Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7OL93K)

DOT Name Metabotropic glutamate receptor 1 (GRM1)
Synonyms mGluR1
Gene Name GRM1
Related Disease
Autosomal recessive spinocerebellar ataxia 13 ( )
Spinocerebellar ataxia 44 ( )
UniProt ID
GRM1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3KS9; 4OR2; 7DGD; 7DGE
Pfam ID
PF00003 ; PF01094 ; PF10606 ; PF07562
Sequence
MVGLLLFFFPAIFLEVSLLPRSPGRKVLLAGASSQRSVARMDGDVIIGALFSVHHQPPAE
KVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSI
EFIRDSLISIRDEKDGINRCLPDGQSLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDI
PQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESG
MDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRERLPKARVVVCFCEGMTVRGLL
SAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLRLD
TNTRNPWFPEFWQHRFQCRLPGHLLENPNFKRICTGNESLEENYVQDSKMGFVINAIYAM
AHGLQNMHHALCPGHVGLCDAMKPIDGSKLLDFLIKSSFIGVSGEEVWFDEKGDAPGRYD
IMNLQYTEANRYDYVHVGTWHEGVLNIDDYKIQMNKSGVVRSVCSEPCLKGQIKVIRKGE
VSCCWICTACKENEYVQDEFTCKACDLGWWPNADLTGCEPIPVRYLEWSNIESIIAIAFS
CLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQ
RLLVGLSSAMCYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTL
VVTLIIMEPPMPILSYPSIKEVYLICNTSNLGVVAPLGYNGLLIMSCTYYAFKTRNVPAN
FNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCMFTPKMYIIIA
KPERNVRSAFTTSDVVRMHVGDGKLPCRSNTFLNIFRRKKAGAGNANSNGKSVSWSEPGG
GQVPKGQHMWHRLSVHVKTNETACNQTAVIKPLTKSYQGSGKSLTFSDTSTKTLYNVEEE
EDAQPIRFSPPGSPSMVVHRRVPSAATTPPLPSHLTAEETPLFLAEPALPKGLPPPLQQQ
QQPPPQQKSLMDQLQGVVSNFSTAIPDFHAVLAGPGGPGNGLRSLYPPPPPPQHLQMLPL
QLSTFGEELVSPPADDDDDSERFKLLQEYVYEHEREGNTEEDELEEEEEDLQAASKLTPD
DSPALTPPSPFRDSVASGSSVPSSPVSESVLCTPPNVSYASVILRDYKQSSSTL
Function
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 activates a phosphatidylinositol-calcium second messenger system. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum. May function in the light response in the retina.
Tissue Specificity Detected in brain.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )
FoxO sig.ling pathway (hsa04068 )
Phospholipase D sig.ling pathway (hsa04072 )
Neuroactive ligand-receptor interaction (hsa04080 )
Gap junction (hsa04540 )
Long-term potentiation (hsa04720 )
Retrograde endocan.binoid sig.ling (hsa04723 )
Glutamatergic sy.pse (hsa04724 )
Long-term depression (hsa04730 )
Taste transduction (hsa04742 )
Estrogen sig.ling pathway (hsa04915 )
Spinocerebellar ataxia (hsa05017 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Reactome Pathway
Class C/3 (Metabotropic glutamate/pheromone receptors) (R-HSA-420499 )
Neurexins and neuroligins (R-HSA-6794361 )
Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207 )
G alpha (q) signalling events (R-HSA-416476 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive spinocerebellar ataxia 13 DISDBSE9 Strong Autosomal recessive [1]
Spinocerebellar ataxia 44 DISZ9ED6 Strong Autosomal dominant [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Metabotropic glutamate receptor 1 (GRM1). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Metabotropic glutamate receptor 1 (GRM1). [4]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Metabotropic glutamate receptor 1 (GRM1). [5]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Metabotropic glutamate receptor 1 (GRM1). [6]
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References

1 Autosomal-recessive congenital cerebellar ataxia is caused by mutations in metabotropic glutamate receptor 1. Am J Hum Genet. 2012 Sep 7;91(3):553-64. doi: 10.1016/j.ajhg.2012.07.019. Epub 2012 Aug 16.
2 Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44. Am J Hum Genet. 2017 Sep 7;101(3):451-458. doi: 10.1016/j.ajhg.2017.08.005.
3 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
4 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
5 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
6 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.