Target Information
Target General Information | Top | |||||
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Target ID |
T42392
(Former ID: TTDI01970)
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Target Name |
Glutamate receptor AMPA 2 (GRIA2)
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Synonyms |
Glutamate receptor ionotropic, AMPA 2; Glutamate receptor 2; GluRK2; GluRB; GluR2; GluR-K2; GluR-B; GluR-2; GluA2; AMPAselective glutamate receptor 2; AMPA-selective glutamate receptor 2
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Gene Name |
GRIA2
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Neuropathy [ICD-11: 8C0Z] | |||||
Function |
L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate. Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission.
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BioChemical Class |
Glutamate-gated ion channel
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UniProt ID | ||||||
Sequence |
MQKIMHISVLLSPVLWGLIFGVSSNSIQIGGLFPRGADQEYSAFRVGMVQFSTSEFRLTP
HIDNLEVANSFAVTNAFCSQFSRGVYAIFGFYDKKSVNTITSFCGTLHVSFITPSFPTDG THPFVIQMRPDLKGALLSLIEYYQWDKFAYLYDSDRGLSTLQAVLDSAAEKKWQVTAINV GNINNDKKDEMYRSLFQDLELKKERRVILDCERDKVNDIVDQVITIGKHVKGYHYIIANL GFTDGDLLKIQFGGANVSGFQIVDYDDSLVSKFIERWSTLEEKEYPGAHTTTIKYTSALT YDAVQVMTEAFRNLRKQRIEISRRGNAGDCLANPAVPWGQGVEIERALKQVQVEGLSGNI KFDQNGKRINYTINIMELKTNGPRKIGYWSEVDKMVVTLTELPSGNDTSGLENKTVVVTT ILESPYVMMKKNHEMLEGNERYEGYCVDLAAEIAKHCGFKYKLTIVGDGKYGARDADTKI WNGMVGELVYGKADIAIAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFLD PLAYEIWMCIVFAYIGVSVVLFLVSRFSPYEWHTEEFEDGRETQSSESTNEFGIFNSLWF SLGAFMQQGCDISPRSLSGRIVGGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDL SKQTEIAYGTLDSGSTKEFFRRSKIAVFDKMWTYMRSAEPSVFVRTTAEGVARVRKSKGK YAYLLESTMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSSLRNAVNLAVLKLNEQGLL DKLKNKWWYDKGECGSGGGDSKEKTSALSLSNVAGVFYILVGGLGLAMLVALIEFCYKSR AEAKRMKVAKNAQNINPSSSQNSQNFATYKEGYNVYGIESVKI Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T14JBS |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | E-2007 | Drug Info | Approved | Diabetic neuropathy | [2], [3] | |
Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | Paliroden | Drug Info | Phase 2 | Parkinson disease | [4] | |
Mode of Action | [+] 4 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | E-2007 | Drug Info | [1] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Paliroden | Drug Info | [5] | |||
Agonist | [+] 2 Agonist drugs | + | ||||
1 | (S)-5-fluorowillardiine | Drug Info | [6] | |||
2 | [3H]AMPA | Drug Info | [6] | |||
Antagonist | [+] 2 Antagonist drugs | + | ||||
1 | ATPO | Drug Info | [6] | |||
2 | [3H]CNQX | Drug Info | [6] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
1 | IL2 Signaling Pathway | |||||
Panther Pathway | [+] 2 Panther Pathways | + | ||||
1 | Ionotropic glutamate receptor pathway | |||||
2 | Metabotropic glutamate receptor group III pathway | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | N-cadherin signaling events |
References | Top | |||||
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REF 1 | Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7050). | |||||
REF 3 | Nat Rev Drug Discov. 2013 Feb;12(2):87-90. | |||||
REF 4 | ClinicalTrials.gov (NCT00285025) Study of the Effect of SR57667B in Patients With Alzheimer's Disease. U.S. National Institutes of Health. | |||||
REF 5 | Mechanism of inhibition of the GluA2 AMPA receptor channel opening by talampanel and its enantiomer: the stereochemistry of the 4-methyl group on the diazepine ring of 2,3-benzodiazepine derivatives.ACS Chem Neurosci.2013 Apr 17;4(4):635-44. | |||||
REF 6 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 445). |
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