CP51A_BOVIN
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 03-AUG-2022, entry version 112.
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 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: A cytochrome P450 monooxygenase involved in sterol
CC biosynthesis. Catalyzes 14-alpha demethylation of lanosterol and 24,25-
CC dihydrolanosterol likely through sequential oxidative conversion of 14-
CC alpha methyl group to hydroxymethyl, then to carboxylaldehyde, followed
CC by the formation of the delta 14,15 double bond in the sterol core and
CC concomitant release of formic acid. 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 (CPR; NADPH-ferrihemoprotein reductase).
CC {ECO:0000250|UniProtKB:Q16850, 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:Q16850,
CC ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000250|UniProtKB:Q16850,
CC 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:Q16850,
CC ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287;
CC Evidence={ECO:0000250|UniProtKB:Q16850,
CC 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:Q16850,
CC ECO:0000250|UniProtKB:Q64654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45961;
CC Evidence={ECO:0000250|UniProtKB:Q16850,
CC 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}.
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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; Q4PJW3; -.
DR PRIDE; Q4PJW3; -.
DR Ensembl; ENSBTAT00000002582; ENSBTAP00000002582; ENSBTAG00000001992.
DR GeneID; 505060; -.
DR KEGG; bta:505060; -.
DR CTD; 1595; -.
DR VEuPathDB; HostDB:ENSBTAG00000001992; -.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00930000151026; -.
DR HOGENOM; CLU_001570_15_0_1; -.
DR InParanoid; Q4PJW3; -.
DR OMA; AWTLIEL; -.
DR OrthoDB; 572303at2759; -.
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 tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
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 Gene3D; 1.10.630.10; -; 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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 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
