CP2B4_RABIT
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 03-AUG-2022, entry version 165.
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;
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;
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 + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; 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 RefSeq; NP_001164602.1; NM_001171131.1.
DR PDB; 1PO5; X-ray; 1.60 A; A=25-491.
DR PDB; 1SUO; X-ray; 1.90 A; A=25-491.
DR PDB; 2BDM; X-ray; 2.30 A; A=25-491.
DR PDB; 2Q6N; X-ray; 3.20 A; A/B/C/D/E/F/G=25-491.
DR PDB; 3G5N; X-ray; 2.50 A; A/B/C/D=25-491.
DR PDB; 3G93; X-ray; 3.20 A; A/B/C/D=25-491.
DR PDB; 3KW4; X-ray; 2.67 A; A=25-491.
DR PDB; 3ME6; X-ray; 3.10 A; A/B/C/D=25-491.
DR PDB; 3MVR; X-ray; 1.76 A; A/B=25-491.
DR PDB; 3R1A; X-ray; 3.50 A; A/B/C/D/E/F/G/H=25-491.
DR PDB; 3R1B; X-ray; 3.00 A; A/B/C/D=25-491.
DR PDB; 3TK3; X-ray; 2.80 A; A/B/C/D=25-491.
DR PDB; 3TMZ; X-ray; 2.25 A; A=25-491.
DR PDB; 3UAS; X-ray; 2.94 A; A=25-491.
DR PDB; 4H1N; X-ray; 2.99 A; A=25-491.
DR PDB; 4JLT; X-ray; 2.14 A; A=25-491.
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=25-491.
DR PDB; 5IUZ; X-ray; 2.73 A; A/B=25-491.
DR PDB; 6BWW; X-ray; 2.10 A; A=30-491.
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; -.
DR AlphaFoldDB; P00178; -.
DR SMR; P00178; -.
DR STRING; 9986.ENSOCUP00000022188; -.
DR BindingDB; P00178; -.
DR ChEMBL; CHEMBL1743542; -.
DR iPTMnet; P00178; -.
DR PRIDE; P00178; -.
DR GeneID; 100328948; -.
DR KEGG; ocu:100328948; -.
DR eggNOG; KOG0156; Eukaryota.
DR InParanoid; P00178; -.
DR OrthoDB; 702827at2759; -.
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:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01685; EP450ICYP2B.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
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 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..88
FT /evidence="ECO:0007829|PDB:1PO5"
FT TURN 89..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 135..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 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 221..225
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 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 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 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
