ID   GRM2_RAT                Reviewed;         872 AA.
AC   P31421;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   24-JAN-2024, entry version 179.
DE   RecName: Full=Metabotropic glutamate receptor 2;
DE            Short=mGluR2;
DE   Flags: Precursor;
GN   Name=Grm2; Synonyms=Gprc1b, Mglur2;
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   INTERACTION WITH TAMALIN.
RX   PubMed=11850456; DOI=10.1523/jneurosci.22-04-01280.2002;
RA   Kitano J., Kimura K., Yamazaki Y., Soda T., Shigemoto R., Nakajima Y.,
RA   Nakanishi S.;
RT   "Tamalin, a PDZ domain-containing protein, links a protein complex
RT   formation of group 1 metabotropic glutamate receptors and the guanine
RT   nucleotide exchange factor cytohesins.";
RL   J. Neurosci. 22:1280-1289(2002).
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       May mediate suppression of neurotransmission or may be involved in
CC       synaptogenesis or synaptic stabilization.
CC   -!- SUBUNIT: Interacts with HTR2A (By similarity). Interacts with TAMALIN.
CC       {ECO:0000250, ECO:0000269|PubMed:11850456}.
CC   -!- INTERACTION:
CC       P31421; P14842: Htr2a; NbExp=3; IntAct=EBI-7090147, EBI-7090176;
CC       P31421; Q96S59: RANBP9; Xeno; NbExp=4; IntAct=EBI-7090147, EBI-636085;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC       Synapse {ECO:0000250}. Cell projection, dendrite {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Is widely distributed in the CNS and prominent
CC       expression is seen in Golgi cells of the cerebellum and some particular
CC       neuronal cells in other brain regions.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC       {ECO:0000305}.
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DR   EMBL; M92075; -; NOT_ANNOTATED_CDS; mRNA.
DR   PIR; JH0561; JH0561.
DR   RefSeq; NP_001099181.1; NM_001105711.1.
DR   RefSeq; XP_017450945.1; XM_017595456.1.
DR   RefSeq; XP_017450946.1; XM_017595457.1.
DR   AlphaFoldDB; P31421; -.
DR   SMR; P31421; -.
DR   BioGRID; 246580; 3.
DR   DIP; DIP-41937N; -.
DR   IntAct; P31421; 2.
DR   MINT; P31421; -.
DR   STRING; 10116.ENSRNOP00000017607; -.
DR   BindingDB; P31421; -.
DR   ChEMBL; CHEMBL2851; -.
DR   DrugCentral; P31421; -.
DR   GuidetoPHARMACOLOGY; 290; -.
DR   GlyCosmos; P31421; 5 sites, No reported glycans.
DR   GlyGen; P31421; 5 sites.
DR   iPTMnet; P31421; -.
DR   PhosphoSitePlus; P31421; -.
DR   PaxDb; 10116-ENSRNOP00000017607; -.
DR   Ensembl; ENSRNOT00000017607.4; ENSRNOP00000017607.2; ENSRNOG00000013171.4.
DR   Ensembl; ENSRNOT00055020073; ENSRNOP00055016160; ENSRNOG00055011818.
DR   Ensembl; ENSRNOT00060030031; ENSRNOP00060024237; ENSRNOG00060017564.
DR   Ensembl; ENSRNOT00065013122; ENSRNOP00065009696; ENSRNOG00065008268.
DR   GeneID; 24415; -.
DR   KEGG; rno:24415; -.
DR   UCSC; RGD:2743; rat.
DR   AGR; RGD:2743; -.
DR   CTD; 2912; -.
DR   RGD; 2743; Grm2.
DR   eggNOG; KOG1056; Eukaryota.
DR   GeneTree; ENSGT01030000234595; -.
DR   HOGENOM; CLU_005389_0_0_1; -.
DR   InParanoid; P31421; -.
DR   OMA; IPWATPS; -.
DR   OrthoDB; 5388627at2759; -.
DR   PhylomeDB; P31421; -.
DR   TreeFam; TF313240; -.
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:P31421; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Bgee; ENSRNOG00000013171; Expressed in frontal cortex and 3 other cell types or tissues.
DR   GO; GO:0097449; C:astrocyte projection; IDA:ARUK-UCL.
DR   GO; GO:0030424; C:axon; IDA:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR   GO; GO:0043005; C:neuron projection; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR   GO; GO:0042734; C:presynaptic membrane; IDA:UniProtKB.
DR   GO; GO:0005246; F:calcium channel regulator activity; ISO:RGD.
DR   GO; GO:0001641; F:group II metabotropic glutamate receptor activity; IMP:RGD.
DR   GO; GO:0097110; F:scaffold protein binding; IPI:ARUK-UCL.
DR   GO; GO:0035095; P:behavioral response to nicotine; IMP:RGD.
DR   GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0010467; P:gene expression; ISO:RGD.
DR   GO; GO:0007215; P:glutamate receptor signaling pathway; IMP:ARUK-UCL.
DR   GO; GO:0014047; P:glutamate secretion; IDA:UniProtKB.
DR   GO; GO:0090461; P:intracellular glutamate homeostasis; ISO:RGD.
DR   GO; GO:0060292; P:long-term synaptic depression; ISO:RGD.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:ARUK-UCL.
DR   GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0014059; P:regulation of dopamine secretion; IMP:RGD.
DR   GO; GO:0014048; P:regulation of glutamate secretion; IMP:RGD.
DR   GO; GO:0046928; P:regulation of neurotransmitter secretion; NAS:UniProtKB.
DR   GO; GO:2001023; P:regulation of response to drug; IMP:RGD.
DR   GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR   GO; GO:0042220; P:response to cocaine; IMP:RGD.
DR   CDD; cd15447; 7tmC_mGluR2; 1.
DR   CDD; cd06375; PBP1_mGluR_groupII; 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; IPR001458; GPCR_3_mGluR2.
DR   InterPro; IPR000162; GPCR_3_mtglu_rcpt.
DR   InterPro; IPR028082; Peripla_BP_I.
DR   PANTHER; PTHR24060; METABOTROPIC GLUTAMATE RECEPTOR; 1.
DR   PANTHER; PTHR24060:SF147; METABOTROPIC GLUTAMATE RECEPTOR 2; 1.
DR   Pfam; PF00003; 7tm_3; 1.
DR   Pfam; PF01094; ANF_receptor; 1.
DR   Pfam; PF07562; NCD3G; 1.
DR   PRINTS; PR00248; GPCRMGR.
DR   PRINTS; PR01052; MTABOTROPC2R.
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.
DR   Genevisible; P31421; RN.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Disulfide bond; G-protein coupled receptor;
KW   Glycoprotein; Membrane; Receptor; Reference proteome; Signal; Synapse;
KW   Transducer; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..872
FT                   /note="Metabotropic glutamate receptor 2"
FT                   /id="PRO_0000012926"
FT   TOPO_DOM        19..567
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        568..590
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        591..604
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        605..625
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        626..636
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        637..655
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        656..679
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        680..700
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        701..725
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        726..747
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        748..760
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        761..783
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        784..793
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        794..819
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        820..872
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          677..685
FT                   /note="Important for interaction with HTR2A"
FT                   /evidence="ECO:0000250"
FT   BINDING         145
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         166..168
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         216
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         295
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         377
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        203
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        338
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        547
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        50..92
FT                   /evidence="ECO:0000250"
FT   DISULFID        234..518
FT                   /evidence="ECO:0000250"
FT   DISULFID        355..362
FT                   /evidence="ECO:0000250"
FT   DISULFID        400..407
FT                   /evidence="ECO:0000250"
FT   DISULFID        500..519
FT                   /evidence="ECO:0000250"
FT   DISULFID        504..522
FT                   /evidence="ECO:0000250"
FT   DISULFID        525..537
FT                   /evidence="ECO:0000250"
FT   DISULFID        540..553
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   872 AA;  95774 MW;  1E74CABD6AD4BED9 CRC64;
     MESLLGFLAL LLLWGAVAEG PAKKVLTLEG DLVLGGLFPV HQKGGPAEEC GPVNEHRGIQ
     RLEAMLFALD RINRDPHLLP GVRLGAHILD SCSKDTHALE QALDFVRASL SRGADGSRHI
     CPDGSYATHS DAPTAVTGVI GGSYSDVSIQ VANLLRLFQI PQISYASTSA KLSDKSRYDY
     FARTVPPDFF QAKAMAEILR FFNWTYVSTV ASEGDYGETG IEAFELEARA RNICVATSEK
     VGRAMSRAAF EGVVRALLQK PSARVAVLFT RSEDARELLA ATQRLNASFT WVASDGWGAL
     ESVVAGSERA AEGAITIELA SYPISDFASY FQSLDPWNNS RNPWFREFWE ERFHCSFRQR
     DCAAHSLRAV PFEQESKIMF VVNAVYAMAH ALHNMHRALC PNTTHLCDAM RPVNGRRLYK
     DFVLNVKFDA PFRPADTDDE VRFDRFGDGI GRYNIFTYLR AGSGRYRYQK VGYWAEGLTL
     DTSFIPWASP SAGPLPASRC SEPCLQNEVK SVQPGEVCCW LCIPCQPYEY RLDEFTCADC
     GLGYWPNASL TGCFELPQEY IRWGDAWAVG PVTIACLGAL ATLFVLGVFV RHNATPVVKA
     SGRELCYILL GGVFLCYCMT FVFIAKPSTA VCTLRRLGLG TAFSVCYSAL LTKTNRIARI
     FGGAREGAQR PRFISPASQV AICLALISGQ LLIVAAWLVV EAPGTGKETA PERREVVTLR
     CNHRDASMLG SLAYNVLLIA LCTLYAFKTR KCPENFNEAK FIGFTMYTTC IIWLAFLPIF
     YVTSSDYRVQ TTTMCVSVSL SGSVVLGCLF APKLHIILFQ PQKNVVSHRA PTSRFGSAAP
     RASANLGQGS GSQFVPTVCN GREVVDSTTS SL
//