ID   CP2B4_RABIT             Reviewed;         491 AA.
AC   P00178; P00177;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   02-SEP-2026, entry version 181.
DE   RecName: Full=Cytochrome P450 2B4;
DE            EC=1.14.14.1;
DE   AltName: Full=CYPIIB4;
DE   AltName: Full=Cytochrome P450 isozyme 2;
DE            Short=Cytochrome P450 LM2;
DE   AltName: Full=Cytochrome P450 type B0;
DE   AltName: Full=Cytochrome P450 type B1;
GN   Name=CYP2B4;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2826996; DOI=10.1016/s0026-895x(25)13097-6;
RA   Gasser R., Negishi M., Philpot R.M.;
RT   "Primary structures of multiple forms of cytochrome P-450 isozyme 2 derived
RT   from rabbit pulmonary and hepatic cDNAs.";
RL   Mol. Pharmacol. 33:22-30(1988).
RN   [2]
RP   PROTEIN SEQUENCE.
RX   PubMed=6579541; DOI=10.1073/pnas.80.21.6552;
RA   Tarr G.E., Black S.D., Fujita V.S., Coon M.J.;
RT   "Complete amino acid sequence and predicted membrane topology of
RT   phenobarbital-induced cytochrome P-450 (isozyme 2) from rabbit liver
RT   microsomes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:6552-6556(1983).
RN   [3]
RP   PROTEIN SEQUENCE.
RX   PubMed=6833251; DOI=10.1016/s0021-9258(18)32605-x;
RA   Heinemann F.S., Ozols J.;
RT   "The complete amino acid sequence of rabbit phenobarbital-induced liver
RT   microsomal cytochrome P-450.";
RL   J. Biol. Chem. 258:4195-4201(1983).
RN   [4]
RP   PROTEIN SEQUENCE OF 1-24.
RX   PubMed=2881760; DOI=10.1016/s0090-9556(25)06609-7;
RA   Parandoosh Z., Fujita V.S., Coon M.J., Philpot R.M.;
RT   "Cytochrome P-450 isozymes 2 and 5 in rabbit lung and liver. Comparisons of
RT   structure and inducibility.";
RL   Drug Metab. Dispos. 15:59-67(1987).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 301-491 (B1).
RX   PubMed=2831964; DOI=10.1021/bi00401a013;
RA   Komori M., Imai Y., Tsunasawa S., Sato R.;
RT   "Microheterogeneity in the major phenobarbital-inducible forms of rabbit
RT   liver microsomal cytochrome P-450 as revealed by nucleotide sequencing of
RT   cloned cDNAs.";
RL   Biochemistry 27:73-80(1988).
RN   [6]
RP   MUTAGENESIS OF CYS-436.
RX   PubMed=12237221; DOI=10.1016/s0162-0134(02)00438-5;
RA   Vatsis K.P., Peng H.-M., Coon M.J.;
RT   "Replacement of active-site cysteine-436 by serine converts cytochrome P450
RT   2B4 into an NADPH oxidase with negligible monooxygenase activity.";
RL   J. Inorg. Biochem. 91:542-553(2002).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX   PubMed=14563924; DOI=10.1073/pnas.2133986100;
RA   Scott E.E., He Y.A., Wester M.R., White M.A., Chin C.C., Halpert J.R.,
RA   Johnson E.F., Stout C.D.;
RT   "An open conformation of mammalian cytochrome P450 2B4 at 1.6-A
RT   resolution.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:13196-13201(2003).
CC   -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases.
CC       In liver microsomes, this enzyme is involved in an NADPH-dependent
CC       electron transport pathway. It oxidizes a variety of structurally
CC       unrelated compounds, including steroids, fatty acids, and xenobiotics.
CC       In the epoxidation of arachidonic acid it has a unique preference for
CC       the 5,6-olefin.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an organic molecule + reduced [NADPH--hemoprotein reductase] +
CC         O2 = an alcohol + oxidized [NADPH--hemoprotein reductase] + H2O +
CC         H(+); Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:142491; EC=1.14.14.1;
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC       membrane protein. Microsome membrane; Peripheral membrane protein.
CC   -!- INDUCTION: By phenobarbital.
CC   -!- POLYMORPHISM: Types B0 and B1 are probably allelic variants.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; M20856; AAA65840.1; -; mRNA.
DR   EMBL; M20857; AAA31224.1; -; mRNA.
DR   PIR; A00179; O4RBPC.
DR   PIR; S31277; S31277.
DR   PDB; 1PO5; X-ray; 1.60 A; A=20-491.
DR   PDB; 1SUO; X-ray; 1.90 A; A=20-491.
DR   PDB; 2BDM; X-ray; 2.30 A; A=20-491.
DR   PDB; 2Q6N; X-ray; 3.20 A; A/B/C/D/E/F/G=20-491.
DR   PDB; 3G5N; X-ray; 2.50 A; A/B/C/D=20-491.
DR   PDB; 3G93; X-ray; 3.20 A; A/B/C/D=20-491.
DR   PDB; 3KW4; X-ray; 2.67 A; A=20-491.
DR   PDB; 3ME6; X-ray; 3.10 A; A/B/C/D=20-491.
DR   PDB; 3MVR; X-ray; 1.76 A; A/B=22-491.
DR   PDB; 3R1A; X-ray; 3.50 A; A/B/C/D/E/F/G/H=20-491.
DR   PDB; 3R1B; X-ray; 3.00 A; A/B/C/D=20-491.
DR   PDB; 3TK3; X-ray; 2.80 A; A/B/C/D=20-491.
DR   PDB; 3TMZ; X-ray; 2.25 A; A=20-491.
DR   PDB; 3UAS; X-ray; 2.94 A; A=20-491.
DR   PDB; 4H1N; X-ray; 2.99 A; A=20-491.
DR   PDB; 4JLT; X-ray; 2.14 A; A=20-491.
DR   PDB; 4MGJ; X-ray; 2.41 A; A=30-491.
DR   PDB; 5EM4; X-ray; 3.02 A; A/B=1-491.
DR   PDB; 5IUT; X-ray; 2.34 A; A=20-491.
DR   PDB; 5IUZ; X-ray; 2.73 A; A/B=20-491.
DR   PDB; 6BWW; X-ray; 2.10 A; A=30-491.
DR   AlphaFoldDB; P00178; -.
DR   SMR; P00178; -.
DR   FunCoup; P00178; 685.
DR   STRING; 9986.ENSOCUP00000039568; -.
DR   BindingDB; P00178; -.
DR   ChEMBL; CHEMBL1743542; -.
DR   iPTMnet; P00178; -.
DR   PaxDb; 9986-ENSOCUP00000039568; -.
DR   KEGG; ocu:100328948; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   InParanoid; P00178; -.
DR   OrthoDB; 1055148at2759; -.
DR   SABIO-RK; P00178; -.
DR   EvolutionaryTrace; P00178; -.
DR   PRO; PR:P00178; -.
DR   Proteomes; UP000001811; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008392; F:arachidonate epoxygenase activity; IEA:TreeGrafter.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0016712; F: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; IEA:UniProtKB-EC.
DR   GO; GO:0019373; P:epoxygenase P450 pathway; IEA:TreeGrafter.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IEA:TreeGrafter.
DR   CDD; cd20672; CYP2B; 1.
DR   FunFam; 1.10.630.10:FF:000001; Cytochrome P450, family 2; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR008068; Cyt_P450_E_grp-I_CYP2B-like.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   InterPro; IPR050182; Cytochrome_P450_fam2.
DR   PANTHER; PTHR24300:SF406; CYTOCHROME P450 2B6; 1.
DR   PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR01685; EP450ICYP2B.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   PDBsum; 1PO5; -.
DR   PDBsum; 1SUO; -.
DR   PDBsum; 2BDM; -.
DR   PDBsum; 2Q6N; -.
DR   PDBsum; 3G5N; -.
DR   PDBsum; 3G93; -.
DR   PDBsum; 3KW4; -.
DR   PDBsum; 3ME6; -.
DR   PDBsum; 3MVR; -.
DR   PDBsum; 3R1A; -.
DR   PDBsum; 3R1B; -.
DR   PDBsum; 3TK3; -.
DR   PDBsum; 3TMZ; -.
DR   PDBsum; 3UAS; -.
DR   PDBsum; 4H1N; -.
DR   PDBsum; 4JLT; -.
DR   PDBsum; 4MGJ; -.
DR   PDBsum; 5EM4; -.
DR   PDBsum; 5IUT; -.
DR   PDBsum; 5IUZ; -.
DR   PDBsum; 6BWW; -.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
KW   Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..491
FT                   /note="Cytochrome P450 2B4"
FT                   /id="PRO_0000051681"
FT   BINDING         436
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT   MOD_RES         128
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250|UniProtKB:P00176"
FT   VARIANT         39
FT                   /note="V -> I (in B1)"
FT   VARIANT         174
FT                   /note="I -> V (in B1)"
FT   VARIANT         290
FT                   /note="L -> I (in B1)"
FT   VARIANT         314
FT                   /note="M -> L (in B1)"
FT   VARIANT         420
FT                   /note="L -> M (in B1)"
FT   MUTAGEN         436
FT                   /note="C->S: Conversion into an NADPH oxidase with
FT                   negligible monooxygenase activity."
FT                   /evidence="ECO:0000269|PubMed:12237221"
FT   CONFLICT        91
FT                   /note="Q -> E (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        95..96
FT                   /note="FS -> SF (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        99..100
FT                   /note="Missing (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        135..136
FT                   /note="FG -> GY (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        193
FT                   /note="P -> K (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        221
FT                   /note="P -> S (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        303
FT                   /note="T -> A (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        461..465
FT                   /note="SPVPP -> GNLSL (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           30..32
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           34..36
FT                   /evidence="ECO:0007829|PDB:3MVR"
FT   TURN            38..40
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           43..45
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           51..62
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          64..70
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          73..78
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           81..85
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           86..90
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   TURN            91..95
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           101..104
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           105..108
FT                   /evidence="ECO:0007829|PDB:3MVR"
FT   HELIX           112..115
FT                   /evidence="ECO:0007829|PDB:3MVR"
FT   HELIX           118..134
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   TURN            136..138
FT                   /evidence="ECO:0007829|PDB:3R1A"
FT   HELIX           139..159
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   TURN            160..162
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          165..167
FT                   /evidence="ECO:0007829|PDB:3ME6"
FT   HELIX           168..184
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           187..189
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           193..205
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   TURN            206..208
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           213..219
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           222..226
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           231..253
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          258..260
FT                   /evidence="ECO:0007829|PDB:3ME6"
FT   HELIX           264..275
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           282..316
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           318..331
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          334..336
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           337..339
FT                   /evidence="ECO:0007829|PDB:2Q6N"
FT   HELIX           340..345
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           347..360
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          362..365
FT                   /evidence="ECO:0007829|PDB:4H1N"
FT   STRAND          375..377
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          380..382
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          387..390
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           392..396
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   TURN            399..401
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          402..404
FT                   /evidence="ECO:0007829|PDB:1SUO"
FT   HELIX           410..413
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          418..420
FT                   /evidence="ECO:0007829|PDB:3R1A"
FT   HELIX           421..423
FT                   /evidence="ECO:0007829|PDB:3R1B"
FT   HELIX           432..434
FT                   /evidence="ECO:0007829|PDB:3MVR"
FT   HELIX           439..456
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          457..460
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   HELIX           465..467
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          473..480
FT                   /evidence="ECO:0007829|PDB:1SUO"
FT   HELIX           481..483
FT                   /evidence="ECO:0007829|PDB:1PO5"
FT   STRAND          486..490
FT                   /evidence="ECO:0007829|PDB:1PO5"
SQ   SEQUENCE   491 AA;  55713 MW;  0DB943C6CDCF690B CRC64;
     MEFSLLLLLA FLAGLLLLLF RGHPKAHGRL PPGPSPLPVL GNLLQMDRKG LLRSFLRLRE
     KYGDVFTVYL GSRPVVVLCG TDAIREALVD QAEAFSGRGK IAVVDPIFQG YGVIFANGER
     WRALRRFSLA TMRDFGMGKR SVEERIQEEA RCLVEELRKS KGALLDNTLL FHSITSNIIC
     SIVFGKRFDY KDPVFLRLLD LFFQSFSLIS SFSSQVFELF PGFLKHFPGT HRQIYRNLQE
     INTFIGQSVE KHRATLDPSN PRDFIDVYLL RMEKDKSDPS SEFHHQNLIL TVLSLFFAGT
     ETTSTTLRYG FLLMLKYPHV TERVQKEIEQ VIGSHRPPAL DDRAKMPYTD AVIHEIQRLG
     DLIPFGVPHT VTKDTQFRGY VIPKNTEVFP VLSSALHDPR YFETPNTFNP GHFLDANGAL
     KRNEGFMPFS LGKRICLGEG IARTELFLFF TTILQNFSIA SPVPPEDIDL TPRESGVGNV
     PPSYQIRFLA R
//