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 27-MAR-2024, entry version 244. 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)21:3;1-z;ft191; 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; 269-SER--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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, CC ChEBI:CHEBI:28744, 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47280, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, CC ChEBI:CHEBI:57618, 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47260, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15826, CC ChEBI:CHEBI:17026, 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, CC ChEBI:CHEBI:17898, 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42088, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17898, CC ChEBI:CHEBI:35291, 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 CC [NADPH--hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 uM for testosterone(6-beta-hydroxylation) CC {ECO:0000269|PubMed:10426814}; CC KM=25 uM for progesterone (6-beta-hydroxylation) CC {ECO:0000269|PubMed:10426814}; CC KM=23 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 CC (2-hydroxylation) {ECO:0000269|PubMed:10426814}; CC Vmax=0.91 nmol/min/nmol enzyme for 17-beta-estradiol CC (4-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 CC (16-alpha-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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 18. 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; DB14737; Cannabinol. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB00694; Daunorubicin. DR DrugBank; DB01248; Docetaxel. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB00470; Dronabinol. 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 GlyGen; Q16678; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000478561; -. DR PeptideAtlas; Q16678; -. DR ProteomicsDB; 61033; -. DR Antibodypedia; 29477; 486 antibodies from 36 providers. DR DNASU; 1545; -. DR Ensembl; ENST00000490576.2; ENSP00000478839.2; ENSG00000138061.12. 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 AGR; HGNC:2597; -. 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; LPCLDDQ; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; Q16678; -. DR TreeFam; TF105095; -. DR BioCyc; MetaCyc:HS06443-MONOMER; -. 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; 12 hits in 1154 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 208 other cell types or tissues. DR ExpressionAtlas; Q16678; baseline and differential. 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: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:0097237; P:cellular response to toxic substance; 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:1904681; P:response to 3-methylcholanthrene; IEA:Ensembl. 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: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 CDD; cd20675; CYP1B1-like; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24289:SF15; CYTOCHROME P450 FAMILY 1 SUBFAMILY C POLYPEPTIDE 1; 1. DR PANTHER; PTHR24289; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; Q16678; HS. 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; uncertain significance; FT dbSNP:rs72549382)" FT /evidence="ECO:0000269|PubMed:11527932" FT /id="VAR_054247" FT VARIANT 330 FT /note="A -> F (in GLC3A; uncertain significance; requires 2 FT nucleotide substitutions)" 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 a 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 FT 17beta-estradiol 4-hydroxylation activity but no change in FT 17beta-estradiol 2-hydroxylation activity; 2-fold reduction FT in 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; uncertain significance; allele FT CYP1B1*7; 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; uncertain 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 4OHE2:2OHE2 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 //