CYP26B1

Cytochrome P450 26B1 is a protein that in humans is encoded by the CYP26B1 gene.

CYP26B1
Identifiers
Aliases	CYP26B1, CYP26A2, P450RAI-2, P450RAI2, RHFCA, cytochrome P450 family 26 subfamily B member 1
External IDs	OMIM: 605207; MGI: 2176159; HomoloGene: 23179; GeneCards: CYP26B1; OMA:CYP26B1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2p13.2 Start 72,129,238 bp End 72,147,862 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6|6 C3 Start 84,548,396 bp End 84,570,890 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pons skin of arm cerebellar vermis cerebellar hemisphere right hemisphere of cerebellum skin of leg adipose tissue subcutaneous adipose tissue decidua skin of abdomen Top expressed in hand skin of external ear otolith organ utricle endocardial cushion lip decidua neuromere rhombomere foot More reference expression data BioGPS More reference expression data
Gene ontology Molecular function iron ion binding retinoic acid binding metal ion binding monooxygenase activity heme binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen oxidoreductase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen retinoic acid 4-hydroxylase activity Cellular component cytoplasm organelle membrane endoplasmic reticulum membrane membrane intracellular membrane-bounded organelle endoplasmic reticulum Biological process cellular response to retinoic acid proximal/distal pattern formation retinoic acid catabolic process tongue morphogenesis establishment of skin barrier positive regulation of tongue muscle cell differentiation regulation of retinoic acid receptor signaling pathway negative regulation of retinoic acid receptor signaling pathway male meiotic nuclear division bone morphogenesis positive regulation of gene expression retinoic acid receptor signaling pathway embryonic limb morphogenesis vitamin metabolic process spermatogenesis establishment of T cell polarity cornification cell fate determination inflammatory response regulation of T cell differentiation xenobiotic metabolic process sterol metabolic process response to retinoic acid response to vitamin A kidney development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 56603 232174 Ensembl ENSG00000003137 ENSMUSG00000063415 UniProt Q9NR63 Q811W2 RefSeq (mRNA) NM_001277742 NM_019885 NM_001177713 NM_175475 RefSeq (protein) NP_001264671 NP_063938 NP_001171184 NP_780684 Location (UCSC) Chr 2: 72.13 – 72.15 Mb Chr 6: 84.55 – 84.57 Mb PubMed search
Wikidata
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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.

In the mouse, it has been shown that retinoid-degrading enzyme coded for by the gene, CYP26B1, also plays a major role in male gonad development and spermatogenesis. The actions of retinoic acid(RA) are suppressed by CYP26B1 which halts male germ cell differentiation. RA is responsible for the activation of Stra8 which signals XX germ cells to progress to meiotic prophase I. The actions of Stra8 are inhibited by CYP26B1 until a male is of pubertal age. The mechanism by which CYP26B1 is downregulated in the testis has yet to be discovered.

In a genome-wide study, CCHCR1, TCN2, TNXB, LTA, FASN, and CYP26B1 were identified as loci associated with a risk for developing esophageal squamous cell carcinoma. Of these loci, CYP26B1 exhibited the highest effect size. Moreover, the CYP26B1 locus was found to have two alleles with differing capacities to catabolize all-trans retinoic acid, a chemotherapeutic agent. When the allele with the higher catabolic capacity, rs138478634-GA, was overexpressed, cell proliferation was significantly enhanced in comparison to the other allele, rs138478634-GG. Additionally, research is suggestive of a lifestyle interaction where individuals with the risk allele who partake in smoking or drinking present with an odd-ratio over 2-fold higher than smokers or drinkers without the variant or individuals who refrain.

See also

• Cytochrome P450 oxidoreductase deficiency

External links

• Human CYP26B1 genome location and CYP26B1 gene details page in the UCSC Genome Browser.

Further reading

• Rat E, Billaut-Laden I, Allorge D, et al. (2006). "Evidence for a functional genetic polymorphism of the human retinoic acid-metabolizing enzyme CYP26A1, an enzyme that may be involved in spina bifida". Birth Defects Res. A. 76 (6): 491–8. doi:10.1002/bdra.20275. PMID 16933217.
• Bowles J, Knight D, Smith C, et al. (2006). "Retinoid signaling determines germ cell fate in mice". Science. 312 (5773): 596–600. Bibcode:2006Sci...312..596B. doi:10.1126/science.1125691. PMID 16574820. S2CID 2514848.
• Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. Bibcode:2005Natur.434..724H. doi:10.1038/nature03466. PMID 15815621.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Trofimova-Griffin ME, Juchau MR (2002). "Developmental expression of cytochrome CYP26B1 (P450RAI-2) in human cephalic tissues". Brain Res. Dev. Brain Res. 136 (2): 175–8. doi:10.1016/S0165-3806(02)00305-X. PMID 12101034.
• Abu-Abed S, MacLean G, Fraulob V, et al. (2002). "Differential expression of the retinoic acid-metabolizing enzymes CYP26A1 and CYP26B1 during murine organogenesis". Mech. Dev. 110 (1–2): 173–7. doi:10.1016/S0925-4773(01)00572-X. PMID 11744378. S2CID 9286863.
• White JA, Ramshaw H, Taimi M, et al. (2000). "Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism". Proc. Natl. Acad. Sci. U.S.A. 97 (12): 6403–8. Bibcode:2000PNAS...97.6403W. doi:10.1073/pnas.120161397. PMC 18615. PMID 10823918.
• Saba R, Wu Q, Saga Y (2014). "CYP26B1 promotes male germ cell differentiation by suppressing STRA8-dependent meiotic and STRA8-independent mitotic pathways". Dev. Biol. 389 (2): 173–181. doi:10.1016/j.ydbio.2014.02.013. PMID 24576537.
• Bowles J, Knight D, Smith C, Wilhelm D, Richman J, Mamiya S, Yashiro K, Chawengsaksophak K, Wilson MJ, Rossant J, Hamada H, Koopman P (2006). "Retinoid Signaling Determines Germ Cell Fate in Mice". Science. 312 (5773): 596–600. Bibcode:2006Sci...312..596B. doi:10.1126/science.1125691. PMID 16574820. S2CID 2514848.