ID   CP2B1_RAT               Reviewed;         491 AA.
AC   P00176; Q64584;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 169.
DE   RecName: Full=Cytochrome P450 2B1;
DE            EC=1.14.14.1;
DE   AltName: Full=CYPIIB1;
DE   AltName: Full=Cytochrome P450-B;
DE            Short=Cytochrome P450b;
DE   AltName: Full=Cytochrome P450-LM2;
DE   AltName: Full=Cytochrome P450-PB1;
DE   AltName: Full=Cytochrome P450-PB2;
GN   Name=Cyp2b1 {ECO:0000303|PubMed:19401463, ECO:0000312|RGD:2466};
GN   Synonyms=Cyp2b-1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6306654; DOI=10.1073/pnas.80.13.3958;
RA   Mizukami Y., Sogawa K., Suwa Y., Muramatsu M., Fujii-Kuriyama Y.;
RT   "Gene structure of a phenobarbital-inducible cytochrome P-450 in rat
RT   liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:3958-3962(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2989270; DOI=10.1016/s0021-9258(17)39550-9;
RA   Suwa Y., Mizukami Y., Sogawa K., Fujii-Kuriyama Y.;
RT   "Gene structure of a major form of phenobarbital-inducible cytochrome P-450
RT   in rat liver.";
RL   J. Biol. Chem. 260:7980-7984(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 6-491 (ISOZYMES PB1 AND PB2).
RX   PubMed=6953431; DOI=10.1073/pnas.79.9.2793;
RA   Fujii-Kuriyama Y., Mizukami Y., Kawajiri K., Sogawa K., Muramatsu M.;
RT   "Primary structure of a cytochrome P-450: coding nucleotide sequence of
RT   phenobarbital-inducible cytochrome P-450 cDNA from rat liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 79:2793-2797(1982).
RN   [4]
RP   SEQUENCE REVISION TO 166; 292 AND 378 (ISOZYMES PB1 AND PB2).
RA   Fujii-Kuriyama Y., Mizukami Y., Kawajiri K., Sogawa K., Muramatsu M.;
RL   Proc. Natl. Acad. Sci. U.S.A. 79:5443-5443(1982).
RN   [5]
RP   PROTEIN SEQUENCE OF 1-18; 146-165; 329-379 AND 401-423.
RX   PubMed=2539047; DOI=10.1016/0003-9861(89)90003-9;
RA   Oesch F., Waxman D.J., Morrissey J.J., Honscha W., Kissel W., Friedberg T.;
RT   "Antibodies targeted against hypervariable and constant regions of
RT   cytochromes P450IIB1 and P450IIB2.";
RL   Arch. Biochem. Biophys. 270:23-32(1989).
RN   [6]
RP   PROTEIN SEQUENCE OF 1-22.
RX   PubMed=109438; DOI=10.1016/s0021-9258(18)50461-0;
RA   Botelho L.H., Ryan D.E., Levin W.;
RT   "Amino acid compositions and partial amino acid sequences of three highly
RT   purified forms of liver microsomal cytochrome P-450 from rats treated with
RT   polychlorinated biphenyls, phenobarbital, or 3-methylcholanthrene.";
RL   J. Biol. Chem. 254:5635-5640(1979).
RN   [7]
RP   PROTEIN SEQUENCE OF 273-283 AND 290-301.
RX   PubMed=8142377; DOI=10.1021/bi00178a037;
RA   Roberts E.S., Hopkins N.E., Zaluzec E.J., Gage D.A., Alworth W.L.,
RA   Hollenberg P.F.;
RT   "Identification of active-site peptides from 3H-labeled 2-
RT   ethynylnaphthalene-inactivated P450 2B1 and 2B4 using amino acid sequencing
RT   and mass spectrometry.";
RL   Biochemistry 33:3766-3771(1994).
RN   [8]
RP   PHOSPHORYLATION AT SER-128.
RX   PubMed=2583091; DOI=10.1002/j.1460-2075.1989.tb08450.x;
RA   Pyerin W., Taniguchi H.;
RT   "Phosphorylation of hepatic phenobarbital-inducible cytochrome P-450.";
RL   EMBO J. 8:3003-3010(1989).
RN   [9]
RP   SUBCELLULAR LOCATION, INTERACTION WITH HSP70, INTERACTION WITH HSP90,
RP   MUTAGENESIS OF SER-128, AND TOPOLOGY.
RX   PubMed=19401463; DOI=10.1074/jbc.m109.007492;
RA   Anandatheerthavarada H.K., Sepuri N.B., Avadhani N.G.;
RT   "Mitochondrial targeting of cytochrome P450 proteins containing NH2-
RT   terminal chimeric signals involves an unusual TOM20/TOM22 bypass
RT   mechanism.";
RL   J. Biol. Chem. 284:17352-17363(2009).
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   -!- 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; Evidence={ECO:0000250};
CC   -!- SUBUNIT: Interacts with chaperones HSP70 and HSP90; this interaction is
CC       required for initial targeting to mitochondria.
CC       {ECO:0000269|PubMed:19401463}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC       membrane protein. Microsome membrane; Peripheral membrane protein.
CC       Mitochondrion inner membrane {ECO:0000305|PubMed:19401463}; Peripheral
CC       membrane protein {ECO:0000305|PubMed:19401463}. Note=Post-
CC       translationally targeted to mitochondria. Requires the cytosolic
CC       chaperones HSP70 and HSP90, for initial targeting to mitochondria, and
CC       then requires all three of the receptor proteins in the TOM complex,
CC       TOMM70, TOMM20 and TOMM22 for translocation across the mitochondrial
CC       outer membrane. After translocation into the matrix, associates with
CC       the inner membrane as a membrane extrinsic protein.
CC       {ECO:0000305|PubMed:19401463}.
CC   -!- INDUCTION: By phenobarbital.
CC   -!- PTM: Phosphorylation is accompanied by a decrease in enzyme activity.
CC       {ECO:0000269|PubMed:2583091}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; L00320; AAA41046.1; -; Genomic_DNA.
DR   EMBL; L00313; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; L00314; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; L00315; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; L00316; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; L00317; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; L00318; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; L00319; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; M11251; AAA41046.1; JOINED; Genomic_DNA.
DR   EMBL; J00719; AAA41024.1; -; mRNA.
DR   EMBL; M37134; AAC42028.1; -; mRNA.
DR   PIR; A00176; O4RTPB.
DR   PIR; A21162; O4RTP2.
DR   AlphaFoldDB; P00176; -.
DR   SMR; P00176; -.
DR   IntAct; P00176; 36.
DR   STRING; 10116.ENSRNOP00000049925; -.
DR   BindingDB; P00176; -.
DR   ChEMBL; CHEMBL3335; -.
DR   DrugBank; DB00869; Dorzolamide.
DR   DrugBank; DB00409; Remoxipride.
DR   iPTMnet; P00176; -.
DR   PhosphoSitePlus; P00176; -.
DR   PaxDb; 10116-ENSRNOP00000049925; -.
DR   UCSC; RGD:2466; rat.
DR   AGR; RGD:2466; -.
DR   RGD; 2466; Cyp2b1.
DR   eggNOG; KOG0156; Eukaryota.
DR   InParanoid; P00176; -.
DR   PhylomeDB; P00176; -.
DR   Reactome; R-RNO-211935; Fatty acids.
DR   Reactome; R-RNO-211945; Phase I - Functionalization of compounds.
DR   Reactome; R-RNO-211981; Xenobiotics.
DR   Reactome; R-RNO-211999; CYP2E1 reactions.
DR   PRO; PR:P00176; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR   GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR   GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR   GO; GO:0030544; F:Hsp70 protein binding; IDA:UniProtKB.
DR   GO; GO:0051879; F:Hsp90 protein binding; IDA:UniProtKB.
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; IBA:GO_Central.
DR   GO; GO:0008395; F:steroid hydroxylase activity; IDA:RGD.
DR   GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR   GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR   GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR   GO; GO:0032868; P:response to insulin; IEP:RGD.
DR   GO; GO:0010038; P:response to metal ion; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0010477; P:response to sulfur dioxide; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IDA:RGD.
DR   CDD; cd20672; CYP2B; 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   PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1.
DR   PANTHER; PTHR24300:SF366; CYTOCHROME P450-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.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW   Metal-binding; Microsome; Mitochondrion; Mitochondrion inner membrane;
KW   Monooxygenase; Oxidoreductase; Phosphoprotein; Reference proteome.
FT   CHAIN           1..491
FT                   /note="Cytochrome P450 2B1"
FT                   /id="PRO_0000051678"
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:0000269|PubMed:2583091"
FT   VARIANT         303
FT                   /note="S -> G (in isozyme PB2)"
FT   VARIANT         321..322
FT                   /note="AE -> TV (in isozyme PB2)"
FT   VARIANT         337
FT                   /note="L -> P (in isozyme PB2)"
FT   VARIANT         339
FT                   /note="T -> S (in isozyme PB2)"
FT   VARIANT         344
FT                   /note="S -> T (in isozyme PB2)"
FT   MUTAGEN         128
FT                   /note="S->A: Reduces interaction with HSP70; impairs
FT                   interaction with HSP90."
FT                   /evidence="ECO:0000269|PubMed:19401463"
FT   CONFLICT        4
FT                   /note="T -> S (in Ref. 2 and 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        92
FT                   /note="A -> P (in Ref. 2; AAA41046)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        161
FT                   /note="Q -> E (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        205
FT                   /note="T -> R (in Ref. 2; AAA41046)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        328
FT                   /note="I -> V (in Ref. 2; AAA41046)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        357
FT                   /note="Q -> H (in Ref. 2; AAA41046)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        392
FT                   /note="L -> R (in Ref. 2; AAA41046)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        416
FT                   /note="A -> V (in Ref. 2; AAA41046)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        434
FT                   /note="R -> H (in Ref. 2; AAA41046)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        473
FT                   /note="K -> M (in Ref. 1; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   491 AA;  55934 MW;  74615501AD5497DD CRC64;
     MEPTILLLLA LLVGFLLLLV RGHPKSRGNF PPGPRPLPLL GNLLQLDRGG LLNSFMQLRE
     KYGDVFTVHL GPRPVVMLCG TDTIKEALVG QAEDFSGRGT IAVIEPIFKE YGVIFANGER
     WKALRRFSLA TMRDFGMGKR SVEERIQEEA QCLVEELRKS QGAPLDPTFL FQCITANIIC
     SIVFGERFDY TDRQFLRLLE LFYRTFSLLS SFSSQVFEFF SGFLKYFPGA HRQISKNLQE
     ILDYIGHIVE KHRATLDPSA PRDFIDTYLL RMEKEKSNHH TEFHHENLMI SLLSLFFAGT
     ETSSTTLRYG FLLMLKYPHV AEKVQKEIDQ VIGSHRLPTL DDRSKMPYTD AVIHEIQRFS
     DLVPIGVPHR VTKDTMFRGY LLPKNTEVYP ILSSALHDPQ YFDHPDSFNP EHFLDANGAL
     KKSEAFMPFS TGKRICLGEG IARNELFLFF TTILQNFSVS SHLAPKDIDL TPKESGIGKI
     PPTYQICFSA R
//