Human Gene CYP2B6 (uc002opr.1)
  Description: Homo sapiens cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), mRNA.
RefSeq Summary (NM_000767): This gene, CYP2B6, encodes a member of 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. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Transcript (Including UTRs)
   Position: hg19 chr19:41,497,204-41,524,301 Size: 27,098 Total Exon Count: 9 Strand: +
Coding Region
   Position: hg19 chr19:41,497,211-41,522,732 Size: 25,522 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:41,497,204-41,524,301)mRNA (may differ from genome)Protein (491 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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GeneNetworkHGNCHPRDLynxMalacardsMGI
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: CP2B6_HUMAN
DESCRIPTION: RecName: Full=Cytochrome P450 2B6; EC=1.14.13.-; AltName: Full=1,4-cineole 2-exo-monooxygenase; AltName: Full=CYPIIB6; AltName: Full=Cytochrome P450 IIB1;
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, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
CATALYTIC ACTIVITY: 1,4-cineole + NADPH + O(2) = 2-exo-hydroxy- 1,4-cineole + NADP(+) + H(2)O.
COFACTOR: Heme group.
COFACTOR: Heme group (By similarity).
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=360 uM for 1,4-cineole; Vmax=3.4 nmol/min/nmol enzyme toward 2-exo-hydroxy-1,4-cineole;
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
TISSUE SPECIFICITY: Expressed in liver, lung and heart right ventricle.
INDUCTION: By phenobarbital.
PTM: Phosphorylation is accompanied by a decrease in enzyme activity (By similarity).
POLYMORPHISM: Genetic variations in CYP2B6 are responsible for poor metabolism of efavirenz and, therefore, susceptibility to efavirenz toxicity in the central nervous system [MIM:614546]. Efavirenz is a non-nucleoside reverse transcriptase inhibitor frequently prescribed with 2 nucleoside reverse transcriptase inhibitors as initial therapy for human immunodeficiency virus (HIV) infection. Up to half of patients treated with efavirenz, experience side effects in the central nervous system, including dizziness, insomnia, impaired concentration, somnolence, and abnormal dreams. Severe depression, aggressive behavior, and paranoid or manic reactions may also occur, depending on efavirenz concentration in the plasma.
SIMILARITY: Belongs to the cytochrome P450 family.
WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; Note=CYP2B6 alleles; URL="http://www.cypalleles.ki.se/cyp2b6.htm";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cyp2b6/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CYP2B6
CDC HuGE Published Literature: CYP2B6
Positive Disease Associations: cyclophosphamide bioactivation , cyclophosphamide phamacokinetics , cyclophosphamide pharmacokinetics , efavirenz pharmacokinetics HIV , methadone levels , nevaprine pharmacokinetics , nicotine smoking behavior , Smoking , smoking behavior
Related Studies:
  1. cyclophosphamide bioactivation
    Xie, H. J. et al. 2003, Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation, The pharmacogenomics journal. 2003 ;3(1):53-61. [PubMed 12629583]
    Our results demonstrate that the polymorphic CYP2B6 is a major enzyme in the bioactivation of CPA. Moreover, we identified a strong impact of CYP2B6*6 on CPA 4-hydroxylation.
  2. cyclophosphamide phamacokinetics
    Timm, R. et al. 2005, Association of cyclophosphamide pharmacokinetics to polymorphic cytochrome P450 2C19., The pharmacogenomics journal. 2005 ;5(6):365-73. [PubMed 16116487]
  3. cyclophosphamide pharmacokinetics
    Nakajima, M. et al. 2007, Genetic polymorphisms of CYP2B6 affect the pharmacokinetics/pharmacodynamics of cyclophosphamide in Japanese cancer patients, Pharmacogenet Genomics 2007 17(6) 431-45. [PubMed 17502835]
    We clarified that the single nucleotide polymorphisms in the promoter region or introns in the CYP2B6 affect the potency of cyclophosphamide activation to 4-hydroxycyclophosphamide. This information would be valuable for predicting adverse reactions and the clinical efficacy of cyclophosphamide.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: CYP2B6
Diseases sorted by gene-association score: efavirenz, poor metabolism of* (600), cyp2b6-related altered drug metabolism* (100), acute frontal sinusitis (11), retinitis pigmentosa 56 (8), frontal sinusitis (7), femoral neuropathy (7), kidney cortex necrosis (7), conjunctival degeneration (6), ovarian brenner tumor (5), retinitis pigmentosa 44 (5), pinguecula (5), histidinemia (4), histidine metabolism disease (4), tuberculosis (4), holoprosencephaly 3 (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 73.27 RPKM in Liver
Total median expression: 84.02 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -494.221569-0.315 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001128 - Cyt_P450
IPR017972 - Cyt_P450_CS
IPR002401 - Cyt_P450_E_grp-I
IPR008068 - Cyt_P450_E_grp-I_CYP2B-like

Pfam Domains:
PF00067 - Cytochrome P450

SCOP Domains:
48264 - Cytochrome P450

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3IBD - X-ray MuPIT 3QOA - X-ray MuPIT 3QU8 - X-ray MuPIT 3UA5 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P20813
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologGenome BrowserNo ortholog
 Gene Details  Gene Details 
 Gene Sorter  Gene Sorter 
 RGD  WormBase 
 Protein Sequence  Protein Sequence 
 Alignment  Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004497 monooxygenase activity
GO:0005506 iron ion binding
GO:0008392 arachidonic acid epoxygenase activity
GO:0008395 steroid hydroxylase activity
GO:0016491 oxidoreductase activity
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
GO:0016712 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
GO:0020037 heme binding
GO:0046872 metal ion binding

Biological Process:
GO:0006805 xenobiotic metabolic process
GO:0008202 steroid metabolic process
GO:0017144 drug metabolic process
GO:0019373 epoxygenase P450 pathway
GO:0042180 cellular ketone metabolic process
GO:0042738 exogenous drug catabolic process
GO:0055114 oxidation-reduction process

Cellular Component:
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0016020 membrane
GO:0031090 organelle membrane
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  BC067430 - Homo sapiens cytochrome P450, family 2, subfamily B, polypeptide 6, mRNA (cDNA clone MGC:79256 IMAGE:7002137), complete cds.
BC067431 - Homo sapiens cytochrome P450, family 2, subfamily B, polypeptide 6, mRNA (cDNA clone MGC:79257 IMAGE:7002142), complete cds.
M29874 - Human cytochrome P450-IIB (hIIB1) mRNA, complete cds.
KJ896680 - Synthetic construct Homo sapiens clone ccsbBroadEn_06074 CYP2B6 gene, encodes complete protein.
KR711979 - Synthetic construct Homo sapiens clone CCSBHm_00034480 CYP2B6 (CYP2B6) mRNA, encodes complete protein.
KR711980 - Synthetic construct Homo sapiens clone CCSBHm_00034481 CYP2B6 (CYP2B6) mRNA, encodes complete protein.
KR711981 - Synthetic construct Homo sapiens clone CCSBHm_00034483 CYP2B6 (CYP2B6) mRNA, encodes complete protein.
KR711982 - Synthetic construct Homo sapiens clone CCSBHm_00034485 CYP2B6 (CYP2B6) mRNA, encodes complete protein.
AF182277 - Homo sapiens cytochrome P450-2B6 (CYP2B6) mRNA, complete cds.
E10616 - Human cDNA encoding cytochrome P4502B6.
E10861 - cDNA encoding human cytochrome P450.
X13494 - Human mRNA for cytochrome P-450IIB6.
AK301620 - Homo sapiens cDNA FLJ50266 complete cds, highly similar to Cytochrome P450 2B6 (EC 1.14.14.1).
X06399 - Human cytochrome P450 (IIB subfamily) mRNA fragment.
X06400 - Human cytochrome P450 (IIB subfamily) mRNA fragment.
JD129811 - Sequence 110835 from Patent EP1572962.
JD352950 - Sequence 333974 from Patent EP1572962.
JD526263 - Sequence 507287 from Patent EP1572962.
JD407524 - Sequence 388548 from Patent EP1572962.
JD212954 - Sequence 193978 from Patent EP1572962.
JD268831 - Sequence 249855 from Patent EP1572962.
JD408776 - Sequence 389800 from Patent EP1572962.
JD408777 - Sequence 389801 from Patent EP1572962.
JD072274 - Sequence 53298 from Patent EP1572962.
JD242890 - Sequence 223914 from Patent EP1572962.
JD490169 - Sequence 471193 from Patent EP1572962.
JD342226 - Sequence 323250 from Patent EP1572962.
JD522086 - Sequence 503110 from Patent EP1572962.
JD435398 - Sequence 416422 from Patent EP1572962.
JD529903 - Sequence 510927 from Patent EP1572962.
JD435399 - Sequence 416423 from Patent EP1572962.
JD254535 - Sequence 235559 from Patent EP1572962.
JD312048 - Sequence 293072 from Patent EP1572962.
JD312049 - Sequence 293073 from Patent EP1572962.
JD346540 - Sequence 327564 from Patent EP1572962.
JD346541 - Sequence 327565 from Patent EP1572962.
JD346542 - Sequence 327566 from Patent EP1572962.
JD315262 - Sequence 296286 from Patent EP1572962.
JD092456 - Sequence 73480 from Patent EP1572962.
JD506018 - Sequence 487042 from Patent EP1572962.
JD341412 - Sequence 322436 from Patent EP1572962.
JD563652 - Sequence 544676 from Patent EP1572962.
JD224109 - Sequence 205133 from Patent EP1572962.
JD325893 - Sequence 306917 from Patent EP1572962.
JD153083 - Sequence 134107 from Patent EP1572962.
JD160937 - Sequence 141961 from Patent EP1572962.
JD546524 - Sequence 527548 from Patent EP1572962.
JD492102 - Sequence 473126 from Patent EP1572962.
JD513665 - Sequence 494689 from Patent EP1572962.
JD122210 - Sequence 103234 from Patent EP1572962.
JD181374 - Sequence 162398 from Patent EP1572962.
JD353341 - Sequence 334365 from Patent EP1572962.
JD259721 - Sequence 240745 from Patent EP1572962.
JD527618 - Sequence 508642 from Patent EP1572962.
JD527619 - Sequence 508643 from Patent EP1572962.
JD161182 - Sequence 142206 from Patent EP1572962.
JD546978 - Sequence 528002 from Patent EP1572962.
JD493275 - Sequence 474299 from Patent EP1572962.
JD268828 - Sequence 249852 from Patent EP1572962.
JD321700 - Sequence 302724 from Patent EP1572962.
JD158103 - Sequence 139127 from Patent EP1572962.
JD072521 - Sequence 53545 from Patent EP1572962.
JD364384 - Sequence 345408 from Patent EP1572962.
JD364383 - Sequence 345407 from Patent EP1572962.
JD242410 - Sequence 223434 from Patent EP1572962.
JD344310 - Sequence 325334 from Patent EP1572962.
JD525445 - Sequence 506469 from Patent EP1572962.
JD122442 - Sequence 103466 from Patent EP1572962.
JD297250 - Sequence 278274 from Patent EP1572962.
JD307703 - Sequence 288727 from Patent EP1572962.
JD431874 - Sequence 412898 from Patent EP1572962.
JD161850 - Sequence 142874 from Patent EP1572962.
JD525385 - Sequence 506409 from Patent EP1572962.
JD359817 - Sequence 340841 from Patent EP1572962.
JD567104 - Sequence 548128 from Patent EP1572962.
JD301203 - Sequence 282227 from Patent EP1572962.
JD298916 - Sequence 279940 from Patent EP1572962.
JD561922 - Sequence 542946 from Patent EP1572962.
JD549649 - Sequence 530673 from Patent EP1572962.
JD072291 - Sequence 53315 from Patent EP1572962.
JD285509 - Sequence 266533 from Patent EP1572962.
JD505492 - Sequence 486516 from Patent EP1572962.
JD239637 - Sequence 220661 from Patent EP1572962.
JD242060 - Sequence 223084 from Patent EP1572962.
JD438687 - Sequence 419711 from Patent EP1572962.
JD159444 - Sequence 140468 from Patent EP1572962.
JD347674 - Sequence 328698 from Patent EP1572962.
JD549721 - Sequence 530745 from Patent EP1572962.
JD500103 - Sequence 481127 from Patent EP1572962.
JD379641 - Sequence 360665 from Patent EP1572962.
JD094105 - Sequence 75129 from Patent EP1572962.
JD273150 - Sequence 254174 from Patent EP1572962.
JD253827 - Sequence 234851 from Patent EP1572962.
JD148526 - Sequence 129550 from Patent EP1572962.
JD384825 - Sequence 365849 from Patent EP1572962.
JD489525 - Sequence 470549 from Patent EP1572962.
JD290692 - Sequence 271716 from Patent EP1572962.
JD565499 - Sequence 546523 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00590 - Arachidonic acid metabolism
hsa00830 - Retinol metabolism
hsa00980 - Metabolism of xenobiotics by cytochrome P450
hsa00982 - Drug metabolism - cytochrome P450
hsa01100 - Metabolic pathways

BioCarta from NCI Cancer Genome Anatomy Project
h_nuclearRsPathway - Nuclear Receptors in Lipid Metabolism and Toxicity

Reactome (by CSHL, EBI, and GO)

Protein P20813 (Reactome details) participates in the following event(s):

R-HSA-211991 Cyclophosphamide is 4-hydroxylated by CYP2B6
R-HSA-76354 Vinyl chloride is oxidized to 2-Chloroethylene oxide
R-HSA-76397 Acetaminophen oxidised to N-acetylbenzoquinoneimine (NAPQI)
R-HSA-76416 Benzene is hydroxylated to phenol
R-HSA-76434 Dehalogenation of carbon tetrachloride to form a free radical
R-HSA-76475 Dehalogenation of the poly-halogenated hydrocarbon Halothane to form the acylhalide Trifluoroacetlychloride and hydrogen bromide
R-HSA-143468 MEOS oxidizes ethanol to acetaldehyde
R-HSA-211910 CYP2C8 inactivates paclitaxel by 6alpha-hydroxylation
R-HSA-211988 CYP2C9 inactivates tolbutamide by 4methyl-hydroxylation
R-HSA-212005 CYP2F1 dehydrogenates 3-methylindole
R-HSA-211929 CYP2C19 5-hydroxylates omeprazole
R-HSA-211983 CYP2J2 oxidises ARA
R-HSA-211881 Coumarin is 7-hydroxylated by CYP2A13
R-HSA-211981 Xenobiotics
R-HSA-211999 CYP2E1 reactions
R-HSA-211935 Fatty acids
R-HSA-211897 Cytochrome P450 - arranged by substrate type
R-HSA-211945 Phase I - Functionalization of compounds
R-HSA-211859 Biological oxidations
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: CP2B6_HUMAN, NM_000767, NP_000758, P20813, Q2V565, Q9UK46
UCSC ID: uc002opr.1
RefSeq Accession: NM_000767
Protein: P20813 (aka CP2B6_HUMAN or CPB6_HUMAN)
CCDS: CCDS12570.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000767.4
exon count: 9CDS single in 3' UTR: no RNA size: 3052
ORF size: 1476CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2839.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.