CP51B_ASPFN
ID CP51B_ASPFN Reviewed; 491 AA.
AC B8NFL5;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2020, sequence version 2.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Sterol 14-alpha demethylase {ECO:0000303|PubMed:18775650};
DE EC=1.14.14.154 {ECO:0000305|PubMed:18775650};
DE AltName: Full=Cytochrome P450 monooxygenase 51B {ECO:0000303|PubMed:18775650};
DE AltName: Full=Ergosterol biosynthesis protein cyp51B {ECO:0000303|PubMed:18775650};
GN Name=cyp51B {ECO:0000303|PubMed:18775650}; ORFNames=AFLA_131060;
OS Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS / JCM 12722 / SRRC 167).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=332952;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RX PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT aflatoxin contamination of food and feed.";
RL Genome Announc. 3:E0016815-E0016815(2015).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF HIS-389; ASP-401 AND THR-444.
RX PubMed=18775650; DOI=10.1016/j.ijantimicag.2008.06.018;
RA Krishnan-Natesan S., Chandrasekar P.H., Alangaden G.J., Manavathu E.K.;
RT "Molecular characterisation of cyp51A and cyp51B genes coding for P450
RT 14alpha-lanosterol demethylases A (CYP51Ap) and B (CYP51Bp) from
RT voriconazole-resistant laboratory isolates of Aspergillus flavus.";
RL Int. J. Antimicrob. Agents 32:519-524(2008).
RN [3]
RP FUNCTION, AND INDUCTION.
RX PubMed=29311090; DOI=10.1128/aac.01928-17;
RA Sharma C., Kumar R., Kumar N., Masih A., Gupta D., Chowdhary A.;
RT "Investigation of multiple resistance mechanisms in voriconazole-resistant
RT Aspergillus flavus clinical isolates from a chest hospital surveillance in
RT Delhi, India.";
RL Antimicrob. Agents Chemother. 62:0-0(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase involved in the biosynthesis of
CC ergosterol (By similarity). The existence of several duplicated sterol
CC 14-alpha demethylase genes could be a good strategy to modulate the
CC composition and fluidity of the cell membrane (By similarity).
CC Catalyzes C14-demethylation of erburicol to produce 4,4,24-trimethyl
CC cholesta-8,24(28)-dien-3-beta-ol (By similarity). Shows a slight
CC substrate preference toward eburicol over obtusifoliol (By similarity).
CC As a target of azole drugs, plays a crucial role in azole
CC susceptibility (PubMed:18775650, PubMed:29311090).
CC {ECO:0000250|UniProtKB:E9QY26, ECO:0000250|UniProtKB:Q4WNT5,
CC ECO:0000269|PubMed:18775650, ECO:0000269|PubMed:29311090}.
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:E9QY26};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000250|UniProtKB:E9QY26};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:E9QY26};
CC -!- PATHWAY: Steroid biosynthesis; sterol biosynthesis.
CC {ECO:0000250|UniProtKB:E9QY26}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Over-expressed in azole-resistant clinical isolates.
CC {ECO:0000269|PubMed:29311090}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EED50354.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EQ963478; EED50354.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_002379130.1; XM_002379089.1.
DR AlphaFoldDB; B8NFL5; -.
DR SMR; B8NFL5; -.
DR STRING; 5059.CADAFLAP00006995; -.
DR EnsemblFungi; EED50354; EED50354; AFLA_131060.
DR eggNOG; KOG0684; Eukaryota.
DR HOGENOM; CLU_001570_15_0_1; -.
DR UniPathway; UPA00766; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
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:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008398; F:sterol 14-demethylase activity; TAS:PHI-base.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-UniPathway.
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; 2.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding;
KW Methyltransferase; Monooxygenase; Oxidoreductase; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..491
FT /note="Sterol 14-alpha demethylase"
FT /id="PRO_0000448947"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 430
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:E9QY26"
FT MUTAGEN 389
FT /note="H->P: Leads to resistance to voriconazole; when
FT associated with N-401."
FT /evidence="ECO:0000269|PubMed:18775650"
FT MUTAGEN 401
FT /note="D->N: Leads to resistance to voriconazole; when
FT associated with P-389."
FT /evidence="ECO:0000269|PubMed:18775650"
FT MUTAGEN 444
FT /note="T->P: Leads to resistance to voriconazole."
FT /evidence="ECO:0000269|PubMed:18775650"
SQ SEQUENCE 491 AA; 55410 MW; B5DDF24AB2E536D2 CRC64;
MGILAVILDS VCERCSGSSL WMLSTVALLS ILVVSVVINV LRQLLFKNYK EPPLVFHWFP
FIGSTISYGM DPYRFFFNCR EKYGDIFTFV LLGKKTTVYL GTKGNDFILN GKLRDVCAEE
VYSPLTTPVF GRHVVYDCPN AKLMEQKKGP NGVFDVCKTI AEITIYTASR SLQGKEVRSR
FDSTFAELYH DLDMGFAPIN FMLPWAPLPH NRKRDAAQKR MTETYMEIIK ERRKAGSKKD
SEDMVWNLMS CMYKDGTPVP DEEIAHMMIA LLMAGQHSSS STAAWIVLHL AASPEITEEL
YQEQLRILGH DMPPLTYENL QKLDLHAKVI KETLRIHAPI HSIIRAVKNP MPVEGTPYVI
PTSHNVLSSP GVTARSEEHF PDPLEWKPHR WDEAIAVSSE DEEKVDYGYG LVTKGTNSPY
LPFGAGRHRC IGEQFAYVQL GAITAALVRL FKFSNLPGVQ TLPDTDYSSL FSKPLGNSKI
QFEKREPVTK A
