CP1B1_HUMAN
ID CP1B1_HUMAN Reviewed; 543 AA.
AC Q16678; Q5TZW8; Q93089; Q9H316;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Cytochrome P450 1B1 {ECO:0000303|PubMed:10426814};
DE EC=1.14.14.1 {ECO:0000269|PubMed:10426814, ECO:0000269|PubMed:22888116};
DE AltName: Full=CYPIB1;
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase {ECO:0000305|PubMed:21068195};
DE EC=4.2.1.152 {ECO:0000269|PubMed:21068195};
GN Name=CYP1B1 {ECO:0000303|PubMed:8910454, ECO:0000312|HGNC:HGNC:2597};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=8175734; DOI=10.1016/s0021-9258(17)36803-5;
RA Sutter T.R., Tang Y.M., Hayes C.L., Wo Y.-Y.P., Jabs E.W., Li X., Yin H.,
RA Cody C.W., Greenlee W.F.;
RT "Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new
RT gene subfamily of cytochrome P450 that maps to chromosome 2.";
RL J. Biol. Chem. 269:13092-13099(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8910454; DOI=10.1074/jbc.271.45.28324;
RA Tang Y.M., Wo Y.-Y.P., Stewart J., Hawkins A.L., Griffin C.A., Sutter T.R.,
RA Greenlee W.F.;
RT "Isolation and characterization of the human cytochrome P450 CYP1B1 gene.";
RL J. Biol. Chem. 271:28324-28330(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Gorry M.C., Zhang Y., Marks J.J., Suppe B., Hart P.S., Cortelli J.R.,
RA Pallos D., Hart T.C.;
RT "Physical/genetic map of the 2p22-2p21 region on chromosome 2.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-453.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-48; SER-119; ASN-206;
RP LEU-266; VAL-432 AND SER-453.
RG NIEHS SNPs program;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-112, AND VARIANT GLY-48.
RA Guillemette C.;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CHARACTERIZATION OF VARIANTS SER-119 AND VAL-432.
RX PubMed=10426814; DOI=10.1093/carcin/20.8.1607;
RA Shimada T., Watanabe J., Kawajiri K., Sutter T.R., Guengerich F.P.,
RA Gillam E.M.J., Inoue K.;
RT "Catalytic properties of polymorphic human cytochrome P450 1B1 variants.";
RL Carcinogenesis 20:1607-1613(1999).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10681376;
RA Chen H., Howald W.N., Juchau M.R.;
RT "Biosynthesis of all-trans-retinoic acid from all-trans-retinol: catalysis
RT of all-trans-retinol oxidation by human P-450 cytochromes.";
RL Drug Metab. Dispos. 28:315-322(2000).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=11555828; DOI=10.1053/meta.2001.25592;
RA Badawi A.F., Cavalieri E.L., Rogan E.G.;
RT "Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and
RT 16alpha-hydroxylation of 17beta-estradiol.";
RL Metabolism 50:1001-1003(2001).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=12865317; DOI=10.1210/en.2003-0192;
RA Lee A.J., Cai M.X., Thomas P.E., Conney A.H., Zhu B.T.;
RT "Characterization of the oxidative metabolites of 17beta-estradiol and
RT estrone formed by 15 selectively expressed human cytochrome p450
RT isoforms.";
RL Endocrinology 144:3382-3398(2003).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
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 [13]
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
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 [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21068195; DOI=10.1124/dmd.110.035121;
RA Bui P., Imaizumi S., Beedanagari S.R., Reddy S.T., Hankinson O.;
RT "Human CYP2S1 metabolizes cyclooxygenase- and lipoxygenase-derived
RT eicosanoids.";
RL Drug Metab. Dispos. 39:180-190(2011).
RN [16]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=22888116; DOI=10.1093/jb/mvs087;
RA Jang H.H., Kim S.Y., Kang J.Y., Park S.H., Ryu S.H., Ahn T., Yun C.H.;
RT "Increase of human CYP1B1 activities by acidic phospholipids and kinetic
RT deuterium isotope effects on CYP1B1 substrate oxidation.";
RL J. Biochem. 152:433-442(2012).
RN [17]
RP ACTIVITY REGULATION.
RX PubMed=22935222; DOI=10.1017/s0007114512003595;
RA Poon C.H., Wong T.Y., Wang Y., Tsuchiya Y., Nakajima M., Yokoi T.,
RA Leung L.K.;
RT "The citrus flavanone naringenin suppresses CYP1B1 transactivation through
RT antagonising xenobiotic-responsive element binding.";
RL Br. J. Nutr. 109:1598-1605(2013).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP VAL-395.
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).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 51-543 IN COMPLEX WITH HEME AND
RP THE INHIBITOR ALPHA-NAPHTOFLAVONE, AND COFACTOR.
RX PubMed=21147782; DOI=10.1074/jbc.m110.204420;
RA Wang A., Savas U., Stout C.D., Johnson E.F.;
RT "Structural characterization of the complex between alpha-naphthoflavone
RT and human cytochrome P450 1B1.";
RL J. Biol. Chem. 286:5736-5743(2011).
RN [20]
RP VARIANTS GLC3A GLU-61; ASN-374 AND TRP-469.
RX PubMed=9463332; DOI=10.1086/301725;
RA Bejjani B.A., Lewis R.A., Tomey K.F., Anderson K.L., Dueker D.K., Jabak M.,
RA Astle W.F., Otterud B., Leppert M., Lupski J.R.;
RT "Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant
RT cause of primary congenital glaucoma in Saudi Arabia.";
RL Am. J. Hum. Genet. 62:325-333(1998).
RN [21]
RP VARIANT GLC3A TRP-365, AND VARIANTS CYS-57; GLU-61; TRP-365; LEU-379;
RP LYS-387; HIS-390; VAL-432; LEU-437 AND TRP-469.
RX PubMed=9497261; DOI=10.1086/301764;
RA Stoilov I., Akarsu A.N., Alozie I., Child A., Barsoum-Homsy M.,
RA Turacli M.E., Or M., Lewis R.A., Ozdemir N., Brice G., Aktan S.G.,
RA Chevrette L., Coca-Prados M., Sarfarazi M.;
RT "Sequence analysis and homology modeling suggest that primary congenital
RT glaucoma on 2p21 results from mutations disrupting either the hinge region
RT or the conserved core structures of cytochrome P4501B1.";
RL Am. J. Hum. Genet. 62:573-584(1998).
RN [22]
RP VARIANTS VAL-432 AND SER-453.
RX PubMed=9823305;
RA Bailey L.R., Roodi N., Dupont W.D., Parl F.F.;
RT "Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid
RT receptor status in breast cancer.";
RL Cancer Res. 58:5038-5041(1998).
RN [23]
RP ERRATUM OF PUBMED:9823305.
RA Bailey L.R., Roodi N., Dupont W.D., Parl F.F.;
RL Cancer Res. 59:1388-1388(1999).
RN [24]
RP VARIANT GLC3A LYS-387.
RX PubMed=10227395;
RA Plasilova M., Stoilov I., Sarfarazi M., Kadasi L., Ferakova E., Ferak V.;
RT "Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies
RT (Roms) affected with primary congenital glaucoma.";
RL J. Med. Genet. 36:290-294(1999).
RN [25]
RP VARIANTS GLC3A GLU-61; PRO-77; 269-SER--PHE-271 DEL; HIS-368; ASN-374;
RP SER-390 AND TRP-469, AND VARIANTS GLY-48; SER-119; VAL-432 AND SER-453.
RX PubMed=10655546; DOI=10.1093/hmg/9.3.367;
RA Bejjani B.A., Stockton D.W., Lewis R.A., Tomey K.F., Dueker D.K., Jabak M.,
RA Astle W.F., Lupski J.R.;
RT "Multiple CYP1B1 mutations and incomplete penetrance in an inbred
RT population segregating primary congenital glaucoma suggest frequent de novo
RT events and a dominant modifier locus.";
RL Hum. Mol. Genet. 9:367-374(2000).
RN [26]
RP ERRATUM OF PUBMED:10655546.
RA Bejjani B.A., Stockton D.W., Lewis R.A., Tomey K.F., Dueker D.K., Jabak M.,
RA Astle W.F., Lupski J.R.;
RL Hum. Mol. Genet. 9:1141-1141(2000).
RN [27]
RP VARIANT GLC3A MET-364.
RX PubMed=11184479; DOI=10.1076/1381-6810(200009)2131-zft191;
RA Ohtake Y., Kubota R., Tanino T., Miyata H., Mashima Y.;
RT "Novel compound heterozygous mutations in the cytochrome P4501B1 gene
RT (CYP1B1) in a Japanese patient with primary congenital glaucoma.";
RL Ophthalmic Genet. 21:191-193(2000).
RN [28]
RP VARIANTS SER-119 AND VAL-432, AND ASSOCIATION WITH BREAST OR LUNG CANCER.
RX PubMed=10739169; DOI=10.1097/00008571-200002000-00004;
RA Watanabe J., Shimada T., Gillam E.M., Ikuta T., Suemasu K., Higashi Y.,
RA Gotoh O., Kawajiri K.;
RT "Association of CYP1B1 genetic polymorphism with incidence to breast and
RT lung cancer.";
RL Pharmacogenetics 10:25-33(2000).
RN [29]
RP VARIANTS GLC3A VAL-192; ILE-198; LEU-320; PHE-330; MET-364; GLN-444 AND
RP GLY-499, AND VARIANTS GLY-48; SER-119 AND VAL-432.
RX PubMed=11527932;
RA Mashima Y., Suzuki Y., Sergeev Y., Ohtake Y., Tanino T., Kimura I.,
RA Miyata H., Aihara M., Tanihara H., Inatani M., Azuma N., Iwata T.,
RA Araie M.;
RT "Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with
RT primary congenital glaucoma.";
RL Invest. Ophthalmol. Vis. Sci. 42:2211-2216(2001).
RN [30]
RP ERRATUM OF PUBMED:11527932.
RA Mashima Y., Suzuki Y., Sergeev Y., Ohtake Y., Tanino T., Kimura I.,
RA Miyata H., Aihara M., Tanihara H., Inatani M., Azuma N., Iwata T.,
RA Araie M.;
RL Invest. Ophthalmol. Vis. Sci. 42:2775-2775(2001).
RN [31]
RP INVOLVEMENT IN ASGD6.
RX PubMed=11403040; DOI=10.1136/jmg.38.5.324;
RA Vincent A., Billingsley G., Priston M., Williams-Lyn D., Sutherland J.,
RA Glaser T., Oliver E., Walter M.A., Heathcote G., Levin A., Heon E.;
RT "Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters'
RT anomaly.";
RL J. Med. Genet. 38:324-326(2001).
RN [32]
RP VARIANT GLC3A PHE-345, VARIANT GLC1A HIS-368, AND VARIANT VAL-432.
RX PubMed=11774072; DOI=10.1086/338709;
RA Vincent A.L., Billingsley G., Buys Y., Levin A.V., Priston M., Trope G.,
RA Williams-Lyn D., Heon E.;
RT "Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier
RT gene.";
RL Am. J. Hum. Genet. 70:448-460(2002).
RN [33]
RP VARIANTS GLC3A GLU-61; LEU-193; LYS-229 AND HIS-368, AND VARIANTS GLY-48;
RP SER-184 AND VAL-432.
RX PubMed=11980847;
RA Panicker S.G., Reddy A.B.M., Mandal A.K., Ahmed N., Nagarajaram H.A.,
RA Hasnain S.E., Balasubramanian D.;
RT "Identification of novel mutations causing familial primary congenital
RT glaucoma in Indian pedigrees.";
RL Invest. Ophthalmol. Vis. Sci. 43:1358-1366(2002).
RN [34]
RP VARIANTS GLC3A HIS-368; LYS-387; LEU-437 AND GLY-443, AND VARIANTS GLY-48;
RP SER-119; VAL-432 AND SER-453.
RX PubMed=12036985;
RA Stoilov I.R., Costa V.P., Vasconcellos J.P.C., Melo M.B., Betinjane A.J.,
RA Carani J.C.E., Oltrogge E.V., Sarfarazi M.;
RT "Molecular genetics of primary congenital glaucoma in Brazil.";
RL Invest. Ophthalmol. Vis. Sci. 43:1820-1827(2002).
RN [35]
RP VARIANTS GLY-48; SER-119; VAL-432; GLY-443 AND SER-453.
RX PubMed=11854439; DOI=10.1124/mol.61.3.586;
RA Aklillu E., Oscarson M., Hidestrand M., Leidvik B., Otter C.,
RA Ingelman-Sundberg M.;
RT "Functional analysis of six different polymorphic CYP1B1 enzyme variants
RT found in an Ethiopian population.";
RL Mol. Pharmacol. 61:586-594(2002).
RN [36]
RP VARIANTS GLC3A ARG-144 AND CYS-445.
RX PubMed=14640114; DOI=10.1007/s00439-003-1035-0;
RA Chakrabarti S., Komatireddy S., Mandal A.K., Balasubramanian D.;
RT "Gene symbol: CYP1B1. Disease: glaucoma, primary congenital.";
RL Hum. Genet. 113:556-558(2003).
RN [37]
RP VARIANTS GLC3A LYS-229; ARG-232; LYS-387; SER-390; SER-399 AND TYR-423, AND
RP VARIANTS GLY-48; SER-119; VAL-432 AND SER-453.
RX PubMed=14635112; DOI=10.1002/humu.9197;
RA Colomb E., Kaplan J., Garchon H.-J.;
RT "Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary
RT congenital glaucoma in France.";
RL Hum. Mutat. 22:496-496(2003).
RN [38]
RP VARIANTS GLC3A ILE-215; 355-ARG--ALA-358 DEL AND MET-364, AND VARIANTS
RP GLY-48; SER-119; VAL-432 AND SER-453.
RX PubMed=12525557; DOI=10.1136/jmg.40.1.e9;
RA Sitorus R., Ardjo S.M., Lorenz B., Preising M.;
RT "CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and
RT European patients.";
RL J. Med. Genet. 40:E9-E9(2003).
RN [39]
RP VARIANTS GLC3A ASN-81; LYS-229; ARG-232; SER-269--PHE-271 DEL; LYS-387;
RP HIS-390; TYR-423 AND GLY-443, AND VARIANTS GLY-48; SER-119; VAL-432 AND
RP SER-453.
RX PubMed=15342693; DOI=10.1136/jmg.2004.020024;
RA Melki R., Colomb E., Lefort N., Brezin A.P., Garchon H.-J.;
RT "CYP1B1 mutations in French patients with early-onset primary open-angle
RT glaucoma.";
RL J. Med. Genet. 41:647-651(2004).
RN [40]
RP VARIANTS GLC3A PRO-77; PRO-115; ARG-132; PRO-144; LEU-193; LYS-229;
RP ARG-239; HIS-368; HIS-390; CYS-390; LEU-437 AND ASP-466, AND VARIANTS
RP GLY-48; SER-119; VAL-432 AND SER-453.
RX PubMed=15475877;
RA Reddy A.B.M., Kaur K., Mandal A.K., Panicker S.G., Thomas R., Hasnain S.E.,
RA Balasubramanian D., Chakrabarti S.;
RT "Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma
RT patients.";
RL Mol. Vis. 10:696-702(2004).
RN [41]
RP VARIANT GLC3A CYS-390.
RX PubMed=15255109; DOI=10.1076/opge.25.1.3.28999;
RA Curry S.M., Daou A.G., Hermanns P., Molinari A., Lewis R.A., Bejjani B.A.;
RT "Cytochrome P4501B1 mutations cause only part of primary congenital
RT glaucoma in Ecuador.";
RL Ophthalmic Genet. 25:3-9(2004).
RN [42]
RP VARIANTS GLC3A GLU-61; HIS-368 AND THR-388, AND VARIANT GLY-422.
RX PubMed=16490498; DOI=10.1016/j.ajo.2005.11.001;
RA Alfadhli S., Behbehani A., Elshafey A., Abdelmoaty S., Al-Awadi S.;
RT "Molecular and clinical evaluation of primary congenital glaucoma in
RT Kuwait.";
RL Am. J. Ophthalmol. 141:512-516(2006).
RN [43]
RP VARIANTS GLC3A CYS-57; LYS-229; HIS-368; LEU-515; THR-523 AND GLY-530, AND
RP VARIANTS GLY-48; SER-119; VAL-432; SER-453 AND ALA-518.
RX PubMed=16688110;
RA Acharya M., Mookherjee S., Bhattacharjee A., Bandyopadhyay A.K.,
RA Daulat Thakur S.K., Bhaduri G., Sen A., Ray K.;
RT "Primary role of CYP1B1 in Indian juvenile-onset POAG patients.";
RL Mol. Vis. 12:399-404(2006).
RN [44]
RP VARIANTS GLC3A GLU-61; ASN-81; LYS-229; LEU-343 DEL; HIS-368; LYS-387 AND
RP TRP-469.
RX PubMed=16735994;
RA Chavarria-Soley G., Michels-Rautenstrauss K., Pasutto F., Flikier D.,
RA Flikier P., Cirak S., Bejjani B., Winters D.L., Lewis R.A., Mardin C.,
RA Reis A., Rautenstrauss B.;
RT "Primary congenital glaucoma and Rieger's anomaly: extended haplotypes
RT reveal founder effects for eight distinct CYP1B1 mutations.";
RL Mol. Vis. 12:523-531(2006).
RN [45]
RP VARIANTS GLC3A TRP-28; GLU-61; ASN-81; TRP-145; LYS-229; PHE-409 AND
RP GLY-443, AND VARIANTS LEU-52; HIS-144; PRO-189 AND SER-330.
RX PubMed=16862072;
RA Lopez-Garrido M.-P., Sanchez-Sanchez F., Lopez-Martinez F.,
RA Aroca-Aguilar J.-D., Blanco-Marchite C., Coca-Prados M., Escribano J.;
RT "Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-
RT angle glaucoma.";
RL Mol. Vis. 12:748-755(2006).
RN [46]
RP CHARACTERIZATION OF VARIANTS GLC3A GLU-61; ASN-81; SER-203; LYS-229 AND
RP LEU-343 DEL.
RX PubMed=18470941; DOI=10.1002/humu.20786;
RA Chavarria-Soley G., Sticht H., Aklillu E., Ingelman-Sundberg M.,
RA Pasutto F., Reis A., Rautenstrauss B.;
RT "Mutations in CYP1B1 cause primary congenital glaucoma by reduction of
RT either activity or abundance of the enzyme.";
RL Hum. Mutat. 29:1147-1153(2008).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC various endogenous substrates, including fatty acids, steroid hormones
CC and vitamins (PubMed:20972997, PubMed:11555828, PubMed:12865317,
CC PubMed:10681376, PubMed:15258110). Mechanistically, uses molecular
CC oxygen inserting one oxygen atom into a substrate, and reducing the
CC second into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (NADPH--hemoprotein reductase)
CC (PubMed:20972997, PubMed:11555828, PubMed:12865317, PubMed:10681376,
CC PubMed:15258110). Exhibits catalytic activity for the formation of
CC hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely
CC 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity
CC toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317).
CC Metabolizes testosterone and progesterone to B or D ring hydroxylated
CC metabolites (PubMed:10426814). May act as a major enzyme for all-trans
CC retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two
CC successive oxidative transformation of all-trans retinol to all-trans
CC retinal and then to the active form all-trans retinoic acid
CC (PubMed:10681376, 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:20972997). Additionally, displays dehydratase activity toward
CC oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This
CC activity is independent of cytochrome P450 reductase, NADPH, and O2
CC (PubMed:21068195). Also involved in the oxidative metabolism of
CC xenobiotics, particularly converting polycyclic aromatic hydrocarbons
CC and heterocyclic aryl amines procarcinogens to DNA-damaging products
CC (PubMed:10426814). Plays an important role in retinal vascular
CC development. Under hyperoxic O2 conditions, promotes retinal
CC angiogenesis and capillary morphogenesis, likely by metabolizing the
CC oxygenated products generated during the oxidative stress. Also,
CC contributes to oxidative homeostasis and ultrastructural organization
CC and function of trabecular meshwork tissue through modulation of POSTN
CC expression (By similarity). {ECO:0000250|UniProtKB:Q64429,
CC ECO:0000269|PubMed:10426814, ECO:0000269|PubMed:10681376,
CC ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:15258110, ECO:0000269|PubMed:20972997,
CC ECO:0000269|PubMed:21068195}.
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:10426814, ECO:0000269|PubMed:22888116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305};
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:10426814, ECO:0000269|PubMed:11555828,
CC ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:22888116,
CC ECO:0000269|PubMed:23821647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213;
CC Evidence={ECO:0000305|PubMed:10426814, ECO:0000305|PubMed:11555828,
CC ECO:0000305|PubMed:12865317, 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:10426814, ECO:0000269|PubMed:11555828,
CC ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:22888116,
CC ECO:0000269|PubMed:23821647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47281;
CC Evidence={ECO:0000305|PubMed:10426814, ECO:0000305|PubMed:11555828,
CC ECO:0000305|PubMed:12865317, 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:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:22888116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209;
CC Evidence={ECO:0000305|PubMed:12865317};
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:0000269|PubMed:12865317,
CC ECO:0000269|PubMed:22888116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47293;
CC Evidence={ECO:0000305|PubMed:12865317};
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:0000269|PubMed:10426814};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46297;
CC Evidence={ECO:0000305|PubMed:10426814};
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:0000269|PubMed:10426814};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47253;
CC Evidence={ECO:0000305|PubMed:10426814};
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:0000269|PubMed:10426814};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47261;
CC Evidence={ECO:0000305|PubMed:10426814};
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:10681376};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093;
CC Evidence={ECO:0000305|PubMed:10681376};
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:10681376};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42089;
CC Evidence={ECO:0000305|PubMed:10681376};
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] = (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:0000269|PubMed:21068195};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48633;
CC Evidence={ECO:0000305|PubMed:21068195};
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:0000269|PubMed:21068195};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37948;
CC Evidence={ECO:0000305|PubMed:21068195};
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:0000269|PubMed:21068195};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48717;
CC Evidence={ECO:0000305|PubMed:21068195};
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:0000269|PubMed:21068195};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637;
CC Evidence={ECO:0000305|PubMed:21068195};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:21147782};
CC -!- ACTIVITY REGULATION: Enzyme activity is increased by liposomes
CC containing anionic phospholipids, phosphatidic acid and cardiolipin.
CC Inhibited by naringenin with an IC(50) of 5 uM (PubMed:22888116,
CC PubMed:22935222). Enzyme activity is increased by cytochrome b5.
CC {ECO:0000269|PubMed:22888116, ECO:0000269|PubMed:22935222}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.9 uM for 17-beta-estradiol (2-hydroxylation)
CC {ECO:0000269|PubMed:10426814};
CC KM=5.1 uM for 17-beta-estradiol (4-hydroxylation)
CC {ECO:0000269|PubMed:10426814};
CC KM=17.0 uM for testosterone(6-beta-hydroxylation)
CC {ECO:0000269|PubMed:10426814};
CC KM=25.0 uM for progesterone (6-beta-hydroxylation)
CC {ECO:0000269|PubMed:10426814};
CC KM=23.0 uM for progesterone (16-alpha-hydroxylation)
CC {ECO:0000269|PubMed:10426814};
CC KM=18.5 uM for all-trans-retinol {ECO:0000269|PubMed:15258110};
CC KM=11 uM for all-trans retinol {ECO:0000269|PubMed:10681376};
CC KM=8.5 uM for all-trans-retinal {ECO:0000269|PubMed:15258110};
CC KM=29.8 uM for arachidonic acid {ECO:0000269|PubMed:15258110};
CC KM=212.8 uM for 7,12-dimethyltetraphene
CC {ECO:0000269|PubMed:15258110};
CC Vmax=0.42 nmol/min/nmol enzyme for 17-beta-estradiol (2-
CC hydroxylation) {ECO:0000269|PubMed:10426814};
CC Vmax=0.91 nmol/min/nmol enzyme for 17-beta-estradiol (4-
CC hydroxylation) {ECO:0000269|PubMed:10426814};
CC Vmax=2.2 nmol/min/nmol enzyme for testosterone (6-beta-hydroxylation)
CC {ECO:0000269|PubMed:10426814};
CC Vmax=0.6 nmol/min/nmol enzyme for progesterone (6-beta-hydroxylation)
CC {ECO:0000269|PubMed:10426814};
CC Vmax=2.3 nmol/min/nmol enzyme for progesterone (16-alpha-
CC hydroxylation) {ECO:0000269|PubMed:10426814};
CC Vmax=493 pmol/min/nmol enzyme toward all-trans retinol
CC {ECO:0000269|PubMed:10681376};
CC Note=kcat is 0.15 min(-1) for retinol, 0.77 min(-1) for retinal, 2.86
CC min(-1) for 7,12-dimethyltetraphene, 0.48 min(-1) for arachidonic
CC acid. {ECO:0000269|PubMed:15258110};
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:11555828,
CC ECO:0000269|PubMed:12865317}.
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:15258110}.
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000269|PubMed:20972997}.
CC -!- INTERACTION:
CC Q16678; Q02763: TEK; NbExp=6; IntAct=EBI-1055133, EBI-2257090;
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 -!- TISSUE SPECIFICITY: Expressed in heart, brain, lung, skeletal muscle,
CC kidney, spleen, thymus, prostate, testis, ovary, small intestine,
CC colon, and peripheral blood leukocytes (PubMed:8175734). Expressed in
CC retinal endothelial cells and umbilical vein endothelial cells (at
CC protein level) (PubMed:19005183). {ECO:0000269|PubMed:19005183,
CC ECO:0000269|PubMed:8175734}.
CC -!- INDUCTION: By polycyclic aromatic hydrocarbons (PAH) and 2,3,7,8-
CC tetrachlorodibenzo-p-dioxin (TCDD). {ECO:0000269|PubMed:8175734}.
CC -!- POLYMORPHISM: Various CYP1B1 alleles are known. The sequence shown is
CC that of allele CYP1B1*1.
CC -!- DISEASE: Anterior segment dysgenesis 6 (ASGD6) [MIM:617315]: A form of
CC anterior segment dysgenesis, a group of defects affecting anterior
CC structures of the eye including cornea, iris, lens, trabecular
CC meshwork, and Schlemm canal. Anterior segment dysgeneses result from
CC abnormal migration or differentiation of the neural crest derived
CC mesenchymal cells that give rise to components of the anterior chamber
CC during eye development. Different anterior segment anomalies may exist
CC alone or in combination, including iris hypoplasia, enlarged or reduced
CC corneal diameter, corneal vascularization and opacity, posterior
CC embryotoxon, corectopia, polycoria, abnormal iridocorneal angle,
CC ectopia lentis, and anterior synechiae between the iris and posterior
CC corneal surface. Clinical conditions falling within the phenotypic
CC spectrum of anterior segment dysgeneses include aniridia, Axenfeld
CC anomaly, Reiger anomaly/syndrome, Peters anomaly, and
CC iridogoniodysgenesis. ASGD6 patients predominantly manifest Peters
CC anomaly. Peters anomaly consists of corneal leukoma, defects in the
CC posterior structures of the cornea such as absence of the posterior
CC corneal stroma and Descemet membrane, and a variable degree of
CC iridocorneal and/or keratolenticular adhesions. Over 50% of patients
CC develop glaucoma in childhood. {ECO:0000269|PubMed:11403040}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An
CC autosomal recessive form of primary congenital glaucoma (PCG). PCG is
CC characterized by marked increase of intraocular pressure at birth or
CC early childhood, large ocular globes (buphthalmos) and corneal edema.
CC It results from developmental defects of the trabecular meshwork and
CC anterior chamber angle of the eye that prevent adequate drainage of
CC aqueous humor. {ECO:0000269|PubMed:10227395,
CC ECO:0000269|PubMed:10655546, ECO:0000269|PubMed:11184479,
CC ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:11774072,
CC ECO:0000269|PubMed:11980847, ECO:0000269|PubMed:12036985,
CC ECO:0000269|PubMed:12525557, ECO:0000269|PubMed:14635112,
CC ECO:0000269|PubMed:14640114, ECO:0000269|PubMed:15255109,
CC ECO:0000269|PubMed:15342693, ECO:0000269|PubMed:15475877,
CC ECO:0000269|PubMed:16490498, ECO:0000269|PubMed:16688110,
CC ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:16862072,
CC ECO:0000269|PubMed:18470941, ECO:0000269|PubMed:9463332,
CC ECO:0000269|PubMed:9497261}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry.
CC -!- DISEASE: Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: A form of
CC primary open angle glaucoma (POAG). POAG is characterized by a specific
CC pattern of optic nerve and visual field defects. The angle of the
CC anterior chamber of the eye is open, and usually the intraocular
CC pressure is increased. However, glaucoma can occur at any intraocular
CC pressure. The disease is generally asymptomatic until the late stages,
CC by which time significant and irreversible optic nerve damage has
CC already taken place. {ECO:0000269|PubMed:11774072}. Note=The gene
CC represented in this entry acts as a disease modifier. Digenic mutations
CC in CYP1B1 and MYOC have been found in a family segregating both primary
CC adult-onset and juvenile forms of open angle glaucoma
CC (PubMed:11774072). All affected family members with mutations in both
CC MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC
CC mutation had the adult-onset form (PubMed:11774072).
CC {ECO:0000269|PubMed:11774072}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP1B1 alleles;
CC URL="https://www.pharmvar.org/gene/CYP1B1";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cyp1b1/";
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DR EMBL; U03688; AAA19567.1; -; mRNA.
DR EMBL; U56438; AAC50809.1; -; Genomic_DNA.
DR EMBL; AF450132; AAM50512.1; -; Genomic_DNA.
DR EMBL; AF450131; AAM50512.1; JOINED; Genomic_DNA.
DR EMBL; BT019979; AAV38782.1; -; mRNA.
DR EMBL; AY393998; AAQ87875.1; -; Genomic_DNA.
DR EMBL; BC012049; AAH12049.1; -; mRNA.
DR EMBL; AF171066; AAG43404.1; -; Genomic_DNA.
DR CCDS; CCDS1793.1; -.
DR PIR; A54116; A54116.
DR RefSeq; NP_000095.2; NM_000104.3.
DR PDB; 3PM0; X-ray; 2.70 A; A=51-543.
DR PDB; 6IQ5; X-ray; 3.70 A; A/B=68-530.
DR PDBsum; 3PM0; -.
DR PDBsum; 6IQ5; -.
DR AlphaFoldDB; Q16678; -.
DR SMR; Q16678; -.
DR BioGRID; 107925; 16.
DR IntAct; Q16678; 6.
DR STRING; 9606.ENSP00000478561; -.
DR BindingDB; Q16678; -.
DR ChEMBL; CHEMBL4878; -.
DR DrugBank; DB02342; 2-Methoxyestradiol.
DR DrugBank; DB00613; Amodiaquine.
DR DrugBank; DB06732; beta-Naphthoflavone.
DR DrugBank; DB00443; Betamethasone.
DR DrugBank; DB00121; Biotin.
DR DrugBank; DB01222; Budesonide.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB01254; Dasatinib.
DR DrugBank; DB00694; Daunorubicin.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB00530; Erlotinib.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR DrugBank; DB00655; Estrone.
DR DrugBank; DB07776; Flavone.
DR DrugBank; DB00499; Flutamide.
DR DrugBank; DB01645; Genistein.
DR DrugBank; DB01381; Ginkgo biloba.
DR DrugBank; DB00741; Hydrocortisone.
DR DrugBank; DB01064; Isoprenaline.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB00448; Lansoprazole.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB01065; Melatonin.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB00959; Methylprednisolone.
DR DrugBank; DB01204; Mitoxantrone.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB03467; Naringenin.
DR DrugBank; DB00338; Omeprazole.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB14631; Prednisolone phosphate.
DR DrugBank; DB00635; Prednisone.
DR DrugBank; DB01087; Primaquine.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB04216; Quercetin.
DR DrugBank; DB02709; Resveratrol.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB00624; Testosterone.
DR DrugBank; DB13946; Testosterone undecanoate.
DR DrugBank; DB00277; Theophylline.
DR DrugBank; DB12245; Triclabendazole.
DR DrugBank; DB11155; Triclocarban.
DR DrugCentral; Q16678; -.
DR GuidetoPHARMACOLOGY; 1320; -.
DR SwissLipids; SLP:000001331; -.
DR iPTMnet; Q16678; -.
DR PhosphoSitePlus; Q16678; -.
DR BioMuta; CYP1B1; -.
DR DMDM; 48429256; -.
DR EPD; Q16678; -.
DR jPOST; Q16678; -.
DR MassIVE; Q16678; -.
DR MaxQB; Q16678; -.
DR PaxDb; Q16678; -.
DR PeptideAtlas; Q16678; -.
DR PRIDE; Q16678; -.
DR ProteomicsDB; 61033; -.
DR Antibodypedia; 29477; 453 antibodies from 36 providers.
DR DNASU; 1545; -.
DR Ensembl; ENST00000610745.5; ENSP00000478561.1; ENSG00000138061.12.
DR Ensembl; ENST00000614273.1; ENSP00000483678.1; ENSG00000138061.12.
DR GeneID; 1545; -.
DR KEGG; hsa:1545; -.
DR MANE-Select; ENST00000610745.5; ENSP00000478561.1; NM_000104.4; NP_000095.2.
DR UCSC; uc032njx.2; human.
DR CTD; 1545; -.
DR DisGeNET; 1545; -.
DR GeneCards; CYP1B1; -.
DR GeneReviews; CYP1B1; -.
DR HGNC; HGNC:2597; CYP1B1.
DR HPA; ENSG00000138061; Low tissue specificity.
DR MalaCards; CYP1B1; -.
DR MIM; 137750; phenotype.
DR MIM; 231300; phenotype.
DR MIM; 601771; gene.
DR MIM; 617315; phenotype.
DR neXtProt; NX_Q16678; -.
DR OpenTargets; ENSG00000138061; -.
DR Orphanet; 98976; Congenital glaucoma.
DR Orphanet; 98977; Juvenile glaucoma.
DR Orphanet; 353225; NON RARE IN EUROPE: Primary adult open-angle glaucoma.
DR Orphanet; 708; Peters anomaly.
DR PharmGKB; PA27094; -.
DR VEuPathDB; HostDB:ENSG00000138061; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00950000183037; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; Q16678; -.
DR OMA; QIRLGNC; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q16678; -.
DR TreeFam; TF105095; -.
DR BioCyc; MetaCyc:HS06443-MON; -.
DR PathwayCommons; Q16678; -.
DR Reactome; R-HSA-211976; Endogenous sterols.
DR Reactome; R-HSA-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR Reactome; R-HSA-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR Reactome; R-HSA-5579000; Defective CYP1B1 causes Glaucoma.
DR SABIO-RK; Q16678; -.
DR SignaLink; Q16678; -.
DR SIGNOR; Q16678; -.
DR UniPathway; UPA00383; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 1545; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; CYP1B1; human.
DR EvolutionaryTrace; Q16678; -.
DR GeneWiki; CYP1B1; -.
DR GenomeRNAi; 1545; -.
DR Pharos; Q16678; Tchem.
DR PRO; PR:Q16678; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q16678; protein.
DR Bgee; ENSG00000138061; Expressed in pericardium and 207 other tissues.
DR ExpressionAtlas; Q16678; baseline and differential.
DR Genevisible; Q16678; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0101020; F:estrogen 16-alpha-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA: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: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; IEA:Ensembl.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0042537; P:benzene-containing compound metabolic process; IEA:Ensembl.
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: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; ISS: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; IDA: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; ISS:UniProtKB.
DR GO; GO:0006304; P:DNA modification; IEA:Ensembl.
DR GO; GO:0043542; P:endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0071603; P:endothelial cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0019373; P:epoxygenase P450 pathway; TAS:Reactome.
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; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
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:0097267; P:omega-hydroxylase P450 pathway; TAS:Reactome.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl.
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; 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; IEA:Ensembl.
DR GO; GO:0061304; P:retinal blood vessel morphogenesis; ISS: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; IDA:UniProtKB.
DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR GO; GO:0009404; P:toxin metabolic process; IEA:Ensembl.
DR GO; GO:0002930; P:trabecular meshwork development; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA: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 3D-structure; Disease variant; Endoplasmic reticulum;
KW Fatty acid metabolism; Glaucoma; Heme; Iron; Lipid metabolism; Lyase;
KW Membrane; Metal-binding; Microsome; Mitochondrion; Monooxygenase;
KW Oxidoreductase; Peters anomaly; Reference proteome; Steroid metabolism.
FT CHAIN 1..543
FT /note="Cytochrome P450 1B1"
FT /id="PRO_0000051660"
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:0000269|PubMed:21147782,
FT ECO:0007744|PDB:3PM0"
FT SITE 395
FT /note="Major determinant of CYP1B1 17beta-estradiol
FT hydroxylation regiospecificity"
FT VARIANT 28
FT /note="S -> W (in GLC3A; dbSNP:rs780002791)"
FT /evidence="ECO:0000269|PubMed:16862072"
FT /id="VAR_054227"
FT VARIANT 48
FT /note="R -> G (in allele CYP1B1*2, allele CYP1B1*5, allele
FT CYP1B1*6 and allele CYP1B1*7; dbSNP:rs10012)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:11854439,
FT ECO:0000269|PubMed:11980847, ECO:0000269|PubMed:12036985,
FT ECO:0000269|PubMed:12525557, ECO:0000269|PubMed:14635112,
FT ECO:0000269|PubMed:15342693, ECO:0000269|PubMed:15475877,
FT ECO:0000269|PubMed:16688110, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.7"
FT /id="VAR_011752"
FT VARIANT 52
FT /note="P -> L (in dbSNP:rs201824781)"
FT /evidence="ECO:0000269|PubMed:16862072"
FT /id="VAR_054228"
FT VARIANT 57
FT /note="W -> C (in GLC3A; juvenile onset; allele CYP1B1*11;
FT dbSNP:rs72549387)"
FT /evidence="ECO:0000269|PubMed:16688110,
FT ECO:0000269|PubMed:9497261"
FT /id="VAR_008350"
FT VARIANT 61
FT /note="G -> E (in GLC3A; allele CYP1B1*12; reduces
FT enzymatic activity; dbSNP:rs28936700)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:11980847, ECO:0000269|PubMed:16490498,
FT ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:16862072,
FT ECO:0000269|PubMed:18470941, ECO:0000269|PubMed:9463332,
FT ECO:0000269|PubMed:9497261"
FT /id="VAR_001244"
FT VARIANT 68
FT /note="Q -> R (in dbSNP:rs9282670)"
FT /id="VAR_028735"
FT VARIANT 77
FT /note="L -> P (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:15475877"
FT /id="VAR_054229"
FT VARIANT 81
FT /note="Y -> N (in GLC3A; adult-onset; hypomorphic allele;
FT reduces the abundance of the enzyme; dbSNP:rs9282671)"
FT /evidence="ECO:0000269|PubMed:15342693,
FT ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:16862072,
FT ECO:0000269|PubMed:18470941"
FT /id="VAR_028736"
FT VARIANT 115
FT /note="A -> P (in GLC3A; dbSNP:rs764338357)"
FT /evidence="ECO:0000269|PubMed:15475877"
FT /id="VAR_054230"
FT VARIANT 119
FT /note="A -> S (in allele CYP1B1*2, allele CYP1B1*6 and
FT allele CYP1B1*7; significantly associated with breast or
FT lung cancer; no significant change in 17beta-estradiol
FT 2- and 4-hydroxylation activities and 17beta-estradiol
FT affinity; 1.5-fold reduction in testosterone affinity but
FT nearly no change in testosterone 6beta-hydroxylation
FT activity; 2-fold increase in progesterone 6beta- and
FT 16alpha-hydroxylation activities and 5-fold reduction in
FT progesterone affinity; dbSNP:rs1056827)"
FT /evidence="ECO:0000269|PubMed:10426814,
FT ECO:0000269|PubMed:10655546, ECO:0000269|PubMed:10739169,
FT ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:11854439,
FT ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:12525557,
FT ECO:0000269|PubMed:14635112, ECO:0000269|PubMed:15475877,
FT ECO:0000269|PubMed:16688110, ECO:0000269|Ref.5"
FT /id="VAR_011753"
FT VARIANT 132
FT /note="M -> R (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:15475877"
FT /id="VAR_054231"
FT VARIANT 144
FT /note="Q -> H"
FT /evidence="ECO:0000269|PubMed:16862072"
FT /id="VAR_054232"
FT VARIANT 144
FT /note="Q -> P (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:15475877"
FT /id="VAR_054233"
FT VARIANT 144
FT /note="Q -> R (in GLC3A; dbSNP:rs753847648)"
FT /evidence="ECO:0000269|PubMed:14640114"
FT /id="VAR_054234"
FT VARIANT 145
FT /note="R -> W (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:16862072"
FT /id="VAR_054235"
FT VARIANT 184
FT /note="G -> S"
FT /evidence="ECO:0000269|PubMed:11980847"
FT /id="VAR_054236"
FT VARIANT 189
FT /note="A -> P (associated with ocular hypertension
FT susceptibility; dbSNP:rs1326854156)"
FT /evidence="ECO:0000269|PubMed:16862072"
FT /id="VAR_054237"
FT VARIANT 192
FT /note="D -> V (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:11527932"
FT /id="VAR_054238"
FT VARIANT 193
FT /note="P -> L (in GLC3A; dbSNP:rs529769268)"
FT /evidence="ECO:0000269|PubMed:11980847,
FT ECO:0000269|PubMed:15475877"
FT /id="VAR_054239"
FT VARIANT 198
FT /note="V -> I (in GLC3A; dbSNP:rs59472972)"
FT /evidence="ECO:0000269|PubMed:11527932"
FT /id="VAR_054240"
FT VARIANT 203
FT /note="N -> S (in GLC3A; reduces enzymatic activity;
FT dbSNP:rs1426636145)"
FT /evidence="ECO:0000269|PubMed:18470941"
FT /id="VAR_054241"
FT VARIANT 206
FT /note="S -> N (in dbSNP:rs9341248)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_018869"
FT VARIANT 215
FT /note="S -> I (in GLC3A; dbSNP:rs72549384)"
FT /evidence="ECO:0000269|PubMed:12525557"
FT /id="VAR_054242"
FT VARIANT 229
FT /note="E -> K (in GLC3A; juvenile-onset; hypomorphic
FT allele; reduces the abundance of the enzyme;
FT dbSNP:rs57865060)"
FT /evidence="ECO:0000269|PubMed:11980847,
FT ECO:0000269|PubMed:14635112, ECO:0000269|PubMed:15342693,
FT ECO:0000269|PubMed:15475877, ECO:0000269|PubMed:16688110,
FT ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:16862072,
FT ECO:0000269|PubMed:18470941"
FT /id="VAR_054243"
FT VARIANT 232
FT /note="G -> R (in GLC3A; adult-onset; dbSNP:rs104893628)"
FT /evidence="ECO:0000269|PubMed:14635112,
FT ECO:0000269|PubMed:15342693"
FT /id="VAR_054244"
FT VARIANT 239
FT /note="S -> R (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:15475877"
FT /id="VAR_054245"
FT VARIANT 266
FT /note="R -> L (in dbSNP:rs9341250)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_018870"
FT VARIANT 269..271
FT /note="Missing (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:10655546"
FT /id="VAR_054246"
FT VARIANT 320
FT /note="V -> L (in GLC3A; unknown pathological significance;
FT dbSNP:rs72549382)"
FT /evidence="ECO:0000269|PubMed:11527932"
FT /id="VAR_054247"
FT VARIANT 330
FT /note="A -> F (in GLC3A; requires 2 nucleotide
FT substitutions; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:11527932"
FT /id="VAR_054248"
FT VARIANT 330
FT /note="A -> S (associated with ocular hypertension
FT susceptibility; dbSNP:rs752456881)"
FT /evidence="ECO:0000269|PubMed:16862072"
FT /id="VAR_054249"
FT VARIANT 343
FT /note="Missing (in GLC3A; reduces enzymatic activity and
FT also the abundance of the enzyme)"
FT /evidence="ECO:0000269|PubMed:16735994,
FT ECO:0000269|PubMed:18470941"
FT /id="VAR_054250"
FT VARIANT 345
FT /note="L -> F (in GLC3A; dbSNP:rs66583685)"
FT /evidence="ECO:0000269|PubMed:11774072"
FT /id="VAR_054251"
FT VARIANT 355..358
FT /note="Missing (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:12525557"
FT /id="VAR_054252"
FT VARIANT 364
FT /note="V -> M (in GLC3A; dbSNP:rs72549379)"
FT /evidence="ECO:0000269|PubMed:11184479,
FT ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:12525557"
FT /id="VAR_054253"
FT VARIANT 365
FT /note="G -> W (in GLC3A; allele CYP1B1*18;
FT dbSNP:rs55771538)"
FT /evidence="ECO:0000269|PubMed:9497261"
FT /id="VAR_001245"
FT VARIANT 368
FT /note="R -> H (in GLC3A and GLC1A; acts as GLC1A disease
FT modifier in patients also carrying Val-399 mutation in
FT MYOC; dbSNP:rs79204362)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:11774072, ECO:0000269|PubMed:11980847,
FT ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:15475877,
FT ECO:0000269|PubMed:16490498, ECO:0000269|PubMed:16688110,
FT ECO:0000269|PubMed:16735994"
FT /id="VAR_016034"
FT VARIANT 374
FT /note="D -> N (in GLC3A; dbSNP:rs104893622)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:9463332"
FT /id="VAR_001246"
FT VARIANT 379
FT /note="P -> L (in allele CYP1B1*19; dbSNP:rs56305281)"
FT /evidence="ECO:0000269|PubMed:9497261"
FT /id="VAR_008351"
FT VARIANT 387
FT /note="E -> K (in GLC3A; allele CYP1B1*20;
FT dbSNP:rs55989760)"
FT /evidence="ECO:0000269|PubMed:10227395,
FT ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:14635112,
FT ECO:0000269|PubMed:15342693, ECO:0000269|PubMed:16735994,
FT ECO:0000269|PubMed:9497261"
FT /id="VAR_008352"
FT VARIANT 388
FT /note="A -> T (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:16490498"
FT /id="VAR_054254"
FT VARIANT 390
FT /note="R -> C (in GLC3A; dbSNP:rs148542782)"
FT /evidence="ECO:0000269|PubMed:15255109,
FT ECO:0000269|PubMed:15475877"
FT /id="VAR_054255"
FT VARIANT 390
FT /note="R -> H (in GLC3A; allele CYP1B1*21;
FT dbSNP:rs56010818)"
FT /evidence="ECO:0000269|PubMed:15342693,
FT ECO:0000269|PubMed:15475877, ECO:0000269|PubMed:9497261"
FT /id="VAR_008353"
FT VARIANT 390
FT /note="R -> S (in GLC3A; dbSNP:rs148542782)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:14635112"
FT /id="VAR_054256"
FT VARIANT 399
FT /note="I -> S (in GLC3A; dbSNP:rs72549378)"
FT /evidence="ECO:0000269|PubMed:14635112"
FT /id="VAR_054257"
FT VARIANT 409
FT /note="V -> F (in GLC3A; dbSNP:rs957253424)"
FT /evidence="ECO:0000269|PubMed:16862072"
FT /id="VAR_054258"
FT VARIANT 422
FT /note="V -> G"
FT /evidence="ECO:0000269|PubMed:16490498"
FT /id="VAR_054259"
FT VARIANT 423
FT /note="N -> Y (in GLC3A; juvenile-onset;
FT dbSNP:rs104893629)"
FT /evidence="ECO:0000269|PubMed:14635112,
FT ECO:0000269|PubMed:15342693"
FT /id="VAR_054260"
FT VARIANT 432
FT /note="L -> V (in allele CYP1B1*3, allele CYP1B1*5, allele
FT CYP1B1*6 and allele CYP1B1*7; 1.6-fold increase in 17beta-
FT estradiol 4-hydroxylation activity but no change in 17beta-
FT estradiol 2-hydroxylation activity; 2-fold reduction in
FT testosterone 6beta-hydroxylation activity and 3-fold
FT reduction in testosterone affinity; 6-fold and 4-fold
FT increase in progesterone 6beta- and 16alpha-hydroxylation
FT activity, respectively and 7-fold reduction in progesterone
FT affinity; dbSNP:rs1056836)"
FT /evidence="ECO:0000269|PubMed:10426814,
FT ECO:0000269|PubMed:10655546, ECO:0000269|PubMed:10739169,
FT ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:11774072,
FT ECO:0000269|PubMed:11854439, ECO:0000269|PubMed:11980847,
FT ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:12525557,
FT ECO:0000269|PubMed:14635112, ECO:0000269|PubMed:15342693,
FT ECO:0000269|PubMed:15475877, ECO:0000269|PubMed:16688110,
FT ECO:0000269|PubMed:9497261, ECO:0000269|PubMed:9823305,
FT ECO:0000269|Ref.5"
FT /id="VAR_001248"
FT VARIANT 437
FT /note="P -> L (in GLC3A; allele CYP1B1*23;
FT dbSNP:rs56175199)"
FT /evidence="ECO:0000269|PubMed:12036985,
FT ECO:0000269|PubMed:15475877, ECO:0000269|PubMed:9497261"
FT /id="VAR_008354"
FT VARIANT 441
FT /note="D -> H (in dbSNP:rs4986887)"
FT /id="VAR_028737"
FT VARIANT 443
FT /note="A -> G (in GLC3A; allele CYP1B1*7; unknown
FT pathological significance; dbSNP:rs4986888)"
FT /evidence="ECO:0000269|PubMed:11854439,
FT ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:15342693,
FT ECO:0000269|PubMed:16862072"
FT /id="VAR_018774"
FT VARIANT 444
FT /note="R -> Q (in GLC3A; dbSNP:rs72549376)"
FT /evidence="ECO:0000269|PubMed:11527932"
FT /id="VAR_054261"
FT VARIANT 445
FT /note="F -> C (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:14640114"
FT /id="VAR_054262"
FT VARIANT 449
FT /note="D -> E (in dbSNP:rs1056837)"
FT /id="VAR_028738"
FT VARIANT 453
FT /note="N -> S (in allele CYP1B1*4; dbSNP:rs1800440)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:11854439, ECO:0000269|PubMed:12036985,
FT ECO:0000269|PubMed:12525557, ECO:0000269|PubMed:14635112,
FT ECO:0000269|PubMed:15342693, ECO:0000269|PubMed:15475877,
FT ECO:0000269|PubMed:16688110, ECO:0000269|PubMed:9823305,
FT ECO:0000269|Ref.4, ECO:0000269|Ref.5"
FT /id="VAR_008355"
FT VARIANT 466
FT /note="G -> D (in GLC3A; dbSNP:rs868208502)"
FT /evidence="ECO:0000269|PubMed:15475877"
FT /id="VAR_054263"
FT VARIANT 469
FT /note="R -> W (in GLC3A; allele CYP1B1*25;
FT dbSNP:rs28936701)"
FT /evidence="ECO:0000269|PubMed:10655546,
FT ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:9463332,
FT ECO:0000269|PubMed:9497261"
FT /id="VAR_001247"
FT VARIANT 499
FT /note="E -> G (in GLC3A; dbSNP:rs72549372)"
FT /evidence="ECO:0000269|PubMed:11527932"
FT /id="VAR_054264"
FT VARIANT 515
FT /note="S -> L (in GLC3A; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16688110"
FT /id="VAR_054265"
FT VARIANT 518
FT /note="V -> A"
FT /evidence="ECO:0000269|PubMed:16688110"
FT /id="VAR_054266"
FT VARIANT 523
FT /note="R -> T (in GLC3A; juvenile-onset)"
FT /evidence="ECO:0000269|PubMed:16688110"
FT /id="VAR_054267"
FT VARIANT 530
FT /note="D -> G (in GLC3A)"
FT /evidence="ECO:0000269|PubMed:16688110"
FT /id="VAR_054268"
FT MUTAGEN 395
FT /note="V->L: Invertes the 4OH E2:2OH E2 hydroxylation
FT preference from 5.1 to 0.45."
FT /evidence="ECO:0000269|PubMed:23821647"
FT HELIX 70..81
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:3PM0"
FT TURN 108..113
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 121..125
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 139..154
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 162..183
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 184..188
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 219..224
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 228..235
FT /evidence="ECO:0007829|PDB:3PM0"
FT TURN 241..243
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 245..249
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 253..282
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 292..304
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 320..348
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 350..363
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 372..377
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 379..392
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 407..409
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 419..424
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 425..428
FT /evidence="ECO:0007829|PDB:3PM0"
FT TURN 431..433
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 435..439
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 442..445
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 454..457
FT /evidence="ECO:0007829|PDB:3PM0"
FT HELIX 473..490
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 491..495
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 505..513
FT /evidence="ECO:0007829|PDB:3PM0"
FT STRAND 518..524
FT /evidence="ECO:0007829|PDB:3PM0"
SQ SEQUENCE 543 AA; 60846 MW; 46B6DA7368F63EA2 CRC64;
MGTSLSPNDP WPLNPLSIQQ TTLLLLLSVL ATVHVGQRLL RQRRRQLRSA PPGPFAWPLI
GNAAAVGQAA HLSFARLARR YGDVFQIRLG SCPIVVLNGE RAIHQALVQQ GSAFADRPAF
ASFRVVSGGR SMAFGHYSEH WKVQRRAAHS MMRNFFTRQP RSRQVLEGHV LSEARELVAL
LVRGSADGAF LDPRPLTVVA VANVMSAVCF GCRYSHDDPE FRELLSHNEE FGRTVGAGSL
VDVMPWLQYF PNPVRTVFRE FEQLNRNFSN FILDKFLRHC ESLRPGAAPR DMMDAFILSA
EKKAAGDSHG GGARLDLENV PATITDIFGA SQDTLSTALQ WLLLLFTRYP DVQTRVQAEL
DQVVGRDRLP CMGDQPNLPY VLAFLYEAMR FSSFVPVTIP HATTANTSVL GYHIPKDTVV
FVNQWSVNHD PLKWPNPENF DPARFLDKDG LINKDLTSRV MIFSVGKRRC IGEELSKMQL
FLFISILAHQ CDFRANPNEP AKMNFSYGLT IKPKSFKVNV TLRESMELLD SAVQNLQAKE
TCQ
