Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHO7KC4)

• DOT Name: Cytochrome P450 4A22 (CYP4A22)
• Synonyms: CYPIVA22; Fatty acid omega-hydroxylase; Lauric acid omega-hydroxylase; Long-chain fatty acid omega-monooxygenase; EC 1.14.14.80
• Gene Name: CYP4A22
• Related Disease:
  Autosomal recessive polycystic kidney disease
  Hepatocellular carcinoma
  High blood pressure
• UniProt ID: CP4AM_HUMAN
• EC Number: 1.14.14.80
• Pfam ID: PF00067
• Sequence:
  MSVSVLSPSRRLGGVSGILQVTSLLILLLLLIKAAQLYLHRQWLLKALQQFPCPPSHWLF
  GHIQEFQHDQELQRIQERVKTFPSACPYWIWGGKVRVQLYDPDYMKVILGRSDPKSHGSY
  KFLAPRIGYGLLLLNGQTWFQHRRMLTPAFHNDILKPYVGLMADSVRVMLDKWEELLGQD
  SPLEVFQHVSLMTLDTIMKSAFSHQGSIQVDRNSQSYIQAISDLNSLVFCCMRNAFHEND
  TIYSLTSAGRWTHRACQLAHQHTDQVIQLRKAQLQKEGELEKIKRKRHLDFLDILLLAKM
  ENGSILSDKDLRAEVDTFMFEGHDTTASGISWILYALATHPKHQERCREEIHGLLGDGAS
  ITWNHLDQMPYTTMCIKEALRLYPPVPGIGRELSTPVTFPDGRSLPKGIMVLLSIYGLHH
  NPKVWPNLEVFDPSRFAPGSAQHSHAFLPFSGGSRNCIGKQFAMNQLKVARALTLLRFEL
  LPDPTRIPIPMARLVLKSKNGIHLRLRRLPNPCEDKDQL
• Function: Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate and palmitate. Shows no activity towards arachidonic acid and prostaglandin A1. Lacks functional activity in the kidney and does not contribute to renal 20-hydroxyeicosatetraenoic acid (20-HETE) biosynthesis.
• Reactome Pathway:
  Miscellaneous substrates (R-HSA-211958)
  Eicosanoids (R-HSA-211979)
  Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691)
  Fatty acids (R-HSA-211935)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive polycystic kidney disease	DISPUS40	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
High blood pressure	DISY2OHH	Disputed	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Cytochrome P450 4A22 (CYP4A22).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cytochrome P450 4A22 (CYP4A22).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cytochrome P450 4A22 (CYP4A22).	[6]

References

• [1] Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD.Am J Physiol Renal Physiol. 2009 Mar;296(3):F575-82. doi: 10.1152/ajprenal.90705.2008. Epub 2009 Jan 7.
• [2] Cytochrome P450 4A11 expression in tumor cells: A favorable prognostic factor for hepatocellular carcinoma patients.J Gastroenterol Hepatol. 2019 Jan;34(1):224-233. doi: 10.1111/jgh.14406. Epub 2018 Aug 29.
• [3] Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats.Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2455-65. doi: 10.1152/ajpheart.00512.2008. Epub 2008 Oct 24.
• [4] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.