CYP1B1

CYP1B1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3PM0
Identifiers
Aliases	CYP1B1, CP1B, CYPIB1, GLC3A, P4501B1, cytochrome P450 family 1 subfamily B member 1, ASGD6
External IDs	OMIM: 601771; MGI: 88590; HomoloGene: 68035; GeneCards: CYP1B1; OMA:CYP1B1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2p22.2 Start 38,066,973 bp End 38,109,902 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17|17 E3 Start 80,008,966 bp End 80,022,490 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pericardium cartilage tissue synovial joint trigeminal ganglion spinal ganglia synovial membrane tendon of biceps brachii superficial temporal artery hair follicle urethra Top expressed in stroma of bone marrow vestibular membrane of cochlear duct renal corpuscle cumulus cell ciliary body lactiferous gland mesenteric lymph nodes vas deferens ankle joint tunica media of zone of aorta More reference expression data BioGPS More reference expression data
Gene ontology Molecular function iron ion binding oxygen binding metal ion binding heme binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen oxidoreductase activity aromatase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen monooxygenase activity Cellular component organelle membrane endoplasmic reticulum membrane intracellular membrane-bounded organelle membrane endoplasmic reticulum mitochondrion Biological process toxin metabolic process steroid metabolic process retina vasculature development in camera-type eye cellular response to organic cyclic compound epoxygenase P450 pathway endothelial cell-cell adhesion omega-hydroxylase P450 pathway angiogenesis cellular aromatic compound metabolic process sterol metabolic process response to toxic substance visual perception blood vessel morphogenesis trabecular meshwork development negative regulation of NF-kappaB transcription factor activity regulation of reactive oxygen species metabolic process retinal metabolic process endothelial cell migration nitric oxide biosynthetic process retinol metabolic process cell adhesion negative regulation of cell population proliferation positive regulation of apoptotic process positive regulation of receptor signaling pathway via JAK-STAT negative regulation of cell adhesion mediated by integrin xenobiotic metabolic process cellular response to hydrogen peroxide membrane lipid catabolic process retinal blood vessel morphogenesis positive regulation of angiogenesis positive regulation of vascular endothelial growth factor production intrinsic apoptotic signaling pathway in response to oxidative stress arachidonic acid metabolic process negative regulation of cell migration estrogen metabolic process collagen fibril organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1545 13078 Ensembl ENSG00000138061 ENSMUSG00000024087 UniProt Q16678 Q64429 RefSeq (mRNA) NM_000104 NM_009994 NM_001364889 RefSeq (protein) NP_000095 NP_034124 NP_001351818 Location (UCSC) Chr 2: 38.07 – 38.11 Mb Chr 17: 80.01 – 80.02 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Cytochrome P450 1B1 is an enzyme that in humans is encoded by the CYP1B1 gene.

Function

CYP1B1 belongs to the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. The enzyme encoded by this gene localizes to the endoplasmic reticulum (ER) and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol.

Despite over 20 years of research on CYP1A1 and CYP1A2, CYP1B1 was not identified and sequenced until 1994. Nucleic and amino acid analysis showed approximately 40% identity with CYP1A1. Despite this similarity, these two enzymes have very different catalytic efficiencies and metabolites when incubated with common substrates, such as retinoic acid and arachidonic acid. Recently CYP1B1 has been shown to be physiologically important in fetal development, since mutations in CYP1B1 are linked with a form of primary congenital glaucoma.

CYP1A1 and CYP1B1 are regulated by the aryl hydrocarbon receptor, a ligand activated transcription factor. They are part of the Phase I reactions of drug metabolism.

Clinical significance

Mutations in this gene have been associated with primary congenital glaucoma; therefore it is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid.

P450 is highly expressed in tumours and implicated in drug resistance, and is a research target to combat cancer. Developed inhibitors include flavonoids, trans-stilbenes, quinazolines, and derivatives of bentranil, a herbicide.

Further reading

• Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica. 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
• Sasaki M, Kaneuchi M, Fujimoto S, et al. (2004). "CYP1B1 gene in endometrial cancer". Mol. Cell. Endocrinol. 202 (1–2): 171–6. doi:10.1016/S0303-7207(03)00079-0. PMID 12770747. S2CID 45263828.
• Nelson DR, Zeldin DC, Hoffman SM, et al. (2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants". Pharmacogenetics. 14 (1): 1–18. doi:10.1097/00008571-200401000-00001. PMID 15128046.
• Paracchini V, Raimondi S, Gram IT, et al. (2007). "Meta- and pooled analyses of the cytochrome P-450 1B1 Val432Leu polymorphism and breast cancer: a HuGE-GSEC review". Am. J. Epidemiol. 165 (2): 115–25. doi:10.1093/aje/kwj365. PMID 17053044.
• Coca-Prados M, Escribano J (2007). "New perspectives in aqueous humor secretion and in glaucoma: the ciliary body as a multifunctional neuroendocrine gland". Progress in Retinal and Eye Research. 26 (3): 239–62. doi:10.1016/j.preteyeres.2007.01.002. PMID 17321191. S2CID 2706077.
• Sutter TR, Guzman K, Dold KM, Greenlee WF (1991). "Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta". Science. 254 (5030): 415–8. Bibcode:1991Sci...254..415S. doi:10.1126/science.1925598. PMID 1925598.
• Sutter TR, Tang YM, Hayes CL, et al. (1994). "Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2". J. Biol. Chem. 269 (18): 13092–9. doi:10.1016/S0021-9258(17)36803-5. PMID 8175734.
• Tang YM, Wo YY, Stewart J, et al. (1996). "Isolation and characterization of the human cytochrome P450 CYP1B1 gene". J. Biol. Chem. 271 (45): 28324–30. doi:10.1074/jbc.271.45.28324. PMID 8910454.
• Stoilov I, Akarsu AN, Sarfarazi M (1997). "Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21". Hum. Mol. Genet. 6 (4): 641–7. doi:10.1093/hmg/6.4.641. PMID 9097971.
• Bejjani BA, Lewis RA, Tomey KF, et al. (1998). "Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia". Am. J. Hum. Genet. 62 (2): 325–33. doi:10.1086/301725. PMC 1376900. PMID 9463332.
• Stoilov I, Akarsu AN, Alozie I, et al. (1998). "Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1". Am. J. Hum. Genet. 62 (3): 573–84. doi:10.1086/301764. PMC 1376958. PMID 9497261.
• Bailey LR, Roodi N, Dupont WD, Parl FF (1998). "Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid receptor status in breast cancer". Cancer Res. 58 (22): 5038–41. PMID 9823305.
• Plásilová M, Stoilov I, Sarfarazi M, et al. (1999). "Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma". J. Med. Genet. 36 (4): 290–4. doi:10.1136/jmg.36.4.290. PMC 1734351. PMID 10227395.
• Lewis DF, Lake BG, George SG, et al. (2000). "Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6 and CYP1B1 based on sequence homology with CYP102". Toxicology. 139 (1–2): 53–79. doi:10.1016/S0300-483X(99)00098-0. PMID 10614688.
• Vincent A, Billingsley G, Priston M, et al. (2001). "Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly". J. Med. Genet. 38 (5): 324–6. doi:10.1136/jmg.38.5.324. PMC 1734880. PMID 11403040.
• Bofinger DP, Feng L, Chi LH, et al. (2001). "Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of human endometrium". Toxicol. Sci. 62 (2): 299–314. doi:10.1093/toxsci/62.2.299. PMID 11452143.
• Michels-Rautenstrauss KG, Mardin CY, Zenker M, et al. (2002). "Primary congenital glaucoma: three case reports on novel mutations and combinations of mutations in the GLC3A (CYP1B1) gene". J. Glaucoma. 10 (4): 354–7. doi:10.1097/00061198-200108000-00017. PMID 11558822. S2CID 42833828.
• Lai J, Vesprini D, Chu W, et al. (2002). "CYP gene polymorphisms and early menarche". Mol. Genet. Metab. 74 (4): 449–57. doi:10.1006/mgme.2001.3260. PMID 11749050.
• Vincent AL, Billingsley G, Buys Y, et al. (2002). "Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene". Am. J. Hum. Genet. 70 (2): 448–60. doi:10.1086/338709. PMC 384919. PMID 11774072.

External links

• cytochrome+P-450+CYP1B1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• CYP1B1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• GeneReview/NCBI/NIH/UW entry on Primary Congenital Glaucoma
• Human CYP1B1 genome location and CYP1B1 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.