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    GRM4 glutamate metabotropic receptor 4 [ Homo sapiens (human) ]

    Gene ID: 2914, updated on 11-Apr-2024

    Summary

    Official Symbol
    GRM4provided by HGNC
    Official Full Name
    glutamate metabotropic receptor 4provided by HGNC
    Primary source
    HGNC:HGNC:4596
    See related
    Ensembl:ENSG00000124493 MIM:604100; AllianceGenome:HGNC:4596
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    mGlu4; GPRC1D; MGLUR4
    Summary
    L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See GRM4 in Genome Data Viewer
    Location:
    6p21.31
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (34018643..34155622, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (33839943..33979214, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (33986420..34123399, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901308 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33922205-33922705 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33925615-33926355 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33926356-33927095 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33961394-33962166 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33967681-33968182 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33973921-33974803 Neighboring gene microRNA 1275 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33993583-33994310 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17058 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33999095-33999617 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24375 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:34015538-34016092 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:34016093-34016646 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:34016647-34017200 Neighboring gene Sharpr-MPRA regulatory region 5466 Neighboring gene Sharpr-MPRA regulatory region 4098 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:34031248-34031829 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:34044839-34045669 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:34046709-34047454 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:34050139-34050978 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:34050979-34051818 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:34074290-34074790 Neighboring gene MPRA-validated peak5759 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:34087978-34088766 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:34099315-34100141 Neighboring gene Sharpr-MPRA regulatory region 15272 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:34121411-34122268 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17059 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24376 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24377 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24378 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24379 Neighboring gene keratin 18 pseudogene 9 Neighboring gene CYCS pseudogene 55

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat The gene expression of GRM4 is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ98710, MGC177594

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G protein-coupled receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables adenylate cyclase inhibiting G protein-coupled glutamate receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables glutamate receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in presynapse IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    metabotropic glutamate receptor 4
    Names
    glutamate receptor, metabotropic 4

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029677.3 RefSeqGene

      Range
      14536..141980
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000841.4NP_000832.1  metabotropic glutamate receptor 4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_000832.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL590403, BM683737, DA094245, X80818
      Consensus CDS
      CCDS4787.1
      UniProtKB/Swiss-Prot
      B3KVL9, B7Z1T9, B7Z1U6, F5GXM5, Q14833, Q5SZ84, Q6ZMQ2
      UniProtKB/TrEMBL
      A1L4F9, A8K0F9, A8K0G9
      Related
      ENSP00000440556.1, ENST00000538487.7
      Conserved Domains (3) summary
      pfam07562
      Location:517566
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cd15452
      Location:586912
      7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors
      cl10011
      Location:47508
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
    2. NM_001256809.3NP_001243738.1  metabotropic glutamate receptor 4 isoform 2

      See identical proteins and their annotated locations for NP_001243738.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence, and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform 1.
      Source sequence(s)
      AK131536, AL590403, BM683737
      Consensus CDS
      CCDS59012.1
      UniProtKB/Swiss-Prot
      Q14833
      Related
      ENSP00000363292.3, ENST00000374177.7
      Conserved Domains (4) summary
      pfam00003
      Location:483728
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:103361
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:401448
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cl10011
      Location:104392
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
    3. NM_001256811.3NP_001243740.1  metabotropic glutamate receptor 4 isoform 4 precursor

      See identical proteins and their annotated locations for NP_001243740.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AK131536, AK312300, AL590403, BC144057, BM683737
      Consensus CDS
      CCDS75432.1
      UniProtKB/TrEMBL
      A8K0F9, A8K0G9, B7ZLU9
      Related
      ENSP00000363296.4, ENST00000374181.8
      Conserved Domains (4) summary
      pfam00003
      Location:552797
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:77430
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:470517
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cl10011
      Location:47461
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
    4. NM_001256812.2NP_001243741.1  metabotropic glutamate receptor 4 isoform 5

      See identical proteins and their annotated locations for NP_001243741.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) has a shorter and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AK131536, AK293913, AL590403, BM683737
      Consensus CDS
      CCDS59011.1
      UniProtKB/TrEMBL
      A8K0G9
      Related
      ENSP00000437730.1, ENST00000544773.6
      Conserved Domains (3) summary
      pfam07562
      Location:348397
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cd15452
      Location:417743
      7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors
      cl10011
      Location:4339
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
    5. NM_001256813.3NP_001243742.1  metabotropic glutamate receptor 4 isoform 6

      See identical proteins and their annotated locations for NP_001243742.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (6) has a shorter and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AK122982, AK131536, AL590403, BM683737
      Consensus CDS
      CCDS59010.1
      UniProtKB/TrEMBL
      A8K0G9
      Related
      ENSP00000477466.1, ENST00000609222.5
      Conserved Domains (4) summary
      pfam00003
      Location:466711
      7tm_3; 7 transmembrane sweet-taste receptor of 3 GCPR
      pfam01094
      Location:39344
      ANF_receptor; Receptor family ligand binding region
      pfam07562
      Location:384431
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cl10011
      Location:40375
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily
    6. NM_001282847.2NP_001269776.1  metabotropic glutamate receptor 4 isoform 8

      See identical proteins and their annotated locations for NP_001269776.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) uses an alternate 5' structure and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (8) with a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AK131536, AK312300, AL590403, BM683737
      UniProtKB/TrEMBL
      A8K0J8, B3KX58
      Conserved Domains (3) summary
      pfam07562
      Location:209258
      NCD3G; Nine Cysteines Domain of family 3 GPCR
      cd15452
      Location:278604
      7tmC_mGluR4; metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors
      cl10011
      Location:1200
      Periplasmic_Binding_Protein_Type_1; Type 1 periplasmic binding fold superfamily

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      34018643..34155622 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      33839943..33979214 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001256810.1: Suppressed sequence

      Description
      NM_001256810.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    2. NM_001256814.1: Suppressed sequence

      Description
      NM_001256814.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.