GRM1

Protein identityUniProt · HPA

UniProt accession

Q13255

Gene

GRM1

Ensembl

ENSG00000152822

Chromosome

6

Canonical length

1194 aa

Protein class

Disease related genes, G-protein coupled receptors, Human disease related genes, Plasma proteins, Potential drug targets, Predicted membrane proteins, Transporters

Subcellular location

Vesicles

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a metabotropic glutamate receptor that functions by activating phospholipase C. 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 canonical alpha isoform of the encoded protein is a disulfide-linked homodimer whose activity is mediated by a G-protein-coupled phosphatidylinositol-calcium second messenger system. This gene may be associated with many disease states, including schizophrenia, bipolar disorder, depression, and breast cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

Canonical amino-acid sequenceUniProt

1194 residues, UniProt reviewed canonical sequence.

>Q13255|GRM1
     1  MVGLLLFFFP AIFLEVSLLP RSPGRKVLLA GASSQRSVAR MDGDVIIGAL FSVHHQPPAE
    61  KVPERKCGEI REQYGIQRVE AMFHTLDKIN ADPVLLPNIT LGSEIRDSCW HSSVALEQSI
   121  EFIRDSLISI RDEKDGINRC LPDGQSLPPG RTKKPIAGVI GPGSSSVAIQ VQNLLQLFDI
   181  PQIAYSATSI DLSDKTLYKY FLRVVPSDTL QARAMLDIVK RYNWTYVSAV HTEGNYGESG
   241  MDAFKELAAQ EGLCIAHSDK IYSNAGEKSF DRLLRKLRER LPKARVVVCF CEGMTVRGLL
   301  SAMRRLGVVG EFSLIGSDGW ADRDEVIEGY EVEANGGITI KLQSPEVRSF DDYFLKLRLD
   361  TNTRNPWFPE FWQHRFQCRL PGHLLENPNF KRICTGNESL EENYVQDSKM GFVINAIYAM
   421  AHGLQNMHHA LCPGHVGLCD AMKPIDGSKL LDFLIKSSFI GVSGEEVWFD EKGDAPGRYD
   481  IMNLQYTEAN RYDYVHVGTW HEGVLNIDDY KIQMNKSGVV RSVCSEPCLK GQIKVIRKGE
   541  VSCCWICTAC KENEYVQDEF TCKACDLGWW PNADLTGCEP IPVRYLEWSN IESIIAIAFS
   601  CLGILVTLFV TLIFVLYRDT PVVKSSSREL CYIILAGIFL GYVCPFTLIA KPTTTSCYLQ
   661  RLLVGLSSAM CYSALVTKTN RIARILAGSK KKICTRKPRF MSAWAQVIIA SILISVQLTL
   721  VVTLIIMEPP MPILSYPSIK EVYLICNTSN LGVVAPLGYN GLLIMSCTYY AFKTRNVPAN
   781  FNEAKYIAFT MYTTCIIWLA FVPIYFGSNY KIITTCFAVS LSVTVALGCM FTPKMYIIIA
   841  KPERNVRSAF TTSDVVRMHV GDGKLPCRSN TFLNIFRRKK AGAGNANSNG KSVSWSEPGG
   901  GQVPKGQHMW HRLSVHVKTN ETACNQTAVI KPLTKSYQGS GKSLTFSDTS TKTLYNVEEE
   961  EDAQPIRFSP PGSPSMVVHR RVPSAATTPP LPSHLTAEET PLFLAEPALP KGLPPPLQQQ
  1021  QQPPPQQKSL MDQLQGVVSN FSTAIPDFHA VLAGPGGPGN GLRSLYPPPP PPQHLQMLPL
  1081  QLSTFGEELV SPPADDDDDS ERFKLLQEYV YEHEREGNTE EDELEEEEED LQAASKLTPD
  1141  DSPALTPPSP FRDSVASGSS VPSSPVSESV LCTPPNVSYA SVILRDYKQS SSTL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRM1 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)

0.41

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRM1.

Disease | AllUniProt

Conditions GRM1 is implicated in, by any mechanism.

• Spinocerebellar ataxia, autosomal recessive, 13 (SCAR13) MIM:614831
• Spinocerebellar ataxia 44 (SCA44) MIM:617691

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 445 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive spinocerebellar ataxia 13
• Spinocerebellar ataxia 44
• Global developmental delay
• Cerebellar ataxia

Disease | AutoantibodyPubMed

Conditions in which antibodies against GRM1 are reported. Each links to that disease's full target list.

• Encephalitis 11
• Autoimmune Diseases of the Nervous System 6
• Cerebellar Ataxia 6
• Hashimoto Disease 6

Showing 4 of 7 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for GRM1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.42

gnomAD pLI

0.14

gnomAD missense Z

2.58

DepMap mean gene effect

0.12

DepMap dependency class

selective

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

• cellular response to electrical stimulus
• chemical synaptic transmission
• G protein-coupled glutamate receptor signaling pathway
• G protein-coupled receptor signaling pathway
• L-glutamate import across plasma membrane
• locomotory behavior
• phospholipase C-activating G protein-coupled glutamate receptor signaling pathway
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of MAPK cascade
• regulation of sensory perception of pain
• regulation of synaptic transmission, glutamatergic
• sensory perception of pain
• synaptic signaling via neuropeptide

Molecular functions

• adenylate cyclase inhibiting G protein-coupled glutamate receptor activity
• G protein-coupled receptor activity
• G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential
• glutamate receptor activity
• neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration
• G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration

Cellular components

• dendriole
• glutamatergic synapse
• nucleus
• plasma membrane
• postsynaptic density membrane
• Schaffer collateral - CA1 synapse
• G protein-coupled receptor dimeric complex
• G protein-coupled receptor homodimeric complex

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
• Metabotropic glutamate receptor, Homer-binding domain
• 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
• Homer-binding domain of metabotropic glutamate receptor
• GPCR, family 3, metabotropic glutamate receptor 1

KeywordsUniProt

• Cell membrane
• Cell projection
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Membrane
• Neurodegeneration
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Signal
• Spinocerebellar ataxia
• Synapse
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GRM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ITPR1
• RYR1
• RYR2
• SHANK1
• SHANK3
• SIAH1
• TAMALIN
• HOMER1