Defective CYP26C1 does not 4-hydroxylate 9cRA

Stable Identifier
R-HSA-5602050
Type
Reaction [transition]
Species
Homo sapiens
Compartment
endoplasmic reticulum membrane, cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective CYP26C1 does not 4-hydroxylate 9cRA
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Retinoic acid (RA) is a biologically active analogue of vitamin A (retinol). RA plays an important role in regulating cell growth and differentiation. CYP26C1 is involved in the metabolic breakdown of RA by 4-hydroxylation. While CYP26C1 can hydroxylate the trans form, it is unique in hydroxylating the 9-cis isomer of RA (9cRA) (Taimi et al. 2004). Defects in CYP26C1 can cause focal facial dermal dysplasia 4 (FFDD4; MIM:614974), a rare syndrome characterised by facial lesions. Slavotinek et al. identified compound heterozygosity for a 7-bp tandem duplication (844_851dupCCATGCA) in exon 4 of the CYP26C1 gene, causing a frameshift mutation, Q477Hfs*129, and a 1433A-G transition in exon 6 that results in an R478R missense mutation. Both mutations caused loss of CYP26C1 function when transfected into COS-1 cells (Slavotinek et al. 2013).
Literature References
PubMed ID Title Journal Year
23161670 Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1

Tang, PL, Petkovich, M, Lao, R, Chu, C, Yahyavi, M, Nazarenko, I, Mehrotra, P, Frieden, I, Prescott, T, Devriendt, K, Morren, MA, Cordoro, K, Marqueling, AL, Chou, C, Kwok, PY, Slavotinek, AM, Cameron, D, Li, B, Desnick, RJ, Glaser, T

Hum. Mol. Genet. 2013
14532297 A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid

White, J, Taimi, M, Helvig, C, Petkovich, M, Ramshaw, H, Korczak, B, Amad, M, Wisniewski, J

J Biol Chem 2004
Participants
Input
Participates
as an event of
Catalyst Activity

retinoic acid 4-hydroxylase activity of CYP26C1 mutants [endoplasmic reticulum membrane]

Physical Entity
CYP26C1 mutants [endoplasmic reticulum membrane] (Homo sapiens)
Activity
retinoic acid 4-hydroxylase activity (GO:0008401)
Normal reaction
CYP26C1 4-hydroxylates 9cRA (Homo sapiens)
Functional status

Loss of function of CYP26C1 mutations [endoplasmic reticulum membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
skin benign neoplasm DOID:3165 neoplasm of skin (disorder), tumor of the skin, neoplasm of skin by site, skin neoplasm
Authored
Jassal, B  (2014-06-17)
Reviewed
Nakaki, T  (2014-11-03)
Created
Jassal, B  (2014-06-17)
Cite Us!