P20813 (CP2B6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 2B6
EC=1.14.14.1

Alternative name(s):
CYPIIB6
Cytochrome P450 IIB1

Gene names

Name:

CYP2B6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	491 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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.
Catalytic activity	RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.
Cofactor	Heme group By similarity.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Tissue specificity	Expressed in liver, lung and heart right ventricle. Ref.6
Induction	By phenobarbital.
Post-translational modification	Phosphorylation is accompanied by a decrease in enzyme activity By similarity.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular ketone metabolic process Inferred from direct assay. Source: BHF-UCL exogenous drug catabolic process Inferred from direct assay. Source: BHF-UCL steroid metabolic process Inferred from mutant phenotype. Source: BHF-UCL xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome microsome Non-traceable author statement. Source: UniProtKB
Molecular function	aromatase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 491

491

Cytochrome P450 2B6

PRO_0000051683

Sites

Metal binding

436

1

Iron (heme axial ligand) By similarity

Amino acid modifications

Modified residue

128

1

Phosphoserine; by PKA By similarity

Natural variations

Natural variant

21

1

Q → L in allele CYP2B6*10. Ref.12
Corresponds to variant rs34883432 [ dbSNP | Ensembl ].

VAR_023563

Natural variant

22

1

R → C in allele CYP2B6*2 and allele CYP2B6*10. Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
Corresponds to variant rs8192709 [ dbSNP | Ensembl ].

VAR_016927

Natural variant

26

1

T → S. Ref.3
Corresponds to variant rs33973337 [ dbSNP | Ensembl ].

VAR_025206

Natural variant

28

1

D → G. Ref.3
Corresponds to variant rs33980385 [ dbSNP | Ensembl ].

VAR_025207

Natural variant

29

1

R → P.
Corresponds to variant rs34284776 [ dbSNP | Ensembl ].

VAR_033819

Natural variant

29

1

R → S. Ref.3
Corresponds to variant rs33926104 [ dbSNP | Ensembl ].

VAR_025208

Natural variant

46

1

M → V in allele CYP2B6*11. Ref.12
Corresponds to variant rs35303484 [ dbSNP | Ensembl ].

VAR_023564

Natural variant

99

1

G → E in allele CYP2B6*12. Ref.12
Corresponds to variant rs36060847 [ dbSNP | Ensembl ].

VAR_023565

Natural variant

139

1

K → E in allele CYP2B6*8 and allele CYP2B6*13. Ref.11 Ref.12

VAR_016948

Natural variant

140

1

R → Q in allele CYP2B6*14. Ref.12
Corresponds to variant rs35773040 [ dbSNP | Ensembl ].

VAR_023566

Natural variant

167

1

P → A. Ref.2 Ref.10
Corresponds to variant rs3826711 [ dbSNP | Ensembl ].

VAR_016924

Natural variant

172

1

Q → H in allele CYP2B6*6, allele CYP2B6*7, allele CYP2B6*9 and allele CYP2B6*13. Ref.2 Ref.3 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
Corresponds to variant rs3745274 [ dbSNP | Ensembl ].

VAR_016925

Natural variant

259

1

S → R in allele CYP2B6*3. Ref.8 Ref.9
Corresponds to variant rs45482602 [ dbSNP | Ensembl ].

VAR_016928

Natural variant

262

1

K → R in allele CYP2B6*4, allele CYP2B6*6, allele CYP2B6*7 and allele CYP2B6*13; slight decrease in activity. Ref.2 Ref.3 Ref.8 Ref.9 Ref.13
Corresponds to variant rs2279343 [ dbSNP | Ensembl ].

VAR_016926

Natural variant

289

1

N → K. Ref.3
Corresponds to variant rs34277950 [ dbSNP | Ensembl ].

VAR_025209

Natural variant

306

1

T → S. Ref.3
Corresponds to variant rs34698757 [ dbSNP | Ensembl ].

VAR_025210

Natural variant

328

1

I → T. Ref.3 Ref.13
Corresponds to variant rs28399499 [ dbSNP | Ensembl ].

VAR_024716

Natural variant

391

1

I → N in allele CYP2B6*15. Ref.12
Corresponds to variant rs35979566 [ dbSNP | Ensembl ].

VAR_023567

Natural variant

487

1

R → C in allele CYP2B6*5 and allele CYP2B6*7. Ref.3 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
Corresponds to variant rs3211371 [ dbSNP | Ensembl ].

VAR_016929

Experimental info

Sequence conflict

146

1

I → T in AAF13602. Ref.2

Sequence conflict

238

1

L → P in AAF13602. Ref.2

Secondary structure

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491

Helix Strand Turn

Details...

Helix

43 – 45

3

Helix

52 – 61

10

Beta strand

65 – 69

5

Beta strand

74 – 78

5

Helix

82 – 88

7

Turn

89 – 95

7

Turn

102 – 104

3

Helix

105 – 108

4

Helix

120 – 134

15

Helix

142 – 159

18

Helix

168 – 183

16

Helix

193 – 209

17

Helix

216 – 220

5

Helix

224 – 226

3

Helix

231 – 244

14

Helix

248 – 254

7

Helix

264 – 274

11

Beta strand

275 – 278

4

Helix

283 – 285

3

Helix

288 – 297

10

Helix

301 – 308

8

Helix

312 – 316

5

Helix

318 – 331

14

Helix

340 – 345

6

Helix

347 – 360

14

Beta strand

387 – 390

4

Helix

392 – 396

5

Turn

399 – 401

3

Beta strand

402 – 404

3

Helix

410 – 413

4

Helix

442 – 456

15

Beta strand

457 – 460

4

Helix

465 – 467

3

Beta strand

486 – 490

5

Sequences

	Sequence		Length	Mass (Da)
	P20813 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: B9799164BE8FBF1D	FASTA	491	56,278
	10 20 30 40 50 60 MELSVLLFLA LLTGLLLLLV QRHPNTHDRL PPGPRPLPLL GNLLQMDRRG LLKSFLRFRE 70 80 90 100 110 120 KYGDVFTVHL GPRPVVMLCG VEAIREALVD KAEAFSGRGK IAMVDPFFRG YGVIFANGNR 130 140 150 160 170 180 WKVLRRFSVT TMRDFGMGKR SVEERIQEEA QCLIEELRKS KGALMDPTFL FQSITANIIC 190 200 210 220 230 240 SIVFGKRFHY QDQEFLKMLN LFYQTFSLIS SVFGQLFELF SGFLKYFPGA HRQVYKNLQE 250 260 270 280 290 300 INAYIGHSVE KHRETLDPSA PKDLIDTYLL HMEKEKSNAH SEFSHQNLNL NTLSLFFAGT 310 320 330 340 350 360 ETTSTTLRYG FLLMLKYPHV AERVYREIEQ VIGPHRPPEL HDRAKMPYTE AVIYEIQRFS 370 380 390 400 410 420 DLLPMGVPHI VTQHTSFRGY IIPKDTEVFL ILSTALHDPH YFEKPDAFNP DHFLDANGAL 430 440 450 460 470 480 KKTEAFIPFS LGKRICLGEG IARAELFLFF TTILQNFSMA SPVAPEDIDL TPQECGVGKI 490 PPTYQIRFLP R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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." Yamano S., Nhamburo P.T., Aoyama T., Meyer U.A., Inaba T., Kalow W., Gelboin H.V., McBride O.W., Gonzalez F.J. Biochemistry 28:7340-7348(1989) [PubMed: 2573390] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Sequence of a new human cytochrome P450-2B6 cDNA." Zhuge J., Qian Y., Xie H., Yu Y. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-167; HIS-172 AND ARG-262. Tissue: Liver.
[3]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-22; SER-26; GLY-28; SER-29; HIS-172; ARG-262; LYS-289; SER-306; THR-328 AND CYS-487.
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Alternative splicing in the human cytochrome P450IIB6 gene generates a high level of aberrant messages." Miles J.S., McLaren A.W., Wolf C.R. Nucleic Acids Res. 17:8241-8255(1989) [PubMed: 2813061] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 26-491.
[6]	"Gene expression in distinct regions of the heart." Thum T., Borlak J. Lancet 355:979-983(2000) [PubMed: 10768437] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"A single nucleotide polymorphism of CYP2b6 found in Japanese enhances catalytic activity by autoactivation." Ariyoshi N., Miyazaki M., Toide K., Sawamura Y.I., Kamataki T. Biochem. Biophys. Res. Commun. 281:1256-1260(2001) [PubMed: 11243870] [Abstract] Cited for: VARIANT HIS-172.
[8]	"Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver." Lang T., Klein K., Fischer J., Nussler A.K., Neuhaus P., Hofmann U., Eichelbaum M., Schwab M., Zanger U.M. Pharmacogenetics 11:399-415(2001) [PubMed: 11470993] [Abstract] Cited for: VARIANTS CYS-22; HIS-172; ARG-259; ARG-262 AND CYS-487.
[9]	"Functional characterization of cytochrome P450 2B6 allelic variants." Jinno H., Tanaka-Kagawa T., Ohno A., Makino Y., Matsushima E., Hanioka N., Ando M. Drug Metab. Dispos. 31:398-403(2003) [PubMed: 12642465] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS CYS-22; HIS-172; ARG-259; ARG-262 AND CYS-487.
[10]	"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population." Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y. J. Hum. Genet. 48:249-270(2003) [PubMed: 12721789] [Abstract] Cited for: VARIANTS CYS-22; ALA-167; HIS-172 AND CYS-487.
[11]	"Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression." Lamba V., Lamba J., Yasuda K., Strom S., Davila J., Hancock M.L., Fackenthal J.D., Rogan P.K., Ring B., Wrighton S.A., Schuetz E.G. J. Pharmacol. Exp. Ther. 307:906-922(2003) [PubMed: 14551287] [Abstract] Cited for: VARIANTS CYS-22; GLU-139; HIS-172 AND CYS-487.
[12]	"Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles." Lang T., Klein K., Richter T., Zibat A., Kerb R., Eichelbaum M., Schwab M., Zanger U.M. J. Pharmacol. Exp. Ther. 311:34-43(2004) [PubMed: 15190123] [Abstract] Cited for: VARIANTS LEU-21; VAL-46; GLU-99; GLU-139; GLN-140 AND ASN-391.
[13]	"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population." Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P. Pharmacogenomics 5:895-931(2004) [PubMed: 15469410] [Abstract] Cited for: VARIANTS CYS-22; HIS-172; ARG-262; THR-328 AND CYS-487.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP2B6 alleles

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M29874 mRNA. Translation: AAA52144.1.
AF182277 mRNA. Translation: AAF13602.1.
DQ298753 Genomic DNA. Translation: ABB84469.1.
AC023172 Genomic DNA. Translation: AAF32444.1.
X13494 mRNA. No translation available.

IPI

IPI00025829.

PIR

A32969.

RefSeq

NP_000758.1. NM_000767.4.

UniGene

Hs.1360.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IBD	X-ray	2.00	A	30-491	[»]
3QOA	X-ray	2.10	A	30-491	[»]
3QU8	X-ray	2.80	A/B/C/D/E/F	30-491	[»]

ProteinModelPortal

P20813.

SMR

P20813. Positions 42-491.

ModBase

Search...

Protein-protein interaction databases

STRING

P20813.

PTM databases

PhosphoSite

P20813.

Polymorphism databases

DMDM

117205.

Proteomic databases

PRIDE

P20813.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000324071; ENSP00000324648; ENSG00000197408.

GeneID

1555.

KEGG

hsa:1555.

NMPDR

fig|9606.3.peg.16494.

UCSC

uc002opr.1. human.

Organism-specific databases

CTD

1555.

GeneCards

GC19P041497.

H-InvDB

HIX0039979.

HGNC

HGNC:2615. CYP2B6.

MIM

123930. gene.

neXtProt

NX_P20813.

Orphanet

240869. Efavirenz toxicity.
240969. Susceptibility to adverse reaction due to efavirenz treatment.

PharmGKB

PA123.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10968.

HOGENOM

HBG749920.

HOVERGEN

HBG015789.

InParanoid

P20813.

OMA

PKDTEVF.

OrthoDB

EOG40K7ZR.

PhylomeDB

P20813.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000167594-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P20813.

Bgee

P20813.

CleanEx

HS_CYP2B6.

Genevestigator

P20813.

GermOnline

ENSG00000197408. Homo sapiens.

Family and domain databases

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008068. Cyt_P450_E_grp-I_CYP2B-like.
[Graphical view]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

KO

K07412.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR01685. EP450ICYP2B.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01156. Bupropion.
DB00241. Butalbital.
DB00564. Carbamazepine.
DB00758. Clopidogrel.
DB00531. Cyclophosphamide.
DB00625. Efavirenz.
DB01181. Ifosfamide.
DB01043. Memantine.
DB00454. Meperidine.
DB00532. Mephenytoin.
DB00333. Methadone.
DB00849. Methylphenobarbital.
DB00683. Midazolam.
DB00220. Nelfinavir.
DB00238. Nevirapine.
DB00184. Nicotine.
DB01173. Orphenadrine.
DB00252. Phenytoin.
DB00818. Propofol.
DB00503. Ritonavir.
DB01037. Selegiline.
DB01104. Sertraline.
DB00208. Ticlopidine.
DB01361. Troleandomycin.

NextBio

6423.

SOURCE

Search...

Entry information

Entry name

CP2B6_HUMAN

Accession

Primary (citable) accession number: P20813
Secondary accession number(s): Q2V565, Q9UK46

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	January 25, 2012
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.