Details of Drug Off-Target (DOT)

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

• DOT Name: Cytochrome P450 4Z1 (CYP4Z1)
• Synonyms: EC 1.14.14.1; CYPIVZ1; Laurate 7-monooxygenase; EC 1.14.14.130
• Gene Name: CYP4Z1
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Classic Hodgkin lymphoma
  Estrogen-receptor positive breast cancer
  Neoplasm
  Metastatic malignant neoplasm
• UniProt ID: CP4Z1_HUMAN
• EC Number: 1.14.14.1; 1.14.14.130
• Pfam ID: PF00067
• Sequence:
  MEPSWLQELMAHPFLLLILLCMSLLLFQVIRLYQRRRWMIRALHLFPAPPAHWFYGHKEF
  YPVKEFEVYHKLMEKYPCAVPLWVGPFTMFFSVHDPDYAKILLKRQDPKSAVSHKILESW
  VGRGLVTLDGSKWKKHRQIVKPGFNISILKIFITMMSESVRMMLNKWEEHIAQNSRLELF
  QHVSLMTLDSIMKCAFSHQGSIQLDSTLDSYLKAVFNLSKISNQRMNNFLHHNDLVFKFS
  SQGQIFSKFNQELHQFTEKVIQDRKESLKDKLKQDTTQKRRWDFLDILLSAKSENTKDFS
  EADLQAEVKTFMFAGHDTTSSAISWILYCLAKYPEHQQRCRDEIRELLGDGSSITWEHLS
  QMPYTTMCIKECLRLYAPVVNISRLLDKPITFPDGRSLPAGITVFINIWALHHNPYFWED
  PQVFNPLRFSRENSEKIHPYAFIPFSAGLRNCIGQHFAIIECKVAVALTLLRFKLAPDHS
  RPPQPVRQVVLKSKNGIHVFAKKVC
• Function: A cytochrome P450 monooxygenase that catalyzes the in-chain oxidation of fatty acids. Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates lauric and myristic acids predominantly at the omega-4 and omega-2 positions, respectively. Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Displays an absolute stereoselectivity in the epoxidation of arachidonic acid producing the 14(S),15(R)-epoxyeicosatrienoic acid (EET) enantiomer. 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: Preferentially detected in breast carcinoma tissue and mammary gland, whereas only marginal expression is found in all other tested tissues.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Genetic Variation	[3]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[6]

This DOT Affected the Regulation of Drug Effects of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
20-HETE	DM5BAJ9	Investigative	Cytochrome P450 4Z1 (CYP4Z1) increases the abundance of 20-HETE.	[5]
Lauric Acid	DM9C8KQ	Investigative	Cytochrome P450 4Z1 (CYP4Z1) decreases the abundance of Lauric Acid.	[5]
MYRISTIC ACID	DMYX0BL	Investigative	Cytochrome P450 4Z1 (CYP4Z1) decreases the abundance of MYRISTIC ACID.	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cytochrome P450 4Z1 (CYP4Z1).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cytochrome P450 4Z1 (CYP4Z1).	[7]

References

• [1] CYP4Z1 - A Human Cytochrome P450 Enzyme that Might Hold the Key to Curing Breast Cancer.Curr Pharm Des. 2017;23(14):2060-2064. doi: 10.2174/1381612823666170207150156.
• [2] Correction to: The 3'UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1.Breast Cancer Res Treat. 2020 Jan;179(2):521-522. doi: 10.1007/s10549-019-05478-4.
• [3] WebHERV: A Web Server for the Computational Investigation of Gene Expression Associated With Endogenous Retrovirus-Like Sequences.Front Microbiol. 2018 Nov 5;9:2384. doi: 10.3389/fmicb.2018.02384. eCollection 2018.
• [4] Competing endogenous RNA networks of CYP4Z1 and pseudogene CYP4Z2P confer tamoxifen resistance in breast cancer.Mol Cell Endocrinol. 2016 May 15;427:133-42. doi: 10.1016/j.mce.2016.03.012. Epub 2016 Mar 12.
• [5] Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer. Toxicol Appl Pharmacol. 2012 Oct 1;264(1):73-83. doi: 10.1016/j.taap.2012.07.019. Epub 2012 Jul 25.
• [6] Efficient substrate screening and inhibitor testing of human CYP4Z1 using permeabilized recombinant fission yeast.Biochem Pharmacol. 2017 Dec 15;146:174-187. doi: 10.1016/j.bcp.2017.09.011. Epub 2017 Sep 23.
• [7] Conditional regulation of the human CYP4X1 and CYP4Z1 genes. Arch Biochem Biophys. 2005 Apr 15;436(2):377-85. doi: 10.1016/j.abb.2005.02.022.
• [8] Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer. Toxicol Appl Pharmacol. 2012 Oct 1;264(1):73-83. doi: 10.1016/j.taap.2012.07.019. Epub 2012 Jul 25.