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Q14416

- GRM2_HUMAN

UniProt

Q14416 - GRM2_HUMAN

Protein

Metabotropic glutamate receptor 2

Gene

GRM2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 2 (27 Sep 2005)
      Previous versions | rss
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    Functioni

    G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei145 – 1451GlutamateBy similarity
    Binding sitei216 – 2161GlutamateBy similarity
    Binding sitei295 – 2951GlutamateBy similarity
    Binding sitei377 – 3771GlutamateBy similarity

    GO - Molecular functioni

    1. calcium channel regulator activity Source: RefGenome
    2. glutamate receptor activity Source: UniProtKB
    3. G-protein coupled receptor activity Source: UniProtKB
    4. group II metabotropic glutamate receptor activity Source: RefGenome

    GO - Biological processi

    1. adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: RefGenome
    2. glutamate secretion Source: Ensembl
    3. negative regulation of adenylate cyclase activity Source: ProtInc
    4. regulation of synaptic transmission, glutamatergic Source: RefGenome
    5. synaptic transmission Source: ProtInc

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Enzyme and pathway databases

    ReactomeiREACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
    REACT_19231. G alpha (i) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Metabotropic glutamate receptor 2
    Short name:
    mGluR2
    Gene namesi
    Name:GRM2
    Synonyms:GPRC1B, MGLUR2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:4594. GRM2.

    Subcellular locationi

    GO - Cellular componenti

    1. axon Source: Ensembl
    2. cell junction Source: UniProtKB-KW
    3. dendrite Source: UniProtKB-SubCell
    4. integral component of plasma membrane Source: RefGenome
    5. intracellular Source: Ensembl
    6. plasma membrane Source: Reactome
    7. presynaptic membrane Source: RefGenome

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Membrane, Synapse

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi677 – 6771A → S: Impairs interaction with HTR2A. 1 Publication
    Mutagenesisi681 – 6811A → F: Impairs interaction with HTR2A. 1 Publication
    Mutagenesisi685 – 6851A → G: Impairs interaction with HTR2A. 1 Publication

    Organism-specific databases

    PharmGKBiPA28991.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 872854Metabotropic glutamate receptor 2PRO_0000012925Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi50 ↔ 92By similarity
    Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi234 ↔ 518By similarity
    Glycosylationi286 – 2861N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi338 – 3381N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi355 ↔ 362By similarity
    Disulfide bondi400 ↔ 407By similarity
    Glycosylationi402 – 4021N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi500 ↔ 519By similarity
    Disulfide bondi504 ↔ 522By similarity
    Disulfide bondi525 ↔ 537By similarity
    Disulfide bondi540 ↔ 553By similarity
    Glycosylationi547 – 5471N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ14416.
    PRIDEiQ14416.

    PTM databases

    PhosphoSiteiQ14416.

    Expressioni

    Tissue specificityi

    Detected in brain cortex (at protein level). Widely expressed in different regions of the adult brain as well as in fetal brain.1 Publication

    Gene expression databases

    ArrayExpressiQ14416.
    BgeeiQ14416.
    CleanExiHS_GRM2.
    GenevestigatoriQ14416.

    Interactioni

    Subunit structurei

    Interacts with GRASP By similarity. Interacts with HTR2A.By similarity3 Publications

    Protein-protein interaction databases

    DIPiDIP-59826N.
    STRINGi9606.ENSP00000378492.

    Structurei

    3D structure databases

    ProteinModelPortaliQ14416.
    SMRiQ14416. Positions 23-558.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini19 – 567549ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini591 – 60414CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini626 – 63611ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini656 – 67924CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini701 – 72525ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini748 – 76013CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini784 – 79310ExtracellularSequence Analysis
    Topological domaini820 – 87253CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei568 – 59023Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei605 – 62521Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei637 – 65519Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei680 – 70021Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei726 – 74722Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei761 – 78323Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei794 – 81926Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni166 – 1683Glutamate bindingBy similarity
    Regioni677 – 6859Important for interaction with HTR2A

    Sequence similaritiesi

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG295200.
    HOGENOMiHOG000218635.
    HOVERGENiHBG107965.
    KOiK04605.
    OMAiVTLKCNN.
    OrthoDBiEOG7Z0JXG.
    PhylomeDBiQ14416.
    TreeFamiTF313240.

    Family and domain databases

    InterProiIPR001828. ANF_lig-bd_rcpt.
    IPR000337. GPCR_3.
    IPR011500. GPCR_3_9-Cys_dom.
    IPR017978. GPCR_3_C.
    IPR017979. GPCR_3_CS.
    IPR000162. GPCR_3_mtglu_rcpt.
    IPR001458. GPCR_3_mtglu_rcpt_2.
    IPR028082. Peripla_BP_I.
    [Graphical view]
    PfamiPF00003. 7tm_3. 1 hit.
    PF01094. ANF_receptor. 1 hit.
    PF07562. NCD3G. 1 hit.
    [Graphical view]
    PRINTSiPR00248. GPCRMGR.
    PR01052. MTABOTROPC2R.
    PR00593. MTABOTROPICR.
    SUPFAMiSSF53822. SSF53822. 1 hit.
    PROSITEiPS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
    PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
    PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
    PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q14416-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGSLLALLAL LLLWGAVAEG PAKKVLTLEG DLVLGGLFPV HQKGGPAEDC    50
    GPVNEHRGIQ RLEAMLFALD RINRDPHLLP GVRLGAHILD SCSKDTHALE 100
    QALDFVRASL SRGADGSRHI CPDGSYATHG DAPTAITGVI GGSYSDVSIQ 150
    VANLLRLFQI PQISYASTSA KLSDKSRYDY FARTVPPDFF QAKAMAEILR 200
    FFNWTYVSTV ASEGDYGETG IEAFELEARA RNICVATSEK VGRAMSRAAF 250
    EGVVRALLQK PSARVAVLFT RSEDARELLA ASQRLNASFT WVASDGWGAL 300
    ESVVAGSEGA AEGAITIELA SYPISDFASY FQSLDPWNNS RNPWFREFWE 350
    QRFRCSFRQR DCAAHSLRAV PFEQESKIMF VVNAVYAMAH ALHNMHRALC 400
    PNTTRLCDAM RPVNGRRLYK DFVLNVKFDA PFRPADTHNE VRFDRFGDGI 450
    GRYNIFTYLR AGSGRYRYQK VGYWAEGLTL DTSLIPWASP SAGPLPASRC 500
    SEPCLQNEVK SVQPGEVCCW LCIPCQPYEY RLDEFTCADC GLGYWPNASL 550
    TGCFELPQEY IRWGDAWAVG PVTIACLGAL ATLFVLGVFV RHNATPVVKA 600
    SGRELCYILL GGVFLCYCMT FIFIAKPSTA VCTLRRLGLG TAFSVCYSAL 650
    LTKTNRIARI FGGAREGAQR PRFISPASQV AICLALISGQ LLIVVAWLVV 700
    EAPGTGKETA PERREVVTLR CNHRDASMLG SLAYNVLLIA LCTLYAFKTR 750
    KCPENFNEAK FIGFTMYTTC IIWLAFLPIF YVTSSDYRVQ TTTMCVSVSL 800
    SGSVVLGCLF APKLHIILFQ PQKNVVSHRA PTSRFGSAAA RASSSLGQGS 850
    GSQFVPTVCN GREVVDSTTS SL 872
    Length:872
    Mass (Da):95,568
    Last modified:September 27, 2005 - v2
    Checksum:i801976D034AA8100
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti12 – 121L → P in AAA76855. (PubMed:7620613)Curated
    Sequence conflicti210 – 2101V → E in AAA76855. (PubMed:7620613)Curated
    Sequence conflicti496 – 4961P → A in AAA76855. (PubMed:7620613)Curated
    Sequence conflicti748 – 7481K → N in AAA76855. (PubMed:7620613)Curated
    Sequence conflicti776 – 7761F → L in AAA76855. (PubMed:7620613)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L35318 mRNA. Translation: AAA76855.1.
    AB045011 Genomic DNA. Translation: BAB19817.1.
    AY999299 mRNA. Translation: AAY14640.1.
    EU432122 mRNA. Translation: ABY87921.1.
    CH471055 Genomic DNA. Translation: EAW65150.1.
    BC113615 mRNA. Translation: AAI13616.1.
    BC113619 mRNA. Translation: AAI13620.1.
    CCDSiCCDS2834.1.
    RefSeqiNP_000830.2. NM_000839.3.
    NP_001123535.1. NM_001130063.1.
    XP_006713184.1. XM_006713121.1.
    UniGeneiHs.121510.

    Genome annotation databases

    EnsembliENST00000395052; ENSP00000378492; ENSG00000164082.
    GeneIDi2912.
    KEGGihsa:2912.
    UCSCiuc010hlv.3. human.

    Polymorphism databases

    DMDMi76803802.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L35318 mRNA. Translation: AAA76855.1 .
    AB045011 Genomic DNA. Translation: BAB19817.1 .
    AY999299 mRNA. Translation: AAY14640.1 .
    EU432122 mRNA. Translation: ABY87921.1 .
    CH471055 Genomic DNA. Translation: EAW65150.1 .
    BC113615 mRNA. Translation: AAI13616.1 .
    BC113619 mRNA. Translation: AAI13620.1 .
    CCDSi CCDS2834.1.
    RefSeqi NP_000830.2. NM_000839.3.
    NP_001123535.1. NM_001130063.1.
    XP_006713184.1. XM_006713121.1.
    UniGenei Hs.121510.

    3D structure databases

    ProteinModelPortali Q14416.
    SMRi Q14416. Positions 23-558.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-59826N.
    STRINGi 9606.ENSP00000378492.

    Chemistry

    BindingDBi Q14416.
    ChEMBLi CHEMBL5137.
    DrugBanki DB00659. Acamprosate.
    DB00184. Nicotine.
    GuidetoPHARMACOLOGYi 290.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q14416.

    Polymorphism databases

    DMDMi 76803802.

    Proteomic databases

    PaxDbi Q14416.
    PRIDEi Q14416.

    Protocols and materials databases

    DNASUi 2912.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000395052 ; ENSP00000378492 ; ENSG00000164082 .
    GeneIDi 2912.
    KEGGi hsa:2912.
    UCSCi uc010hlv.3. human.

    Organism-specific databases

    CTDi 2912.
    GeneCardsi GC03P051716.
    HGNCi HGNC:4594. GRM2.
    MIMi 604099. gene.
    neXtProti NX_Q14416.
    PharmGKBi PA28991.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG295200.
    HOGENOMi HOG000218635.
    HOVERGENi HBG107965.
    KOi K04605.
    OMAi VTLKCNN.
    OrthoDBi EOG7Z0JXG.
    PhylomeDBi Q14416.
    TreeFami TF313240.

    Enzyme and pathway databases

    Reactomei REACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
    REACT_19231. G alpha (i) signalling events.

    Miscellaneous databases

    GeneWikii Metabotropic_glutamate_receptor_2.
    GenomeRNAii 2912.
    NextBioi 11543.
    PROi Q14416.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14416.
    Bgeei Q14416.
    CleanExi HS_GRM2.
    Genevestigatori Q14416.

    Family and domain databases

    InterProi IPR001828. ANF_lig-bd_rcpt.
    IPR000337. GPCR_3.
    IPR011500. GPCR_3_9-Cys_dom.
    IPR017978. GPCR_3_C.
    IPR017979. GPCR_3_CS.
    IPR000162. GPCR_3_mtglu_rcpt.
    IPR001458. GPCR_3_mtglu_rcpt_2.
    IPR028082. Peripla_BP_I.
    [Graphical view ]
    Pfami PF00003. 7tm_3. 1 hit.
    PF01094. ANF_receptor. 1 hit.
    PF07562. NCD3G. 1 hit.
    [Graphical view ]
    PRINTSi PR00248. GPCRMGR.
    PR01052. MTABOTROPC2R.
    PR00593. MTABOTROPICR.
    SUPFAMi SSF53822. SSF53822. 1 hit.
    PROSITEi PS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
    PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
    PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
    PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2."
      Flor P.J., Lindauer K., Puttner I., Ruegg D., Lukic S., Knopfel T., Kuhn R.
      Eur. J. Neurosci. 7:622-629(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    2. "Structure and polymorphisms of the human metabotropic glutamate receptor type 2 (hmGluR2) gene: analysis of association with schizophrenia."
      Yasuyuki F., Akiko J.
      Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Complete coding sequence of human metabotropic glutamate receptor 2."
      Bonner T.I., Kauffman D., Nagle J.W.
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    4. Kaighin V.A., Martin A.L., Aronstam R.S.
      Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain cortex.
    7. Cited for: INTERACTION WITH HTR2A, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    8. "Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its psychoactive behavioral function."
      Moreno J.L., Muguruza C., Umali A., Mortillo S., Holloway T., Pilar-Cuellar F., Mocci G., Seto J., Callado L.F., Neve R.L., Milligan G., Sealfon S.C., Lopez-Gimenez J.F., Meana J.J., Benson D.L., Gonzalez-Maeso J.
      J. Biol. Chem. 287:44301-44319(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HTR2A, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ALA-677; ALA-681 AND ALA-685.
    9. "Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades."
      Delille H.K., Becker J.M., Burkhardt S., Bleher B., Terstappen G.C., Schmidt M., Meyer A.H., Unger L., Marek G.J., Mezler M.
      Neuropharmacology 62:2184-2191(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HTR2A, FUNCTION, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiGRM2_HUMAN
    AccessioniPrimary (citable) accession number: Q14416
    Secondary accession number(s): B0M0K7
    , Q14CU5, Q52MC6, Q9H3N6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: September 27, 2005
    Last modified: October 1, 2014
    This is version 115 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3