ID CP51A_BOVIN Reviewed; 502 AA.
AC Q4PJW3; A6QPJ2; Q3YM99;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 24-JAN-2024, entry version 118.
DE RecName: Full=Lanosterol 14-alpha demethylase {ECO:0000250|UniProtKB:Q16850};
DE Short=LDM;
DE EC=1.14.14.154 {ECO:0000250|UniProtKB:Q16850, ECO:0000250|UniProtKB:Q64654};
DE AltName: Full=CYPLI;
DE AltName: Full=Cytochrome P450 51A1;
DE Short=CYP51 {ECO:0000250|UniProtKB:Q64654};
DE AltName: Full=Cytochrome P450-14DM;
DE Short=Cytochrome P45014DM;
DE AltName: Full=Cytochrome P450LI;
DE AltName: Full=Sterol 14-alpha demethylase;
GN Name=CYP51A1 {ECO:0000250|UniProtKB:Q16850};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=15836952; DOI=10.1016/j.mce.2004.11.009;
RA Rozman D., Seliskar M., Cotman M., Fink M.;
RT "Pre-cholesterol precursors in gametogenesis.";
RL Mol. Cell. Endocrinol. 234:47-56(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16508140; DOI=10.1248/bpb.29.430;
RA Wang F., Shen Y., Song X., Xia G., Chen X., Zhou B., Lei L.;
RT "cDNA cloning, genomic structure and expression analysis of the bovine
RT lanosterol 14alpha-demethylase (CYP51) in gonads.";
RL Biol. Pharm. Bull. 29:430-436(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal medulla;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Sterol 14alpha-demethylase that plays a critical role in the
CC cholesterol biosynthesis pathway, being cholesterol the major sterol
CC component in mammalian membranes as well as a precursor for bile acid
CC and steroid hormone synthesis. Cytochrome P450 monooxygenase that
CC catalyzes the three-step oxidative removal of the 14alpha-methyl group
CC (C-32) of sterols such as lanosterol (lanosta-8,24-dien-3beta-ol) and
CC 24,25-dihydrolanosterol (DHL) in the form of formate, and converts the
CC sterols to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol and 4,4-
CC dimethyl-8,14-cholestadien-3beta-ol, respectively, which are
CC intermediates of cholesterol biosynthesis. Can also demethylate
CC substrates not intrinsic to mammals, such as eburicol (24-methylene-
CC 24,25-dihydrolanosterol), but at a lower rate than DHL.
CC {ECO:0000250|UniProtKB:Q64654}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4
CC H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 4
CC H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:25286, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:16521, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.154;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=24,25-dihydrolanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = 4,4-dimethyl-8,14-cholestadien-3beta-ol + formate + 4
CC H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:45960, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:28113, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:78904;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45961;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + O2 + reduced [NADPH--hemoprotein
CC reductase] = a 14alpha-hydroxymethyl steroid + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68060, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:138029, ChEBI:CHEBI:176901;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68061;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-hydroxymethyl steroid + O2 + reduced [NADPH--
CC hemoprotein reductase] = a 14alpha-formyl steroid + H(+) + 2 H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68064,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:176901, ChEBI:CHEBI:176902;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68065;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-formyl steroid + O2 + reduced [NADPH--hemoprotein
CC reductase] = a Delta(14) steroid + formate + 2 H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68068, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:138031,
CC ChEBI:CHEBI:176902; Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68069;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-
CC hydroxylanosterol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:75103, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16521, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:166806; Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75104;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 32-oxolanosterol + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75107, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:166681, ChEBI:CHEBI:166806;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75108;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-oxolanosterol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 2
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:75111, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:17813, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:166681;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75112;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=24,25-dihydrolanosterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 32-hydroxy-24,25-dihydrolanosterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75079,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:28113,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87057;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75080;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxy-24,25-dihydrolanosterol + O2 + reduced [NADPH--
CC hemoprotein reductase] = 32-oxo-24,25-dihydrolanosterol + H(+) + 2
CC H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75087,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:87057, ChEBI:CHEBI:87060;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75088;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-oxo-24,25-dihydrolanosterol + O2 + reduced [NADPH--
CC hemoprotein reductase] = 4,4-dimethyl-8,14-cholestadien-3beta-ol +
CC formate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:75083, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:78904, ChEBI:CHEBI:87060;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75084;
CC Evidence={ECO:0000250|UniProtKB:Q64654};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q16850};
CC -!- ACTIVITY REGULATION: Inhibited by azalanstat. Inhibited by azole
CC antifungal agents ketoconazole, itraconazole and fluconazole.
CC {ECO:0000250|UniProtKB:Q64654}.
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 1/6. {ECO:0000250|UniProtKB:Q64654}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q64654}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:Q64654};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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; DQ078267; AAY82452.1; -; mRNA.
DR EMBL; DQ085625; AAZ74630.1; -; mRNA.
DR EMBL; BC149346; AAI49347.1; -; mRNA.
DR RefSeq; NP_001020490.1; NM_001025319.2.
DR AlphaFoldDB; Q4PJW3; -.
DR SMR; Q4PJW3; -.
DR STRING; 9913.ENSBTAP00000002582; -.
DR PaxDb; 9913-ENSBTAP00000002582; -.
DR Ensembl; ENSBTAT00000002582.6; ENSBTAP00000002582.5; ENSBTAG00000001992.6.
DR GeneID; 505060; -.
DR KEGG; bta:505060; -.
DR CTD; 1595; -.
DR VEuPathDB; HostDB:ENSBTAG00000001992; -.
DR VGNC; VGNC:110275; CYP51A1.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00930000151026; -.
DR HOGENOM; CLU_001570_15_0_1; -.
DR InParanoid; Q4PJW3; -.
DR OMA; AWTLIEL; -.
DR OrthoDB; 5474434at2759; -.
DR TreeFam; TF105091; -.
DR BRENDA; 1.14.14.154; 908.
DR Reactome; R-BTA-191273; Cholesterol biosynthesis.
DR Reactome; R-BTA-211976; Endogenous sterols.
DR UniPathway; UPA00770; UER00754.
DR Proteomes; UP000009136; Chromosome 4.
DR Bgee; ENSBTAG00000001992; Expressed in diaphragm and 103 other cell types or tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008398; F:sterol 14-demethylase activity; ISS:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006694; P:steroid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR CDD; cd11042; CYP51-like; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR PANTHER; PTHR24304:SF2; 24-HYDROXYCHOLESTEROL 7-ALPHA-HYDROXYLASE; 1.
DR PANTHER; PTHR24304; CYTOCHROME P450 FAMILY 7; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW Microsome; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..502
FT /note="Lanosterol 14-alpha demethylase"
FT /id="PRO_0000051997"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 448
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250"
SQ SEQUENCE 502 AA; 56596 MW; 5D1C5AFA43E067A1 CRC64;
MLDLLQAGGS VLGQAMEQVT GGNLASMLLI ACAFTLSLVY LFRLAVGHLA PPLPTGAKSP
PYIVSPIPFL GHAIAFGKSP IEFLEDAYEK YGPVFSFTMV GKTFTYLLGS EAAALLFNSK
NEDLNAEEVY SRLTTPVFGK GVAYDVPNTV FLEQKKMLKS GLNIAHFRQH VSIIEKETKE
YFKSWGESGE KNLFEALSEL IILTASHCLH GKEIRSQLNE KVAQLYADLD GGFSHAAWLL
PGWLPLPSFR RRDRAHREIK NIFYKAIQKR RESGEKIDDI LQTLLESTYK DGRPLTDDEV
AGMLIGLLLA GQHTSSTTSA WMGFFLARDK TLQEKCFLEQ KTVCGENLPP LTYDQLKDLN
LLDRCIKETL RLRPPIMTMM RLAKTPLTVA GYTIPPGHQV CVSPTVNQRL KDSWVERLDF
NPDRYLEDSP ASGEKFAYVP FGAGRHRCIG ENFAYVQIKT IWSTMLRLYE FDLIDGYFPT
VNYTTMIHTP EKPIIRYKRR SK
//
