ID A0A852MPM2_9PASS Unreviewed; 448 AA. AC A0A852MPM2; DT 29-SEP-2021, integrated into UniProtKB/TrEMBL. DT 29-SEP-2021, sequence version 1. DT 24-JUL-2024, entry version 14. 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=Cyp39a1 {ECO:0000313|EMBL:NXY07382.1}; GN ORFNames=PTEMEL_R14458 {ECO:0000313|EMBL:NXY07382.1}; OS Pteruthius melanotis. OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; OC Coelurosauria; Aves; Neognathae; Passeriformes; Sylvioidea; Timaliidae; OC Pteruthius. OX NCBI_TaxID=357074 {ECO:0000313|EMBL:NXY07382.1, ECO:0000313|Proteomes:UP000603297}; RN [1] {ECO:0000313|EMBL:NXY07382.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=B10K-IZ-033-77 {ECO:0000313|EMBL:NXY07382.1}; RA Zhang G.; RT "Bird 10,000 Genomes (B10K) Project - Family phase."; RL Submitted (FEB-2020) to the EMBL/GenBank/DDBJ databases. 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|ARBA:ARBA00001971, CC ECO:0000256|PIRSR:PIRSR000047-1}; CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis. CC {ECO:0000256|ARBA:ARBA00004860}. 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}. CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:NXY07382.1}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; WEIY01000383; NXY07382.1; -; Genomic_DNA. DR AlphaFoldDB; A0A852MPM2; -. DR Proteomes; UP000603297; Unassembled WGS sequence. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0020037; F:heme binding; IEA:InterPro. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0008396; F:oxysterol 7-alpha-hydroxylase activity; IEA:TreeGrafter. DR GO; GO:0008387; F:steroid 7-alpha-hydroxylase activity; IEA:TreeGrafter. DR GO; GO:0006699; P:bile acid biosynthetic process; IEA:TreeGrafter. DR GO; GO:0042632; P:cholesterol homeostasis; IEA:TreeGrafter. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW. DR CDD; cd20635; CYP39A1; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR050529; CYP450_sterol_14alpha_dmase. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR024204; Cyt_P450_CYP7A1-type. 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 PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 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:PIRSR000047-1}; KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRSR:PIRSR000047-1}; KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023221}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, KW ECO:0000256|PIRSR:PIRSR000047-1}; KW Monooxygenase {ECO:0000256|RuleBase:RU000461}; KW Oxidoreductase {ECO:0000256|RuleBase:RU000461}; KW Reference proteome {ECO:0000313|Proteomes:UP000603297}; KW Steroid metabolism {ECO:0000256|ARBA:ARBA00023221}; KW Sterol metabolism {ECO:0000256|ARBA:ARBA00023166}. FT BINDING 256 FT /ligand="substrate" FT /evidence="ECO:0000256|PIRSR:PIRSR000047-2" FT BINDING 393 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:PIRSR000047-1" FT NON_TER 1 FT /evidence="ECO:0000313|EMBL:NXY07382.1" FT NON_TER 448 FT /evidence="ECO:0000313|EMBL:NXY07382.1" SQ SEQUENCE 448 AA; 51360 MW; 62E27AC64275EDF1 CRC64; LLFQLRNPSS PPCIRSWIPW FGAAFQFGKA PLEFIEQARN KHGPVFTIFA LGKRFTFVTE EEGTEAFFKS EDLNFEQAVQ QAVQNAVSVP AEAFYQNHGN LYSMMKGKMS PSNLHMFSGT LCKELHEHMA HLGTEGTGDL NDLVRHVMYP AVVNTLFGKG ICPTSQSEIK EFEEHFQKYD EDFEYASQMP ECFLRNWSKS KKWLLKLFEK VVLDAERTNP SEAASKTLLQ HLLDNLQGKH LAPNYGLLML WAAQANAVPV AFWTLAFILS NPAIYKKVME DLASVFGKAG KDKLEVSEED LKRMPFIKWC TLEAIRLRSP GAITKKVINP IRIKNFTIPA GDMLMLSPYW LHRNPKYFPD PEMFKPDRWK EANLEKNAFL DSFVAFGGGK HQCPGRWFAI MEIQLFVVLF LYKYEFVLLD AVPKESPLHL VGTQQPMAPL RVRYKCRE //