CP2B1_RAT
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 03-AUG-2022, entry version 162.
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 DrugBank; DB08834; Tauroursodeoxycholic acid.
DR iPTMnet; P00176; -.
DR PhosphoSitePlus; P00176; -.
DR PaxDb; P00176; -.
DR UCSC; RGD:2466; rat.
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-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; IDA:RGD.
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:0006082; P:organic acid metabolic process; 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 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 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
