ID GRM3_RAT Reviewed; 879 AA. AC P31422; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 10-JUN-2026, entry version 175. DE RecName: Full=Metabotropic glutamate receptor 3; DE Short=mGluR3; DE Flags: Precursor; GN Name=Grm3; Synonyms=Gprc1c, Mglur3; 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). RN [3] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-439, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=24090084; DOI=10.1021/pr400783j; RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R., RA Graham M.E., Packer N.H., Cordwell S.J.; RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome RT heterogeneity."; RL J. Proteome Res. 12:5791-5800(2013). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 25-575 IN COMPLEXES WITH RP GLUTAMATE, GLYCOSYLATION AT ASN-209, AND DISULFIDE BONDS. RX PubMed=17360426; DOI=10.1073/pnas.0611577104; RA Muto T., Tsuchiya D., Morikawa K., Jingami H.; RT "Structures of the extracellular regions of the group II/III metabotropic RT glutamate receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 104:3759-3764(2007). 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 TAMALIN. {ECO:0000269|PubMed:11850456}. 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 neuronal cells of the cerebral cortex, CC dentate gyrus, and glial cells throughout brain regions. CC -!- SIMILARITY: Belongs to the G protein-coupled receptor 3 family. CC {ECO:0000305}. 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; M92076; -; NOT_ANNOTATED_CDS; mRNA. DR PIR; JH0562; JH0562. DR RefSeq; NP_001099182.1; NM_001105712.1. DR RefSeq; XP_038962943.1; XM_039107015.2. DR RefSeq; XP_063141591.1; XM_063285521.1. DR PDB; 2E4U; X-ray; 2.35 A; A/B=25-575. DR PDB; 2E4V; X-ray; 2.40 A; A/B=25-575. DR PDB; 2E4W; X-ray; 2.40 A; A/B=25-575. DR PDB; 2E4X; X-ray; 2.75 A; A/B=25-575. DR PDB; 2E4Y; X-ray; 3.40 A; A/B=25-575. DR PDB; 8TQB; EM; 3.30 A; A/B=1-879. DR PDB; 8TR0; EM; 3.20 A; A/B=1-879. DR PDB; 8TR2; EM; 3.50 A; A/B=1-879. DR PDB; 8TRC; EM; 3.30 A; A/B=1-879. DR PDB; 8TRD; EM; 3.40 A; A/B=1-879. DR AlphaFoldDB; P31422; -. DR EMDB; EMD-41501; -. DR EMDB; EMD-41567; -. DR EMDB; EMD-41568; -. DR EMDB; EMD-41577; -. DR EMDB; EMD-41578; -. DR SMR; P31422; -. DR BioGRID; 246581; 2. DR DIP; DIP-41143N; -. DR FunCoup; P31422; 1323. DR IntAct; P31422; 4. DR MINT; P31422; -. DR STRING; 10116.ENSRNOP00000069396; -. DR BindingDB; P31422; -. DR ChEMBL; CHEMBL3067; -. DR DrugCentral; P31422; -. DR GuidetoPHARMACOLOGY; 291; -. DR GlyCosmos; P31422; 4 sites, 9 glycans. DR GlyGen; P31422; 5 sites, 9 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P31422; -. DR PhosphoSitePlus; P31422; -. DR PaxDb; 10116-ENSRNOP00000069396; -. DR Ensembl; ENSRNOT00000109555.2; ENSRNOP00000096683.2; ENSRNOG00000005519.9. DR Ensembl; ENSRNOT00055032353; ENSRNOP00055026175; ENSRNOG00055018984. DR Ensembl; ENSRNOT00060021592; ENSRNOP00060017062; ENSRNOG00060012716. DR Ensembl; ENSRNOT00065030463; ENSRNOP00065024237; ENSRNOG00065018177. DR GeneID; 24416; -. DR KEGG; rno:24416; -. DR AGR; RGD:2744; -. DR CTD; 2913; -. DR RGD; 2744; Grm3. DR eggNOG; KOG1056; Eukaryota. DR GeneTree; ENSGT01030000234595; -. DR HOGENOM; CLU_005389_0_0_1; -. DR InParanoid; P31422; -. DR OrthoDB; 425344at2759; -. DR PhylomeDB; P31422; -. DR Reactome; R-RNO-418594; G alpha (i) signalling events. DR Reactome; R-RNO-420499; Class C/3 (Metabotropic glutamate/pheromone receptors). DR EvolutionaryTrace; P31422; -. DR PRO; PR:P31422; -. DR Proteomes; UP000002494; Chromosome 4. DR Bgee; ENSRNOG00000005519; Expressed in Ammon's horn and 4 other cell types or tissues. DR ExpressionAtlas; P31422; baseline and differential. DR GO; GO:0097449; C:astrocyte projection; IDA:ARUK-UCL. DR GO; GO:0030424; C:axon; IDA:ARUK-UCL. DR GO; GO:0043197; C:dendritic spine; ISO:RGD. 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; ISO:RGD. DR GO; GO:0014069; C:postsynaptic density; ISO:RGD. DR GO; GO:0045211; C:postsynaptic membrane; ISO:RGD. DR GO; GO:0042734; C:presynaptic membrane; ISO:RGD. 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:0033554; P:cellular response to stress; ISO:RGD. DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; ISO:RGD. DR GO; GO:0010467; P:gene expression; ISO:RGD. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:RGD. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; ISO:RGD. DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central. DR GO; GO:0019233; P:sensory perception of pain; TAS:UniProtKB. DR CDD; cd15448; 7tmC_mGluR3; 1. DR CDD; cd06375; PBP1_mGluR_groupII; 1. DR FunFam; 2.10.50.30:FF:000001; metabotropic glutamate receptor 1; 1. DR FunFam; 3.40.50.2300:FF:000029; Metabotropic glutamate receptor 3; 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; IPR001234; GPCR_3_mGluR3. DR InterPro; IPR000162; GPCR_3_mtglu_rcpt. DR InterPro; IPR050726; mGluR. DR InterPro; IPR028082; Peripla_BP_I. DR PANTHER; PTHR24060; METABOTROPIC GLUTAMATE RECEPTOR; 1. DR Pfam; PF00003; 7tm_3; 1. DR Pfam; PF01094; ANF_receptor; 1. DR Pfam; PF07562; NCD3G; 1. DR PRINTS; PR00248; GPCRMGR. DR PRINTS; PR01053; MTABOTROPC3R. 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 PDBsum; 2E4U; -. DR PDBsum; 2E4V; -. DR PDBsum; 2E4W; -. DR PDBsum; 2E4X; -. DR PDBsum; 2E4Y; -. DR PDBsum; 8TQB; -. DR PDBsum; 8TR0; -. DR PDBsum; 8TR2; -. DR PDBsum; 8TRC; -. DR PDBsum; 8TRD; -. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; G protein-coupled receptor; KW Glycoprotein; Membrane; Receptor; Reference proteome; Signal; Transducer; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..879 FT /note="Metabotropic glutamate receptor 3" FT /id="PRO_0000012929" FT TOPO_DOM 23..576 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 577..599 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 600..613 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 614..634 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 635..645 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 646..664 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 665..688 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 689..709 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 710..734 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 735..756 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 757..769 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 770..792 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 793..802 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 803..828 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 829..879 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT BINDING 68 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT BINDING 151 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT BINDING 172..174 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT BINDING 222 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT BINDING 301 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT BINDING 389 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT CARBOHYD 209 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17360426" FT CARBOHYD 292 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 414 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 439 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0007744|PubMed:24090084" FT DISULFID 57..99 FT /evidence="ECO:0000269|PubMed:17360426" FT DISULFID 240..527 FT /evidence="ECO:0000269|PubMed:17360426" FT DISULFID 361..373 FT /evidence="ECO:0000269|PubMed:17360426" FT DISULFID 412..419 FT /evidence="ECO:0000269|PubMed:17360426" FT DISULFID 509..528 FT /evidence="ECO:0000269|PubMed:17360426" FT DISULFID 513..531 FT /evidence="ECO:0000269|PubMed:17360426" FT DISULFID 534..546 FT /evidence="ECO:0000269|PubMed:17360426" FT DISULFID 549..562 FT /evidence="ECO:0000269|PubMed:17360426" FT STRAND 33..35 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 38..45 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 52..55 FT /evidence="ECO:0007829|PDB:8TRC" FT STRAND 56..60 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 62..67 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 68..81 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 83..86 FT /evidence="ECO:0007829|PDB:2E4X" FT STRAND 91..97 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 102..114 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 142..147 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 151..161 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 162..164 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 168..172 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 176..179 FT /evidence="ECO:0007829|PDB:2E4U" FT TURN 181..183 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 187..191 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 194..207 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 212..220 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 223..235 FT /evidence="ECO:0007829|PDB:2E4U" FT TURN 236..238 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 240..247 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 249..252 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 253..264 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 271..275 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 278..290 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 296..299 FT /evidence="ECO:0007829|PDB:2E4U" FT TURN 301..305 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 307..309 FT /evidence="ECO:0007829|PDB:2E4U" FT TURN 310..312 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 314..317 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 321..325 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:8TRC" FT HELIX 331..338 FT /evidence="ECO:0007829|PDB:2E4U" FT TURN 342..344 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 351..358 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 360..362 FT /evidence="ECO:0007829|PDB:8TRC" FT STRAND 363..368 FT /evidence="ECO:0007829|PDB:2E4V" FT STRAND 370..372 FT /evidence="ECO:0007829|PDB:8TR0" FT TURN 381..383 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 390..411 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 420..422 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 427..434 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 435..437 FT /evidence="ECO:0007829|PDB:8TR0" FT STRAND 438..440 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 443..445 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 448..450 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 453..455 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 458..460 FT /evidence="ECO:0007829|PDB:2E4X" FT HELIX 462..464 FT /evidence="ECO:0007829|PDB:8TRC" FT STRAND 466..472 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 474..477 FT /evidence="ECO:0007829|PDB:2E4X" FT STRAND 479..491 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 494..496 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 497..499 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 500..502 FT /evidence="ECO:0007829|PDB:2E4V" FT HELIX 511..514 FT /evidence="ECO:0007829|PDB:2E4U" FT TURN 515..517 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 518..521 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 524..527 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 530..533 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 538..542 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 545..548 FT /evidence="ECO:0007829|PDB:2E4U" FT STRAND 553..555 FT /evidence="ECO:0007829|PDB:2E4U" FT TURN 556..558 FT /evidence="ECO:0007829|PDB:8TQB" FT STRAND 559..564 FT /evidence="ECO:0007829|PDB:2E4U" FT HELIX 565..567 FT /evidence="ECO:0007829|PDB:8TQB" FT STRAND 569..572 FT /evidence="ECO:0007829|PDB:8TR2" FT HELIX 573..576 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 580..601 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 611..613 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 614..634 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 641..663 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 687..710 FT /evidence="ECO:0007829|PDB:8TR0" FT TURN 711..713 FT /evidence="ECO:0007829|PDB:8TRC" FT STRAND 715..718 FT /evidence="ECO:0007829|PDB:8TQB" FT STRAND 722..724 FT /evidence="ECO:0007829|PDB:8TRC" FT STRAND 726..729 FT /evidence="ECO:0007829|PDB:8TQB" FT HELIX 733..759 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 764..785 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 786..788 FT /evidence="ECO:0007829|PDB:8TR0" FT STRAND 789..793 FT /evidence="ECO:0007829|PDB:8TR0" FT TURN 795..797 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 798..819 FT /evidence="ECO:0007829|PDB:8TR0" FT HELIX 823..827 FT /evidence="ECO:0007829|PDB:8TQB" SQ SEQUENCE 879 AA; 98960 MW; 3E5965EDD5E6DEED CRC64; MKMLTRLQIL MLALFSKGFL LSLGDHNFMR REIKIEGDLV LGGLFPINEK GTGTEECGRI NEDRGIQRLE AMLFAIDEIN KDNYLLPGVK LGVHILDTCS RDTYALEQSL EFVRASLTKV DEAEYMCPDG SYAIQENIPL LIAGVIGGSY SSVSIQVANL LRLFQIPQIS YASTSAKLSD KSRYDYFART VPPDFYQAKA MAEILRFFNW TYVSTVASEG DYGETGIEAF EQEARLRNIC IATAEKVGRS NIRKSYDSVI RELLQKPNAR VVVLFMRSDD SRELIAAANR VNASFTWVAS DGWGAQESIV KGSEHVAYGA ITLELASHPV RQFDRYFQSL NPYNNHRNPW FRDFWEQKFQ CSLQNKRNHR QVCDKHLAID SSNYEQESKI MFVVNAVYAM AHALHKMQRT LCPNTTKLCD AMKILDGKKL YKEYLLKINF TAPFNPNKGA DSIVKFDTFG DGMGRYNVFN LQQTGGKYSY LKVGHWAETL SLDVDSIHWS RNSVPTSQCS DPCAPNEMKN MQPGDVCCWI CIPCEPYEYL VDEFTCMDCG PGQWPTADLS GCYNLPEDYI KWEDAWAIGP VTIACLGFLC TCIVITVFIK HNNTPLVKAS GRELCYILLF GVSLSYCMTF FFIAKPSPVI CALRRLGLGT SFAICYSALL TKTNCIARIF DGVKNGAQRP KFISPSSQVF ICLGLILVQI VMVSVWLILE TPGTRRYTLP EKRETVILKC NVKDSSMLIS LTYDVVLVIL CTVYAFKTRK CPENFNEAKF IGFTMYTTCI IWLAFLPIFY VTSSDYRVQT TTMCISVSLS GFVVLGCLFA PKVHIVLFQP QKNVVTHRLH LNRFSVSGTA TTYSQSSAST YVPTVCNGRE VLDSTTSSL //