RGS2_HUMAN
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 03-AUG-2022, entry version 201.
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="http://atlasgeneticsoncology.org/Genes/RGS2ID42102ch1q31.html";
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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; P41220; -.
DR PeptideAtlas; P41220; -.
DR PRIDE; P41220; -.
DR ProteomicsDB; 55425; -. [P41220-1]
DR ProteomicsDB; 55426; -. [P41220-2]
DR ProteomicsDB; 55427; -. [P41220-3]
DR ProteomicsDB; 55428; -. [P41220-4]
DR Antibodypedia; 34461; 288 antibodies from 30 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 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 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; 11 hits in 1079 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 208 other tissues.
DR ExpressionAtlas; P41220; baseline and differential.
DR Genevisible; P41220; HS.
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:0043005; C:neuron projection; IEA:Ensembl.
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:0007420; P:brain development; IEA:Ensembl.
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:0140194; P:negative regulation of adenylate cyclase-inhibiting adrenergic receptor signaling pathway involved in heart process; ISS:BHF-UCL.
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:0030728; P:ovulation; 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: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 Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.10.196.10; -; 1.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR034947; RGS2.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR024066; RGS_subdom1/3.
DR InterPro; IPR044926; RGS_subdomain_2.
DR PANTHER; PTHR10845:SF43; PTHR10845:SF43; 1.
DR Pfam; PF00615; RGS; 1.
DR PRINTS; PR01301; RGSPROTEIN.
DR SMART; SM00315; RGS; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR PROSITE; PS50132; RGS; 1.
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 (rare variant; unknown pathological
FT significance; decreased down-regulation of angiotensin-
FT activated signaling pathway; decreased RGS2 protein
FT 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 (likely benign variant; no effect on down-
FT regulation of 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 (likely benign variant; no effect on down-
FT regulation of 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 (likely benign variant; no effect on down-
FT regulation of 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 (likely benign variant; no effect on down-
FT regulation of 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 (likely benign variant; no effect on down-
FT regulation of angiotensin-activated signaling pathway;
FT dbSNP:rs74466425)"
FT /evidence="ECO:0000269|PubMed:27535533,
FT ECO:0000269|PubMed:28784619"
FT /id="VAR_079243"
FT VARIANT 23
FT /note="G -> D (likely benign variant; no effect on down-
FT regulation of 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 (unknown pathological significance; decreased
FT down-regulation of angiotensin-activated signaling pathway;
FT reduced localization at the cell membrane;
FT dbSNP:rs201233692)"
FT /evidence="ECO:0000269|PubMed:27535533,
FT ECO:0000269|PubMed:28784619"
FT /id="VAR_079245"
FT VARIANT 44
FT /note="R -> H (unknown pathological significance; decreased
FT down-regulation of angiotensin-activated signaling pathway;
FT reduced localization at the cell membrane;
FT 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 (likely benign variant; no effect on down-
FT regulation of angiotensin-activated signaling pathway;
FT dbSNP:rs80221024)"
FT /evidence="ECO:0000269|PubMed:27535533,
FT ECO:0000269|PubMed:28784619"
FT /id="VAR_079247"
FT VARIANT 55
FT /note="P -> L (likely benign variant; no effect on down-
FT regulation of 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 (likely benign variant; no effect on down-
FT regulation of 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 (likely benign variant; no effect on down-
FT regulation of 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 (likely benign variant; no effect on down-
FT regulation of 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 (rare variant; unknown pathological
FT significance; decreased down-regulation of angiotensin-
FT activated signaling pathway; reduced interaction with GNAQ;
FT dbSNP:rs369752935)"
FT /evidence="ECO:0000269|PubMed:27535533,
FT ECO:0000269|PubMed:28784619"
FT /id="VAR_079252"
FT VARIANT 196
FT /note="Q -> R (likely benign variant; no effect on down-
FT regulation of 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; S-
FT 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; S-
FT 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; S-
FT 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; L-
FT 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; L-
FT 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; L-
FT 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; L-
FT 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; L-
FT 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; L-
FT 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
