UniProt ID: Q1JPY5 |
FUNCTION: Sterol 14alpha-demethylase that plays a critical role in the cholesterol biosynthesis pathway, being cholesterol the major sterol component in deuterostome membranes as well as a precursor for steroid hormone synthesis (PubMed:24361620). Cytochrome P450 monooxygenase that catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of sterols such as lanosterol (lanosta-8,24-dien-3beta-ol) and 24,25-dihydrolanosterol (DHL) in the form of formate, and converts the sterols to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol and 4,4- dimethyl-8,14-cholestadien-3beta-ol, respectively, which are intermediates of cholesterol biosynthesis (PubMed:24361620). Can also demethylate susbtrates not intrinsic to deuterostomes, such as eburicol (24-methylene-24,25-dihydrolanosterol), but at a lower rate than DHL (By similarity). {ECO:0000250|UniProtKB:Q64654, ECO:0000269|PubMed:24361620}. CATALYTIC ACTIVITY: Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH-- hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154; Evidence={ECO:0000269|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029; Evidence={ECO:0000269|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=lanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:25286, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:16521, ChEBI:CHEBI:17813, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.154; Evidence={ECO:0000269|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287; Evidence={ECO:0000269|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=24,25-dihydrolanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] = 4,4-dimethyl-8,14-cholestadien-3beta-ol + formate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:45960, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:28113, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78904; Evidence={ECO:0000250|UniProtKB:Q64654}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45961; Evidence={ECO:0000250|UniProtKB:Q64654}; CATALYTIC ACTIVITY: Reaction=a 14alpha-methyl steroid + O2 + reduced [NADPH--hemoprotein reductase] = a 14alpha-hydroxymethyl steroid + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68060, Rhea:RHEA- COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:138029, ChEBI:CHEBI:176901; Evidence={ECO:0000305|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68061; Evidence={ECO:0000305|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=a 14alpha-hydroxymethyl steroid + O2 + reduced [NADPH-- hemoprotein reductase] = a 14alpha-formyl steroid + H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68064, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:176901, ChEBI:CHEBI:176902; Evidence={ECO:0000305|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68065; Evidence={ECO:0000305|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=a 14alpha-formyl steroid + O2 + reduced [NADPH--hemoprotein reductase] = a Delta(14) steroid + formate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68068, Rhea:RHEA- COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:138031, ChEBI:CHEBI:176902; Evidence={ECO:0000305|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68069; Evidence={ECO:0000305|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=lanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32- hydroxylanosterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75103, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16521, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:166806; Evidence={ECO:0000305|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75104; Evidence={ECO:0000305|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=32-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-oxolanosterol + H(+) + 2 H2O + oxidized [NADPH-- hemoprotein reductase]; Xref=Rhea:RHEA:75107, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:166681, ChEBI:CHEBI:166806; Evidence={ECO:0000305|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75108; Evidence={ECO:0000305|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=32-oxolanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75111, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:17813, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:166681; Evidence={ECO:0000305|PubMed:24361620}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75112; Evidence={ECO:0000305|PubMed:24361620}; CATALYTIC ACTIVITY: Reaction=24,25-dihydrolanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-hydroxy-24,25-dihydrolanosterol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75079, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:28113, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87057; Evidence={ECO:0000250|UniProtKB:Q64654}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75080; Evidence={ECO:0000250|UniProtKB:Q64654}; CATALYTIC ACTIVITY: Reaction=32-hydroxy-24,25-dihydrolanosterol + O2 + reduced [NADPH-- hemoprotein reductase] = 32-oxo-24,25-dihydrolanosterol + H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75087, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87057, ChEBI:CHEBI:87060; Evidence={ECO:0000250|UniProtKB:Q64654}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75088; Evidence={ECO:0000250|UniProtKB:Q64654}; CATALYTIC ACTIVITY: Reaction=32-oxo-24,25-dihydrolanosterol + O2 + reduced [NADPH-- hemoprotein reductase] = 4,4-dimethyl-8,14-cholestadien-3beta-ol + formate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75083, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78904, ChEBI:CHEBI:87060; Evidence={ECO:0000250|UniProtKB:Q64654}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75084; Evidence={ECO:0000250|UniProtKB:Q64654}; COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250|UniProtKB:Q16850}; ACTIVITY REGULATION: Inhibited by ketoconazole. May also be inhibited to a lesser extent by propiconazole. {ECO:0000269|PubMed:24361620}. PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 1/6. {ECO:0000305|PubMed:24361620}. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q64654}; Single-pass membrane protein {ECO:0000255}. Membrane {ECO:0000305|PubMed:24361620}; Single-pass membrane protein {ECO:0000255}. TISSUE SPECIFICITY: Strongly expressed in intestine. Moderately expressed in liver, with higher levels in females compared to males. Also detected at low levels in brain, eye, kidney and testis. {ECO:0000269|PubMed:24361620}. SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255|RuleBase:RU000461, ECO:0000305}. |
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