RGS8_HUMAN
ID RGS8_HUMAN Reviewed; 180 AA.
AC P57771; B4DGL9; Q3SYD2;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Regulator of G-protein signaling 8;
DE Short=RGS8;
GN Name=RGS8;
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 2).
RX PubMed=11318611; DOI=10.1006/geno.2001.6500;
RA Sood R., Bonner T.I., Malakowska I., Stephan D.A., Robbins C.M.,
RA Connors T.D., Morgenbesser S.D., Su K., Faruque M.U., Pinkett H.,
RA Graham C., Baxevanis A.D., Klinger K.W., Landes G.M., Trent J.M.,
RA Carpten J.D.;
RT "Cloning and characterization of 13 novel transcripts and the human RGS8
RT gene from the 1q25 region encompassing the hereditary prostate cancer
RT (HPC1) locus.";
RL Genomics 73:211-222(2001).
RN [2]
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 (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Thalamus;
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 [4]
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 42-173 IN COMPLEX WITH GNAI3,
RP FUNCTION, AND INTERACTION WITH GNAI3.
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).
CC -!- FUNCTION: Regulates G protein-coupled receptor signaling cascades,
CC including signaling via muscarinic acetylcholine receptor CHRM2 and
CC dopamine receptor DRD2 (By similarity). Inhibits signal transduction by
CC increasing the GTPase activity of G protein alpha subunits, thereby
CC driving them into their inactive GDP-bound form (PubMed:18434541).
CC Modulates the activity of potassium channels that are activated in
CC response to DRD2 and CHRM2 signaling (By similarity).
CC {ECO:0000250|UniProtKB:P49804, ECO:0000269|PubMed:18434541}.
CC -!- SUBUNIT: Interacts with GNAO1 (By similarity). Interacts with GNAI3.
CC {ECO:0000250|UniProtKB:P49804, ECO:0000269|PubMed:18434541}.
CC -!- INTERACTION:
CC P57771; Q08379: GOLGA2; NbExp=3; IntAct=EBI-10216117, EBI-618309;
CC P57771-2; Q15834: CCDC85B; NbExp=3; IntAct=EBI-12058229, EBI-739674;
CC P57771-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12058229, EBI-618309;
CC P57771-2; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-12058229, EBI-10961706;
CC P57771-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-12058229, EBI-10171697;
CC P57771-2; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-12058229, EBI-742388;
CC P57771-2; Q8TAS1-2: UHMK1; NbExp=3; IntAct=EBI-12058229, EBI-12157345;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P49804};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P49804}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:P49804}. Membrane
CC {ECO:0000250|UniProtKB:P49804}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P49804}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P49804}. Perikaryon
CC {ECO:0000250|UniProtKB:P49804}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P49804}. Nucleus {ECO:0000250|UniProtKB:P49804}.
CC Note=Detected in Purkinje cell soma and dendrites. Associated with
CC Purkinje cell membranes. Not detected in Purkinje cell nuclei. Detected
CC in the nucleus after heterologous expression. Recruited to the cell
CC membrane in the presence of GNAO1. {ECO:0000250|UniProtKB:P49804}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P57771-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P57771-2; Sequence=VSP_036421;
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; AF297015; AAG45337.1; -; mRNA.
DR EMBL; AF300649; AAG18443.1; -; mRNA.
DR EMBL; AK296514; BAG59146.1; -; mRNA.
DR EMBL; AK294660; BAG57830.1; -; mRNA.
DR EMBL; AL353778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91130.1; -; Genomic_DNA.
DR EMBL; BC069677; AAH69677.1; -; mRNA.
DR EMBL; BC069718; AAH69718.1; -; mRNA.
DR EMBL; BC103865; AAI03866.1; -; mRNA.
DR EMBL; BC103866; AAI03867.1; -; mRNA.
DR EMBL; BC103867; AAI03868.1; -; mRNA.
DR CCDS; CCDS1349.1; -. [P57771-2]
DR CCDS; CCDS41443.1; -. [P57771-1]
DR RefSeq; NP_001095920.1; NM_001102450.2. [P57771-1]
DR RefSeq; NP_203131.1; NM_033345.3. [P57771-2]
DR RefSeq; XP_005245612.1; XM_005245555.3. [P57771-1]
DR RefSeq; XP_011508391.1; XM_011510089.2. [P57771-2]
DR RefSeq; XP_011508392.1; XM_011510090.2. [P57771-1]
DR RefSeq; XP_016858120.1; XM_017002631.1. [P57771-2]
DR RefSeq; XP_016858121.1; XM_017002632.1. [P57771-2]
DR RefSeq; XP_016858122.1; XM_017002633.1. [P57771-2]
DR RefSeq; XP_016858123.1; XM_017002634.1. [P57771-2]
DR RefSeq; XP_016858124.1; XM_017002635.1.
DR RefSeq; XP_016858125.1; XM_017002636.1.
DR RefSeq; XP_016858126.1; XM_017002637.1. [P57771-1]
DR PDB; 2IHD; X-ray; 1.70 A; A=42-173.
DR PDB; 2ODE; X-ray; 1.90 A; B/D=42-180.
DR PDB; 5DO9; X-ray; 2.60 A; B/D/F=42-173.
DR PDBsum; 2IHD; -.
DR PDBsum; 2ODE; -.
DR PDBsum; 5DO9; -.
DR AlphaFoldDB; P57771; -.
DR SMR; P57771; -.
DR BioGRID; 124512; 12.
DR DIP; DIP-59093N; -.
DR IntAct; P57771; 10.
DR STRING; 9606.ENSP00000258302; -.
DR BindingDB; P57771; -.
DR ChEMBL; CHEMBL2034803; -.
DR GuidetoPHARMACOLOGY; 2813; -.
DR iPTMnet; P57771; -.
DR PhosphoSitePlus; P57771; -.
DR BioMuta; RGS8; -.
DR DMDM; 13124465; -.
DR MassIVE; P57771; -.
DR PaxDb; P57771; -.
DR PeptideAtlas; P57771; -.
DR PRIDE; P57771; -.
DR ProteomicsDB; 57032; -. [P57771-1]
DR ProteomicsDB; 57033; -. [P57771-2]
DR Antibodypedia; 34440; 130 antibodies from 21 providers.
DR DNASU; 85397; -.
DR Ensembl; ENST00000258302.8; ENSP00000258302.4; ENSG00000135824.12. [P57771-2]
DR Ensembl; ENST00000367556.5; ENSP00000356527.1; ENSG00000135824.12. [P57771-1]
DR Ensembl; ENST00000367557.8; ENSP00000356528.4; ENSG00000135824.12. [P57771-1]
DR Ensembl; ENST00000483095.6; ENSP00000426289.1; ENSG00000135824.12. [P57771-1]
DR GeneID; 85397; -.
DR KEGG; hsa:85397; -.
DR UCSC; uc001gpm.2; human. [P57771-1]
DR CTD; 85397; -.
DR DisGeNET; 85397; -.
DR GeneCards; RGS8; -.
DR HGNC; HGNC:16810; RGS8.
DR HPA; ENSG00000135824; Group enriched (brain, retina).
DR MIM; 607189; gene.
DR neXtProt; NX_P57771; -.
DR OpenTargets; ENSG00000135824; -.
DR PharmGKB; PA34379; -.
DR VEuPathDB; HostDB:ENSG00000135824; -.
DR eggNOG; KOG3589; Eukaryota.
DR GeneTree; ENSGT00940000154304; -.
DR HOGENOM; CLU_059863_3_1_1; -.
DR InParanoid; P57771; -.
DR OMA; WSESFDS; -.
DR OrthoDB; 1588190at2759; -.
DR PhylomeDB; P57771; -.
DR TreeFam; TF315837; -.
DR PathwayCommons; P57771; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P57771; -.
DR BioGRID-ORCS; 85397; 11 hits in 1060 CRISPR screens.
DR ChiTaRS; RGS8; human.
DR EvolutionaryTrace; P57771; -.
DR GeneWiki; RGS8; -.
DR GenomeRNAi; 85397; -.
DR Pharos; P57771; Tchem.
DR PRO; PR:P57771; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P57771; protein.
DR Bgee; ENSG00000135824; Expressed in lateral nuclear group of thalamus and 86 other tissues.
DR ExpressionAtlas; P57771; baseline and differential.
DR Genevisible; P57771; HS.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; TAS:Reactome.
DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; ISS:UniProtKB.
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:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0060159; P:regulation of dopamine receptor signaling pathway; ISS:UniProtKB.
DR CDD; cd08711; RGS_RGS8; 1.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.10.196.10; -; 2.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR034948; RGS8.
DR InterPro; IPR034949; RGS_RGS8.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR024066; RGS_subdom1/3.
DR InterPro; IPR044926; RGS_subdomain_2.
DR PANTHER; PTHR10845:SF147; PTHR10845:SF147; 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 splicing; Cell membrane; Cell projection;
KW GTPase activation; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Signal transduction inhibitor.
FT CHAIN 1..180
FT /note="Regulator of G-protein signaling 8"
FT /id="PRO_0000204199"
FT DOMAIN 56..171
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49804"
FT VAR_SEQ 1..9
FT /note="MAALLMPRR -> MWNTLTRSLSDHPVGKDPQAMRTGQRQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:11318611,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_036421"
FT HELIX 47..52
FT /evidence="ECO:0007829|PDB:2IHD"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 57..61
FT /evidence="ECO:0007829|PDB:2IHD"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:2IHD"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:2IHD"
FT HELIX 98..112
FT /evidence="ECO:0007829|PDB:2IHD"
FT HELIX 125..134
FT /evidence="ECO:0007829|PDB:2IHD"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:2IHD"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:2IHD"
FT HELIX 158..163
FT /evidence="ECO:0007829|PDB:2IHD"
FT HELIX 166..169
FT /evidence="ECO:0007829|PDB:2IHD"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:5DO9"
SQ SEQUENCE 180 AA; 20917 MW; 198965B4C27F64C9 CRC64;
MAALLMPRRN KGMRTRLGCL SHKSDSCSDF TAILPDKPNR ALKRLSTEEA TRWADSFDVL
LSHKYGVAAF RAFLKTEFSE ENLEFWLACE EFKKTRSTAK LVSKAHRIFE EFVDVQAPRE
VNIDFQTREA TRKNLQEPSL TCFDQAQGKV HSLMEKDSYP RFLRSKMYLD LLSQSQRRLS
