CP51A_PIG
ID CP51A_PIG Reviewed; 503 AA.
AC O46420;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 145.
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=10788789; DOI=10.1093/oxfordjournals.jbchem.a022673;
RA Kojima M., Morozumi T., Onishi A., Mitsuhashi T.;
RT "Structure of the pig sterol 14 alpha-demethylase (CYP51) gene and its
RT expression in the testis and other tissues.";
RL J. Biochem. 127:805-811(2000).
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 -!- TISSUE SPECIFICITY: Strongly expressed in liver and testis. Also
CC detected in kidney, lung and epididymis. {ECO:0000269|PubMed:10788789}.
CC -!- DEVELOPMENTAL STAGE: In testis, expression levels are low in young
CC animals and increase rapidly after 10 weeks of age.
CC {ECO:0000269|PubMed:10788789}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AB009988; BAA24134.1; -; mRNA.
DR EMBL; AB042982; BAA96092.1; -; Genomic_DNA.
DR PIR; JC7243; JC7243.
DR RefSeq; NP_999597.1; NM_214432.1.
DR AlphaFoldDB; O46420; -.
DR SMR; O46420; -.
DR STRING; 9823.ENSSSCP00000016238; -.
DR PaxDb; O46420; -.
DR PeptideAtlas; O46420; -.
DR PRIDE; O46420; -.
DR Ensembl; ENSSSCT00000037678; ENSSSCP00000041656; ENSSSCG00000015311.
DR Ensembl; ENSSSCT00005069883; ENSSSCP00005043505; ENSSSCG00005043421.
DR Ensembl; ENSSSCT00055045792; ENSSSCP00055036514; ENSSSCG00055023185.
DR Ensembl; ENSSSCT00065053577; ENSSSCP00065023290; ENSSSCG00065039138.
DR Ensembl; ENSSSCT00070028829; ENSSSCP00070024028; ENSSSCG00070014693.
DR GeneID; 403334; -.
DR KEGG; ssc:403334; -.
DR CTD; 1595; -.
DR VGNC; VGNC:103377; CYP51A1.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00930000151026; -.
DR HOGENOM; CLU_001570_15_0_1; -.
DR InParanoid; O46420; -.
DR OMA; AWTLIEL; -.
DR OrthoDB; 572303at2759; -.
DR TreeFam; TF105091; -.
DR Reactome; R-SSC-191273; Cholesterol biosynthesis.
DR Reactome; R-SSC-211976; Endogenous sterols.
DR UniPathway; UPA00770; UER00754.
DR Proteomes; UP000008227; Chromosome 9.
DR Proteomes; UP000314985; Chromosome 9.
DR Bgee; ENSSSCG00000015311; Expressed in testis and 41 other tissues.
DR ExpressionAtlas; O46420; baseline and differential.
DR Genevisible; O46420; SS.
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; IEA:InterPro.
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; IEA:UniProtKB-EC.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
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..503
FT /note="Lanosterol 14-alpha demethylase"
FT /id="PRO_0000051999"
FT TRANSMEM 24..44
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 449
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 503 AA; 56867 MW; 0302949CE461AFD6 CRC64;
MVLLGLLQAG GSVLGQAMEQ VTGVNLLSSL LLACAFTLIL VYLFRQAIGH LAPLPAGAKS
PPYIFSPIPF LGHAIAFGKS PIEFLENAYE KYGPVFSFTM VGKTFTYLLG SDAAALLFNS
KNEDLNAEDV YSRLTTPVFG KGVAYDVPNP VFLEQKKMLK SGLNIAHFRQ HVSIIEKETK
EYFQSWGESG ERNLFEALSE LIILTASHCL HGKEIRSQLN EKVAQLYADL DGGFSHAAWL
LPGWLPLPSF RRRDRAHREI KNIFYKAIQK RRQSEEKIDD ILQTLLDSTY KDGRPLTDDE
VAGMLIGLLL AGQHTSSTTS AWMGFFLARD KTLQEKCYLE QKTVCGEDLP PLTYDQLKDL
NLLDRCIKET LRLRPPIMTM MRMAKTPQTV AGYTIPPGHQ VCVSPTVNQR LKDSWVERLD
FNPDRYLQDN PASGEKFAYV PFGAGRHRCI GENFAYVQIK TIWSTMLRLY EFDLIDGYFP
TVNYTTMIHT PENPVIRYKR RSK
