CYP26B1
Description
The CYP26B1 (cytochrome P450 family 26 subfamily B member 1) is a protein-coding gene located on chromosome 2.
Cytochrome P450 26B1 is a protein that in humans is encoded by the CYP26B1 gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids and other lipids. The enzyme encoded by this gene is involved in the specific inactivation of all-trans-retinoic acid to hydroxylated forms, such as 4-oxo-, 4-OH-, and 18-OH-all-trans-retinoic acid. In a developing mouse embryo, CYP26B1 is expressed in the distal tip of the forming limb bud with an abundance in the apical ectodermal ridge. In a knockout mouse model, mice manifest with severe limb malformations and die after birth due to respiratory distress. However, if the expression of CYP26B1 is conditionally deleted only prior to E9.5, the limbs are not as severely truncated and more digits are visible. Research suggests that this difference is attributable to the timing of chondroblast differentiation. CYP26B1 has been shown to be over-expressed in colorectal cancer cells compared to normal colonic epithelium. CYP26B1 expression was also independently prognostic in patients with colorectal cancer and strong expression was associated with a poorer outcome.
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. Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling. Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination. Involved in the convertion of atRA to all-trans-4-oxo-RA. 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. Shows preference for the following substrates: atRA > 9-cis-RA > 13-cis-RA. Plays a central role in germ cell development: acts by degrading RAs in the developing testis, preventing STRA8 expression, thereby leading to delay of meiosis. Required for the maintenance of the undifferentiated state of male germ cells during embryonic development in Sertoli cells, inducing arrest in G0 phase of the cell cycle and preventing meiotic entry. Plays a role in skeletal development, both at the level of patterning and in the ossification of bone and the establishment of some synovial joints. Essential for postnatal survival.
CYP26B1 is also known as CYP26A2, P450RAI-2, P450RAI2, RHFCA.
