Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7Q68XE)

• DOT Name: Neuromedin-K receptor (TACR3)
• Synonyms: NKR; NK-3 receptor; NK-3R; Neurokinin B receptor; Tachykinin receptor 3
• Gene Name: TACR3
• Related Disease:
  Hypogonadotropic hypogonadism 11 with or without anosmia
  Hypogonadotropic hypogonadism 7 with or without anosmia
  Hypogonadotropic hypogonadism
  Kallmann syndrome
• UniProt ID: NK3R_HUMAN
• Pfam ID: PF00001
• Sequence:
  MATLPAAETWIDGGGGVGADAVNLTASLAAGAATGAVETGWLQLLDQAGNLSSSPSALGL
  PVASPAPSQPWANLTNQFVQPSWRIALWSLAYGVVVAVAVLGNLIVIWIILAHKRMRTVT
  NYFLVNLAFSDASMAAFNTLVNFIYALHSEWYFGANYCRFQNFFPITAVFASIYSMTAIA
  VDRYMAIIDPLKPRLSATATKIVIGSIWILAFLLAFPQCLYSKTKVMPGRTLCFVQWPEG
  PKQHFTYHIIVIILVYCFPLLIMGITYTIVGITLWGGEIPGDTCDKYHEQLKAKRKVVKM
  MIIVVMTFAICWLPYHIYFILTAIYQQLNRWKYIQQVYLASFWLAMSSTMYNPIIYCCLN
  KRFRAGFKRAFRWCPFIKVSSYDELELKTTRFHPNRQSSMYTVTRMESMTVVFDPNDADT
  TRSSRKKRATPRDPSFNGCSRRNSKSASATSSFISSPYTSVDEYS
• Function: This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K > substance P.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Tachykinin receptors bind tachykinins (R-HSA-380095)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypogonadotropic hypogonadism 11 with or without anosmia	DISHMP3P	Strong	Autosomal recessive	[1]
Hypogonadotropic hypogonadism 7 with or without anosmia	DISPBWEU	Strong	Autosomal recessive	[2]
Hypogonadotropic hypogonadism	DIS8JSKR	Supportive	Autosomal dominant	[2]
Kallmann syndrome	DISO3HDG	Supportive	Autosomal dominant	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cocaine	DMSOX7I	Approved	Neuromedin-K receptor (TACR3) increases the response to substance of Cocaine.	[6]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuromedin-K receptor (TACR3).	[4]

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 increases the methylation of Neuromedin-K receptor (TACR3).	[5]

References

• [1] TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. J Clin Endocrinol Metab. 2010 May;95(5):2287-95. doi: 10.1210/jc.2009-2600. Epub 2010 Mar 1.
• [2] TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet. 2009 Mar;41(3):354-358. doi: 10.1038/ng.306. Epub 2008 Dec 11.
• [3] Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] The tachykinin receptor 3 is associated with alcohol and cocaine dependence. Alcohol Clin Exp Res. 2008 Jun;32(6):1023-30. doi: 10.1111/j.1530-0277.2008.00663.x. Epub 2008 Apr 15.