Reviewed, UniProtKB/Swiss-Prot P00178 (CP2B4_RABIT)

Names and origin

Protein names

Recommended name:
    Cytochrome P450 2B4
    EC=1.14.14.1
Alternative name(s):
    CYPIIB4
    P450-LM2
    Isozyme 2
    P450 types B0 and B1

Gene names

Name:

CYP2B4

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	491 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. In the epoxidation of arachidonic acid it has a unique preference for the 5,6-olefin.
Catalytic activity	RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.
Cofactor	Heme group.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Induction	By phenobarbital.
Polymorphism	Types B0 and B1 are probably allelic variants.
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 Direct protein sequencing
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from electronic annotation. Source: UniProtKB-SubCell
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 2B4

PRO_0000051681

Sites

Metal binding

436

1

Iron (heme axial ligand)

Amino acid modifications

Modified residue

128

1

Phosphoserine; by PKA By similarity

Natural variations

Natural variant

39

1

V → I in B1.

Natural variant

174

1

I → V in B1.

Natural variant

290

1

L → I in B1.

Natural variant

314

1

M → L in B1.

Natural variant

420

1

L → M in B1.

Experimental info

Mutagenesis

436

1

C → S: Conversion into an NADPH oxidase with negligible monooxygenase activity. Ref.6

Sequence conflict

91

1

Q → E AA sequence Ref.3

Sequence conflict

95 – 96

2

FS → SF AA sequence Ref.3

Sequence conflict

99 – 100

2

Missing AA sequence Ref.3

Sequence conflict

135 – 136

2

FG → GY AA sequence Ref.3

Sequence conflict

193

1

P → K AA sequence Ref.3

Sequence conflict

221

1

P → S AA sequence Ref.3

Sequence conflict

303

1

T → A AA sequence Ref.3

Sequence conflict

461 – 465

5

SPVPP → GNLSL AA sequence Ref.3

Secondary structure

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491

Helix Strand Turn

Details...

Turn

38 – 40

3

Helix

43 – 45

3

Helix

51 – 62

12

Beta strand

64 – 70

7

Beta strand

73 – 78

6

Helix

81 – 88

8

Turn

89 – 95

7

Helix

101 – 104

4

Helix

118 – 134

17

Helix

139 – 159

21

Turn

160 – 162

3

Helix

168 – 184

17

Helix

193 – 205

13

Turn

206 – 208

3

Helix

213 – 219

7

Helix

221 – 225

5

Helix

231 – 253

23

Helix

264 – 275

12

Helix

282 – 316

35

Helix

318 – 331

14

Beta strand

334 – 336

3

Helix

340 – 345

6

Helix

347 – 360

14

Beta strand

375 – 377

3

Beta strand

380 – 382

3

Beta strand

387 – 390

4

Helix

392 – 396

5

Turn

399 – 401

3

Helix

410 – 413

4

Helix

439 – 456

18

Beta strand

457 – 460

4

Helix

465 – 467

3

Beta strand

486 – 490

5

Sequences

	Sequence		Length	Mass (Da)
	P00178-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 0DB943C6CDCF690B	FASTA	491	55,713
	10 20 30 40 50 60 MEFSLLLLLA FLAGLLLLLF RGHPKAHGRL PPGPSPLPVL GNLLQMDRKG LLRSFLRLRE 70 80 90 100 110 120 KYGDVFTVYL GSRPVVVLCG TDAIREALVD QAEAFSGRGK IAVVDPIFQG YGVIFANGER 130 140 150 160 170 180 WRALRRFSLA TMRDFGMGKR SVEERIQEEA RCLVEELRKS KGALLDNTLL FHSITSNIIC 190 200 210 220 230 240 SIVFGKRFDY KDPVFLRLLD LFFQSFSLIS SFSSQVFELF PGFLKHFPGT HRQIYRNLQE 250 260 270 280 290 300 INTFIGQSVE KHRATLDPSN PRDFIDVYLL RMEKDKSDPS SEFHHQNLIL TVLSLFFAGT 310 320 330 340 350 360 ETTSTTLRYG FLLMLKYPHV TERVQKEIEQ VIGSHRPPAL DDRAKMPYTD AVIHEIQRLG 370 380 390 400 410 420 DLIPFGVPHT VTKDTQFRGY VIPKNTEVFP VLSSALHDPR YFETPNTFNP GHFLDANGAL 430 440 450 460 470 480 KRNEGFMPFS LGKRICLGEG IARTELFLFF TTILQNFSIA SPVPPEDIDL TPRESGVGNV 490 PPSYQIRFLA R

References

[1]	"Primary structures of multiple forms of cytochrome P-450 isozyme 2 derived from rabbit pulmonary and hepatic cDNAs." Gasser R., Negishi M., Philpot R.M. Mol. Pharmacol. 33:22-30(1988) [PubMed: 2826996] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complete amino acid sequence and predicted membrane topology of phenobarbital-induced cytochrome P-450 (isozyme 2) from rabbit liver microsomes." Tarr G.E., Black S.D., Fujita V.S., Coon M.J. Proc. Natl. Acad. Sci. U.S.A. 80:6552-6556(1983) [PubMed: 6579541] [Abstract] Cited for: PROTEIN SEQUENCE.
[3]	"The complete amino acid sequence of rabbit phenobarbital-induced liver microsomal cytochrome P-450." Heinemann F.S., Ozols J. J. Biol. Chem. 258:4195-4201(1983) [PubMed: 6833251] [Abstract] Cited for: PROTEIN SEQUENCE.
[4]	"Cytochrome P-450 isozymes 2 and 5 in rabbit lung and liver. Comparisons of structure and inducibility." Parandoosh Z., Fujita V.S., Coon M.J., Philpot R.M. Drug Metab. Dispos. 15:59-67(1987) [PubMed: 2881760] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-24.
[5]	"Microheterogeneity in the major phenobarbital-inducible forms of rabbit liver microsomal cytochrome P-450 as revealed by nucleotide sequencing of cloned cDNAs." Komori M., Imai Y., Tsunasawa S., Sato R. Biochemistry 27:73-80(1988) [PubMed: 2831964] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 301-491 (B1).
[6]	"Replacement of active-site cysteine-436 by serine converts cytochrome P450 2B4 into an NADPH oxidase with negligible monooxygenase activity." Vatsis K.P., Peng H.-M., Coon M.J. J. Inorg. Biochem. 91:542-553(2002) [PubMed: 12237221] [Abstract] Cited for: MUTAGENESIS OF CYS-436.
[7]	"An open conformation of mammalian cytochrome P450 2B4 at 1.6-A resolution." Scott E.E., He Y.A., Wester M.R., White M.A., Chin C.C., Halpert J.R., Johnson E.F., Stout C.D. Proc. Natl. Acad. Sci. U.S.A. 100:13196-13201(2003) [PubMed: 14563924] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M20856 mRNA. Translation: AAA65840.1.
M20857 mRNA. Translation: AAA31224.1.

PIR

O4RBPC. A00179.
S31277.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PO5	X-ray	1.60	A	30-491	[»]
1SUO	X-ray	1.90	A	30-491	[»]
2BDM	X-ray	2.30	A	30-491	[»]
2Q6N	X-ray	3.20	A/B/C/D/E/F/G	30-491	[»]

ModBase

Search...

Phylogenomic databases

HOVERGEN

P00178.

Enzyme and pathway databases

BRENDA

1.14.14.1. 255.

Family and domain databases

InterPro

IPR001128. Cyt_P450.
IPR017973. Cyt_P450_C.
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.

PANTHER

PTHR19383. Cyt_P450. 1 hit.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

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

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB04794. Bifonazole.

Entry information

Entry name

CP2B4_RABIT

Accession

Primary (citable) accession number: P00178
Secondary accession number(s): P00177

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	June 16, 2009
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)