Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT95APPM)

• DOT Name: Anti-Muellerian hormone type-2 receptor (AMHR2)
• Synonyms: EC 2.7.11.30; Anti-Muellerian hormone type II receptor; AMH type II receptor; MIS type II receptor; MISRII; MRII
• Gene Name: AMHR2
• Related Disease: Persistent Mullerian duct syndrome
• UniProt ID: AMHR2_HUMAN
• PDB ID: 7L0J
• EC Number: 2.7.11.30
• Pfam ID: PF00069
• Sequence:
  MLGSLGLWALLPTAVEAPPNRRTCVFFEAPGVRGSTKTLGELLDTGTELPRAIRCLYSRC
  CFGIWNLTQDRAQVEMQGCRDSDEPGCESLHCDPSPRAHPSPGSTLFTCSCGTDFCNANY
  SHLPPPGSPGTPGSQGPQAAPGESIWMALVLLGLFLLLLLLLGSIILALLQRKNYRVRGE
  PVPEPRPDSGRDWSVELQELPELCFSQVIREGGHAVVWAGQLQGKLVAIKAFPPRSVAQF
  QAERALYELPGLQHDHIVRFITASRGGPGRLLSGPLLVLELHPKGSLCHYLTQYTSDWGS
  SLRMALSLAQGLAFLHEERWQNGQYKPGIAHRDLSSQNVLIREDGSCAIGDLGLALVLPG
  LTQPPAWTPTQPQGPAAIMEAGTQRYMAPELLDKTLDLQDWGMALRRADIYSLALLLWEI
  LSRCPDLRPDSSPPPFQLAYEAELGNTPTSDELWALAVQERRRPYIPSTWRCFATDPDGL
  RELLEDCWDADPEARLTAECVQQRLAALAHPQESHPFPESCPRGCPPLCPEDCTSIPAPT
  ILPCRPQRSACHFSVQQGPCSRNPQPACTLSPV
• Function: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for anti-Muellerian hormone.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta sig.ling pathway (hsa04350)
• Reactome Pathway: Signaling by BMP (R-HSA-201451)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Persistent Mullerian duct syndrome	DISJ491E	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[5]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[8]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Anti-Muellerian hormone type-2 receptor (AMHR2).	[9]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [9] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.