CP51A_MACFA
ID CP51A_MACFA Reviewed; 509 AA.
AC Q4R8S6; Q4R5W7;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 3.
DT 03-AUG-2022, entry version 96.
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}; Synonyms=CYP51;
GN ORFNames=QtsA-11582, QtsA-20162;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Uno Y., Kito G., Kamataki T., Nagata R.;
RT "Identification of CYP cDNAs from cynomolgus monkey liver.";
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) 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}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-7 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE01508.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; DQ074804; AAZ29450.1; -; mRNA.
DR EMBL; AB168372; BAE00495.1; -; mRNA.
DR EMBL; AB169425; BAE01508.1; ALT_INIT; mRNA.
DR RefSeq; NP_001274625.1; NM_001287696.1.
DR AlphaFoldDB; Q4R8S6; -.
DR SMR; Q4R8S6; -.
DR STRING; 9541.XP_005550295.1; -.
DR Ensembl; ENSMFAT00000015743; ENSMFAP00000041467; ENSMFAG00000041456.
DR GeneID; 102146764; -.
DR CTD; 1595; -.
DR VGNC; VGNC:83109; CYP51A1.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00930000151026; -.
DR OrthoDB; 572303at2759; -.
DR UniPathway; UPA00770; UER00754.
DR Proteomes; UP000233100; Chromosome 3.
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: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 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..509
FT /note="Lanosterol 14-alpha demethylase"
FT /id="PRO_0000052000"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 455
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|UniProtKB:Q16850"
SQ SEQUENCE 509 AA; 57287 MW; 681FFF7E95B2CBCC CRC64;
MAAAAGMMLL GLLQAGGSVL GQAMEKVTGG NLLSMLLIAC AFTLSLVYLF RLAAGHLVQL
PAGAKSPPYI FSPIPFLGHA IAFGKSPVEF LENAYEKYGP VFSFTMVGKT FTYLLGSDAA
ALLFNSKNED LNAEDVYSRL TTPVFGKGVA YDVPNPVFLE QKKMLKSGLN IAHFKQHVSI
IEKETKEYFQ SWGESGEKNV FEALSELIIL TASHCLHGKE IRSQLNEKVA QLYADLDGGF
SHAAWLLPGW LPLPSFRRRD RAHREIKNIF YKAIQKRRQS QEKIDDILQT LLDATYKDGR
PLTDDEVAGM LIGLLLAGQH TSSTTSAWMG FFLARDKTLQ EKCYLEQKTV CGENLPPLTY
DQLKDLNLLD RCIKETLRLR PPIMIMMRMA RTPQTVAGYT IPPGHQVCVS PTVNQRLKDS
WVERLDFNPD RYLQDNPASG EKFAYVPFGA GRHRCIGENF AYVQIKTIWS TMLRLYEFDL
IDGYFPTVNY TTMIHTPENP VIRYKRRSK
