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Protein

Cytochrome P450 2B6

Gene

CYP2B6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

1,4-cineole + NADPH + O2 = 2-exo-hydroxy-1,4-cineole + NADP+ + H2O.1 Publication

Cofactori

heme3 Publications

Kineticsi

  1. KM=360 µM for 1,4-cineole1 Publication
  1. Vmax=3.4 nmol/min/nmol enzyme toward 2-exo-hydroxy-1,4-cineole1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi436Iron (heme axial ligand)1

GO - Molecular functioni

GO - Biological processi

  • cellular ketone metabolic process Source: BHF-UCL
  • drug metabolic process Source: BHF-UCL
  • epoxygenase P450 pathway Source: GO_Central
  • exogenous drug catabolic process Source: BHF-UCL
  • oxidation-reduction process Source: BHF-UCL
  • steroid metabolic process Source: BHF-UCL
  • xenobiotic metabolic process Source: UniProtKB

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
LigandHeme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS09587-MONOMER
BRENDAi1.14.14.1 2681
ReactomeiR-HSA-211935 Fatty acids
R-HSA-211981 Xenobiotics
R-HSA-211999 CYP2E1 reactions
SABIO-RKiP20813
SIGNORiP20813

Chemistry databases

SwissLipidsiSLP:000001346

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 2B6 (EC:1.14.13.-)
Alternative name(s):
1,4-cineole 2-exo-monooxygenase
CYPIIB6
Cytochrome P450 IIB1
Gene namesi
Name:CYP2B6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000197408.8
HGNCiHGNC:2615 CYP2B6
MIMi123930 gene
neXtProtiNX_P20813

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi1555
MalaCardsiCYP2B6
MIMi614546 phenotype
OpenTargetsiENSG00000197408
Orphaneti240869 Efavirenz toxicity
PharmGKBiPA123

Chemistry databases

ChEMBLiCHEMBL4729
DrugBankiDB08369 1-(biphenyl-4-ylmethyl)-1H-imidazole
DB02974 4-(4-Chlorophenyl)Imidazole
DB00321 Amitriptyline
DB00381 Amlodipine
DB00701 Amprenavir
DB01435 Antipyrine
DB06413 Armodafinil
DB06697 Artemether
DB01076 Atorvastatin
DB00972 Azelastine
DB04975 Banoxantrone
DB00865 Benzphetamine
DB06770 Benzyl alcohol
DB04794 Bifonazole
DB00835 Brompheniramine
DB01156 Bupropion
DB00564 Carbamazepine
DB00748 Carbinoxamine
DB00439 Cerivastatin
DB00169 Cholecalciferol
DB00568 Cinnarizine
DB00604 Cisapride
DB00515 Cisplatin
DB00215 Citalopram
DB00349 Clobazam
DB00636 Clofibrate
DB00758 Clopidogrel
DB01559 Clotiazepam
DB00257 Clotrimazole
DB01394 Colchicine
DB05219 Crisaborole
DB08865 Crizotinib
DB04664 Cyclohexyl-pentyl-maltoside
DB00531 Cyclophosphamide
DB01151 Desipramine
DB01234 Dexamethasone
DB00514 Dextromethorphan
DB00829 Diazepam
DB00586 Diclofenac
DB01075 Diphenhydramine
DB01184 Domperidone
DB00997 Doxorubicin
DB00625 Efavirenz
DB08899 Enzalutamide
DB00751 Epinastine
DB00199 Erythromycin
DB00655 Estrone
DB00898 Ethanol
DB01466 Ethylmorphine
DB04841 Flunarizine
DB01544 Flunitrazepam
DB00472 Fluoxetine
DB01095 Fluvastatin
DB00176 Fluvoxamine
DB01320 Fosphenytoin
DB01159 Halothane
DB09054 Idelalisib
DB01181 Ifosfamide
DB00458 Imipramine
DB00762 Irinotecan
DB00753 Isoflurane
DB01167 Itraconazole
DB09570 Ixazomib
DB01221 Ketamine
DB06738 Ketobemidone
DB01026 Ketoconazole
DB00281 Lidocaine
DB00836 Loperamide
DB01601 Lopinavir
DB04871 Lorcaserin
DB09280 Lumacaftor
DB00772 Malathion
DB01043 Memantine
DB00532 Mephenytoin
DB04817 Metamizole
DB00333 Methadone
DB00763 Methimazole
DB01028 Methoxyflurane
DB00849 Methylphenobarbital
DB06710 Methyltestosterone
DB00379 Mexiletine
DB06148 Mianserin
DB01110 Miconazole
DB00683 Midazolam
DB00745 Modafinil
DB00220 Nelfinavir
DB00238 Nevirapine
DB00622 Nicardipine
DB00184 Nicotine
DB01115 Nifedipine
DB04868 Nilotinib
DB00435 Nitric Oxide
DB09074 Olaparib
DB01173 Orphenadrine
DB04938 Ospemifene
DB00715 Paroxetine
DB01074 Perhexiline
DB04930 Permethrin
DB00850 Perphenazine
DB00454 Pethidine
DB03575 Phencyclidine
DB01174 Phenobarbital
DB00252 Phenytoin
DB06209 Prasugrel
DB00794 Primidone
DB01069 Promethazine
DB00818 Propofol
DB01589 Quazepam
DB00908 Quinidine
DB00481 Raloxifene
DB08896 Regorafenib
DB01045 Rifampicin
DB08864 Rilpivirine
DB00503 Ritonavir
DB06176 Romidepsin
DB00296 Ropivacaine
DB00778 Roxithromycin
DB01037 Selegiline
DB01104 Sertraline
DB01236 Sevoflurane
DB00641 Simvastatin
DB00398 Sorafenib
DB06729 Sulfaphenazole
DB01138 Sulfinpyrazone
DB00675 Tamoxifen
DB00231 Temazepam
DB00624 Testosterone
DB04572 Thiotepa
DB00208 Ticlopidine
DB00193 Tramadol
DB00755 Tretinoin
DB00197 Troglitazone
DB00313 Valproic Acid
DB00285 Venlafaxine
DB00661 Verapamil
DB09068 Vortioxetine
GuidetoPHARMACOLOGYi1324

Polymorphism and mutation databases

BioMutaiCYP2B6
DMDMi117205

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000516831 – 491Cytochrome P450 2B6Add BLAST491

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei128Phosphoserine; by PKABy similarity1

Post-translational modificationi

Phosphorylation is accompanied by a decrease in enzyme activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP20813
PeptideAtlasiP20813
PRIDEiP20813

PTM databases

iPTMnetiP20813
PhosphoSitePlusiP20813

Expressioni

Tissue specificityi

Expressed in liver, lung and heart right ventricle.1 Publication

Inductioni

By phenobarbital.

Gene expression databases

BgeeiENSG00000197408
CleanExiHS_CYP2B6
ExpressionAtlasiP20813 baseline and differential
GenevisibleiP20813 HS

Organism-specific databases

HPAiCAB033866
HPA048124
HPA062973

Interactioni

Protein-protein interaction databases

BioGridi107933, 4 interactors
STRINGi9606.ENSP00000324648

Chemistry databases

BindingDBiP20813

Structurei

Secondary structure

1491
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni38 – 40Combined sources3
Helixi43 – 45Combined sources3
Helixi51 – 62Combined sources12
Beta strandi64 – 70Combined sources7
Beta strandi73 – 78Combined sources6
Helixi80 – 88Combined sources9
Turni89 – 91Combined sources3
Helixi92 – 95Combined sources4
Turni102 – 104Combined sources3
Helixi105 – 108Combined sources4
Turni113 – 115Combined sources3
Helixi118 – 131Combined sources14
Turni135 – 137Combined sources3
Helixi142 – 158Combined sources17
Turni159 – 162Combined sources4
Helixi168 – 183Combined sources16
Helixi193 – 210Combined sources18
Helixi212 – 224Combined sources13
Helixi230 – 255Combined sources26
Helixi264 – 274Combined sources11
Turni275 – 277Combined sources3
Beta strandi278 – 280Combined sources3
Helixi285 – 316Combined sources32
Helixi318 – 331Combined sources14
Beta strandi334 – 336Combined sources3
Helixi340 – 345Combined sources6
Helixi347 – 360Combined sources14
Beta strandi375 – 377Combined sources3
Beta strandi380 – 382Combined sources3
Beta strandi387 – 390Combined sources4
Helixi392 – 396Combined sources5
Turni399 – 401Combined sources3
Beta strandi402 – 404Combined sources3
Helixi410 – 413Combined sources4
Helixi432 – 434Combined sources3
Helixi439 – 456Combined sources18
Beta strandi457 – 460Combined sources4
Helixi465 – 467Combined sources3
Beta strandi473 – 480Combined sources8
Beta strandi486 – 490Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3IBDX-ray2.00A30-491[»]
3QOAX-ray2.10A27-491[»]
3QU8X-ray2.80A/B/C/D/E/F27-491[»]
3UA5X-ray2.80A/B27-491[»]
4I91X-ray2.00A27-491[»]
4RQLX-ray2.10A/B27-491[»]
4RRTX-ray2.20A/B27-491[»]
4ZV8X-ray2.24A30-491[»]
5UAPX-ray2.03A/B20-491[»]
5UDAX-ray1.93A/B20-491[»]
5UECX-ray2.27A20-491[»]
5UFGX-ray1.76A20-491[»]
ProteinModelPortaliP20813
SMRiP20813
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP20813

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiKOG0156 Eukaryota
COG2124 LUCA
GeneTreeiENSGT00880000137861
HOGENOMiHOG000036992
HOVERGENiHBG015789
InParanoidiP20813
KOiK17709
OMAiHTSFRGY
OrthoDBiEOG091G0BT8
PhylomeDBiP20813
TreeFamiTF352043

Family and domain databases

Gene3Di1.10.630.10, 1 hit
InterProiView protein in InterPro
IPR001128 Cyt_P450
IPR017972 Cyt_P450_CS
IPR002401 Cyt_P450_E_grp-I
IPR008068 Cyt_P450_E_grp-I_CYP2B-like
IPR036396 Cyt_P450_sf
PfamiView protein in Pfam
PF00067 p450, 1 hit
PRINTSiPR00463 EP450I
PR01685 EP450ICYP2B
PR00385 P450
SUPFAMiSSF48264 SSF48264, 1 hit
PROSITEiView protein in PROSITE
PS00086 CYTOCHROME_P450, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P20813-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELSVLLFLA LLTGLLLLLV QRHPNTHDRL PPGPRPLPLL GNLLQMDRRG
60 70 80 90 100
LLKSFLRFRE KYGDVFTVHL GPRPVVMLCG VEAIREALVD KAEAFSGRGK
110 120 130 140 150
IAMVDPFFRG YGVIFANGNR WKVLRRFSVT TMRDFGMGKR SVEERIQEEA
160 170 180 190 200
QCLIEELRKS KGALMDPTFL FQSITANIIC SIVFGKRFHY QDQEFLKMLN
210 220 230 240 250
LFYQTFSLIS SVFGQLFELF SGFLKYFPGA HRQVYKNLQE INAYIGHSVE
260 270 280 290 300
KHRETLDPSA PKDLIDTYLL HMEKEKSNAH SEFSHQNLNL NTLSLFFAGT
310 320 330 340 350
ETTSTTLRYG FLLMLKYPHV AERVYREIEQ VIGPHRPPEL HDRAKMPYTE
360 370 380 390 400
AVIYEIQRFS DLLPMGVPHI VTQHTSFRGY IIPKDTEVFL ILSTALHDPH
410 420 430 440 450
YFEKPDAFNP DHFLDANGAL KKTEAFIPFS LGKRICLGEG IARAELFLFF
460 470 480 490
TTILQNFSMA SPVAPEDIDL TPQECGVGKI PPTYQIRFLP R
Length:491
Mass (Da):56,278
Last modified:February 1, 1991 - v1
Checksum:iB9799164BE8FBF1D
GO
Isoform 2 (identifier: P20813-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLR → MRCMLTNSHPWCGCDWQ
     162-321: Missing.

Note: No experimental confirmation available.
Show »
Length:291
Mass (Da):33,385
Checksum:iA4B40F24ED632B8D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti146I → T in AAF13602 (Ref. 2) Curated1
Sequence conflicti238L → P in AAF13602 (Ref. 2) Curated1

Polymorphismi

Genetic variations in CYP2B6 are responsible for poor metabolism of efavirenz and, therefore, susceptibility to efavirenz toxicity in the central nervous system [MIMi: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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02356321Q → L in allele CYP2B6*10. 1 PublicationCorresponds to variant dbSNP:rs34883432Ensembl.1
Natural variantiVAR_01692722R → C in allele CYP2B6*2 and allele CYP2B6*10. 6 PublicationsCorresponds to variant dbSNP:rs8192709Ensembl.1
Natural variantiVAR_02520626T → S1 PublicationCorresponds to variant dbSNP:rs33973337Ensembl.1
Natural variantiVAR_02520728D → G1 PublicationCorresponds to variant dbSNP:rs33980385Ensembl.1
Natural variantiVAR_03381929R → P. Corresponds to variant dbSNP:rs34284776Ensembl.1
Natural variantiVAR_02520829R → S1 PublicationCorresponds to variant dbSNP:rs33926104Ensembl.1
Natural variantiVAR_02356446M → V in allele CYP2B6*11. 1 PublicationCorresponds to variant dbSNP:rs35303484Ensembl.1
Natural variantiVAR_02356599G → E in allele CYP2B6*12. 1 PublicationCorresponds to variant dbSNP:rs36060847Ensembl.1
Natural variantiVAR_016948139K → E in allele CYP2B6*8 and allele CYP2B6*13. 2 PublicationsCorresponds to variant dbSNP:rs12721655Ensembl.1
Natural variantiVAR_023566140R → Q in allele CYP2B6*14. 1 PublicationCorresponds to variant dbSNP:rs35773040Ensembl.1
Natural variantiVAR_016924167P → A2 PublicationsCorresponds to variant dbSNP:rs3826711Ensembl.1
Natural variantiVAR_016925172Q → H in allele CYP2B6*6, allele CYP2B6*7, allele CYP2B6*9 and allele CYP2B6*13. 8 PublicationsCorresponds to variant dbSNP:rs3745274EnsemblClinVar.1
Natural variantiVAR_016928259S → R in allele CYP2B6*3. 2 PublicationsCorresponds to variant dbSNP:rs45482602Ensembl.1
Natural variantiVAR_016926262K → R in allele CYP2B6*4, allele CYP2B6*6, allele CYP2B6*7 and allele CYP2B6*13; slight decrease in activity. 5 PublicationsCorresponds to variant dbSNP:rs2279343EnsemblClinVar.1
Natural variantiVAR_025209289N → K1 PublicationCorresponds to variant dbSNP:rs34277950Ensembl.1
Natural variantiVAR_025210306T → S1 PublicationCorresponds to variant dbSNP:rs34698757Ensembl.1
Natural variantiVAR_024716328I → T2 PublicationsCorresponds to variant dbSNP:rs28399499EnsemblClinVar.1
Natural variantiVAR_023567391I → N in allele CYP2B6*15. 1 PublicationCorresponds to variant dbSNP:rs35979566Ensembl.1
Natural variantiVAR_016929487R → C in allele CYP2B6*5 and allele CYP2B6*7. 6 PublicationsCorresponds to variant dbSNP:rs3211371Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0555711 – 57MELSV…KSFLR → MRCMLTNSHPWCGCDWQ in isoform 2. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_055572162 – 321Missing in isoform 2. 1 PublicationAdd BLAST160

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M29874 mRNA Translation: AAA52144.1
AF182277 mRNA Translation: AAF13602.1
AK301620 mRNA Translation: BAG63105.1
DQ298753 Genomic DNA Translation: ABB84469.1
AC023172 Genomic DNA Translation: AAF32444.1
AC011541 Genomic DNA No translation available.
X13494 mRNA No translation available.
CCDSiCCDS12570.1 [P20813-1]
PIRiA32969
RefSeqiNP_000758.1, NM_000767.4 [P20813-1]
XP_011524852.1, XM_011526550.2 [P20813-2]
UniGeneiHs.1360

Genome annotation databases

EnsembliENST00000324071; ENSP00000324648; ENSG00000197408 [P20813-1]
GeneIDi1555
KEGGihsa:1555
UCSCiuc002opr.2 human [P20813-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCP2B6_HUMAN
AccessioniPrimary (citable) accession number: P20813
Secondary accession number(s): B4DWP3, Q2V565, Q9UK46
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: May 23, 2018
This is version 193 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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