Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJSM0V3)

• DOT Name: Cytochrome P450 26C1 (CYP26C1)
• Synonyms: CYP26C1; EC 1.14.14.1
• Gene Name: CYP26C1
• Related Disease: Focal facial dermal dysplasia type IV
• UniProt ID: CP26C_HUMAN
• EC Number: 1.14.14.1
• Pfam ID: PF00067
• Sequence:
  MFPWGLSCLSVLGAAGTALLCAGLLLSLAQHLWTLRWMLSRDRASTLPLPKGSMGWPFFG
  ETLHWLVQGSRFHSSRRERYGTVFKTHLLGRPVIRVSGAENVRTILLGEHRLVRSQWPQS
  AHILLGSHTLLGAVGEPHRRRRKVLARVFSRAALERYVPRLQGALRHEVRSWCAAGGPVS
  VYDASKALTFRMAARILLGLRLDEAQCATLARTFEQLVENLFSLPLDVPFSGLRKGIRAR
  DQLHRHLEGAISEKLHEDKAAEPGDALDLIIHSARELGHEPSMQELKESAVELLFAAFFT
  TASASTSLVLLLLQHPAAIAKIREELVAQGLGRACGCAPGAAGGSEGPPPDCGCEPDLSL
  AALGRLRYVDCVVKEVLRLLPPVSGGYRTALRTFELDGYQIPKGWSVMYSIRDTHETAAV
  YRSPPEGFDPERFGAAREDSRGASSRFHYIPFGGGARSCLGQELAQAVLQLLAVELVRTA
  RWELATPAFPAMQTVPIVHPVDGLRLFFHPLTPSVAGNGLCL
• Function: A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals. RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (Probable). Catalyzes the oxidation of atRA primarily at C-4. Oxidation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination, thereby contributes to the regulation of atRA homeostasis and signaling (Probable). Able to metabolize other RAs such as 9-cis with high efficiency. Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA. Shares sequence similarity with other CYP26 family members, but has higher affinity to 9-cis-RA and is much less sensitive to the inhibitory effects of ketoconazole. In cooperation with Cyp26a1, contributes to the CNS patterning and the development of regions of higher visual acuity.
• Tissue Specificity: Detected in most tissues at very low level.
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  RA biosynthesis pathway (R-HSA-5365859)
  Defective CYP26C1 causes FFDD4 (R-HSA-5579004)
  Vitamins (R-HSA-211916)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Focal facial dermal dysplasia type IV	DISDS4LE	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytochrome P450 26C1 (CYP26C1).	[2]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Cytochrome P450 26C1 (CYP26C1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytochrome P450 26C1 (CYP26C1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cytochrome P450 26C1 (CYP26C1).	[4]

References

• [1] CYP26A1 and CYP26C1 cooperatively regulate anterior-posterior patterning of the developing brain and the production of migratory cranial neural crest cells in the mouse. Dev Biol. 2007 Feb 15;302(2):399-411. doi: 10.1016/j.ydbio.2006.09.045. Epub 2006 Sep 30.
• [2] A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid. J Biol Chem. 2004 Jan 2;279(1):77-85.
• [3] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [4] 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.