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Protein

Metabotropic glutamate receptor 4

Gene

GRM4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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. Signaling inhibits adenylate cyclase activity.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei159GlutamateBy similarity1
Binding sitei230GlutamateBy similarity1
Binding sitei312GlutamateBy similarity1
Binding sitei405GlutamateBy similarity1

GO - Molecular functioni

  • glutamate receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: UniProtKB
  • group III metabotropic glutamate receptor activity Source: GO_Central

GO - Biological processi

  • activation of MAPK activity Source: UniProtKB
  • adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: UniProtKB
  • chemical synaptic transmission Source: ProtInc
  • neurotransmitter secretion Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • regulation of neuron apoptotic process Source: UniProtKB
  • regulation of synaptic transmission, glutamatergic Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124493-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 4
Short name:
mGluR4
Gene namesi
Name:GRM4
Synonyms:GPRC1D, MGLUR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4596. GRM4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 587ExtracellularSequence analysisAdd BLAST555
Transmembranei588 – 610Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini611 – 624CytoplasmicSequence analysisAdd BLAST14
Transmembranei625 – 645Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini646 – 656ExtracellularSequence analysisAdd BLAST11
Transmembranei657 – 675Helical; Name=3Sequence analysisAdd BLAST19
Topological domaini676 – 699CytoplasmicSequence analysisAdd BLAST24
Transmembranei700 – 720Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini721 – 750ExtracellularSequence analysisAdd BLAST30
Transmembranei751 – 772Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini773 – 785CytoplasmicSequence analysisAdd BLAST13
Transmembranei786 – 808Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini809 – 821ExtracellularSequence analysisAdd BLAST13
Transmembranei822 – 847Helical; Name=7Sequence analysisAdd BLAST26
Topological domaini848 – 912CytoplasmicSequence analysisAdd BLAST65

GO - Cellular componenti

  • cytoplasmic vesicle Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular Source: UniProtKB
  • plasma membrane Source: Reactome
  • presynaptic membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2914.
OpenTargetsiENSG00000124493.
PharmGKBiPA28993.

Chemistry databases

ChEMBLiCHEMBL2736.
GuidetoPHARMACOLOGYi292.

Polymorphism and mutation databases

BioMutaiGRM4.
DMDMi2495077.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000001293033 – 912Metabotropic glutamate receptor 4Add BLAST880

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi67 ↔ 109By similarity
Glycosylationi98N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi249 ↔ 538By similarity
Glycosylationi301N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi372 ↔ 388By similarity
Disulfide bondi428 ↔ 435By similarity
Glycosylationi454N-linked (GlcNAc...)Sequence analysis1
Glycosylationi484N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi520 ↔ 539By similarity
Disulfide bondi524 ↔ 542By similarity
Disulfide bondi545 ↔ 557By similarity
Disulfide bondi560 ↔ 573By similarity
Glycosylationi569N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ14833.
PaxDbiQ14833.
PeptideAtlasiQ14833.
PRIDEiQ14833.

PTM databases

iPTMnetiQ14833.
PhosphoSitePlusiQ14833.

Expressioni

Tissue specificityi

Strongly expressed in the cerebellum. Expressed at low levels in hippocampus, hypothalamus and thalamus. No expression detected in liver.2 Publications

Gene expression databases

BgeeiENSG00000124493.
CleanExiHS_GRM4.
ExpressionAtlasiQ14833. baseline and differential.
GenevisibleiQ14833. HS.

Organism-specific databases

HPAiCAB022096.

Interactioni

Subunit structurei

Interacts with PICK1.By similarity

Protein-protein interaction databases

STRINGi9606.ENSP00000363296.

Chemistry databases

BindingDBiQ14833.

Structurei

3D structure databases

ProteinModelPortaliQ14833.
SMRiQ14833.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni180 – 182Glutamate bindingBy similarity3

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14833.
KOiK04607.
OMAiGWGWWWA.
OrthoDBiEOG091G177R.
PhylomeDBiQ14833.
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.
IPR001786. GPCR_3_mtglu_rcpt_4.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01054. MTABOTROPC4R.
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]

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14833-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPGKRGLGWW WARLPLCLLL SLYGPWMPSS LGKPKGHPHM NSIRIDGDIT
60 70 80 90 100
LGGLFPVHGR GSEGKPCGEL KKEKGIHRLE AMLFALDRIN NDPDLLPNIT
110 120 130 140 150
LGARILDTCS RDTHALEQSL TFVQALIEKD GTEVRCGSGG PPIITKPERV
160 170 180 190 200
VGVIGASGSS VSIMVANILR LFKIPQISYA STAPDLSDNS RYDFFSRVVP
210 220 230 240 250
SDTYQAQAMV DIVRALKWNY VSTVASEGSY GESGVEAFIQ KSREDGGVCI
260 270 280 290 300
AQSVKIPREP KAGEFDKIIR RLLETSNARA VIIFANEDDI RRVLEAARRA
310 320 330 340 350
NQTGHFFWMG SDSWGSKIAP VLHLEEVAEG AVTILPKRMS VRGFDRYFSS
360 370 380 390 400
RTLDNNRRNI WFAEFWEDNF HCKLSRHALK KGSHVKKCTN RERIGQDSAY
410 420 430 440 450
EQEGKVQFVI DAVYAMGHAL HAMHRDLCPG RVGLCPRMDP VDGTQLLKYI
460 470 480 490 500
RNVNFSGIAG NPVTFNENGD APGRYDIYQY QLRNDSAEYK VIGSWTDHLH
510 520 530 540 550
LRIERMHWPG SGQQLPRSIC SLPCQPGERK KTVKGMPCCW HCEPCTGYQY
560 570 580 590 600
QVDRYTCKTC PYDMRPTENR TGCRPIPIIK LEWGSPWAVL PLFLAVVGIA
610 620 630 640 650
ATLFVVITFV RYNDTPIVKA SGRELSYVLL AGIFLCYATT FLMIAEPDLG
660 670 680 690 700
TCSLRRIFLG LGMSISYAAL LTKTNRIYRI FEQGKRSVSA PRFISPASQL
710 720 730 740 750
AITFSLISLQ LLGICVWFVV DPSHSVVDFQ DQRTLDPRFA RGVLKCDISD
760 770 780 790 800
LSLICLLGYS MLLMVTCTVY AIKTRGVPET FNEAKPIGFT MYTTCIVWLA
810 820 830 840 850
FIPIFFGTSQ SADKLYIQTT TLTVSVSLSA SVSLGMLYMP KVYIILFHPE
860 870 880 890 900
QNVPKRKRSL KAVVTAATMS NKFTQKGNFR PNGEAKSELC ENLEAPALAT
910
KQTYVTYTNH AI
Length:912
Mass (Da):101,868
Last modified:November 1, 1997 - v1
Checksum:i4A2F36E63A2EAF5A
GO
Isoform 2 (identifier: Q14833-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MPGKRGLGWWWARLPLCLLLSLYGPWMPSSLGK → MVQTLPKLFPHDGAKRKKRTLRTSGPCFGGGGQ
     34-173: Missing.

Note: No experimental confirmation available.
Show »
Length:772
Mass (Da):86,683
Checksum:i5AEAFC7B26F3CFCF
GO
Isoform 3 (identifier: Q14833-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: MPGKRGLGWW...IMVANILRLF → MSC

Show »
Length:743
Mass (Da):83,580
Checksum:i202C4DC3F806DC8F
GO
Isoform 4 (identifier: Q14833-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: MPGKRGLGWW...IMVANILRLF → MAVPLGAPCW...RLLSQHVKPA

Note: No experimental confirmation available.
Show »
Length:779
Mass (Da):87,353
Checksum:iDEEE2F3C60EBD6E1
GO
Isoform 5 (identifier: Q14833-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-173: MPGKRGLGWW...MVANILRLFK → MPAWEPGVAA...PRCLLPESAQ
     343-390: GFDRYFSSRTLDNNRRNIWFAEFWEDNFHCKLSRHALKKGSHVKKCTN → D

Note: No experimental confirmation available.
Show »
Length:796
Mass (Da):88,493
Checksum:iFAE466D1D45D3829
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti449Y → H in BAH11632 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049275169L → F.Corresponds to variant rs452752dbSNPEnsembl.1
Natural variantiVAR_012992797V → I.1 PublicationCorresponds to variant rs149730753dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0467611 – 173MPGKR…LRLFK → MPAWEPGVAASCGWRAPPCS PLRLCIAPHPCTPPSSHQGN LTCRLPPRSFGFCRCVWVRT RGPSLPGEQVSLAAHESEGA AAQLGSSPEIDPRRPRCLLP ESAQ in isoform 5. 1 PublicationAdd BLAST173
Alternative sequenceiVSP_0452181 – 172MPGKR…ILRLF → MSC in isoform 3. 1 PublicationAdd BLAST172
Alternative sequenceiVSP_0467621 – 172MPGKR…ILRLF → MAVPLGAPCWASALPAWAPP GLPHRSLLTRLLSQHVKPA in isoform 4. 1 PublicationAdd BLAST172
Alternative sequenceiVSP_0447401 – 33MPGKR…SSLGK → MVQTLPKLFPHDGAKRKKRT LRTSGPCFGGGGQ in isoform 2. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_04474134 – 173Missing in isoform 2. 1 PublicationAdd BLAST140
Alternative sequenceiVSP_046763343 – 390GFDRY…KKCTN → D in isoform 5. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80818 mRNA. Translation: CAA56784.1.
U92457 mRNA. Translation: AAB51762.1.
AK122982 mRNA. Translation: BAG53831.1.
AK131536 mRNA. Translation: BAD18673.1.
AK293913 mRNA. Translation: BAH11625.1.
AK293949 mRNA. Translation: BAH11632.1.
AL354740 Genomic DNA. No translation available.
AL590403 Genomic DNA. Translation: CAI17348.1.
CCDSiCCDS4787.1. [Q14833-1]
CCDS59010.1. [Q14833-4]
CCDS59011.1. [Q14833-3]
CCDS59012.1. [Q14833-5]
RefSeqiNP_000832.1. NM_000841.3. [Q14833-1]
NP_001243738.1. NM_001256809.2. [Q14833-5]
NP_001243740.1. NM_001256811.2.
NP_001243741.1. NM_001256812.2. [Q14833-3]
NP_001243742.1. NM_001256813.2. [Q14833-4]
NP_001269776.1. NM_001282847.1.
XP_016866279.1. XM_017010790.1. [Q14833-1]
XP_016866280.1. XM_017010791.1. [Q14833-1]
XP_016866282.1. XM_017010793.1. [Q14833-4]
UniGeneiHs.429018.
Hs.435128.
Hs.736330.

Genome annotation databases

EnsembliENST00000374177; ENSP00000363292; ENSG00000124493. [Q14833-5]
ENST00000455714; ENSP00000398456; ENSG00000124493. [Q14833-2]
ENST00000535756; ENSP00000437925; ENSG00000124493. [Q14833-4]
ENST00000538487; ENSP00000440556; ENSG00000124493. [Q14833-1]
ENST00000544773; ENSP00000437730; ENSG00000124493. [Q14833-3]
ENST00000609222; ENSP00000477466; ENSG00000124493. [Q14833-4]
GeneIDi2914.
KEGGihsa:2914.
UCSCiuc003oiq.6. human. [Q14833-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80818 mRNA. Translation: CAA56784.1.
U92457 mRNA. Translation: AAB51762.1.
AK122982 mRNA. Translation: BAG53831.1.
AK131536 mRNA. Translation: BAD18673.1.
AK293913 mRNA. Translation: BAH11625.1.
AK293949 mRNA. Translation: BAH11632.1.
AL354740 Genomic DNA. No translation available.
AL590403 Genomic DNA. Translation: CAI17348.1.
CCDSiCCDS4787.1. [Q14833-1]
CCDS59010.1. [Q14833-4]
CCDS59011.1. [Q14833-3]
CCDS59012.1. [Q14833-5]
RefSeqiNP_000832.1. NM_000841.3. [Q14833-1]
NP_001243738.1. NM_001256809.2. [Q14833-5]
NP_001243740.1. NM_001256811.2.
NP_001243741.1. NM_001256812.2. [Q14833-3]
NP_001243742.1. NM_001256813.2. [Q14833-4]
NP_001269776.1. NM_001282847.1.
XP_016866279.1. XM_017010790.1. [Q14833-1]
XP_016866280.1. XM_017010791.1. [Q14833-1]
XP_016866282.1. XM_017010793.1. [Q14833-4]
UniGeneiHs.429018.
Hs.435128.
Hs.736330.

3D structure databases

ProteinModelPortaliQ14833.
SMRiQ14833.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000363296.

Chemistry databases

BindingDBiQ14833.
ChEMBLiCHEMBL2736.
GuidetoPHARMACOLOGYi292.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ14833.
PhosphoSitePlusiQ14833.

Polymorphism and mutation databases

BioMutaiGRM4.
DMDMi2495077.

Proteomic databases

EPDiQ14833.
PaxDbiQ14833.
PeptideAtlasiQ14833.
PRIDEiQ14833.

Protocols and materials databases

DNASUi2914.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374177; ENSP00000363292; ENSG00000124493. [Q14833-5]
ENST00000455714; ENSP00000398456; ENSG00000124493. [Q14833-2]
ENST00000535756; ENSP00000437925; ENSG00000124493. [Q14833-4]
ENST00000538487; ENSP00000440556; ENSG00000124493. [Q14833-1]
ENST00000544773; ENSP00000437730; ENSG00000124493. [Q14833-3]
ENST00000609222; ENSP00000477466; ENSG00000124493. [Q14833-4]
GeneIDi2914.
KEGGihsa:2914.
UCSCiuc003oiq.6. human. [Q14833-1]

Organism-specific databases

CTDi2914.
DisGeNETi2914.
GeneCardsiGRM4.
HGNCiHGNC:4596. GRM4.
HPAiCAB022096.
MIMi604100. gene.
neXtProtiNX_Q14833.
OpenTargetsiENSG00000124493.
PharmGKBiPA28993.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14833.
KOiK04607.
OMAiGWGWWWA.
OrthoDBiEOG091G177R.
PhylomeDBiQ14833.
TreeFamiTF313240.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124493-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).

Miscellaneous databases

ChiTaRSiGRM4. human.
GeneWikiiMetabotropic_glutamate_receptor_4.
GenomeRNAii2914.
PROiQ14833.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124493.
CleanExiHS_GRM4.
ExpressionAtlasiQ14833. baseline and differential.
GenevisibleiQ14833. HS.

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.
IPR001786. GPCR_3_mtglu_rcpt_4.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01054. MTABOTROPC4R.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiGRM4_HUMAN
AccessioniPrimary (citable) accession number: Q14833
Secondary accession number(s): B3KVL9
, B7Z1T9, B7Z1U6, F5GXM5, Q5SZ84, Q6ZMQ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 148 of the entry and version 1 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 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.