GRM4

Protein identityUniProt · HPA

UniProt accession

Q14833

Gene

GRM4

Ensembl

ENSG00000124493

Chromosome

6

Canonical length

912 aa

Protein class

G-protein coupled receptors, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

912 residues, UniProt reviewed canonical sequence.

>Q14833|GRM4
     1  MPGKRGLGWW WARLPLCLLL SLYGPWMPSS LGKPKGHPHM NSIRIDGDIT LGGLFPVHGR
    61  GSEGKPCGEL KKEKGIHRLE AMLFALDRIN NDPDLLPNIT LGARILDTCS RDTHALEQSL
   121  TFVQALIEKD GTEVRCGSGG PPIITKPERV VGVIGASGSS VSIMVANILR LFKIPQISYA
   181  STAPDLSDNS RYDFFSRVVP SDTYQAQAMV DIVRALKWNY VSTVASEGSY GESGVEAFIQ
   241  KSREDGGVCI AQSVKIPREP KAGEFDKIIR RLLETSNARA VIIFANEDDI RRVLEAARRA
   301  NQTGHFFWMG SDSWGSKIAP VLHLEEVAEG AVTILPKRMS VRGFDRYFSS RTLDNNRRNI
   361  WFAEFWEDNF HCKLSRHALK KGSHVKKCTN RERIGQDSAY EQEGKVQFVI DAVYAMGHAL
   421  HAMHRDLCPG RVGLCPRMDP VDGTQLLKYI RNVNFSGIAG NPVTFNENGD APGRYDIYQY
   481  QLRNDSAEYK VIGSWTDHLH LRIERMHWPG SGQQLPRSIC SLPCQPGERK KTVKGMPCCW
   541  HCEPCTGYQY QVDRYTCKTC PYDMRPTENR TGCRPIPIIK LEWGSPWAVL PLFLAVVGIA
   601  ATLFVVITFV RYNDTPIVKA SGRELSYVLL AGIFLCYATT FLMIAEPDLG TCSLRRIFLG
   661  LGMSISYAAL LTKTNRIYRI FEQGKRSVSA PRFISPASQL AITFSLISLQ LLGICVWFVV
   721  DPSHSVVDFQ DQRTLDPRFA RGVLKCDISD LSLICLLGYS MLLMVTCTVY AIKTRGVPET
   781  FNEAKPIGFT MYTTCIVWLA FIPIFFGTSQ SADKLYIQTT TLTVSVSLSA SVSLGMLYMP
   841  KVYIILFHPE QNVPKRKRSL KAVVTAATMS NKFTQKGNFR PNGEAKSELC ENLEAPALAT
   901  KQTYVTYTNH AI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRM4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

254 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.28

gnomAD pLI

0.99

gnomAD missense Z

2.68

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway
• chemical synaptic transmission
• G protein-coupled glutamate receptor signaling pathway
• neurotransmitter secretion
• positive regulation of MAPK cascade
• regulation of neuron apoptotic process
• regulation of synaptic transmission, glutamatergic

Molecular functions

• adenylate cyclase inhibiting G protein-coupled glutamate receptor activity
• G protein-coupled receptor activity
• glutamate receptor activity

Cellular components

• cytoplasmic vesicle
• plasma membrane
• presynapse

Protein domainsUniProt · Pfam · InterPro

• GPCR, family 3, metabotropic glutamate receptor
• GPCR, family 3
• Receptor, ligand binding region
• GPCR, family 3, nine cysteines domain
• GPCR family 3, C-terminal
• GPCR, family 3, conserved site
• Periplasmic binding protein-like I
• GPCR, family 3, nine cysteines domain superfamily
• Metabotropic Glutamate Receptor
• 7 transmembrane sweet-taste receptor of 3 GCPR
• Receptor family ligand binding region
• Nine Cysteines Domain of family 3 GPCR
• GPCR, family 3, metabotropic glutamate receptor 4

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Membrane
• Receptor
• Signal
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GRM4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PICK1