ID   RGS4_RAT                Reviewed;         205 AA.
AC   P49799;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   10-JUN-2026, entry version 172.
DE   RecName: Full=Regulator of G protein signaling 4;
DE            Short=RGP4;
DE            Short=RGS4;
GN   Name=Rgs4;
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].
RX   PubMed=8602223; DOI=10.1038/379742a0;
RA   Druey K.M., Blumer K.J., Kang V.H., Kehrl J.H.;
RT   "Inhibition of G-protein-mediated MAP kinase activation by a new mammalian
RT   gene family.";
RL   Nature 379:742-746(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley;
RA   Zhou M.-Y., Gomez-Sanchez C.E., Gomez-Sanchez E.P.;
RT   "The complete cDNA sequence analysis of the rat RGS4.";
RL   Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 93-159.
RC   TISSUE=Brain;
RX   PubMed=8548815; DOI=10.1016/s0092-8674(00)80998-8;
RA   Koelle M.R., Horvitz H.R.;
RT   "EGL-10 regulates G protein signaling in the C. elegans nervous system and
RT   shares a conserved domain with many mammalian proteins.";
RL   Cell 84:115-125(1996).
RN   [4]
RP   PHOSPHORYLATION.
RX   PubMed=10702309; DOI=10.1074/jbc.275.10.7365;
RA   Pedram A., Razandi M., Kehrl J., Levin E.R.;
RT   "Natriuretic peptides inhibit G protein activation. Mediation through
RT   cross-talk between cyclic GMP-dependent protein kinase and regulators of G
RT   protein-signaling proteins.";
RL   J. Biol. Chem. 275:7365-7372(2000).
RN   [5]
RP   INHIBITION.
RX   PubMed=9353196; DOI=10.1126/science.278.5340.1132;
RA   Tu Y., Wang J., Ross E.M.;
RT   "Inhibition of brain Gz GAP and other RGS proteins by palmitoylation of G
RT   protein alpha subunits.";
RL   Science 278:1132-1135(1997).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH G(I)-ALPHA.
RX   PubMed=9108480; DOI=10.1016/s0092-8674(00)80204-4;
RA   Tesmer J.J.G., Berman D.M., Gilman A.G., Sprang S.R.;
RT   "Structure of RGS4 bound to AlF4-activated G(i alpha1): stabilization of
RT   the transition state for GTP hydrolysis.";
RL   Cell 89:251-261(1997).
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. Activity on G(z)-alpha is inhibited by
CC       phosphorylation of the G protein. Activity on G(z)-alpha and G(i)-
CC       alpha-1 is inhibited by palmitoylation of the G protein.
CC   -!- PTM: Either Cys-2 or Cys-12 or both are palmitoylated. {ECO:0000250}.
CC   -!- PTM: Phosphorylated by cyclic GMP-dependent protein kinase.
CC       {ECO:0000269|PubMed:10702309}.
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DR   EMBL; U27767; AAC52440.1; -; mRNA.
DR   EMBL; AF117211; AAD12065.1; -; mRNA.
DR   EMBL; U32327; AAC52367.1; -; mRNA.
DR   RefSeq; NP_058910.1; NM_017214.2.
DR   PDB; 1AGR; X-ray; 2.80 A; E/H=1-205.
DR   PDB; 1EZT; NMR; -; A=51-205.
DR   PDB; 1EZY; NMR; -; A=51-205.
DR   AlphaFoldDB; P49799; -.
DR   BMRB; P49799; -.
DR   SMR; P49799; -.
DR   CORUM; P49799; -.
DR   DIP; DIP-6074N; -.
DR   FunCoup; P49799; 239.
DR   IntAct; P49799; 3.
DR   MINT; P49799; -.
DR   STRING; 10116.ENSRNOP00000003774; -.
DR   GuidetoPHARMACOLOGY; 2811; -.
DR   PhosphoSitePlus; P49799; -.
DR   SwissPalm; P49799; -.
DR   PaxDb; 10116-ENSRNOP00000003774; -.
DR   Ensembl; ENSRNOT00000003774.4; ENSRNOP00000003774.2; ENSRNOG00000002773.4.
DR   Ensembl; ENSRNOT00055039881; ENSRNOP00055032358; ENSRNOG00055023189.
DR   Ensembl; ENSRNOT00060037671; ENSRNOP00060031063; ENSRNOG00060021688.
DR   Ensembl; ENSRNOT00065033993; ENSRNOP00065027211; ENSRNOG00065020135.
DR   GeneID; 29480; -.
DR   KEGG; rno:29480; -.
DR   UCSC; RGD:3567; rat.
DR   AGR; RGD:3567; -.
DR   CTD; 5999; -.
DR   RGD; 3567; Rgs4.
DR   eggNOG; KOG3589; Eukaryota.
DR   GeneTree; ENSGT00940000159036; -.
DR   HOGENOM; CLU_059863_3_0_1; -.
DR   InParanoid; P49799; -.
DR   OMA; LIQDLCQ; -.
DR   OrthoDB; 196547at2759; -.
DR   PhylomeDB; P49799; -.
DR   Reactome; R-RNO-416476; G alpha (q) signalling events.
DR   Reactome; R-RNO-418594; G alpha (i) signalling events.
DR   EvolutionaryTrace; P49799; -.
DR   PRO; PR:P49799; -.
DR   Proteomes; UP000002494; Chromosome 13.
DR   Bgee; ENSRNOG00000002773; Expressed in frontal cortex and 20 other cell types or tissues.
DR   ExpressionAtlas; P49799; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0009898; C:cytoplasmic side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0001965; F:G-protein alpha-subunit binding; IDA:RGD.
DR   GO; GO:0005096; F:GTPase activator activity; IDA:RGD.
DR   GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR   GO; GO:1990791; P:dorsal root ganglion development; IEP:RGD.
DR   GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; IDA:RGD.
DR   GO; GO:0060160; P:negative regulation of dopamine receptor signaling pathway; IDA:RGD.
DR   GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; IMP:RGD.
DR   GO; GO:1900924; P:negative regulation of glycine import across plasma membrane; IMP:RGD.
DR   GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; IDA:RGD.
DR   GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IMP:RGD.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; IMP:RGD.
DR   GO; GO:0010460; P:positive regulation of heart rate; IMP:RGD.
DR   GO; GO:0110053; P:regulation of actin filament organization; IDA:RGD.
DR   GO; GO:0051924; P:regulation of calcium ion transport; IDA:RGD.
DR   GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IDA:RGD.
DR   GO; GO:0001975; P:response to amphetamine; IEP:RGD.
DR   GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   CDD; cd08714; RGS_RGS4; 1.
DR   DisProt; DP00063; -.
DR   FunFam; 1.10.167.10:FF:000001; Putative regulator of g-protein signaling 12; 1.
DR   FunFam; 1.10.196.10:FF:000001; Regulator of G-protein signaling 8; 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; IPR034953; RGS_RGS4.
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:SF184; REGULATOR OF G-PROTEIN SIGNALING 4; 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   PDBsum; 1AGR; -.
DR   PDBsum; 1EZT; -.
DR   PDBsum; 1EZY; -.
PE   1: Evidence at protein level;
KW   3D-structure; Lipoprotein; Palmitate; Phosphoprotein; Reference proteome;
KW   Signal transduction inhibitor.
FT   CHAIN           1..205
FT                   /note="Regulator of G protein signaling 4"
FT                   /id="PRO_0000204187"
FT   DOMAIN          62..178
FT                   /note="RGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT   LIPID           2
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           12
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           95
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   HELIX           53..59
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           63..68
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           70..82
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           87..100
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   TURN            104..106
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           107..114
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           115..119
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           131..140
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   TURN            146..149
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           150..160
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           161..165
FT                   /evidence="ECO:0007829|PDB:1AGR"
FT   HELIX           166..170
FT                   /evidence="ECO:0007829|PDB:1EZT"
FT   HELIX           172..175
FT                   /evidence="ECO:0007829|PDB:1AGR"
SQ   SEQUENCE   205 AA;  23249 MW;  9647C0EC909D0F6F CRC64;
     MCKGLAGLPA SCLRSAKDMK HRLGFLLQKS DSCEHSSSHS KKDKVVTCQR VSQEEVKKWA
     ESLENLINHE CGLAAFKAFL KSEYSEENID FWISCEEYKK IKSPSKLSPK AKKIYNEFIS
     VQATKEVNLD SCTREETSRN MLEPTITCFD EAQKKIFNLM EKDSYRRFLK SRFYLDLTNP
     SSCGAEKQKG AKSSADCTSL VPQCA
//