ID   GRM4_RAT                Reviewed;         912 AA.
AC   P31423;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   24-JAN-2024, entry version 158.
DE   RecName: Full=Metabotropic glutamate receptor 4;
DE            Short=mGluR4;
DE   Flags: Precursor;
GN   Name=Grm4; Synonyms=Gprc1d, Mglur4;
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].
RC   TISSUE=Brain;
RX   PubMed=1309649; DOI=10.1016/0896-6273(92)90118-w;
RA   Tanabe Y., Masu M., Ishii T., Shigemoto R., Nakanishi S.;
RT   "A family of metabotropic glutamate receptors.";
RL   Neuron 8:169-179(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=8338667; DOI=10.1016/0896-6273(93)90269-w;
RA   O'Hara P.J., Sheppard P.O., Thoegersen H., Venezia D., Haldeman B.A.,
RA   McGrane V., Houamed K.M., Thomsen C., Gilbert T.L., Mulvihill E.R.;
RT   "The ligand-binding domain in metabotropic glutamate receptors is related
RT   to bacterial periplasmic binding proteins.";
RL   Neuron 11:41-52(1993).
RN   [3]
RP   PROTEIN SEQUENCE OF 347-357 AND 686-692, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RA   Lubec G., Kang S.U., Lubec S.;
RL   Submitted (SEP-2007) to UniProtKB.
RN   [4]
RP   INTERACTION WITH PICK1.
RX   PubMed=11122333; DOI=10.1046/j.1460-9568.2000.01309.x;
RA   El Far O., Airas J., Wischmeyer E., Nehring R.B., Karschin A., Betz H.;
RT   "Interaction of the C-terminal tail region of the metabotropic glutamate
RT   receptor 7 with the protein kinase C substrate PICK1.";
RL   Eur. J. Neurosci. 12:4215-4221(2000).
CC   -!- FUNCTION: G-protein coupled receptor for glutamate. Ligand binding
CC       causes a conformation change that triggers signaling via guanine
CC       nucleotide-binding proteins (G proteins) and modulates the activity of
CC       down-stream effectors. Signaling inhibits adenylate cyclase activity.
CC   -!- SUBUNIT: Interacts with PICK1. {ECO:0000269|PubMed:11122333}.
CC   -!- INTERACTION:
CC       P31423; O08599-1: Stxbp1; Xeno; NbExp=2; IntAct=EBI-7974891, EBI-15809216;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Is widely distributed in the CNS. Predominant
CC       expression is seen in the granule cells of the cerebellum.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC       {ECO:0000305}.
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DR   EMBL; M92077; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; M90518; AAA93190.1; -; mRNA.
DR   PIR; JH0563; JH0563.
DR   RefSeq; NP_073157.1; NM_022666.1.
DR   AlphaFoldDB; P31423; -.
DR   SMR; P31423; -.
DR   BioGRID; 246582; 5.
DR   DIP; DIP-41144N; -.
DR   IntAct; P31423; 5.
DR   MINT; P31423; -.
DR   BindingDB; P31423; -.
DR   ChEMBL; CHEMBL2787; -.
DR   DrugCentral; P31423; -.
DR   GuidetoPHARMACOLOGY; 292; -.
DR   GlyCosmos; P31423; 5 sites, No reported glycans.
DR   GlyGen; P31423; 5 sites.
DR   iPTMnet; P31423; -.
DR   PhosphoSitePlus; P31423; -.
DR   SwissPalm; P31423; -.
DR   PaxDb; 10116-ENSRNOP00000060812; -.
DR   Ensembl; ENSRNOT00000093633.2; ENSRNOP00000082873.1; ENSRNOG00000000487.9.
DR   Ensembl; ENSRNOT00055013207; ENSRNOP00055010582; ENSRNOG00055007857.
DR   Ensembl; ENSRNOT00060009094; ENSRNOP00060006855; ENSRNOG00060005451.
DR   Ensembl; ENSRNOT00065045634; ENSRNOP00065037419; ENSRNOG00065026408.
DR   GeneID; 24417; -.
DR   KEGG; rno:24417; -.
DR   UCSC; RGD:2745; rat.
DR   AGR; RGD:2745; -.
DR   CTD; 2914; -.
DR   RGD; 2745; Grm4.
DR   eggNOG; KOG1056; Eukaryota.
DR   GeneTree; ENSGT01030000234648; -.
DR   InParanoid; P31423; -.
DR   OrthoDB; 5388627at2759; -.
DR   Reactome; R-RNO-418594; G alpha (i) signalling events.
DR   Reactome; R-RNO-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
DR   PRO; PR:P31423; -.
DR   Proteomes; UP000002494; Chromosome 20.
DR   GO; GO:0150048; C:cerebellar granule cell to Purkinje cell synapse; ISO:RGD.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR   GO; GO:0043198; C:dendritic shaft; IDA:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR   GO; GO:0043005; C:neuron projection; ISO:RGD.
DR   GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0048787; C:presynaptic active zone membrane; IDA:UniProtKB.
DR   GO; GO:0043195; C:terminal bouton; IDA:UniProtKB.
DR   GO; GO:0001640; F:adenylate cyclase inhibiting G protein-coupled glutamate receptor activity; IBA:GO_Central.
DR   GO; GO:0048306; F:calcium-dependent protein binding; IPI:RGD.
DR   GO; GO:0005516; F:calmodulin binding; IPI:RGD.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR   GO; GO:0008066; F:glutamate receptor activity; ISS:UniProtKB.
DR   GO; GO:0007196; P:adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0014051; P:gamma-aminobutyric acid secretion; TAS:UniProtKB.
DR   GO; GO:0007612; P:learning; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:UniProtKB.
DR   GO; GO:0050805; P:negative regulation of synaptic transmission; TAS:UniProtKB.
DR   GO; GO:0031175; P:neuron projection development; TAS:UniProtKB.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR   GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0043523; P:regulation of neuron apoptotic process; NAS:UniProtKB.
DR   GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR   GO; GO:0051932; P:synaptic transmission, GABAergic; TAS:UniProtKB.
DR   GO; GO:0035249; P:synaptic transmission, glutamatergic; TAS:UniProtKB.
DR   CDD; cd15452; 7tmC_mGluR4; 1.
DR   CDD; cd06376; PBP1_mGluR_groupIII; 1.
DR   Gene3D; 3.40.50.2300; -; 2.
DR   Gene3D; 2.10.50.30; GPCR, family 3, nine cysteines domain; 1.
DR   InterPro; IPR001828; ANF_lig-bd_rcpt.
DR   InterPro; IPR000337; GPCR_3.
DR   InterPro; IPR011500; GPCR_3_9-Cys_dom.
DR   InterPro; IPR038550; GPCR_3_9-Cys_sf.
DR   InterPro; IPR017978; GPCR_3_C.
DR   InterPro; IPR017979; GPCR_3_CS.
DR   InterPro; IPR001786; GPCR_3_mGluR4.
DR   InterPro; IPR000162; GPCR_3_mtglu_rcpt.
DR   InterPro; IPR028082; Peripla_BP_I.
DR   PANTHER; PTHR24060; METABOTROPIC GLUTAMATE RECEPTOR; 1.
DR   PANTHER; PTHR24060:SF23; METABOTROPIC GLUTAMATE RECEPTOR 4; 1.
DR   Pfam; PF00003; 7tm_3; 1.
DR   Pfam; PF01094; ANF_receptor; 1.
DR   Pfam; PF07562; NCD3G; 1.
DR   PRINTS; PR00248; GPCRMGR.
DR   PRINTS; PR01054; MTABOTROPC4R.
DR   PRINTS; PR00593; MTABOTROPICR.
DR   SUPFAM; SSF53822; Periplasmic binding protein-like I; 1.
DR   PROSITE; PS00979; G_PROTEIN_RECEP_F3_1; 1.
DR   PROSITE; PS00980; G_PROTEIN_RECEP_F3_2; 1.
DR   PROSITE; PS00981; G_PROTEIN_RECEP_F3_3; 1.
DR   PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Direct protein sequencing; Disulfide bond;
KW   G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW   Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255"
FT   CHAIN           33..912
FT                   /note="Metabotropic glutamate receptor 4"
FT                   /id="PRO_0000012931"
FT   TOPO_DOM        33..587
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        588..610
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        611..624
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        625..645
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        646..656
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        657..675
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        676..699
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        700..720
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        721..750
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        751..772
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        773..785
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        786..808
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        809..821
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        822..847
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        848..912
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   BINDING         159
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         180..182
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         230
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         312
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         405
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        98
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        454
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        484
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        569
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        67..109
FT                   /evidence="ECO:0000250"
FT   DISULFID        249..538
FT                   /evidence="ECO:0000250"
FT   DISULFID        372..388
FT                   /evidence="ECO:0000250"
FT   DISULFID        428..435
FT                   /evidence="ECO:0000250"
FT   DISULFID        520..539
FT                   /evidence="ECO:0000250"
FT   DISULFID        524..542
FT                   /evidence="ECO:0000250"
FT   DISULFID        545..557
FT                   /evidence="ECO:0000250"
FT   DISULFID        560..573
FT                   /evidence="ECO:0000250"
FT   CONFLICT        124
FT                   /note="Q -> R (in Ref. 2; AAA93190)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   912 AA;  101819 MW;  336430EF19B4B577 CRC64;
     MSGKGGWAWW WARLPLCLLL SLYAPWVPSS LGKPKGHPHM NSIRIDGDIT LGGLFPVHGR
     GSEGKACGEL KKEKGIHRLE AMLFALDRIN NDPDLLPNIT LGARILDTCS RDTHALEQSL
     TFVQALIEKD GTEVRCGSGG PPIITKPERV VGVIGASGSS VSIMVANILR LFKIPQISYA
     STAPDLSDNS RYDFFSRVVP SDTYQAQAMV DIVRALKWNY VSTLASEGSY GESGVEAFIQ
     KSRENGGVCI AQSVKIPREP KTGEFDKIIK RLLETSNARG IIIFANEDDI RRVLEAARRA
     NQTGHFFWMG SDSWGSKSAP VLRLEEVAEG AVTILPKRMS VRGFDRYFSS RTLDNNRRNI
     WFAEFWEDNF HCKLSRHALK KGSHIKKCTN RERIGQDSAY EQEGKVQFVI DAVYAMGHAL
     HAMHRDLCPG RVGLCPRMDP VDGTQLLKYI RNVNFSGIAG NPVTFNENGD APGRYDIYQY
     QLRNGSAEYK VIGSWTDHLH LRIERMQWPG SGQQLPRSIC SLPCQPGERK KTVKGMACCW
     HCEPCTGYQY QVDRYTCKTC PYDMRPTENR TSCQPIPIVK LEWDSPWAVL PLFLAVVGIA
     ATLFVVVTFV RYNDTPIVKA SGRELSYVLL AGIFLCYATT FLMIAEPDLG TCSLRRIFLG
     LGMSISYAAL LTKTNRIYRI FEQGKRSVSA PRFISPASQL AITFILISLQ LLGICVWFVV
     DPSHSVVDFQ DQRTLDPRFA RGVLKCDISD LSLICLLGYS MLLMVTCTVY AIKTRGVPET
     FNEAKPIGFT MYTTCIVWLA FIPIFFGTSQ SADKLYIQTT TLTVSVSLSA SVSLGMLYMP
     KVYIILFHPE QNVPKRKRSL KAVVTAATMS NKFTQKGNFR PNGEAKSELC ENLETPALAT
     KQTYVTYTNH AI
//