Target Information

Target General Infomation
Target ID
T04507
Former ID
TTDR00806
Target Name
Presynaptic density protein 95
Gene Name
DLG4
Synonyms
Discs, large homolog 4; PSD-95; Postsynaptic density-95; DLG4
Target Type
Clinical Trial
Disease Cerebrovascular ischaemia [ICD9: 434.91; ICD10: I61-I63]
Function
Interacts with the cytoplasmictail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B (By similarity).
BioChemical Class
Membrane-associated guanylate kinase
Target Validation
T04507
UniProt ID
P78352
Sequence
MDCLCIVTTKKYRYQDEDTPPLEHSPAHLPNQANSPPVIVNTDTLEAPGYELQVNGTEGE
MEYEEITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGGAAAQDGRLRVNDSILFV
NEVDVREVTHSAAVEALKEAGSIVRLYVMRRKPPAEKVMEIKLIKGPKGLGFSIAGGVGN
QHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVMHEDAVAALKNTYDVVY
LKVAKPSNAYLSDSYAPPDITTSYSQHLDNEISHSSYLGTDYPTAMTPTSPRRYSPVAKD
LLGEEDIPREPRRIVIHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDQIL
SVNGVDLRNASHEQAAIALKNAGQTVTIIAQYKPEEYSRFEAKIHDLREQLMNSSLGSGT
ASLRSNPKRGFYIRALFDYDKTKDCGFLSQALSFRFGDVLHVIDASDEEWWQARRVHSDS
ETDDIGFIPSKRRVERREWSRLKAKDWGSSSGSQGREDSVLSYETVTQMEVHYARPIIIL
GPTKDRANDDLLSEFPDKFGSCVPHTTRPKREYEIDGRDYHFVSSREKMEKDIQAHKFIE
AGQYNSHLYGTSVQSVREVAEQGKHCILDVSANAVRRLQAAHLHPIAIFIRPRSLENVLE
INKRITEEQARKAFDRATKLEQEFTECFSAIVEGDSFEEIYHKVKRVIEDLSGPYIWVPA
RERL
Drugs and Mode of Action
Drug(s) Tat-NR2B9c Drug Info Phase 3 Cerebrovascular ischaemia [525512], [531828], [533640]
Inhibitor 2-Methyl-2,4-Pentanediol Drug Info [551393]
FETAV Drug Info [529713]
Guanosine-5'-Monophosphate Drug Info [551393]
KSG-LDTKNYKQTSV Drug Info [529713]
KSG-YEKLSSIESDV Drug Info [529713]
N-(3,4-Dichlorophenyl)propyl-ETAV Drug Info [529713]
N-(3,4-Difluorophenyl)propyl-ETAV Drug Info [529713]
N-(Naphthalene-2-yl)ethyl-ETAV Drug Info [529713]
N-Benzyl-ETAV Drug Info [529713]
N-Butyl-ETAV Drug Info [529713]
N-Cyclohexylethyl-ETAV Drug Info [529713]
N-Cyclohexylmethyl-ETAV Drug Info [529713]
N-Ethyl-ETAV Drug Info [529713]
N-Methyl-ETAV Drug Info [529713]
N-Phenylethyl-ETAV Drug Info [529713]
N-Phenylpropyl-ETAV Drug Info [529713]
N-Propyl-ETAV Drug Info [529713]
Tat-NR2B9c Drug Info [525512], [531828], [533640]
YGRKKRRQRRR-KLSSIESDV Drug Info [529713]
Pathways
KEGG Pathway Hippo signaling pathway
Glutamatergic synapse
Huntington&#039
s disease
Cocaine addiction
PANTHER Pathway Huntington disease
Pathway Interaction Database ErbB4 signaling events
Reactome Trafficking of AMPA receptors
Unblocking of NMDA receptor, glutamate binding and activation
CREB phosphorylation through the activation of CaMKII
Ras activation uopn Ca2+ infux through NMDA receptor
RHO GTPases activate CIT
RAF/MAP kinase cascade
WikiPathways Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
L1CAM interactions
References
Ref 525512Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science. 1999 Jun 11;284(5421):1845-8.
Ref 531828Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature. 2012 Feb 29;483(7388):213-7.
Ref 533640Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science. 1995 Sep 22;269(5231):1737-40.
Ref 525512Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science. 1999 Jun 11;284(5421):1845-8.
Ref 529713J Med Chem. 2008 Oct 23;51(20):6450-9. Epub 2008 Sep 24.Modified peptides as potent inhibitors of the postsynaptic density-95/N-methyl-D-aspartate receptor interaction.
Ref 531828Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature. 2012 Feb 29;483(7388):213-7.
Ref 533640Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science. 1995 Sep 22;269(5231):1737-40.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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