ID W5Q7R7_SHEEP Unreviewed; 510 AA.
AC W5Q7R7;
DT 16-APR-2014, integrated into UniProtKB/TrEMBL.
DT 16-APR-2014, sequence version 1.
DT 24-JAN-2024, entry version 52.
DE RecName: Full=Lanosterol 14-alpha demethylase {ECO:0000256|ARBA:ARBA00041158};
DE EC=1.14.14.154 {ECO:0000256|ARBA:ARBA00038974};
DE AltName: Full=CYPLI {ECO:0000256|ARBA:ARBA00042370};
DE AltName: Full=Cytochrome P450 51A1 {ECO:0000256|ARBA:ARBA00042628};
DE AltName: Full=Cytochrome P450-14DM {ECO:0000256|ARBA:ARBA00043156};
DE AltName: Full=Cytochrome P450LI {ECO:0000256|ARBA:ARBA00043041};
GN Name=LOC101113583 {ECO:0000313|Ensembl:ENSOARP00000018759.1};
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940 {ECO:0000313|Ensembl:ENSOARP00000018759.1, ECO:0000313|Proteomes:UP000002356};
RN [1] {ECO:0000313|Ensembl:ENSOARP00000018759.1, ECO:0000313|Proteomes:UP000002356}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Texel {ECO:0000313|Ensembl:ENSOARP00000018759.1,
RC ECO:0000313|Proteomes:UP000002356};
RX PubMed=20809919; DOI=10.1111/j.1365-2052.2010.02100.x;
RA Archibald A.L., Cockett N.E., Dalrymple B.P., Faraut T., Kijas J.W.,
RA Maddox J.F., McEwan J.C., Hutton Oddy V., Raadsma H.W., Wade C., Wang J.,
RA Wang W., Xun X.;
RT "The sheep genome reference sequence: a work in progress.";
RL Anim. Genet. 41:449-453(2010).
RN [2] {ECO:0000313|Ensembl:ENSOARP00000018759.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (JUL-2023) to UniProtKB.
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:0000256|ARBA:ARBA00036094};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45961;
CC Evidence={ECO:0000256|ARBA:ARBA00036094};
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:0000256|ARBA:ARBA00035879};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75080;
CC Evidence={ECO:0000256|ARBA:ARBA00035879};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxy-24,25-dihydrolanosterol + O2 + reduced
CC [NADPH--hemoprotein reductase] = 32-oxo-24,25-dihydrolanosterol +
CC H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:75087, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:87057,
CC ChEBI:CHEBI:87060; Evidence={ECO:0000256|ARBA:ARBA00036454};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75088;
CC Evidence={ECO:0000256|ARBA:ARBA00036454};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 32-oxolanosterol + H(+) + 2 H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75107, 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:166681, ChEBI:CHEBI:166806;
CC Evidence={ECO:0000256|ARBA:ARBA00036809};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75108;
CC Evidence={ECO:0000256|ARBA:ARBA00036809};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-oxo-24,25-dihydrolanosterol + O2 + reduced
CC [NADPH--hemoprotein reductase] = 4,4-dimethyl-8,14-cholestadien-
CC 3beta-ol + formate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:75083, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, 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:0000256|ARBA:ARBA00035773};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75084;
CC Evidence={ECO:0000256|ARBA:ARBA00035773};
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:0000256|ARBA:ARBA00036056};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75112;
CC Evidence={ECO:0000256|ARBA:ARBA00036056};
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:0000256|ARBA:ARBA00036132};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68069;
CC Evidence={ECO:0000256|ARBA:ARBA00036132};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-hydroxymethyl steroid + O2 + reduced
CC [NADPH--hemoprotein reductase] = a 14alpha-formyl steroid + H(+) + 2
CC H2O + 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:0000256|ARBA:ARBA00036638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68065;
CC Evidence={ECO:0000256|ARBA:ARBA00036638};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced
CC [NADPH--hemoprotein reductase] = a Delta(14) steroid + formate + 4
CC H(+) + 4 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:0000256|ARBA:ARBA00036116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000256|ARBA:ARBA00036116};
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:0000256|ARBA:ARBA00035798};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68061;
CC Evidence={ECO:0000256|ARBA:ARBA00035798};
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:0000256|ARBA:ARBA00036211};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287;
CC Evidence={ECO:0000256|ARBA:ARBA00036211};
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:0000256|ARBA:ARBA00036569};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75104;
CC Evidence={ECO:0000256|ARBA:ARBA00036569};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000256|PIRSR:PIRSR602403-1};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 1/6. {ECO:0000256|ARBA:ARBA00037887}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000256|ARBA:ARBA00004389}; Single-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004389}. Microsome membrane
CC {ECO:0000256|ARBA:ARBA00004111}; Single-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004111}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000256|ARBA:ARBA00010617, ECO:0000256|RuleBase:RU000461}.
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DR EMBL; AMGL01085461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AMGL01085462; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; W5Q7R7; -.
DR SMR; W5Q7R7; -.
DR STRING; 9940.ENSOARP00000018759; -.
DR PaxDb; 9940-ENSOARP00000018759; -.
DR Ensembl; ENSOART00000019025.1; ENSOARP00000018759.1; ENSOARG00000017477.1.
DR eggNOG; KOG0684; Eukaryota.
DR HOGENOM; CLU_001570_15_0_1; -.
DR OMA; AWTLIEL; -.
DR Proteomes; UP000002356; Chromosome 4.
DR Bgee; ENSOARG00000017477; Expressed in adrenal cortex and 54 other cell types or tissues.
DR GO; GO:0016020; C: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; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
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 3: Inferred from homology;
KW Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|PIRSR:PIRSR602403-1};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRSR:PIRSR602403-1};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023221};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRSR:PIRSR602403-1};
KW Monooxygenase {ECO:0000256|RuleBase:RU000461};
KW Oxidoreductase {ECO:0000256|RuleBase:RU000461};
KW Reference proteome {ECO:0000313|Proteomes:UP000002356};
KW Steroid metabolism {ECO:0000256|ARBA:ARBA00023221};
KW Sterol metabolism {ECO:0000256|ARBA:ARBA00023166}.
FT BINDING 456
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:0000256|PIRSR:PIRSR602403-1"
SQ SEQUENCE 510 AA; 57677 MW; 96CAB5D0E3CD2653 CRC64;
AGVAAGMVML DLLQAGGSVL EQAMEQVTGS NLPSMLLIAA KMFLLELIFS LFKINGSRSF
LERGMKSPPY IVSPIPFLGH AIAFGKSPIE FLEDAYEKYG PVFSFTMVGK TFTYLLGSEA
AALLFNSKNE DLNAEDVYSR LTTPVFGKGV AYDVPNTVFL EQKKMLKSGL NIAHFRQHVS
IIEKETKDYF RSWGESGEKN LFEALSELII LTASHCLHGK EIRGQLNEKV ARLYADLDGG
FSHAAWLLPG WLPLPSFRRR DRAHREIKNI FYKAIQKRRE SGEKIDDILQ TLLESTYKDG
RPLTDDEIAG MLIGLLLAGQ HTSSTTSAWM GFFLARDKTL QEKCFSEQKT VCGENLPPLS
YDQLKDLNLL DRCIKETLRL RPPIMTMMRL AKTPQTVAGY TIPPGHQVCV SPTVNQRLKD
SWVERLDFNP DRYLEDSLAS GEKFAYVPFG AGRHRCIGEN FAYVQIKTIW STMLRLYEFD
LIDGYFPTVN YTTMIHTPEN PVIRYKRRSK
//