Cytochrome P450 1B1

Details

Name
Cytochrome P450 1B1
Synonyms
  • 1.14.14.1
  • CYPIB1
Gene Name
CYP1B1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016314|Cytochrome P450 1B1
MGTSLSPNDPWPLNPLSIQQTTLLLLLSVLATVHVGQRLLRQRRRQLRSAPPGPFAWPLI
GNAAAVGQAAHLSFARLARRYGDVFQIRLGSCPIVVLNGERAIHQALVQQGSAFADRPAF
ASFRVVSGGRSMAFGHYSEHWKVQRRAAHSMMRNFFTRQPRSRQVLEGHVLSEARELVAL
LVRGSADGAFLDPRPLTVVAVANVMSAVCFGCRYSHDDPEFRELLSHNEEFGRTVGAGSL
VDVMPWLQYFPNPVRTVFREFEQLNRNFSNFILDKFLRHCESLRPGAAPRDMMDAFILSA
EKKAAGDSHGGGARLDLENVPATITDIFGASQDTLSTALQWLLLLFTRYPDVQTRVQAEL
DQVVGRDRLPCMGDQPNLPYVLAFLYEAMRFSSFVPVTIPHATTANTSVLGYHIPKDTVV
FVNQWSVNHDPLKWPNPENFDPARFLDKDGLINKDLTSRVMIFSVGKRRCIGEELSKMQL
FLFISILAHQCDFRANPNEPAKMNFSYGLTIKPKSFKVNVTLRESMELLDSAVQNLQAKE
TCQ
Number of residues
543
Molecular Weight
60845.33
Theoretical pI
9.23
GO Classification
Functions
aromatase activity / heme binding / iron ion binding / monooxygenase 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 / oxygen binding
Processes
angiogenesis / arachidonic acid metabolic process / blood vessel morphogenesis / cell adhesion / cellular aromatic compound metabolic process / cellular response to hydrogen peroxide / cellular response to organic cyclic compound / collagen fibril organization / endothelial cell migration / endothelial cell-cell adhesion / epoxygenase P450 pathway / estrogen metabolic process / intrinsic apoptotic signaling pathway in response to oxidative stress / membrane lipid catabolic process / negative regulation of cell adhesion mediated by integrin / negative regulation of cell migration / negative regulation of cell proliferation / negative regulation of NF-kappaB transcription factor activity / nitric oxide biosynthetic process / omega-hydroxylase P450 pathway / oxidation-reduction process / positive regulation of angiogenesis / positive regulation of apoptotic process / positive regulation of JAK-STAT cascade / positive regulation of vascular endothelial growth factor production / regulation of reactive oxygen species metabolic process / response to toxic substance / retinal blood vessel morphogenesis / retinal metabolic process / retinol metabolic process / small molecule metabolic process / steroid metabolic process / sterol metabolic process / toxin metabolic process / trabecular meshwork development / visual perception / xenobiotic metabolic process
Components
endoplasmic reticulum membrane / mitochondrion
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0016315|Cytochrome P450 1B1 (CYP1B1)
ATGGGCACCAGCCTCAGCCCGAACGACCCTTGGCCGCTAAACCCGCTGTCCATCCAGCAG
ACCACGCTCCTGCTACTCCTGTCGGTGCTGGCCACTGTGCATGTGGGCCAGCGGCTGCTG
AGGCAACGGAGGCGGCAGCTCCGGTCCGCGCCCCCGGGCCCGTTTGCGTGGCCACTGATC
GGAAACGCGGCGGCGGTGGGCCAGGCGGCTCACCTCTCGTTCGCTCGCCTGGCGCGGCGC
TACGGCGACGTTTTCCAGATCCGCCTGGGCAGCTGCCCCATAGTGGTGCTGAATGGCGAG
CGCGCCATCCACCAGGCCCTGGTGCAGCAGGGCTCGGCCTTCGCCGACCGGCCGGCCTTC
GCCTCCTTCCGTGTGGTGTCCGGCGGCCGCAGCATGGCTTTCGGCCACTACTCGGAGCAC
TGGAAGGTGCAGCGGCGCGCAGCCCACAGCATGATGCGCAACTTCTTCACGCGCCAGCCG
CGCAGCCGCCAAGTCCTCGAGGGCCACGTGCTGAGCGAGGCGCGCGAGCTGGTGGCGCTG
CTGGTGCGCGGCAGCGCGGACGGCGCCTTCCTCGACCCGAGGCCGCTGACCGTCGTGGCC
GTGGCCAACGTCATGAGTGCCGTGTGTTTCGGCTGCCGCTACAGCCACGACGACCCCGAG
TTCCGTGAGCTGCTCAGCCACAACGAAGAGTTCGGGCGCACGGTGGGCGCGGGCAGCCTG
GTGGACGTGATGCCCTGGCTGCAGTACTTCCCCAACCCGGTGCGCACCGTTTTCCGCGAA
TTCGAGCAGCTCAACCGCAACTTCAGCAACTTCATCCTGGACAAGTTCTTGAGGCACTGC
GAAAGCCTTCGGCCCGGGGCCGCCCCCCGCGACATGATGGACGCCTTTATCCTCTCTGCG
GAAAAGAAGGCGGCCGGGGACTCGCACGGTGGTGGCGCGCGGCTGGATTTGGAGAACGTA
CCGGCCACTATCACTGACATCTTCGGCGCCAGCCAGGACACCCTGTCCACCGCGCTGCAG
TGGCTGCTCCTCCTCTTCACCAGGTATCCTGATGTGCAGACTCGAGTGCAGGCAGAATTG
GATCAGGTCGTGGGGAGGGACCGTCTGCCTTGTATGGGTGACCAGCCCAACCTGCCCTAT
GTCCTGGCCTTCCTTTATGAAGCCATGCGCTTCTCCAGCTTTGTGCCTGTCACTATTCCT
CATGCCACCACTGCCAACACCTCTGTCTTGGGCTACCACATTCCCAAGGACACTGTGGTT
TTTGTCAACCAGTGGTCTGTGAATCATGACCCACTGAAGTGGCCTAACCCGGAGAACTTT
GATCCAGCTCGATTCTTGGACAAGGATGGCCTCATCAACAAGGACCTGACCAGCAGAGTG
ATGATTTTTTCAGTGGGCAAAAGGCGGTGCATTGGCGAAGAACTTTCTAAGATGCAGCTT
TTTCTCTTCATCTCCATCCTGGCTCACCAGTGCGATTTCAGGGCCAACCCAAATGAGCCT
GCGAAAATGAATTTCAGTTATGGTCTAACCATTAAACCCAAGTCATTTAAAGTCAATGTC
ACTCTCAGAGAGTCCATGGAGCTCCTTGATAGTGCTGTCCAAAATTTACAAGCCAAGGAA
ACTTGCCAATAA
Chromosome Location
2
Locus
2p21
External Identifiers
ResourceLink
UniProtKB IDQ16678
UniProtKB Entry NameCP1B1_HUMAN
GenBank Protein ID501031
GenBank Gene IDU03688
GenAtlas IDCYP1B1
HGNC IDHGNC:2597
General References
  1. Sutter TR, Tang YM, Hayes CL, Wo YY, Jabs EW, Li X, Yin H, Cody CW, Greenlee WF: 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. 1994 May 6;269(18):13092-9. [PubMed:8175734]
  2. Tang YM, Wo YY, Stewart J, Hawkins AL, Griffin CA, Sutter TR, Greenlee WF: Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J Biol Chem. 1996 Nov 8;271(45):28324-30. [PubMed:8910454]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Shimada T, Watanabe J, Kawajiri K, Sutter TR, Guengerich FP, Gillam EM, Inoue K: Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999 Aug;20(8):1607-13. doi: 10.1093/carcin/20.8.1607. [PubMed:10426814]
  5. Vincent A, Billingsley G, Priston M, Williams-Lyn D, Sutherland J, Glaser T, Oliver E, Walter MA, Heathcote G, Levin A, Heon E: Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly. J Med Genet. 2001 May;38(5):324-6. [PubMed:11403040]
  6. Choudhary D, Jansson I, Stoilov I, Sarfarazi M, Schenkman JB: Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos. 2004 Aug;32(8):840-7. [PubMed:15258110]
  7. Jang HH, Kim SY, Kang JY, Park SH, Ryu SH, Ahn T, Yun CH: Increase of human CYP1B1 activities by acidic phospholipids and kinetic deuterium isotope effects on CYP1B1 substrate oxidation. J Biochem. 2012 Nov;152(5):433-42. doi: 10.1093/jb/mvs087. Epub 2012 Aug 9. [PubMed:22888116]
  8. Nishida CR, Everett S, Ortiz de Montellano PR: Specificity determinants of CYP1B1 estradiol hydroxylation. Mol Pharmacol. 2013 Sep;84(3):451-8. doi: 10.1124/mol.113.087700. Epub 2013 Jul 2. [PubMed:23821647]
  9. Poon CH, Wong TY, Wang Y, Tsuchiya Y, Nakajima M, Yokoi T, Leung LK: The citrus flavanone naringenin suppresses CYP1B1 transactivation through antagonising xenobiotic-responsive element binding. Br J Nutr. 2013 May;109(9):1598-605. doi: 10.1017/S0007114512003595. Epub 2012 Aug 31. [PubMed:22935222]
  10. Wang A, Savas U, Stout CD, Johnson EF: Structural characterization of the complex between alpha-naphthoflavone and human cytochrome P450 1B1. J Biol Chem. 2011 Feb 18;286(7):5736-43. doi: 10.1074/jbc.M110.204420. Epub 2010 Dec 8. [PubMed:21147782]
  11. Bejjani BA, Lewis RA, Tomey KF, Anderson KL, Dueker DK, Jabak M, Astle WF, Otterud B, Leppert M, Lupski JR: Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia. Am J Hum Genet. 1998 Feb;62(2):325-33. [PubMed:9463332]
  12. Stoilov I, Akarsu AN, Alozie I, Child A, Barsoum-Homsy M, Turacli ME, Or M, Lewis RA, Ozdemir N, Brice G, Aktan SG, Chevrette L, Coca-Prados M, Sarfarazi M: 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. 1998 Mar;62(3):573-84. [PubMed:9497261]
  13. Bailey LR, Roodi N, Dupont WD, Parl FF: Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid receptor status in breast cancer. Cancer Res. 1998 Nov 15;58(22):5038-41. [PubMed:9823305]
  14. Plasilova M, Stoilov I, Sarfarazi M, Kadasi L, Ferakova E, Ferak V: Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma. J Med Genet. 1999 Apr;36(4):290-4. [PubMed:10227395]
  15. Bejjani BA, Stockton DW, Lewis RA, Tomey KF, Dueker DK, Jabak M, Astle WF, Lupski JR: Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus. Hum Mol Genet. 2000 Feb 12;9(3):367-74. [PubMed:10655546]
  16. Ohtake Y, Kubota R, Tanino T, Miyata H, Mashima Y: Novel compound heterozygous mutations in the cytochrome P4501B1 gene (CYP1B1) in a Japanese patient with primary congenital glaucoma. Ophthalmic Genet. 2000 Sep;21(3):191-3. [PubMed:11184479]
  17. Watanabe J, Shimada T, Gillam EM, Ikuta T, Suemasu K, Higashi Y, Gotoh O, Kawajiri K: Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer. Pharmacogenetics. 2000 Feb;10(1):25-33. [PubMed:10739169]
  18. Mashima Y, Suzuki Y, Sergeev Y, Ohtake Y, Tanino T, Kimura I, Miyata H, Aihara M, Tanihara H, Inatani M, Azuma N, Iwata T, Araie M: Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma. Invest Ophthalmol Vis Sci. 2001 Sep;42(10):2211-6. [PubMed:11527932]
  19. Vincent AL, Billingsley G, Buys Y, Levin AV, Priston M, Trope G, Williams-Lyn D, Heon E: Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am J Hum Genet. 2002 Feb;70(2):448-60. Epub 2002 Jan 3. [PubMed:11774072]
  20. Panicker SG, Reddy AB, Mandal AK, Ahmed N, Nagarajaram HA, Hasnain SE, Balasubramanian D: Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees. Invest Ophthalmol Vis Sci. 2002 May;43(5):1358-66. [PubMed:11980847]
  21. Stoilov IR, Costa VP, Vasconcellos JP, Melo MB, Betinjane AJ, Carani JC, Oltrogge EV, Sarfarazi M: Molecular genetics of primary congenital glaucoma in Brazil. Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1820-7. [PubMed:12036985]
  22. Aklillu E, Oscarson M, Hidestrand M, Leidvik B, Otter C, Ingelman-Sundberg M: Functional analysis of six different polymorphic CYP1B1 enzyme variants found in an Ethiopian population. Mol Pharmacol. 2002 Mar;61(3):586-94. [PubMed:11854439]
  23. Chakrabarti S, Komatireddy S, Mandal AK, Balasubramanian D: Gene symbol: CYP1B1. Disease: glaucoma, primary congenital. Hum Genet. 2003 Nov;113(6):556. [PubMed:14640114]
  24. Colomb E, Kaplan J, Garchon HJ: Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary congenital glaucoma in France. Hum Mutat. 2003 Dec;22(6):496. [PubMed:14635112]
  25. Sitorus R, Ardjo SM, Lorenz B, Preising M: CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and European patients. J Med Genet. 2003 Jan;40(1):e9. [PubMed:12525557]
  26. Melki R, Colomb E, Lefort N, Brezin AP, Garchon HJ: CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma. J Med Genet. 2004 Sep;41(9):647-51. [PubMed:15342693]
  27. Reddy AB, Kaur K, Mandal AK, Panicker SG, Thomas R, Hasnain SE, Balasubramanian D, Chakrabarti S: Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients. Mol Vis. 2004 Sep 30;10:696-702. [PubMed:15475877]
  28. Curry SM, Daou AG, Hermanns P, Molinari A, Lewis RA, Bejjani BA: Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador. Ophthalmic Genet. 2004 Mar;25(1):3-9. [PubMed:15255109]
  29. Alfadhli S, Behbehani A, Elshafey A, Abdelmoaty S, Al-Awadi S: Molecular and clinical evaluation of primary congenital glaucoma in Kuwait. Am J Ophthalmol. 2006 Mar;141(3):512-6. [PubMed:16490498]
  30. Acharya M, Mookherjee S, Bhattacharjee A, Bandyopadhyay AK, Daulat Thakur SK, Bhaduri G, Sen A, Ray K: Primary role of CYP1B1 in Indian juvenile-onset POAG patients. Mol Vis. 2006 Apr 20;12:399-404. [PubMed:16688110]
  31. Chavarria-Soley G, Michels-Rautenstrauss K, Pasutto F, Flikier D, Flikier P, Cirak S, Bejjani B, Winters DL, Lewis RA, Mardin C, Reis A, Rautenstrauss B: Primary congenital glaucoma and Rieger's anomaly: extended haplotypes reveal founder effects for eight distinct CYP1B1 mutations. Mol Vis. 2006 May 22;12:523-31. [PubMed:16735994]
  32. Lopez-Garrido MP, Sanchez-Sanchez F, Lopez-Martinez F, Aroca-Aguilar JD, Blanco-Marchite C, Coca-Prados M, Escribano J: Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma. Mol Vis. 2006 Jul 11;12:748-55. [PubMed:16862072]
  33. Chavarria-Soley G, Sticht H, Aklillu E, Ingelman-Sundberg M, Pasutto F, Reis A, Rautenstrauss B: Mutations in CYP1B1 cause primary congenital glaucoma by reduction of either activity or abundance of the enzyme. Hum Mutat. 2008 Sep;29(9):1147-53. doi: 10.1002/humu.20786. [PubMed:18470941]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01065Melatoninapproved, nutraceutical, vet_approvedunknownsubstrateinhibitorDetails
DB00675TamoxifenapprovedunknownsubstrateinhibitorDetails
DB00818Propofolapproved, investigational, vet_approvedunknowninhibitorDetails
DB02709Resveratrolapproved, experimental, investigationalunknowninhibitorDetails
DB00613Amodiaquineapproved, investigationalunknownsubstrateDetails
DB00121Biotinapproved, investigational, nutraceuticalunknowninducerDetails
DB00201CaffeineapprovedunknownsubstrateDetails
DB00694DaunorubicinapprovedunknowninhibitorDetails
DB01248Docetaxelapproved, investigationalunknownbinderDetails
DB00997Doxorubicinapproved, investigationalunknowninhibitorinducerDetails
DB00783Estradiolapproved, investigational, vet_approvedunknownsubstrateDetails
DB00655EstroneapprovedunknownsubstrateDetails
DB00499Flutamideapproved, investigationalunknownsubstrateDetails
DB01026Ketoconazoleapproved, investigationalunknowninhibitorDetails
DB00448Lansoprazoleapproved, investigationalunknowninducerDetails
DB01204Mitoxantroneapproved, investigationalunknowninhibitorDetails
DB00338Omeprazoleapproved, investigational, vet_approvedunknowninducerDetails
DB01229Paclitaxelapproved, vet_approvedunknowninhibitorDetails
DB01087PrimaquineapprovedunknowninducerDetails
DB00396Progesteroneapproved, vet_approvedunknownsubstrateDetails
DB00624Testosteroneapproved, investigationalunknownsubstrateDetails
DB00277TheophyllineapprovedunknownsubstrateDetails
DB00530Erlotinibapproved, investigationalunknownsubstrateDetails
DB01254Dasatinibapproved, investigationalunknownsubstrateDetails
DB023422-MethoxyestradiolinvestigationalunknownDetails
DB06732beta-NaphthoflavoneexperimentalunknownDetails
DB07776Flavoneapproved, experimentalunknownDetails
DB01645GenisteininvestigationalunknownDetails
DB03467NaringeninexperimentalunknownDetails
DB04216Quercetinexperimental, investigationalunknownDetails
DB13946Testosterone undecanoateapproved, investigationalunknownsubstrateDetails
DB13952Estradiol acetateapproved, investigational, vet_approvedunknownsubstrateDetails
DB13953Estradiol benzoateapproved, investigational, vet_approvedunknownsubstrateDetails
DB13954Estradiol cypionateapproved, investigational, vet_approvedunknownsubstrateDetails
DB13955Estradiol dienanthateapproved, investigational, vet_approvedunknownsubstrateDetails
DB13956Estradiol valerateapproved, investigational, vet_approvedunknownsubstrateDetails
DB14009Medical Cannabisexperimental, investigationalunknowninhibitorDetails
DB11155TriclocarbanapprovedunknowninducerDetails
DB12245Triclabendazoleapproved, investigationalunknownsubstrateDetails
DB09061Cannabidiolapproved, investigationalunknowninhibitorDetails
DB14011NabiximolsinvestigationalunknowninhibitorDetails
DB00635Prednisoneapproved, vet_approvedunknowninducerDetails
DB00741Hydrocortisoneapproved, vet_approvedunknowninducerDetails