Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCMU9NL)

• DOT Name: Mitochondrial import inner membrane translocase subunit TIM16 (PAM16)
• Synonyms: Mitochondria-associated granulocyte macrophage CSF-signaling molecule; Presequence translocated-associated motor subunit PAM16
• Gene Name: PAM16
• Related Disease:
  Autosomal recessive spondylometaphyseal dysplasia, Megarbane type
  Prostate neoplasm
• UniProt ID: TIM16_HUMAN
• Pfam ID: PF03656
• Sequence:
  MAKYLAQIIVMGVQVVGRAFARALRQEFAASRAAADARGRAGHRSAAASNLSGLSLQEAQ
  QILNVSKLSPEEVQKNYEHLFKVNDKSVGGSFYLQSKVVRAKERLDEELKIQAQEDREKG
  QMPHT
• Function: Regulates ATP-dependent protein translocation into the mitochondrial matrix. Inhibits DNAJC19 stimulation of HSPA9/Mortalin ATPase activity.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive spondylometaphyseal dysplasia, Megarbane type	DISBKXS8	Strong	Autosomal recessive	[1]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitochondrial import inner membrane translocase subunit TIM16 (PAM16).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial import inner membrane translocase subunit TIM16 (PAM16).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial import inner membrane translocase subunit TIM16 (PAM16).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mitochondrial import inner membrane translocase subunit TIM16 (PAM16).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Mitochondrial import inner membrane translocase subunit TIM16 (PAM16).	[7]

References

• [1] The impairment of MAGMAS function in human is responsible for a severe skeletal dysplasia. PLoS Genet. 2014 May 1;10(5):e1004311. doi: 10.1371/journal.pgen.1004311. eCollection 2014 May.
• [2] Magmas expression in neoplastic human prostate.J Mol Histol. 2005 Feb;36(1-2):69-75. doi: 10.1007/s10735-004-3840-8.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.