CP1B1_MOUSE
ID CP1B1_MOUSE Reviewed; 543 AA.
AC Q64429; Q3UVA8; Q60593; Q64461;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Cytochrome P450 1B1 {ECO:0000303|PubMed:15258110};
DE EC=1.14.14.1 {ECO:0000269|PubMed:23821647};
DE AltName: Full=CYPIB1;
DE AltName: Full=Cytochrome P450CMEF;
DE Short=Cytochrome P450EF;
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase;
DE EC=4.2.1.152 {ECO:0000250|UniProtKB:Q16678};
GN Name=Cyp1b1 {ECO:0000303|PubMed:7772257, ECO:0000312|MGI:MGI:88590};
GN Synonyms=Cyp1-b1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ;
RX PubMed=7772257; DOI=10.1089/dna.1994.13.763;
RA Shen Z., Liu J., Wells R.L., Elkind M.M.;
RT "cDNA cloning, sequence analysis, and induction by aryl hydrocarbons of a
RT murine cytochrome P450 gene, Cyp1b1.";
RL DNA Cell Biol. 13:763-769(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ;
RX PubMed=8195121; DOI=10.1016/s0021-9258(17)36551-1;
RA Savas U., Bhattacharyya K.K., Christou M., Alexander D.L., Jefcoate C.R.;
RT "Mouse cytochrome P-450EF, representative of a new 1B subfamily of
RT cytochrome P-450s. Cloning, sequence determination, and tissue
RT expression.";
RL J. Biol. Chem. 269:14905-14911(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 361-466.
RX PubMed=7505439; DOI=10.1073/pnas.90.24.11483;
RA Shen Z., Wells R.L., Liu J., Elkind M.M.;
RT "Identification of a cytochrome P450 gene by reverse transcription-PCR
RT using degenerate primers containing inosine.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:11483-11487(1993).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15258110; DOI=10.1124/dmd.32.8.840;
RA Choudhary D., Jansson I., Stoilov I., Sarfarazi M., Schenkman J.B.;
RT "Metabolism of retinoids and arachidonic acid by human and mouse cytochrome
RT P450 1b1.";
RL Drug Metab. Dispos. 32:840-847(2004).
RN [7]
RP FUNCTION IN VASCULAR DEVELOPMENT AND ANGIOGENESIS, AND TISSUE SPECIFICITY.
RX PubMed=19005183; DOI=10.1182/blood-2008-03-145219;
RA Tang Y., Scheef E.A., Wang S., Sorenson C.M., Marcus C.B., Jefcoate C.R.,
RA Sheibani N.;
RT "CYP1B1 expression promotes the proangiogenic phenotype of endothelium
RT through decreased intracellular oxidative stress and thrombospondin-2
RT expression.";
RL Blood 113:744-754(2009).
RN [8]
RP FUNCTION IN ANGIOGENESIS, AND TISSUE SPECIFICITY.
RX PubMed=20032512; DOI=10.1152/ajpcell.00153.2009;
RA Tang Y., Scheef E.A., Gurel Z., Sorenson C.M., Jefcoate C.R., Sheibani N.;
RT "CYP1B1 and endothelial nitric oxide synthase combine to sustain
RT proangiogenic functions of endothelial cells under hyperoxic stress.";
RL Am. J. Physiol. 298:C665-C678(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=23692925; DOI=10.1016/j.bbrc.2013.05.051;
RA Dong H., Shertzer H.G., Genter M.B., Gonzalez F.J., Vasiliou V.,
RA Jefcoate C., Nebert D.W.;
RT "Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins.";
RL Biochem. Biophys. Res. Commun. 435:727-732(2013).
RN [11]
RP FUNCTION IN VASCULAR HOMEOSTASIS, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=23568032; DOI=10.1038/labinvest.2013.55;
RA Palenski T.L., Sorenson C.M., Jefcoate C.R., Sheibani N.;
RT "Lack of Cyp1b1 promotes the proliferative and migratory phenotype of
RT perivascular supporting cells.";
RL Lab. Invest. 93:646-662(2013).
RN [12]
RP FUNCTION IN TRABECULAR MESHWORK DEVELOPMENT, DISRUPTION PHENOTYPE, AND
RP TISSUE SPECIFICITY.
RX PubMed=23979599; DOI=10.1128/mcb.00856-13;
RA Zhao Y., Wang S., Sorenson C.M., Teixeira L., Dubielzig R.R., Peters D.M.,
RA Conway S.J., Jefcoate C.R., Sheibani N.;
RT "Cyp1b1 mediates periostin regulation of trabecular meshwork development by
RT suppression of oxidative stress.";
RL Mol. Cell. Biol. 33:4225-4240(2013).
RN [13]
RP FUNCTION IN ESTROGEN METABOLISM, CATALYTIC ACTIVITY, AND ACTIVITY
RP 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 (PubMed:15258110). 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:15258110). Additionally, displays dehydratase activity toward
CC oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This
CC activity is independent of cytochrome P450 reductase, NADPH, and O2 (By
CC similarity). Also involved in the oxidative metabolism of xenobiotics,
CC particularly converting polycyclic aromatic hydrocarbons and
CC heterocyclic aryl amines procarcinogens to DNA-damaging products (By
CC similarity). Plays an important role in retinal vascular development.
CC Under ambient/hyperoxic O2 conditions, promotes angiogenesis and
CC capillary morphogenesis of retinal endothelial cells and pericytes,
CC likely by metabolizing the oxygenated products symptomatic of oxidative
CC stress (PubMed:19005183, PubMed:20032512, PubMed:23568032). Also,
CC contributes to oxidative homeostasis and ultrastructural organization
CC and function of trabecular meshwork tissue through modulation of POSTN
CC expression (PubMed:23979599). {ECO:0000250|UniProtKB:Q16678,
CC ECO:0000269|PubMed:15258110, ECO:0000269|PubMed:19005183,
CC ECO:0000269|PubMed:20032512, ECO:0000269|PubMed:23568032,
CC ECO:0000269|PubMed:23821647, ECO:0000269|PubMed:23979599}.
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:0000269|PubMed:15258110};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093;
CC Evidence={ECO:0000305|PubMed:15258110};
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:0000269|PubMed:15258110};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089;
CC Evidence={ECO:0000305|PubMed:15258110};
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:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
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:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
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:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
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:0000250|UniProtKB:Q16678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861;
CC Evidence={ECO:0000250|UniProtKB:Q16678};
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=(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 -!- 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 -!- 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=392.2 uM for all-trans-retinol {ECO:0000269|PubMed:15258110};
CC KM=153.9 uM for all-trans-retinal {ECO:0000269|PubMed:15258110};
CC KM=138.9 uM for 7,12-dimethyltetraphene
CC {ECO:0000269|PubMed:15258110};
CC KM=500.0 uM for arachidonic acid {ECO:0000269|PubMed:15258110};
CC Note=kcat is 0.04 min(-1) for retinol, 0.08 min(-1) for retinal, 1.24
CC min(-1) for 7,12-dimethyltetraphene, 0.13 min(-1) for arachidonic
CC acid.;
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:0000269|PubMed:23692925}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23692925}. Microsome membrane
CC {ECO:0000269|PubMed:23692925}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23692925}. Mitochondrion
CC {ECO:0000269|PubMed:23692925}. 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:0000269|PubMed:23692925}.
CC -!- TISSUE SPECIFICITY: Constitutively expressed in retinal and kidney
CC pericytes cells (PubMed:23568032). Expressed in retinal endothelial
CC cells (at protein level). Expressed in cardiac, pulmonary and aortic
CC endothelial cells (PubMed:19005183). Constitutively expressed in
CC trabecular meshwork of the eye (at protein level) (PubMed:23979599).
CC {ECO:0000269|PubMed:19005183, ECO:0000269|PubMed:23568032,
CC ECO:0000269|PubMed:23979599}.
CC -!- INDUCTION: Up-regulated by polycyclic aromatic hydrocarbons (PAH) and
CC 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
CC {ECO:0000269|PubMed:23568032, ECO:0000269|PubMed:23692925}.
CC -!- DISRUPTION PHENOTYPE: Severe ocular drainage structure abnormalities,
CC significant elevated intraocular pressure.
CC {ECO:0000269|PubMed:23979599}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; U03283; AAC52141.1; -; mRNA.
DR EMBL; X78445; CAA55205.1; -; mRNA.
DR EMBL; AK137461; BAE23362.1; -; mRNA.
DR EMBL; CH466537; EDL38490.1; -; Genomic_DNA.
DR EMBL; U02479; AAC52131.1; -; mRNA.
DR CCDS; CCDS28986.1; -.
DR PIR; A53790; A53790.
DR RefSeq; NP_034124.1; NM_009994.1.
DR AlphaFoldDB; Q64429; -.
DR SMR; Q64429; -.
DR BioGRID; 199003; 3.
DR STRING; 10090.ENSMUSP00000024894; -.
DR iPTMnet; Q64429; -.
DR PhosphoSitePlus; Q64429; -.
DR jPOST; Q64429; -.
DR MaxQB; Q64429; -.
DR PaxDb; Q64429; -.
DR PRIDE; Q64429; -.
DR ProteomicsDB; 284107; -.
DR Antibodypedia; 29477; 453 antibodies from 36 providers.
DR DNASU; 13078; -.
DR Ensembl; ENSMUST00000024894; ENSMUSP00000024894; ENSMUSG00000024087.
DR GeneID; 13078; -.
DR KEGG; mmu:13078; -.
DR UCSC; uc008dqc.1; mouse.
DR CTD; 1545; -.
DR MGI; MGI:88590; Cyp1b1.
DR VEuPathDB; HostDB:ENSMUSG00000024087; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00950000183037; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; Q64429; -.
DR OMA; QIRLGNC; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q64429; -.
DR TreeFam; TF105095; -.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR Reactome; R-MMU-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR Reactome; R-MMU-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR SABIO-RK; Q64429; -.
DR UniPathway; UPA00383; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 13078; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Cyp1b1; mouse.
DR PRO; PR:Q64429; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q64429; protein.
DR Bgee; ENSMUSG00000024087; Expressed in stroma of bone marrow and 189 other tissues.
DR ExpressionAtlas; Q64429; baseline and differential.
DR Genevisible; Q64429; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IMP:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
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; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0042537; P:benzene-containing compound metabolic process; ISO:MGI.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; IMP:MGI.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR GO; GO:0006725; P:cellular aromatic compound metabolic process; IDA:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0071387; P:cellular response to cortisol stimulus; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0071393; P:cellular response to progesterone stimulus; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IMP:UniProtKB.
DR GO; GO:0006304; P:DNA modification; ISO:MGI.
DR GO; GO:0043542; P:endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0071603; P:endothelial cell-cell adhesion; IMP:MGI.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0044849; P:estrous cycle; IEA:Ensembl.
DR GO; GO:0061548; P:ganglion development; IEA:Ensembl.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0046466; P:membrane lipid catabolic process; IMP:UniProtKB.
DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IMP:UniProtKB.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0045727; P:positive regulation of translation; ISO:MGI.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:0046685; P:response to arsenic-containing substance; IEA:Ensembl.
DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEA:Ensembl.
DR GO; GO:0071680; P:response to indole-3-methanol; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IMP:MGI.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IMP:MGI.
DR GO; GO:0061304; P:retinal blood vessel morphogenesis; IMP:UniProtKB.
DR GO; GO:0042574; P:retinal metabolic process; IDA:UniProtKB.
DR GO; GO:0042572; P:retinol metabolic process; IDA:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; ISS:UniProtKB.
DR GO; GO:0009404; P:toxin metabolic process; IMP:MGI.
DR GO; GO:0002930; P:trabecular meshwork development; IMP: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 Endoplasmic reticulum; Fatty acid metabolism; Heme; Iron; Lipid metabolism;
KW Lyase; Membrane; Metal-binding; Microsome; Mitochondrion; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid metabolism.
FT CHAIN 1..543
FT /note="Cytochrome P450 1B1"
FT /id="PRO_0000051661"
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 CONFLICT 195
FT /note="Q -> P (in Ref. 2; CAA55205)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="A -> D (in Ref. 2; CAA55205)"
FT /evidence="ECO:0000305"
FT CONFLICT 328
FT /note="F -> G (in Ref. 2; CAA55205)"
FT /evidence="ECO:0000305"
FT CONFLICT 457
FT /note="A -> T (in Ref. 2; CAA55205)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="F -> V (in Ref. 2; CAA55205)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 543 AA; 60537 MW; 7C89B4312CB5BC4A CRC64;
MATSLSADSP QQLSSLSTQQ TTLLLLFSVL AAVHLGQWLL RQWQRKPWSS PPGPFPWPLI
GNAAAVGQAS HLYFARLARR YGDVFQIRLG SCPVVVLNGE SAIHQALVQQ GSIFADRPPF
ASFRVVSGGR SLAFGHYSEH WKTQRRSAYS TMRAFSTRHP RSRGLLEGHA LAEARELVAV
LVRRCAGGAF LDPTQPVIVA VANVMSAVCF GCRYNHDDAE FLELLSHNEE FGRTVGAGSL
VDVLPWLQLF PNPVRTTFRK FEQLNRNFSN FVLDKFLRHR ESLVPGAAPR DMTDAFILSA
EKKASGAPGD DSSGLDLEDV PATITDIFGA SQDTLSTALL WLLILFTRYP DVQARVQAEL
DQVVGRDRLP CMSDQPNLPY VMAFLYESMR FSSFLPVTIP HATTANTFVL GYYIPKNTVV
FVNQWSVNHD PAKWPNPEDF DPARFLDKDG FINKALASSV MIFSVGKRRC IGEELSKMLL
FLFISILAHQ CNFKANQNES SNMSFSYGLT IKPKSFRIHV SLRESMELLD NAVKKLQTEE
GCK
