Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQKNK0D)

• DOT Name: Cytochrome P450 4V2 (CYP4V2)
• Synonyms: Docosahexaenoic acid omega-hydroxylase CYP4V2; EC 1.14.14.79; Long-chain fatty acid omega-monooxygenase; EC 1.14.14.80
• Gene Name: CYP4V2
• Related Disease:
  Bietti crystalline corneoretinal dystrophy
  Rheumatoid arthritis
  Advanced cancer
  Bacterial endocarditis
  Colon carcinoma
  Infective endocarditis
  Leber congenital amaurosis 1
  Neoplasm
  Non-insulin dependent diabetes
  Retinitis pigmentosa
  Venous thromboembolism
  Adult lymphoma
  Classic Hodgkin lymphoma
  Lymphoma
  MALT lymphoma
  Nodal marginal zone lymphoma
  Pediatric lymphoma
  Splenic marginal zone lymphoma
• UniProt ID: CP4V2_HUMAN
• EC Number: 1.14.14.79; 1.14.14.80
• Pfam ID: PF00067
• Sequence:
  MAGLWLGLVWQKLLLWGAASALSLAGASLVLSLLQRVASYARKWQQMRPIPTVARAYPLV
  GHALLMKPDGREFFQQIIEYTEEYRHMPLLKLWVGPVPMVALYNAENVEVILTSSKQIDK
  SSMYKFLEPWLGLGLLTSTGNKWRSRRKMLTPTFHFTILEDFLDIMNEQANILVKKLEKH
  INQEAFNCFFYITLCALDIICETAMGKNIGAQSNDDSEYVRAVYRMSEMIFRRIKMPWLW
  LDLWYLMFKEGWEHKKSLQILHTFTNSVIAERANEMNANEDCRGDGRGSAPSKNKRRAFL
  DLLLSVTDDEGNRLSHEDIREEVDTFMFEGHDTTAAAINWSLYLLGSNPEVQKKVDHELD
  DVFGKSDRPATVEDLKKLRYLECVIKETLRLFPSVPLFARSVSEDCEVAGYRVLKGTEAV
  IIPYALHRDPRYFPNPEEFQPERFFPENAQGRHPYAYVPFSAGPRNCIGQKFAVMEEKTI
  LSCILRHFWIESNQKREELGLEGQLILRPSNGIWIKLKRRNADER
• Function: A cytochrome P450 monooxygenase involved in fatty acid metabolism in the eye. Catalyzes the omega-hydroxylation of polyunsaturated fatty acids (PUFAs) docosahexaenoate (DHA) and its precursor eicosapentaenoate (EPA), and may contribute to the homeostasis of these retinal PUFAs. Omega hydroxylates saturated fatty acids such as laurate, myristate and palmitate, the catalytic efficiency decreasing in the following order: myristate > laurate > palmitate (C14>C12>C16). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).
• Tissue Specificity: Broadly expressed. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, retina, retinal pigment epithelium (RPE) and lymphocytes.
• Reactome Pathway:
  The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)
  Endogenous sterols (R-HSA-211976)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bietti crystalline corneoretinal dystrophy	DISLJ355	Definitive	Autosomal recessive	[1]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Bacterial endocarditis	DIS920N0	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[5]
Infective endocarditis	DIS88NSA	Strong	Biomarker	[4]
Leber congenital amaurosis 1	DISY2B33	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[8]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[9]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[10]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[11]
Classic Hodgkin lymphoma	DISV1LU6	Limited	Biomarker	[11]
Lymphoma	DISN6V4S	Limited	Biomarker	[11]
MALT lymphoma	DIS1AVVE	Limited	Biomarker	[11]
Nodal marginal zone lymphoma	DIS7MP4T	Limited	Biomarker	[11]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[11]
Splenic marginal zone lymphoma	DISCGTZY	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cytochrome P450 4V2 (CYP4V2).	[17]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cytochrome P450 4V2 (CYP4V2).	[22]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cytochrome P450 4V2 (CYP4V2).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[24]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Investigative	2-chloro-5-nitro-N-phenylbenzamide decreases the expression of Cytochrome P450 4V2 (CYP4V2).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Cytochrome P450 4V2 (CYP4V2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cytochrome P450 4V2 (CYP4V2).	[18]

References

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• [9] CHOROIDAL AND RETINAL ATROPHY OF BIETTI CRYSTALLINE DYSTROPHY PATIENTS WITH CYP4V2 MUTATIONS COMPARED TO RETINITIS PIGMENTOSA PATIENTS WITH EYS MUTATIONS.Retina. 2017 Jun;37(6):1193-1202. doi: 10.1097/IAE.0000000000001323.
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• [11] Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial.Hematol Oncol. 2020 Feb;38(1):67-73. doi: 10.1002/hon.2693. Epub 2020 Jan 13.
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• [18] 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.
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• [25] Expression of CYP4V2 in human THP1 macrophages and its transcriptional regulation by peroxisome proliferator-activated receptor gamma. Toxicol Appl Pharmacol. 2017 Sep 1;330:100-106. doi: 10.1016/j.taap.2017.07.009. Epub 2017 Jul 17.