ID Q0KKP4_CHICK Unreviewed; 472 AA.
AC Q0KKP4;
DT 03-OCT-2006, integrated into UniProtKB/TrEMBL.
DT 03-OCT-2006, sequence version 1.
DT 24-JAN-2024, entry version 88.
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 Name=CYP51 {ECO:0000313|EMBL:BAF30488.1};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031 {ECO:0000313|EMBL:BAF30488.1};
RN [1] {ECO:0000313|EMBL:BAF30488.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=White Leghorne {ECO:0000313|EMBL:BAF30488.1};
RC TISSUE=Liver {ECO:0000313|EMBL:BAF30488.1};
RX PubMed=16945562; DOI=10.1016/j.cbpa.2006.07.012;
RA Kojima M., Tagami T., Degawa M.;
RT "Cloning of chicken lanosterol 14alpha-demethylase (CYP51) cDNA: discovery
RT of a testis-specific CYP51 transcript.";
RL Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. 145:383-389(2006).
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 -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000256|ARBA:ARBA00010617, ECO:0000256|RuleBase:RU000461}.
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DR EMBL; AB243876; BAF30488.1; -; mRNA.
DR AlphaFoldDB; Q0KKP4; -.
DR VEuPathDB; HostDB:geneid_420548; -.
DR BRENDA; 1.14.14.154; 1306.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
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 GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
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 Methyltransferase {ECO:0000313|EMBL:BAF30488.1};
KW Monooxygenase {ECO:0000256|RuleBase:RU000461};
KW Oxidoreductase {ECO:0000256|RuleBase:RU000461};
KW Steroid metabolism {ECO:0000256|ARBA:ARBA00023221};
KW Sterol metabolism {ECO:0000256|ARBA:ARBA00023166};
KW Transferase {ECO:0000313|EMBL:BAF30488.1}.
FT BINDING 418
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:BAF30488.1"
SQ SEQUENCE 472 AA; 53517 MW; CC7679801A4DC02A CRC64;
LAASAFALSL GYLFQLGYRR HVGADRTNHP PHIPSSIPFL GHAIAFGKSP IEFLENAYDK
YGPVFSFTMV GKTFTYLLGS DAAALLFNSK NEDLNAEDVY SRLTTPVFGK GVAYDVPNVV
FLEQKKMLKT GLNIAQFKQH VTLIEEETKE YFKAWGESGE RNLFEAFSEL IILTASHCLH
GKEIRSLLNE KVAQLYADLD GGFTHAAWLL PAWLPLPSFR RRDRAHRAIK NIFYKVIQKR
RSSEEKEDDM LQTLLDASYK DGRPLTDDEI AGMLIGLLLA GQHTSSTTSA WLGFFIARDK
AIQEQCYAEQ KAVCGDDLPP LTYDQLKDLS LLDRCLKETL RLRPPIMTIM RLAKTPQTVA
GYNIPPGHQV CVSPTVNQRL KDSWKDALDF KPDRYLRDNP AAGEKFAYIP FGAGRHRCIG
ENFAYVQIKT IWSTLLRLYE FDLVDGYFPS INYTTMIHTP NNPVIRYKRR SL
//