ID   RGS5_HUMAN              Reviewed;         181 AA.
AC   O15539; E9PMP5; Q53XA9; Q599J0;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   24-JAN-2024, entry version 187.
DE   RecName: Full=Regulator of G-protein signaling 5;
DE            Short=RGS5;
GN   Name=RGS5;
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 [MRNA] (ISOFORM 1).
RA   Chatterjee T.K., Fisher R.A.;
RL   Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Neuroblastoma;
RX   PubMed=9747037; DOI=10.1007/s100380050071;
RA   Seki N., Sugano S., Suzuki Y., Nakagawara A., Ohira M., Muramatsu M.-A.,
RA   Saito T., Hori T.;
RT   "Isolation, tissue expression, and chromosomal assignment of human RGS5, a
RT   novel G-protein signaling regulator gene.";
RL   J. Hum. Genet. 43:202-205(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=10471929; DOI=10.1038/12867;
RA   Cismowski M.J., Takesono A., Ma C., Lizano J.S., Xie X., Fuernkranz H.,
RA   Lanier S.M., Duzic E.;
RT   "Genetic screens in yeast to identify mammalian nonreceptor modulators of
RT   G-protein signaling.";
RL   Nat. Biotechnol. 17:878-883(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Eye;
RX   PubMed=15670159; DOI=10.1111/j.1742-4658.2004.04516.x;
RA   Liang Y., Li C., Gozamn V.W., Woodwrad D.F.;
RT   "Identification of a novel alternative splicing variant of RGS5 mRNA in
RT   human ocular tissues.";
RL   FEBS J. 272:791-799(2005).
RN   [5]
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Cervix;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [7]
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   [8]
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   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Brain, and Melanoma;
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   [10]
RP   STRUCTURE BY NMR OF 44-180.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Solution structure of the RGS domain of regulator of G-protein signalling
RT   5 (RGS 5).";
RL   Submitted (NOV-2005) to the PDB data bank.
CC   -!- FUNCTION: Inhibits signal transduction by increasing the GTPase
CC       activity of G protein alpha subunits thereby driving them into their
CC       inactive GDP-bound form. Binds to G(i)-alpha and G(o)-alpha, but not to
CC       G(s)-alpha (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       O15539; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12017832, EBI-16439278;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC       {ECO:0000269|PubMed:15670159}. Membrane {ECO:0000269|PubMed:15670159}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC       {ECO:0000269|PubMed:15670159}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O15539-1; Sequence=Displayed;
CC       Name=2; Synonyms=RGS5s;
CC         IsoId=O15539-2; Sequence=VSP_043094;
CC       Name=3;
CC         IsoId=O15539-3; Sequence=VSP_045086;
CC   -!- MISCELLANEOUS: [Isoform 2]: Acts as an endogenous negative regulator of
CC       isoform 1. {ECO:0000305}.
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DR   EMBL; AF030108; AAB84001.1; -; mRNA.
DR   EMBL; AB008109; BAA22889.1; -; mRNA.
DR   EMBL; AF159570; AAD40957.1; -; mRNA.
DR   EMBL; AJ891044; CAI76926.1; -; mRNA.
DR   EMBL; AF493929; AAM12643.1; -; mRNA.
DR   EMBL; BX537427; CAD97669.1; -; mRNA.
DR   EMBL; AL451063; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL583850; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL499616; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471067; EAW90731.1; -; Genomic_DNA.
DR   EMBL; BC030059; AAH30059.1; -; mRNA.
DR   EMBL; BU172751; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS1244.1; -. [O15539-1]
DR   CCDS; CCDS55652.1; -. [O15539-2]
DR   CCDS; CCDS58041.1; -. [O15539-3]
DR   RefSeq; NP_001182232.1; NM_001195303.2. [O15539-2]
DR   RefSeq; NP_001241677.1; NM_001254748.1. [O15539-2]
DR   RefSeq; NP_001241678.1; NM_001254749.1. [O15539-3]
DR   RefSeq; NP_003608.1; NM_003617.3. [O15539-1]
DR   PDB; 2CRP; NMR; -; A=44-180.
DR   PDBsum; 2CRP; -.
DR   AlphaFoldDB; O15539; -.
DR   SMR; O15539; -.
DR   BioGRID; 114062; 11.
DR   IntAct; O15539; 3.
DR   STRING; 9606.ENSP00000433001; -.
DR   iPTMnet; O15539; -.
DR   PhosphoSitePlus; O15539; -.
DR   BioMuta; RGS5; -.
DR   MassIVE; O15539; -.
DR   PaxDb; 9606-ENSP00000433001; -.
DR   PeptideAtlas; O15539; -.
DR   Antibodypedia; 982; 450 antibodies from 30 providers.
DR   DNASU; 8490; -.
DR   Ensembl; ENST00000313961.10; ENSP00000319308.5; ENSG00000143248.13. [O15539-1]
DR   Ensembl; ENST00000527988.1; ENSP00000432313.1; ENSG00000143248.13. [O15539-2]
DR   Ensembl; ENST00000530507.5; ENSP00000433001.1; ENSG00000143248.13. [O15539-3]
DR   Ensembl; ENST00000618415.4; ENSP00000480891.1; ENSG00000143248.13. [O15539-2]
DR   GeneID; 8490; -.
DR   KEGG; hsa:8490; -.
DR   MANE-Select; ENST00000313961.10; ENSP00000319308.5; NM_003617.4; NP_003608.1.
DR   UCSC; uc001gcn.4; human. [O15539-1]
DR   AGR; HGNC:10001; -.
DR   CTD; 8490; -.
DR   DisGeNET; 8490; -.
DR   GeneCards; RGS5; -.
DR   HGNC; HGNC:10001; RGS5.
DR   HPA; ENSG00000143248; Low tissue specificity.
DR   MalaCards; RGS5; -.
DR   MIM; 603276; gene.
DR   neXtProt; NX_O15539; -.
DR   OpenTargets; ENSG00000143248; -.
DR   PharmGKB; PA34376; -.
DR   VEuPathDB; HostDB:ENSG00000143248; -.
DR   eggNOG; KOG3589; Eukaryota.
DR   GeneTree; ENSGT00940000157380; -.
DR   HOGENOM; CLU_2704096_0_0_1; -.
DR   InParanoid; O15539; -.
DR   OMA; RSEFYHE; -.
DR   OrthoDB; 22856at2759; -.
DR   PhylomeDB; O15539; -.
DR   TreeFam; TF315837; -.
DR   PathwayCommons; O15539; -.
DR   Reactome; R-HSA-416476; G alpha (q) signalling events.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; O15539; -.
DR   BioGRID-ORCS; 8490; 9 hits in 1071 CRISPR screens.
DR   ChiTaRS; RGS5; human.
DR   EvolutionaryTrace; O15539; -.
DR   GeneWiki; RGS5; -.
DR   GenomeRNAi; 8490; -.
DR   Pharos; O15539; Tbio.
DR   PRO; PR:O15539; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; O15539; Protein.
DR   Bgee; ENSG00000143248; Expressed in blood vessel layer and 213 other cell types or tissues.
DR   ExpressionAtlas; O15539; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005096; F:GTPase activator activity; TAS:ProtInc.
DR   GO; GO:0003924; F:GTPase activity; TAS:Reactome.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0009968; P:negative regulation of signal transduction; IEA:UniProtKB-KW.
DR   GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   CDD; cd08717; RGS_RGS5; 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; IPR034956; RGS_RGS5.
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:SF42; REGULATOR OF G-PROTEIN SIGNALING 5; 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; O15539; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Membrane;
KW   Reference proteome; Signal transduction inhibitor.
FT   CHAIN           1..181
FT                   /note="Regulator of G-protein signaling 5"
FT                   /id="PRO_0000204188"
FT   DOMAIN          64..180
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   VAR_SEQ         1..108
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15670159"
FT                   /id="VSP_043094"
FT   VAR_SEQ         128
FT                   /note="E -> EVGLW (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_045086"
FT   HELIX           55..58
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           60..63
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           65..70
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           72..84
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           88..101
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           108..119
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           133..141
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           149..151
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           152..164
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           166..172
FT                   /evidence="ECO:0007829|PDB:2CRP"
FT   HELIX           174..180
FT                   /evidence="ECO:0007829|PDB:2CRP"
SQ   SEQUENCE   181 AA;  20946 MW;  2E08CB0179DE7687 CRC64;
     MCKGLAALPH SCLERAKEIK IKLGILLQKP DSVGDLVIPY NEKPEKPAKT QKTSLDEALQ
     WRDSLDKLLQ NNYGLASFKS FLKSEFSEEN LEFWIACEDY KKIKSPAKMA EKAKQIYEEF
     IQTEAPKEVN IDHFTKDITM KNLVEPSLSS FDMAQKRIHA LMEKDSLPRF VRSEFYQELI
     K
//