ID   RGS12_RAT               Reviewed;        1387 AA.
AC   O08774; O88383;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   24-JAN-2024, entry version 162.
DE   RecName: Full=Regulator of G-protein signaling 12;
DE            Short=RGS12;
GN   Name=Rgs12;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=9168931; DOI=10.1006/bbrc.1997.6537;
RA   Snow B.E., Antonio L., Suggs S., Gutstein H.B., Siderovski D.P.;
RT   "Molecular cloning and expression analysis of rat Rgs12 and Rgs14.";
RL   Biochem. Biophys. Res. Commun. 233:770-777(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND FUNCTION.
RC   TISSUE=Brain;
RX   PubMed=9651375; DOI=10.1074/jbc.273.28.17749;
RA   Snow B.E., Hall R.A., Krumins A.M., Brothers G.M., Bouchard D.,
RA   Brothers C.A., Chung S., Mangion J., Gilman A.G., Lefkowitz R.J.,
RA   Siderovski D.P.;
RT   "GTPase activating specificity of RGS12 and binding specificity of an
RT   alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain.";
RL   J. Biol. Chem. 273:17749-17755(1998).
RN   [3]
RP   FUNCTION, AND INTERACTION WITH GNAI1; GNAI2 AND GNAI3.
RX   PubMed=11387333; DOI=10.1074/jbc.m103208200;
RA   Kimple R.J., De Vries L., Tronchere H., Behe C.I., Morris R.A.,
RA   Gist Farquhar M., Siderovski D.P.;
RT   "RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with
RT   guanine nucleotide dissociation inhibitor activity.";
RL   J. Biol. Chem. 276:29275-29281(2001).
RN   [4]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=16819986; DOI=10.1111/j.1460-9568.2006.04838.x;
RA   Lopez-Aranda M.F., Acevedo M.J., Carballo F.J., Gutierrez A., Khan Z.U.;
RT   "Localization of the GoLoco motif carrier regulator of G-protein signalling
RT   12 and 14 proteins in monkey and rat brain.";
RL   Eur. J. Neurosci. 23:2971-2982(2006).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-171; SER-661; SER-671 AND
RP   SER-879, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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. {ECO:0000269|PubMed:11387333, ECO:0000269|PubMed:9651375}.
CC   -!- SUBUNIT: Interacts with GNAI1, GNAI2 and GNAI3; the interactions are
CC       GDP-dependent. {ECO:0000269|PubMed:11387333}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16819986}. Cytoplasm
CC       {ECO:0000269|PubMed:16819986}. Cell projection, dendrite
CC       {ECO:0000269|PubMed:16819986}. Synapse {ECO:0000269|PubMed:16819986}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=1;
CC         IsoId=O08774-1; Sequence=Displayed;
CC       Name=2; Synonyms=PDZ-less;
CC         IsoId=O08774-2; Sequence=VSP_005688, VSP_005689;
CC   -!- TISSUE SPECIFICITY: Detected in brain cortex GABAergic neurons, in
CC       striatum and substantia nigra, and in the Purkinje cell layer in the
CC       cerebellum and hippocampus (at protein level) (PubMed:16819986).
CC       Expressed at high levels in brain and lung and lower levels in testis,
CC       heart, and spleen (PubMed:9168931). {ECO:0000269|PubMed:16819986,
CC       ECO:0000269|PubMed:9168931}.
CC   -!- DOMAIN: The GoLoco domain is necessary for interaction with GNAI1,
CC       GNAI2 and GNAI3.
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DR   EMBL; U92280; AAC53176.1; -; mRNA.
DR   EMBL; AF035151; AAC40154.1; -; mRNA.
DR   PIR; JC5502; JC5502.
DR   RefSeq; NP_062212.1; NM_019339.1.
DR   AlphaFoldDB; O08774; -.
DR   SMR; O08774; -.
DR   BioGRID; 248512; 10.
DR   IntAct; O08774; 3.
DR   MINT; O08774; -.
DR   STRING; 10116.ENSRNOP00000045065; -.
DR   iPTMnet; O08774; -.
DR   PhosphoSitePlus; O08774; -.
DR   PaxDb; 10116-ENSRNOP00000045065; -.
DR   GeneID; 54292; -.
DR   KEGG; rno:54292; -.
DR   AGR; RGD:3564; -.
DR   CTD; 6002; -.
DR   RGD; 3564; Rgs12.
DR   eggNOG; KOG3589; Eukaryota.
DR   InParanoid; O08774; -.
DR   OrthoDB; 22856at2759; -.
DR   PhylomeDB; O08774; -.
DR   Reactome; R-RNO-418594; G alpha (i) signalling events.
DR   PRO; PR:O08774; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR   GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:RGD.
DR   GO; GO:0005096; F:GTPase activator activity; IDA:RGD.
DR   GO; GO:0030695; F:GTPase regulator activity; ISO:RGD.
DR   GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; IEP:RGD.
DR   GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR   GO; GO:0038032; P:termination of G protein-coupled receptor signaling pathway; IDA:RGD.
DR   CDD; cd00992; PDZ_signaling; 1.
DR   CDD; cd13162; PTB_RGS12; 1.
DR   CDD; cd17136; RBD1_RGS12; 1.
DR   CDD; cd08742; RGS_RGS12; 1.
DR   Gene3D; 1.10.196.10; -; 1.
DR   Gene3D; 2.30.42.10; -; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 1.10.167.10; Regulator of G-protein Signalling 4, domain 2; 1.
DR   InterPro; IPR003109; GoLoco_motif.
DR   InterPro; IPR001478; PDZ.
DR   InterPro; IPR036034; PDZ_sf.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR006020; PTB/PI_dom.
DR   InterPro; IPR003116; RBD_dom.
DR   InterPro; IPR016137; RGS.
DR   InterPro; IPR046995; RGS10/12/14-like.
DR   InterPro; IPR037880; RGS12_RGS.
DR   InterPro; IPR036305; RGS_sf.
DR   InterPro; IPR024066; RGS_subdom1/3.
DR   InterPro; IPR044926; RGS_subdomain_2.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR45945:SF1; REGULATOR OF G-PROTEIN SIGNALING 12; 1.
DR   PANTHER; PTHR45945; REGULATOR OF G-PROTEIN SIGNALING LOCO; 1.
DR   Pfam; PF02188; GoLoco; 1.
DR   Pfam; PF00595; PDZ; 1.
DR   Pfam; PF02196; RBD; 1.
DR   Pfam; PF00615; RGS; 1.
DR   Pfam; PF16613; RGS12_us1; 1.
DR   Pfam; PF16611; RGS12_us2; 1.
DR   Pfam; PF16612; RGS12_usC; 1.
DR   PRINTS; PR01301; RGSPROTEIN.
DR   SMART; SM00390; GoLoco; 1.
DR   SMART; SM00228; PDZ; 1.
DR   SMART; SM00462; PTB; 1.
DR   SMART; SM00455; RBD; 2.
DR   SMART; SM00315; RGS; 1.
DR   SUPFAM; SSF50156; PDZ domain-like; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF48097; Regulator of G-protein signaling, RGS; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 2.
DR   PROSITE; PS50877; GOLOCO; 1.
DR   PROSITE; PS50106; PDZ; 1.
DR   PROSITE; PS01179; PID; 1.
DR   PROSITE; PS50898; RBD; 2.
DR   PROSITE; PS50132; RGS; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell projection; Cytoplasm; GTPase activation;
KW   Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW   Repeat; Signal transduction inhibitor; Synapse; Ubl conjugation.
FT   CHAIN           1..1387
FT                   /note="Regulator of G-protein signaling 12"
FT                   /id="PRO_0000204214"
FT   DOMAIN          21..97
FT                   /note="PDZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT   DOMAIN          227..339
FT                   /note="PID"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT   DOMAIN          715..832
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   DOMAIN          962..1032
FT                   /note="RBD 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT   DOMAIN          1034..1104
FT                   /note="RBD 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT   DOMAIN          1187..1209
FT                   /note="GoLoco"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT   REGION          409..429
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          442..488
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          620..650
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          842..934
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1103..1168
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1224..1325
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1349..1387
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        410..429
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        447..473
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        842..874
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        875..897
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        910..927
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1117..1153
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1154..1168
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1248..1301
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1311..1325
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1364..1378
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         171
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         194
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGE9"
FT   MOD_RES         524
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:O14924"
FT   MOD_RES         633
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGE9"
FT   MOD_RES         661
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         671
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         850
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGE9"
FT   MOD_RES         879
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         943
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CGE9"
FT   CROSSLNK        195
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:O14924"
FT   VAR_SEQ         1..648
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_005688"
FT   VAR_SEQ         649..666
FT                   /note="SFGRSRRFSLTRSLDDLE -> MNLEKGLSDDSDVFIDQQ (in isoform
FT                   2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_005689"
SQ   SEQUENCE   1387 AA;  150469 MW;  958047D106B08310 CRC64;
     MYRAGEPGKR QSGPAPPRVR SVEVARGRAG YGFTLSGQAP CVLSCVMRGS PADFVGLRAG
     DQILAINEIN VKKASHEDVV KLIGKCSGVL RMVISEGSSH VEPSSSDEEG GLCEGKGWLR
     PKLDSKALGI NRAERVVEEV QSGGIFNMIF ESPSLCASGS EPLKLKQRSL SESAALRLDV
     GQDSLCTPHP SMLSKEEISK VINDDSVFTV GLDNHDDFGL DASILNVAMV VGYLGSIELP
     STSSNLEHDS LQAIRGCMRR LRAEQKIHSL VTMKVMHDCV QLVTDRAGVV AEYPAEKLAF
     SAVCPDDRRF FGLVTMQTND DGCLAQEDEG ALRTSCHVFM VDPDLFHHKI HQGIARRFGF
     ACTADPDTSG CLEFPASSLP VLQFISVLYR DMGELIEGVR ARAFLDGDAD AHQNNSTSSN
     SDSGIGNFNQ EEKSNRVLVV DLGGGSSRHG QGSSPGWESV SGRGSQPWSA PWNGTFCHDS
     EAGSPLETSP NTDRFWDLTK HSGPVFHMEV PPATLRSSIP PSKRGATGSS CGFNQRWLPV
     HVLQEWQCGH ASDQESYTDS TDGWSSVNCG TLPPPMSKIP ADRYRVEGSF AQAPLSTQKR
     DWSRKAFGMQ NLFGPHRNVR KTKEDKKSSK LGRGVALAQT SQRTSARRSF GRSRRFSLTR
     SLDDLESATV SDGELTGADL KDCISNNSLS SNASLPSVQS CRRLRERRVA SWAVSFERLL
     QDPVGVRYFS DFLRKEFSEE NILFWQACEC FSHVPAHDKK ELSYRAREIF SKFLCSKATT
     PVNIDSQAQL ADDILNAPHP DMFKEQQLQI FNLMKFDSYT RFLKSQLYQE CVLAEVEGRT
     LPDSQQVPSS PASKHSISSD HSNVSTPKKL SGKSKSGRSL NEDVGEEDSE KKRKGAFFSW
     SRSRSTGRSQ KKKDHGDHAH DALHANGGLC RRESQGSVSS AGSLDLSEAC RTSALERDKA
     AKHCCVHLPD GTSCVVAVKS GFSIKEILSG LCERHGINGA AVDLFLVGGD KPLVLHQDSS
     ILATRDLRLG KRTLFRLDLV PINRSVGLKA KPTKPVTEVL RPVVAKYGLD LGSLLVRLSG
     EKEPLDLGAP ISSLDGQRVI LEERDPSRGK VSTEKQKGAP VKQSSAVNSS PRNHSAMGEE
     RTLGKSNSIK IRGENGKSAR DPRLSKREES IAKIGKKKYQ KINLDEAEEF FELISKAQSN
     RADDQRGLLR KEDLVLPEFL RLPPGSSELA LSSPPPVKGF SKRAVTSHGQ EGAVQTEESY
     SDSPATSPAS AQSPCSAYSP GSAHSPGSAH SPGSAHSTPG PPGTAQPGEK PTKPSCISTV
     QEGTTQAWRR LSPELEAGGI QTVEEEQVAD LTLMGEGDIS SPNSTLLPPP PLPQDTPGPT
     RPGTSRF
//