Cytochrome P450 2B6


NameCytochrome P450 2B6
Synonyms1,4-cineole 2-exo-monooxygenase 1.14.13.- CYPIIB6 Cytochrome P450 IIB1
Gene NameCYP2B6
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006839|Cytochrome P450 2B6
MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLRFRE
KYGDVFTVHLGPRPVVMLCGVEAIREALVDKAEAFSGRGKIAMVDPFFRGYGVIFANGNR
WKVLRRFSVTTMRDFGMGKRSVEERIQEEAQCLIEELRKSKGALMDPTFLFQSITANIIC
SIVFGKRFHYQDQEFLKMLNLFYQTFSLISSVFGQLFELFSGFLKYFPGAHRQVYKNLQE
INAYIGHSVEKHRETLDPSAPKDLIDTYLLHMEKEKSNAHSEFSHQNLNLNTLSLFFAGT
ETTSTTLRYGFLLMLKYPHVAERVYREIEQVIGPHRPPELHDRAKMPYTEAVIYEIQRFS
DLLPMGVPHIVTQHTSFRGYIIPKDTEVFLILSTALHDPHYFEKPDAFNPDHFLDANGAL
KKTEAFIPFSLGKRICLGEGIARAELFLFFTTILQNFSMASPVAPEDIDLTPQECGVGKI
PPTYQIRFLPR
Number of residues491
Molecular Weight56277.81
Theoretical pI8.44
GO Classification
Functions
    iron ion binding
    heme binding
    monooxygenase activity
    oxygen binding
    arachidonic acid epoxygenase 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
    steroid hydroxylase activity
Processes
    cellular ketone metabolic process
    oxidation-reduction process
    steroid metabolic process
    xenobiotic metabolic process
    drug metabolic process
    epoxygenase P450 pathway
    exogenous drug catabolic process
    small molecule metabolic process
Components
    intracellular membrane-bounded organelle
    cytoplasm
    endoplasmic reticulum membrane
General FunctionSteroid hydroxylase activity
Specific FunctionCytochromes 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, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Transmembrane Regions
GenBank Protein ID181296
UniProtKB IDP20813
UniProtKB Entry NameCP2B6_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0019435|Cytochrome P450 2B6 (CYP2B6)
ATGGAACTCAGCGTCCTCCTCTTCCTTGCACTCCTCACAGGACTCTTGCTACTCCTGGTT
CAGCGCCACCCTAACACCCATGACCGCCTCCCACCAGGGCCCCGCCCTCTGCCCCTTTTG
GGAAACCTTCTGCAGATGGATAGAAGAGGCCTACTCAAATCCTTTCTGAGGTTCCGAGAG
AAATATGGGGACGTCTTCACGGTACACCTGGGACCGAGGCCCGTGGTCATGCTGTGTGGA
GTAGAGGCCATACGGGAGGCCCTTGTGGACAAGGCTGAGGCCTTCTCTGGCCGGGGAAAA
ATCGCCATGGTCGACCCATTCTTCCGGGGATATGGTGTGATCTTTGCCAATGGAAACCGC
TGGAAGGTGCTTCGGCGATTCTCTGTGACCACTATGAGGGACTTCGGGATGGGAAAGCGG
AGTGTGGAGGAGCGGATTCAGGAGGAGGCTCAGTGTCTGATAGAGGAGCTTCGGAAATCC
AAGGGGGCCCTCATGGACCCCACCTTCCTCTTCCAGTCCATTACCGCCAACATCATCTGC
TCCATCGTCTTTGGAAAACGATTCCACTACCAAGATCAAGAGTTCCTGAAGATGCTGAAC
TTGTTCTACCAGACTTTTTCACTCATCAGCTCTGTATTCGGCCAGCTGTTTGAGCTCTTC
TCTGGCTTCTTGAAATACTTTCCTGGGGCACACAGGCAAGTTTACAAAAACCTGCAGGAA
ATCAATGCTTACATTGGCCACAGTGTGGAGAAGCACCGTGAAACCCTGGACCCCAGCGCC
CCCAAGGACCTCATCGACACCTACCTGCTCCACATGGAAAAAGAGAAATCCAACGCACAC
AGTGAATTCAGCCACCAGAACCTCAACCTCAACACGCTCTCGCTCTTCTTTGCTGGCACT
GAGACCACCAGCACCACTCTCCGCTACGGCTTCCTGCTCATGCTCAAATACCCTCATGTT
GCAGAGAGAGTCTACAGGGAGATTGAACAGGTGATTGGCCCACATCGCCCTCCAGAGCTT
CATGACCGAGCCAAAATGCCATACACAGAGGCAGTCATCTATGAGATTCAGAGATTTTCC
GACCTTCTCCCCATGGGTGTGCCCCACATTGTCACCCAACACACCAGCTTCCGAGGGTAC
ATCATCCCCAAGGACACAGAAGTATTTCTCATCCTGAGCACTGCTCTCCATGACCCACAC
TACTTTGAAAAACCAGACGCCTTCAATCCTGACCACTTTCTGGATGCCAATGGGGCACTG
AAAAAGACTGAAGCTTTTATCCCCTTCTCCTTAGGGAAGCGGATTTGTCTTGGTGAAGGC
ATCGCCCGTGCGGAATTGTTCCTCTTCTTCACCACCATCCTCCAGAACTTCTCCATGGCC
AGCCCCGTGGCCCCAGAAGACATCGATCTGACACCCCAGGAGTGTGGTGTGGGCAAAATA
CCCCCAACATACCAGATCCGCTTCCTGCCCCGCTGA
GenBank Gene IDM29874
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:2615
Chromosome Location19
Locus19q13.2
References
  1. Yamano S, Nhamburo PT, Aoyama T, Meyer UA, Inaba T, Kalow W, Gelboin HV, McBride OW, Gonzalez FJ: cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver. Biochemistry. 1989 Sep 5;28(18):7340-8.[2573390 ]
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  6. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22.[24275569 ]
  7. Gay SC, Shah MB, Talakad JC, Maekawa K, Roberts AG, Wilderman PR, Sun L, Yang JY, Huelga SC, Hong WX, Zhang Q, Stout CD, Halpert JR: Crystal structure of a cytochrome P450 2B6 genetic variant in complex with the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution. Mol Pharmacol. 2010 Apr;77(4):529-38. doi: 10.1124/mol.109.062570. Epub 2010 Jan 8.[20061448 ]
  8. Shah MB, Pascual J, Zhang Q, Stout CD, Halpert JR: Structures of cytochrome P450 2B6 bound to 4-benzylpyridine and 4-(4-nitrobenzyl)pyridine: insight into inhibitor binding and rearrangement of active site side chains. Mol Pharmacol. 2011 Dec;80(6):1047-55. doi: 10.1124/mol.111.074427. Epub 2011 Aug 29.[21875942 ]
  9. Shah MB, Wilderman PR, Pascual J, Zhang Q, Stout CD, Halpert JR: Conformational adaptation of human cytochrome P450 2B6 and rabbit cytochrome P450 2B4 revealed upon binding multiple amlodipine molecules. Biochemistry. 2012 Sep 18;51(37):7225-38. doi: 10.1021/bi300894z. Epub 2012 Sep 4.[22909231 ]
  10. Haas DW, Ribaudo HJ, Kim RB, Tierney C, Wilkinson GR, Gulick RM, Clifford DB, Hulgan T, Marzolini C, Acosta EP: Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS. 2004 Dec 3;18(18):2391-400.[15622315 ]
  11. Elens L, Vandercam B, Yombi JC, Lison D, Wallemacq P, Haufroid V: Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients. Pharmacogenomics. 2010 Sep;11(9):1223-34. doi: 10.2217/pgs.10.94.[20860463 ]
  12. Ariyoshi N, Miyazaki M, Toide K, Sawamura Yi, Kamataki T: A single nucleotide polymorphism of CYP2b6 found in Japanese enhances catalytic activity by autoactivation. Biochem Biophys Res Commun. 2001 Mar;281(5):1256-60.[11243870 ]
  13. Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofmann U, Eichelbaum M, Schwab M, Zanger UM: Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. 2001 Jul;11(5):399-415.[11470993 ]
  14. Jinno H, Tanaka-Kagawa T, Ohno A, Makino Y, Matsushima E, Hanioka N, Ando M: Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab Dispos. 2003 Apr;31(4):398-403.[12642465 ]
  15. Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y: Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population. J Hum Genet. 2003;48(5):249-70. Epub 2003 Apr 29.[12721789 ]
  16. Lamba V, Lamba J, Yasuda K, Strom S, Davila J, Hancock ML, Fackenthal JD, Rogan PK, Ring B, Wrighton SA, Schuetz EG: Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther. 2003 Dec;307(3):906-22. Epub 2003 Oct 9.[14551287 ]
  17. Lang T, Klein K, Richter T, Zibat A, Kerb R, Eichelbaum M, Schwab M, Zanger UM: Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J Pharmacol Exp Ther. 2004 Oct;311(1):34-43. Epub 2004 Jun 9.[15190123 ]
  18. Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP: Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004 Oct;5(7):895-931.[15469410 ]
  19. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21.[14702039 ]
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Related FRC


FRCD ID Name Exact Mass Structure



Ethanol




46.07



Fipronil




437.141



Rotenone




394.423



Dichlorprop




235.06



Alachlor




269.769



Acetochlor




269.769



Bendiocarb




223.228



Benomyl




290.323



Carbaril




201.225



Chlorpropham




213.661



Fenoxycarb




301.342



Pirimicarb




238.291



Propoxur




209.245



Thiobencarb




257.776



Allethrin




302.414



Resmethrin




338.447



Tetramethrin




331.412



Cypermethrin




416.298



(±)-Metalaxyl




279.336



Metolachlor




283.796



Hydroxytriphenylstannane




367.035



Chlorothalonil




265.902



2,6-Dichlorobenzonitrile




172.008



Fenpropathrin




349.43



Anidulafungin




1140.254



Fenthion




278.321



Azamethiphos




324.672



Acifluorfen




361.657



Ametryn




227.33



Benfluralin




335.283



Bensulide




397.503



Bifenazate




300.358



Boscalid




343.207



Bromacil




261.119



Buprofezin




305.44



Butafenacil




474.817



Chloridazon




221.644



Chloroneb




207.05



Chlorsulfuron




357.769



Cinmethylin




274.404



Clofentezine




303.146



Cyprodinil




225.295



Dichloran




207.01



Diclosulam




406.213



Difenoconazole




406.263



Dimethenamid




275.791



Ethalfluralin




333.267



Etoxazole




359.417



Fenamidone




311.403



Fenamiphos




303.36



Fenitrothion




277.24



Flufenacet




363.331



Flusilazole




315.399



Flutolanil




323.315



Fosthiazate




283.341



Hexazinone




252.318



Enilconazole




297.179



Indoxacarb




527.837



Iprodione




330.165



Isoxaben




332.4



Isoxaflutole




359.319



Lactofen




461.774



Malathion




330.35



Methidathion




302.318



Methoxyfenozide




368.477



Metribuzin




214.287



Myclobutanil




288.779



Napropamide




271.36



Norflurazon




303.669



Oxadiazon




345.22



Penoxsulam




483.37



Phosalone




367.799



Prochloraz




376.662



Prometryn




241.357



Propargite




350.473



Propazine




229.712



Propiconazole




342.22



Pyriproxyfen




321.376



Sethoxydim




327.483



Simazine




201.658



Sulfentrazone




387.183



Tebufenozide




352.478



Tebufenpyrad




333.86



Tebupirimfos




318.372



Tetraconazole




372.145



Thiabendazole




201.247



Thiazopyr




396.376



Triclosan




289.536



Vinclozolin




286.108



Butylparaben




194.23



2-Biphenylol




170.21



Acetamiprid




222.676



Atrazine




215.685



Butralin




295.339



Butylate




217.371



Captafol




349.047



Carboxin




235.301



Chlorethoxyfos




335.985



Clodinafop-propargyl




349.742



Clomazone




239.699



Clopyralid




191.995



Cyclanilide




274.097



Cyproconazole




291.779



Diazoxon




288.284



Diphenylamine




169.227



Dithiopyr




401.41



Diuron




233.092



Ethofumesate




286.342



Fenarimol




331.196



Fenbuconazole




336.823



Fludioxonil




248.189



Fluometuron




232.206



Forchlorfenuron




247.682



Hexaconazole




314.21



Isazofos




313.737



Linuron




249.091



Oryzalin




346.358



Profenofos




373.626



Propyzamide




256.126



Pyrimethanil




199.257



Quinoxyfen




308.133



Terbacil




216.665



Thidiazuron




220.25



Thiram




240.416



Triadimefon




293.751



Triadimenol




295.767



Triflumizole




345.75



Trifluralin




335.283



Triticonazole




317.817



Zoxamide




336.637



2(3H)-Benzothiazolethione




334.488



Ethoxyquin




217.312



Pendimethalin




281.312



Cyfluthrin




434.288



Butachlor




311.85



Cyanazine




240.695



Fluazinam




465.089



Flumioxazin




354.337



Triasulfuron




401.822



Coumaphos




362.761



Prallethrin




300.398



Quintozene




295.321



Dieldrin




380.895



Chlordane




409.758



Disulfoton




274.392



Methoxychlor




345.644



Diazinon




304.35



Dimethylarsinate




136.99



Guthion




317.318



Chlordecone




490.609



Dicofol




370.475



Parathion




291.258



Dimethoate




229.3



(±)-Naled




380.778



Ethoprop




242.332



Mercuric chloride




271.492



Bisphenol A




228.291