBI-725145; CC P41220; Q5S007: LRRK2; NbExp=6; IntAct=EBI-712388, EBI-5323863; CC P41220; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-712388, EBI-742948; CC P41220; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-712388, EBI-11522433; CC P41220; Q9ULJ8: PPP1R9A; NbExp=3; IntAct=EBI-712388, EBI-2515561; CC P41220; O60260-5: PRKN; NbExp=6; IntAct=EBI-712388, EBI-21251460; CC P41220-1; O60337: MARCHF6; NbExp=3; IntAct=EBI-16037474, EBI-2684600; CC P41220-1; P21279: Gnaq; Xeno; NbExp=3; IntAct=EBI-16037474, EBI-771975; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:11278586, ECO:0000269|PubMed:17901199, CC ECO:0000269|PubMed:28784619}. Cytoplasm {ECO:0000269|PubMed:11278586, CC ECO:0000269|PubMed:17901199}. Nucleus, nucleolus CC {ECO:0000269|PubMed:11278586, ECO:0000269|PubMed:17901199}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane CC {ECO:0000269|PubMed:17901199}. Cytoplasm {ECO:0000269|PubMed:17901199}. CC Nucleus, nucleolus {ECO:0000269|PubMed:17901199}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane CC {ECO:0000269|PubMed:17901199}. Cytoplasm {ECO:0000269|PubMed:17901199}. CC Nucleus, nucleolus {ECO:0000269|PubMed:17901199}. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane CC {ECO:0000269|PubMed:17901199}. Mitochondrion CC {ECO:0000269|PubMed:17901199}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=4; CC Name=1; CC IsoId=P41220-1; Sequence=Displayed; CC Name=2; CC IsoId=P41220-2; Sequence=VSP_041296; CC Name=3; CC IsoId=P41220-3; Sequence=VSP_041297; CC Name=4; CC IsoId=P41220-4; Sequence=VSP_041298; CC -!- TISSUE SPECIFICITY: Expressed in acute myelogenous leukemia (AML) and CC in acute lymphoblastic leukemia (ALL). {ECO:0000269|PubMed:7643615}. CC -!- PTM: Phosphorylated by protein kinase C. Phosphorylation by PRKG1 leads CC to activation of RGS2 activity. {ECO:0000269|PubMed:11063746, CC ECO:0000269|PubMed:14608379}. CC -!- MISCELLANEOUS: [Isoform 3]: Lacks type V adenylyl cyclase (AC) CC inhibitory function. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Lacks type V adenylyl cyclase (AC) CC inhibitory function. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42102/RGS2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L13391; AAA20680.1; -; Genomic_DNA. DR EMBL; L13463; AAC37587.1; -; mRNA. DR EMBL; AF493926; AAM12640.1; -; mRNA. DR EMBL; AY971351; AAY40361.1; -; mRNA. DR EMBL; AK313668; BAG36420.1; -; mRNA. DR EMBL; BT007065; AAP35728.1; -; mRNA. DR EMBL; CR457410; CAG33691.1; -; mRNA. DR EMBL; AL035407; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91231.1; -; Genomic_DNA. DR EMBL; BC007049; AAH07049.1; -; mRNA. DR CCDS; CCDS1377.1; -. [P41220-1] DR PIR; I53020; I53020. DR RefSeq; NP_002914.1; NM_002923.3. [P41220-1] DR PDB; 2AF0; X-ray; 2.30 A; A=71-203. DR PDB; 2V4Z; X-ray; 2.80 A; B=71-209. DR PDB; 4EKC; X-ray; 7.40 A; B/D=72-203. DR PDB; 4EKD; X-ray; 2.71 A; B=72-203. DR PDBsum; 2AF0; -. DR PDBsum; 2V4Z; -. DR PDBsum; 4EKC; -. DR PDBsum; 4EKD; -. DR AlphaFoldDB; P41220; -. DR SMR; P41220; -. DR BioGRID; 111929; 78. DR DIP; DIP-44289N; -. DR IntAct; P41220; 61. DR MINT; P41220; -. DR STRING; 9606.ENSP00000235382; -. DR iPTMnet; P41220; -. DR PhosphoSitePlus; P41220; -. DR SwissPalm; P41220; -. DR BioMuta; RGS2; -. DR DMDM; 729545; -. DR EPD; P41220; -. DR MassIVE; P41220; -. DR MaxQB; P41220; -. DR PaxDb; 9606-ENSP00000235382; -. DR PeptideAtlas; P41220; -. DR ProteomicsDB; 55425; -. [P41220-1] DR ProteomicsDB; 55426; -. [P41220-2] DR ProteomicsDB; 55427; -. [P41220-3] DR ProteomicsDB; 55428; -. [P41220-4] DR Antibodypedia; 34461; 306 antibodies from 29 providers. DR DNASU; 5997; -. DR Ensembl; ENST00000235382.7; ENSP00000235382.5; ENSG00000116741.8. [P41220-1] DR GeneID; 5997; -. DR KEGG; hsa:5997; -. DR MANE-Select; ENST00000235382.7; ENSP00000235382.5; NM_002923.4; NP_002914.1. DR UCSC; uc001gsl.4; human. [P41220-1] DR AGR; HGNC:9998; -. DR CTD; 5997; -. DR DisGeNET; 5997; -. DR GeneCards; RGS2; -. DR HGNC; HGNC:9998; RGS2. DR HPA; ENSG00000116741; Low tissue specificity. DR MIM; 600861; gene. DR neXtProt; NX_P41220; -. DR OpenTargets; ENSG00000116741; -. DR PharmGKB; PA34372; -. DR VEuPathDB; HostDB:ENSG00000116741; -. DR eggNOG; KOG3589; Eukaryota. DR GeneTree; ENSGT00940000157937; -. DR HOGENOM; CLU_059863_3_2_1; -. DR InParanoid; P41220; -. DR OMA; GRMKRTI; -. DR OrthoDB; 22856at2759; -. DR PhylomeDB; P41220; -. DR TreeFam; TF315837; -. DR PathwayCommons; P41220; -. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; P41220; -. DR SIGNOR; P41220; -. DR BioGRID-ORCS; 5997; 13 hits in 1162 CRISPR screens. DR ChiTaRS; RGS2; human. DR EvolutionaryTrace; P41220; -. DR GeneWiki; RGS2; -. DR GenomeRNAi; 5997; -. DR Pharos; P41220; Tbio. DR PRO; PR:P41220; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P41220; Protein. DR Bgee; ENSG00000116741; Expressed in secondary oocyte and 210 other cell types or tissues. DR ExpressionAtlas; P41220; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0010855; F:adenylate cyclase inhibitor activity; IEA:Ensembl. DR GO; GO:0048487; F:beta-tubulin binding; IEA:Ensembl. DR GO; GO:0005516; F:calmodulin binding; TAS:ProtInc. DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB. DR GO; GO:0003924; F:GTPase activity; TAS:Reactome. DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISS:BHF-UCL. DR GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; IEA:Ensembl. DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:1900924; P:negative regulation of glycine import across plasma membrane; IEA:Ensembl. DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:BHF-UCL. DR GO; GO:0010519; P:negative regulation of phospholipase activity; ISS:BHF-UCL. DR GO; GO:0017148; P:negative regulation of translation; IEA:Ensembl. DR GO; GO:0060452; P:positive regulation of cardiac muscle contraction; ISS:BHF-UCL. DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0071877; P:regulation of adenylate cyclase-inhibiting adrenergic receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0055119; P:relaxation of cardiac muscle; ISS:BHF-UCL. DR GO; GO:0060087; P:relaxation of vascular associated smooth muscle; IEA:Ensembl. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR CDD; cd08709; RGS_RGS2; 1. DR Gene3D; 1.10.196.10; -; 1. DR Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 1. DR InterPro; IPR016137; RGS. DR InterPro; IPR034947; RGS2_RGS. DR InterPro; IPR036305; RGS_sf. DR InterPro; IPR024066; RGS_subdom1/3. DR InterPro; IPR044926; RGS_subdomain_2. DR PANTHER; PTHR10845; REGULATOR OF G PROTEIN SIGNALING; 1. DR PANTHER; PTHR10845:SF43; REGULATOR OF G-PROTEIN SIGNALING 2; 1. DR Pfam; PF00615; RGS; 1. DR PRINTS; PR01301; RGSPROTEIN. DR SMART; SM00315; RGS; 1. DR SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 1. DR PROSITE; PS50132; RGS; 1. DR Genevisible; P41220; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Cell cycle; Cell membrane; Cytoplasm; KW GTPase activation; Membrane; Mitochondrion; Nucleus; Phosphoprotein; KW Reference proteome; Signal transduction inhibitor; Translation regulation. FT CHAIN 1..211 FT /note="Regulator of G-protein signaling 2" FT /id="PRO_0000204178" FT DOMAIN 83..199 FT /note="RGS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171" FT REGION 14..33 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 32..66 FT /note="Necessary for membrane association" FT /evidence="ECO:0000269|PubMed:11278586" FT REGION 49..68 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 79..116 FT /note="Necessary to inhibit protein synthesis" FT /evidence="ECO:0000269|PubMed:19736320" FT COMPBIAS 17..33 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..32 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:17901199" FT /id="VSP_041298" FT VAR_SEQ 1..15 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17901199" FT /id="VSP_041297" FT VAR_SEQ 1..4 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17901199" FT /id="VSP_041296" FT VARIANT 2 FT /note="Q -> L (found in hypertensive patients; uncertain FT significance; decreased down-regulation of FT angiotensin-activated signaling pathway; decreased RGS2 FT protein abundance; dbSNP:rs141030117)" FT /evidence="ECO:0000269|PubMed:16003176, FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:28784619" FT /id="VAR_079238" FT VARIANT 2 FT /note="Q -> R (found in hypertensive patients; likely FT benign; no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs141030117)" FT /evidence="ECO:0000269|PubMed:16003176, FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:28784619" FT /id="VAR_079239" FT VARIANT 3 FT /note="S -> G (no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs145125159)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079240" FT VARIANT 4 FT /note="A -> V (no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs142499684)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079241" FT VARIANT 5 FT /note="M -> V (found in hypertensive patients; likely FT benign; no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs193051407)" FT /evidence="ECO:0000269|PubMed:16003176, FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:28784619" FT /id="VAR_079242" FT VARIANT 18 FT /note="K -> N (no effect on down-regulation of FT angiotensin-activated signaling pathway; dbSNP:rs74466425)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079243" FT VARIANT 23 FT /note="G -> D (no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs148489044)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079244" FT VARIANT 40 FT /note="D -> Y (decreased down-regulation of FT angiotensin-activated signaling pathway; reduced FT localization at the cell membrane; dbSNP:rs201233692)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079245" FT VARIANT 44 FT /note="R -> H (found in hypertensive patients; uncertain FT significance; decreased down-regulation of FT angiotensin-activated signaling pathway; reduced FT localization at the cell membrane; dbSNP:rs200339834)" FT /evidence="ECO:0000269|PubMed:16003176, FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:28784619" FT /id="VAR_079246" FT VARIANT 50 FT /note="Q -> K (no effect on down-regulation of FT angiotensin-activated signaling pathway; dbSNP:rs80221024)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079247" FT VARIANT 55 FT /note="P -> L (no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs140811638)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079248" FT VARIANT 78 FT /note="Q -> H (found in hypertensive patients; likely FT benign; no effect on down-regulation of FT angiotensin-activated signaling pathway)" FT /evidence="ECO:0000269|PubMed:16003176, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079249" FT VARIANT 99 FT /note="A -> G (no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs139237239)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079250" FT VARIANT 110 FT /note="I -> V (no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs146862218)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079251" FT VARIANT 188 FT /note="R -> H (decreased down-regulation of FT angiotensin-activated signaling pathway; reduced FT interaction with GNAQ; dbSNP:rs369752935)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079252" FT VARIANT 196 FT /note="Q -> R (no effect on down-regulation of FT angiotensin-activated signaling pathway; FT dbSNP:rs112707798)" FT /evidence="ECO:0000269|PubMed:27535533, FT ECO:0000269|PubMed:28784619" FT /id="VAR_079253" FT MUTAGEN 1 FT /note="M->L: Loss of isoform 1 expression." FT /evidence="ECO:0000269|PubMed:17901199" FT MUTAGEN 5 FT /note="M->L: Loss of isoform 2 expression." FT /evidence="ECO:0000269|PubMed:17901199" FT MUTAGEN 16 FT /note="M->L: Loss of isoform 3 expression." FT /evidence="ECO:0000269|PubMed:17901199" FT MUTAGEN 33 FT /note="M->L: Loss of isoform 4 expression." FT /evidence="ECO:0000269|PubMed:17901199" FT MUTAGEN 37 FT /note="L->D: Impairs association with plasma membrane." FT /evidence="ECO:0000269|PubMed:11278586" FT MUTAGEN 38 FT /note="L->D: Impairs association with plasma membrane." FT /evidence="ECO:0000269|PubMed:11278586" FT MUTAGEN 41 FT /note="W->D: Impairs association with plasma membrane." FT /evidence="ECO:0000269|PubMed:11278586" FT MUTAGEN 45 FT /note="L->D: Impairs association with plasma membrane." FT /evidence="ECO:0000269|PubMed:11278586" FT MUTAGEN 48 FT /note="F->D: Impairs association with plasma membrane." FT /evidence="ECO:0000269|PubMed:11278586" FT MUTAGEN 49 FT /note="L->D: Impairs association with plasma membrane." FT /evidence="ECO:0000269|PubMed:11278586" FT MUTAGEN 79 FT /note="L->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with E-86; L-87; FT S-90; K-102; F-105; I-110; E-111 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 86 FT /note="E->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; L-87; FT S-90; K-102; F-105; I-110; E-111 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 87 FT /note="L->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; E-86; FT S-90; K-102; F-105; I-110; E-111 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 90 FT /note="S->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; E-86; FT L-87; K-102; F-105; I-110; E-111 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 102 FT /note="K->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; E-86; FT L-87; S-90; F-105; I-110; E-111 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 105 FT /note="F->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; E-86; FT L-87; S-90; K-102; I-110; E-111 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 106 FT /note="C->S: Changes specificity and confers GNAI1 binding; FT when associated with D-184. Strongly increases affinity for FT GNAI1 and GNAI3; when associated with D-184 and K-191." FT /evidence="ECO:0000269|PubMed:18434541, FT ECO:0000269|PubMed:19478087" FT MUTAGEN 110 FT /note="I->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; E-86; FT L-87; S-90; K-102; F-105; E-111 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 111 FT /note="E->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; E-86; FT L-87; S-90; K-102; F-105; I-110 and L-114." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 114 FT /note="L->A: Near loss of EIF2B5 binding and inhibition of FT in vitro translation; when associated with L-79; E-86; FT L-87; S-90; K-102; F-105; I-110 and E-111." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 149 FT /note="N->A: Decreases GTPase accelerating function but has FT no effect on translation inhibitory activity, suggesting FT that its role in translation is independent of its effects FT on G proteins." FT /evidence="ECO:0000269|PubMed:19736320" FT MUTAGEN 184 FT /note="N->D: Changes specificity and confers GNAI1 binding; FT when associated with D-184. Strongly increases affinity for FT GNAI1 and GNAI3; when associated with S-106 and K-191." FT /evidence="ECO:0000269|PubMed:18434541, FT ECO:0000269|PubMed:19478087" FT MUTAGEN 191 FT /note="E->K: Strongly increases affinity for GNAI1 and FT GNAI3; when associated with S-106 and D-184." FT /evidence="ECO:0000269|PubMed:19478087" FT HELIX 74..79 FT /evidence="ECO:0007829|PDB:2AF0" FT TURN 80..82 FT /evidence="ECO:0007829|PDB:2V4Z" FT HELIX 84..89 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 91..103 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 108..120 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 125..139 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 152..161 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 162..164 FT /evidence="ECO:0007829|PDB:2AF0" FT TURN 167..170 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 171..183 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 185..191 FT /evidence="ECO:0007829|PDB:2AF0" FT HELIX 193..199 FT /evidence="ECO:0007829|PDB:2AF0" SQ SEQUENCE 211 AA; 24382 MW; EFFE4AE47EF9AD8F CRC64; MQSAMFLAVQ HDCRPMDKSA GSGHKSEEKR EKMKRTLLKD WKTRLSYFLQ NSSTPGKPKT GKKSKQQAFI KPSPEEAQLW SEAFDELLAS KYGLAAFRAF LKSEFCEENI EFWLACEDFK KTKSPQKLSS KARKIYTDFI EKEAPKEINI DFQTKTLIAQ NIQEATSGCF TTAQKRVYSL MENNSYPRFL ESEFYQDLCK KPQITTEPHA T //