ID R0L0A4_ANAPL Unreviewed; 397 AA.
AC R0L0A4;
DT 26-JUN-2013, integrated into UniProtKB/TrEMBL.
DT 26-JUN-2013, sequence version 1.
DT 27-MAR-2024, entry version 38.
DE RecName: Full=Lanosterol 14-alpha demethylase {ECO:0000256|ARBA:ARBA00041158};
DE EC=1.14.14.154 {ECO:0000256|ARBA:ARBA00038974};
DE Flags: Fragment;
GN ORFNames=Anapl_11403 {ECO:0000313|EMBL:EOA93702.1};
OS Anas platyrhynchos (Mallard) (Anas boschas).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Anseriformes; Anatidae;
OC Anatinae; Anas.
OX NCBI_TaxID=8839 {ECO:0000313|EMBL:EOA93702.1, ECO:0000313|Proteomes:UP000296049};
RN [1] {ECO:0000313|Proteomes:UP000296049}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=23749191; DOI=10.1038/ng.2657;
RA Huang Y., Li Y., Burt D.W., Chen H., Zhang Y., Qian W., Kim H., Gan S.,
RA Zhao Y., Li J., Yi K., Feng H., Zhu P., Li B., Liu Q., Fairley S.,
RA Magor K.E., Du Z., Hu X., Goodman L., Tafer H., Vignal A., Lee T.,
RA Kim K.W., Sheng Z., An Y., Searle S., Herrero J., Groenen M.A.,
RA Crooijmans R.P., Faraut T., Cai Q., Webster R.G., Aldridge J.R.,
RA Warren W.C., Bartschat S., Kehr S., Marz M., Stadler P.F., Smith J.,
RA Kraus R.H., Zhao Y., Ren L., Fei J., Morisson M., Kaiser P., Griffin D.K.,
RA Rao M., Pitel F., Wang J., Li N.;
RT "The duck genome and transcriptome provide insight into an avian influenza
RT virus reservoir species.";
RL Nat. Genet. 45:776-783(2013).
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}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000256|ARBA:ARBA00010617, ECO:0000256|RuleBase:RU000461}.
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DR EMBL; KB745661; EOA93702.1; -; Genomic_DNA.
DR AlphaFoldDB; R0L0A4; -.
DR Proteomes; UP000296049; Unassembled WGS sequence.
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:0008398; F:sterol 14-demethylase activity; IEA:UniProt.
DR GO; GO:0008202; P:steroid metabolic process; IEA:UniProtKB-KW.
DR CDD; cd20635; CYP39A1; 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 SUPFAM; SSF48264; Cytochrome P450; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Cholesterol metabolism {ECO:0000256|ARBA:ARBA00022548};
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 Membrane {ECO:0000256|SAM:Phobius};
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:UP000296049};
KW Steroid metabolism {ECO:0000256|ARBA:ARBA00023221};
KW Sterol metabolism {ECO:0000256|ARBA:ARBA00023166};
KW Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT TRANSMEM 246..270
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT BINDING 394
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"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:EOA93702.1"
FT NON_TER 397
FT /evidence="ECO:0000313|EMBL:EOA93702.1"
SQ SEQUENCE 397 AA; 45166 MW; 7BA40B49F7A7E74C CRC64;
WFLFQPRNPS CPPCIGSWIP WVGAAFQFGK APLEFIEQAR SKHGPVFTVF ALGKRFTFVT
EEEGAEAFFS SKDLNFEQAV QQAVENAVSV PAEAFYQNHG TLYSMMKGKM GPSNLHMFTG
TLCRELHEHM GHLGTKGAGD LNDLVRHVMY PAVVNTLFGK GICPTSQSEL KEFEEHFQKY
DEDFEYASQM PECFLRNWSK SKKWLLKLFE KVVSDAERTN PSETTSKTLL QHLLDNLQGK
HLAPNYGLLM LWASQANAVP IAFWTLVFIL SYPSIYKKTM EDLTSVFGKA GKDKIEVSEE
DLKNLPFIKW CTLEAIRLRS PGAITKKVVN PIRIQNFTVP AGDMLMLSPY WLHRNPKYFP
DPEMFKPDRW KEANLEKNAF LDSFVAFGGG KHQCPGR
//
