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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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]
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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]
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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.