Details of Drug Off-Target (DOT)

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

• DOT Name: Sideroflexin-5 (SFXN5)
• Gene Name: SFXN5
• Related Disease: Schizophrenia
• UniProt ID: SFXN5_HUMAN
• Pfam ID: PF03820
• Sequence:
  MADTATTASAAAASAASASSDAPPFQLGKPRFQQTSFYGRFRHFLDIIDPRTLFVTERRL
  REAVQLLEDYKHGTLRPGVTNEQLWSAQKIKQAILHPDTNEKIFMPFRMSGYIPFGTPIV
  VGLLLPNQTLASTVFWQWLNQSHNACVNYANRNATKPSPASKFIQGYLGAVISAVSIAVG
  LNVLVQKANKFTPATRLLIQRFVPFPAVASANICNVVLMRYGELEEGIDVLDSDGNLVGS
  SKIAARHALLETALTRVVLPMPILVLPPIVMSMLEKTALLQARPRLLLPVQSLVCLAAFG
  LALPLAISLFPQMSEIETSQLEPEIAQATSSRTVVYNKGL
• Function: Mitochondrial amino-acid transporter. Transports citrate. Does not act as a serine transporter: not able to mediate transport of serine into mitochondria. In brown adipose tissue, plays a role in the regulation of UCP1-dependent thermogenesis probably by supporting mitochondrial glycerol-3-phosphate utilization.
• Tissue Specificity: Primarily expressed in the brain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

10 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 Sideroflexin-5 (SFXN5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sideroflexin-5 (SFXN5).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sideroflexin-5 (SFXN5).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sideroflexin-5 (SFXN5).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Sideroflexin-5 (SFXN5).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sideroflexin-5 (SFXN5).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sideroflexin-5 (SFXN5).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Sideroflexin-5 (SFXN5).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sideroflexin-5 (SFXN5).	[10]
Manganese	DMKT129	Investigative	Manganese increases the expression of Sideroflexin-5 (SFXN5).	[11]

References

• [1] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] 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.
• [11] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.