Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGM19J)

• DTT Name: Inward rectifier potassium channel Kir3.1 (KCNJ3)
• Synonyms: Potassium channel, inwardly rectifying subfamily J member 3; KCNJ3; Inward rectifier K(+) channel Kir3.1; GIRK1; G proteinactivated inward rectifier potassium channel 1
• Gene Name: KCNJ3
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Inward rectifier potassium channel
• UniProt ID: KCNJ3_HUMAN
• TTD ID: T38012
• Sequence:
  MSALRRKFGDDYQVVTTSSSGSGLQPQGPGQDPQQQLVPKKKRQRFVDKNGRCNVQHGNL
  GSETSRYLSDLFTTLVDLKWRWNLFIFILTYTVAWLFMASMWWVIAYTRGDLNKAHVGNY
  TPCVANVYNFPSAFLFFIETEATIGYGYRYITDKCPEGIILFLFQSILGSIVDAFLIGCM
  FIKMSQPKKRAETLMFSEHAVISMRDGKLTLMFRVGNLRNSHMVSAQIRCKLLKSRQTPE
  GEFLPLDQLELDVGFSTGADQLFLVSPLTICHVIDAKSPFYDLSQRSMQTEQFEIVVILE
  GIVETTGMTCQARTSYTEDEVLWGHRFFPVISLEEGFFKVDYSQFHATFEVPTPPYSVKE
  QEEMLLMSSPLIAPAITNSKERHNSVECLDGLDDITTKLPSKLQKITGREDFPKKLLRMS
  STTSEKAYSLGDLPMKLQRISSVPGNSEEKLVSKTTKMLSDPMSQSVADLPPKLQKMAGG
  AARMEGNLPAKLRKMNSDRFT
• Function: This potassium channel is controlled byG proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This receptor plays a crucial role in regulating the heartbeat.
• KEGG Pathway:
  Circadian entrainment (hsa04713)
  Retrograde endocannabinoid signaling (hsa04723)
  Glutamatergic synapse (hsa04724)
  Cholinergic synapse (hsa04725)
  Serotonergic synapse (hsa04726)
  Dopaminergic synapse (hsa04728)
  Estrogen signaling pathway (hsa04915)
  Oxytocin signaling pathway (hsa04921)
  Morphine addiction (hsa05032)
• Reactome Pathway:
  Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits (R-HSA-997272)
  Activation of G protein gated Potassium channels (R-HSA-1296041)

Molecular Interaction Atlas (MIA) of This DTT

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ML297	DMY40UG	Discovery agent	N.A.	Investigative	[2]
PIP2	DMOZV7N	Discovery agent	N.A.	Investigative	[1]

References

• [1] Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma. Nature. 1998 Feb 19;391(6669):803-6.
• [2] ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice. ACS Chem Neurosci. 2013 Sep 18;4(9):1278-86.