CP1B1_RAT
ID CP1B1_RAT Reviewed; 543 AA.
AC Q64678;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Cytochrome P450 1B1;
DE EC=1.14.14.1 {ECO:0000269|PubMed:23821647};
DE AltName: Full=CYPIB1;
DE AltName: Full=Cytochrome P450RAP;
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase;
DE EC=4.2.1.152 {ECO:0000250|UniProtKB:Q16678};
GN Name=Cyp1b1 {ECO:0000303|PubMed:7744798, ECO:0000312|RGD:2460};
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 [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley;
RX PubMed=7744798; DOI=10.1074/jbc.270.19.11595;
RA Bhattacharyya K.K., Brake P.B., Eltom S.E., Otto S.A., Jefcoate C.R.;
RT "Identification of a rat adrenal cytochrome P450 active in polycyclic
RT hydrocarbon metabolism as rat CYP1B1. Demonstration of a unique tissue-
RT specific pattern of hormonal and aryl hydrocarbon receptor-linked
RT regulation.";
RL J. Biol. Chem. 270:11595-11602(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7788849; DOI=10.1093/carcin/16.6.1319;
RA Walker N.J., Gastel J.A., Costa L.T., Clark G.C., Lucier G.W., Sutter T.R.;
RT "Rat CYP1B1: an adrenal cytochrome P450 that exhibits sex-dependent
RT expression in livers and kidneys of TCDD-treated animals.";
RL Carcinogenesis 16:1319-1327(1995).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20972997; DOI=10.1002/rcm.4760;
RA Mesaros C., Lee S.H., Blair I.A.;
RT "Analysis of epoxyeicosatrienoic acids by chiral liquid
RT chromatography/electron capture atmospheric pressure chemical ionization
RT mass spectrometry using [13C]-analog internal standards.";
RL Rapid Commun. Mass Spectrom. 24:3237-3247(2010).
RN [4]
RP INDUCTION.
RX PubMed=21867498; DOI=10.1186/2045-8118-8-23;
RA Jacob A., Hartz A.M., Potin S., Coumoul X., Yousif S., Scherrmann J.M.,
RA Bauer B., Decleves X.;
RT "Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and
RT diesel exhaust particles in rat brain microvessels.";
RL Fluids Barriers CNS 8:23-23(2011).
RN [5]
RP INDUCTION.
RX PubMed=21785971; DOI=10.1007/s11010-011-0994-z;
RA Deb S., Tai J.K., Leung G.S., Chang T.K., Bandiera S.M.;
RT "Estradiol-mediated suppression of CYP1B1 expression in mouse MA-10 Leydig
RT cells is independent of protein kinase A and estrogen receptor.";
RL Mol. Cell. Biochem. 358:387-395(2011).
RN [6]
RP INDUCTION.
RX PubMed=23026235; DOI=10.1016/j.etap.2012.09.004;
RA Brauze D., Rawluszko A.A.;
RT "The effect of aryl hydrocarbon receptor ligands on the expression of
RT polymerase (DNA directed) kappa (Polkappa), polymerase RNA II (DNA
RT directed) polypeptide A (PolR2a), CYP1B1 and CYP1A1 genes in rat liver.";
RL Environ. Toxicol. Pharmacol. 34:819-825(2012).
RN [7]
RP MUTAGENESIS OF LEU-395, FUNCTION IN ESTROGEN METABOLISM, CATALYTIC
RP ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=23821647; DOI=10.1124/mol.113.087700;
RA Nishida C.R., Everett S., Ortiz de Montellano P.R.;
RT "Specificity determinants of CYP1B1 estradiol hydroxylation.";
RL Mol. Pharmacol. 84:451-458(2013).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC various endogenous substrates, including fatty acids, steroid hormones
CC and vitamins (By similarity). Mechanistically, uses molecular oxygen
CC inserting one oxygen atom into a substrate, and reducing the second
CC into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (NADPH--hemoprotein reductase) (By
CC similarity). Exhibits catalytic activity for the formation of
CC hydroxyestrogens from 17beta-estradiol (E2), namely 2- and 4-hydroxy E2
CC (PubMed:23821647). Metabolizes testosterone and progesterone to B or D
CC ring hydroxylated metabolites (By similarity). May act as a major
CC enzyme for all-trans retinoic acid biosynthesis in extrahepatic
CC tissues. Catalyzes two successive oxidative transformation of all-trans
CC retinol to all-trans retinal and then to the active form all-trans
CC retinoic acid (By similarity). Catalyzes the epoxidation of double
CC bonds of certain PUFA. Converts arachidonic acid toward
CC epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and
CC 14,15- EpETrE, that function as lipid mediators in the vascular system
CC (PubMed:20972997). Additionally, displays dehydratase activity toward
CC oxygenated eicosanoids including hydroperoxyeicosatetraenoates
CC (HpETEs). This activity is independent of cytochrome P450 reductase,
CC NADPH, and O2 (By similarity). Also involved in the oxidative
CC metabolism of xenobiotics, particularly converting polycyclic aromatic
CC hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-
CC damaging products (By similarity). Plays an important role in retinal
CC vascular development. Under ambient/hyperoxic O2 conditions, promotes
CC angiogenesis and capillary morphogenesis of retinal endothelial cells
CC and pericytes, likely by metabolizing the oxygenated products
CC symptomatic of oxidative stress (By similarity). Also, contributes to
CC oxidative homeostasis and ultrastructural organization and function of
CC trabecular meshwork tissue through modulation of POSTN expression (By
CC similarity). {ECO:0000250|UniProtKB:Q16678,
CC ECO:0000250|UniProtKB:Q64429, ECO:0000269|PubMed:20972997,
CC ECO:0000269|PubMed:23821647}.
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 Evidence={ECO:0000269|PubMed:23821647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:23821647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:28744,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:23821647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213;
CC Evidence={ECO:0000305|PubMed:23821647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 4-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:47280, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:62845;
CC Evidence={ECO:0000269|PubMed:23821647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281;
CC Evidence={ECO:0000305|PubMed:23821647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2-
CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 4-
CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:47292, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:87602; Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + testosterone =
CC 6beta,17beta-dihydroxyandrost-4-en-3-one + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46296, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17347,
CC ChEBI:CHEBI:34477, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46297;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] =
CC 6beta-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:47252, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:62117; Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47253;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] =
CC 16alpha-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:47260, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15826, ChEBI:CHEBI:17026,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47261;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinal + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-retinoate + 2 H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:42088, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17898, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131975; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131970; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131969; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131964; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131965; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-
CC (6E,8Z,11Z,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48632,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57450, ChEBI:CHEBI:65342;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-
CC (5Z,8Z,10E,14Z)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:37947,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57444, ChEBI:CHEBI:75231;
CC EC=4.2.1.152; Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-
CC octadecadienoate + H2O; Xref=Rhea:RHEA:48716, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57466, ChEBI:CHEBI:90781;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Enzyme activity is increased by cytochrome b5
CC (PubMed:23821647). Enzyme activity is increased by liposomes containing
CC anionic phospholipids, phosphatidic acid and cardiolipin. Inhibited by
CC naringenin with an IC(50) of 5 uM (By similarity).
CC {ECO:0000250|UniProtKB:Q16678, ECO:0000269|PubMed:23821647}.
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:Q16678}.
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000250|UniProtKB:Q16678}.
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000250|UniProtKB:Q16678}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q64429}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q64429}. Microsome membrane
CC {ECO:0000250|UniProtKB:Q64429}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q64429}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q64429}. Note=Located primarily in endoplasmic
CC reticulum. Upon treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin
CC (TCDD), CYP1B1 is also targeted to mitochondria.
CC {ECO:0000250|UniProtKB:Q64429}.
CC -!- INDUCTION: By polycyclic aromatic hydrocarbons (PAH), beta-
CC naphthoflavone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Up-
CC regulated by diesel exhaust particles (DEP). Decreased by estradiol (at
CC protein level). {ECO:0000269|PubMed:21785971,
CC ECO:0000269|PubMed:21867498, ECO:0000269|PubMed:23026235}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; X83867; CAA58748.1; -; mRNA.
DR EMBL; U09540; AAA79864.1; -; mRNA.
DR PIR; I48130; I48130.
DR RefSeq; NP_037072.1; NM_012940.2.
DR RefSeq; XP_017449535.1; XM_017594046.1.
DR AlphaFoldDB; Q64678; -.
DR SMR; Q64678; -.
DR STRING; 10116.ENSRNOP00000061222; -.
DR SwissLipids; SLP:000001591; -.
DR iPTMnet; Q64678; -.
DR PhosphoSitePlus; Q64678; -.
DR PaxDb; Q64678; -.
DR PRIDE; Q64678; -.
DR Ensembl; ENSRNOT00000084171; ENSRNOP00000075074; ENSRNOG00000040287.
DR GeneID; 25426; -.
DR KEGG; rno:25426; -.
DR UCSC; RGD:2460; rat.
DR CTD; 1545; -.
DR RGD; 2460; Cyp1b1.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00950000183037; -.
DR InParanoid; Q64678; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q64678; -.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR Reactome; R-RNO-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR Reactome; R-RNO-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR UniPathway; UPA00383; -.
DR UniPathway; UPA00912; -.
DR PRO; PR:Q64678; -.
DR Proteomes; UP000002494; Chromosome 6.
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:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0101020; F:estrogen 16-alpha-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0106256; F:hydroperoxy icosatetraenoate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0030325; P:adrenal gland development; IEP:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0019369; P:arachidonic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0042537; P:benzene-containing compound metabolic process; IDA:RGD.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0006725; P:cellular aromatic compound metabolic process; IDA:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071387; P:cellular response to cortisol stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISS:UniProtKB.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0071393; P:cellular response to progesterone stimulus; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0030199; P:collagen fibril organization; ISS:UniProtKB.
DR GO; GO:0006304; P:DNA modification; IMP:RGD.
DR GO; GO:0043542; P:endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0071603; P:endothelial cell-cell adhesion; ISO:RGD.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:RGD.
DR GO; GO:0044849; P:estrous cycle; IEP:RGD.
DR GO; GO:0061548; P:ganglion development; IEP:RGD.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0046466; P:membrane lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEP:RGD.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IMP:RGD.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:RGD.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0045727; P:positive regulation of translation; IMP:RGD.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISS:UniProtKB.
DR GO; GO:0046685; P:response to arsenic-containing substance; IEP:RGD.
DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEP:RGD.
DR GO; GO:0071680; P:response to indole-3-methanol; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISO:RGD.
DR GO; GO:0061304; P:retinal blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0042574; P:retinal metabolic process; ISS:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; ISS:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; ISS:UniProtKB.
DR GO; GO:0009404; P:toxin metabolic process; ISO:RGD.
DR GO; GO:0002930; P:trabecular meshwork development; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR032971; CYP1B1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR24299:SF11; PTHR24299:SF11; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
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; Fatty acid metabolism;
KW Heme; Iron; Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome;
KW Mitochondrion; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid metabolism.
FT CHAIN 1..543
FT /note="Cytochrome P450 1B1"
FT /id="PRO_0000051662"
FT BINDING 470
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 /evidence="ECO:0000250"
FT SITE 395
FT /note="Major determinant of CYP1B1 17beta-estradiol
FT hydroxylation regiospecificity"
FT MUTAGEN 395
FT /note="L->V: Shifts the 4OH E2:2OH E2 hydroxylation ratio
FT from 0.38 to 1.8. Has the 4OH-hydroxylation specificity of
FT the human enzyme."
FT /evidence="ECO:0000269|PubMed:23821647"
SQ SEQUENCE 543 AA; 60557 MW; 8D144B0000D5F095 CRC64;
MATSLSADSP QQLSSLSTQQ TILLLLVSVL AIVHLGQWLL RQWRRKPWSS PPGPFPWPLI
GNAASVGRAS HLYFARLARR YGDVFQIRLG SCPVVVLNGE SAIHQALVQQ GGVFADRPPF
ASFRVVSGGR SLAFGHYSER WKERRRAAYG TMRAFSTRHP RSRGLLEGHA LGEARELVAV
LVRRCAGGAC LDPTQPIIVA VANVMSAVCF GCRYNHDDAE FLELLSHNEE FGRTVGAGSL
VDVMPWLQLF PNPVRTIFRE FEQINRNFSN FVLDKFLRHR ESLVPGAAPR DMMDAFILSA
EKKATGDPGD SPSGLDLEDV PATITDIFGA SQDTLSTALL WLLILFTRYP DVQARVQAEL
DQVVGRDRLP CMSDQPNLPY VMAFLYESMR FTSFLPVTLP HATTANTFVL GYYIPKNTVV
FVNQWSVNHD PAKWSNPEDF DPARFLDKDG FINKALASSV MIFSVGKRRC IGEELSKTLL
FLFISILAHQ CNFKANQNEP SNMSFSYGLS IKPKSFKIHV SLRESMKLLD SAVEKLQAEE
ACQ
