CP51A_ASPFN
ID CP51A_ASPFN Reviewed; 513 AA.
AC B8N2C8;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 76.
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 51A {ECO:0000303|PubMed:18775650};
DE AltName: Full=Ergosterol biosynthesis protein cyp51A {ECO:0000303|PubMed:18775650};
GN Name=cyp51A {ECO:0000303|PubMed:18775650}; ORFNames=AFLA_036130;
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 TYR-72; LYS-137 AND THR-469.
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:Q4WNT5, ECO:0000269|PubMed:18775650,
CC 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:Q4WNT5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000250|UniProtKB:Q4WNT5};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q4WNT5};
CC -!- PATHWAY: Steroid biosynthesis; sterol biosynthesis.
CC {ECO:0000250|UniProtKB:Q4WNT5}.
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}.
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DR EMBL; EQ963473; EED56341.1; -; Genomic_DNA.
DR RefSeq; XP_002375123.1; XM_002375082.1.
DR AlphaFoldDB; B8N2C8; -.
DR SMR; B8N2C8; -.
DR STRING; 5059.CADAFLAP00002988; -.
DR EnsemblFungi; EED56341; EED56341; AFLA_036130.
DR VEuPathDB; FungiDB:AFLA_036130; -.
DR eggNOG; KOG0684; Eukaryota.
DR HOGENOM; CLU_001570_15_0_1; -.
DR OMA; FAKWGEN; -.
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; 1.
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; Glycoprotein; Heme; Iron; Membrane; Metal-binding;
KW Methyltransferase; Monooxygenase; Oxidoreductase; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..513
FT /note="Sterol 14-alpha demethylase"
FT /id="PRO_0000448945"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 453
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:Q16850"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 72
FT /note="Y->N: Leads to resistance to voriconazole; when
FT associated with S-469."
FT /evidence="ECO:0000269|PubMed:18775650"
FT MUTAGEN 137
FT /note="K->N: Leads to resistance to voriconazole."
FT /evidence="ECO:0000269|PubMed:18775650"
FT MUTAGEN 469
FT /note="T->S: Leads to resistance to voriconazole; when
FT associated with N-72."
FT /evidence="ECO:0000269|PubMed:18775650"
SQ SEQUENCE 513 AA; 58222 MW; 68769B243C35CF7A CRC64;
MIFSRSMASF TLVSAYAAAG LLAIIVLNLL RQLLFRNKTD PPLVFHWIPF LGSTVTYGMD
PYAFFFSCRQ KYGDIFTFIL LGRKITVYLG IQGNEFILNG KLKDVNAEEI YSPLTTPVFG
SDIVYDCPNS KLMEQKKFIK FGLTQAALES HVPLIEKEVL DYLKTSPNFK GTSGRVEITD
AMAEITIFTA GRALQGEEVR KKLTAEFADL YHDLDRGFTP INFMLPWAPL PRNRKRDAAH
ARMREIYMDI INERRKNPDR ETSDMIWNLM HCTYKNGQPL PDKEIAHMMI TLLMAGQHSS
SSISSWIMLR LASEPAVMEE LYQEQITKLS PDGRTLPPLQ YRDLDLLPLH QNLIKETLRL
HLSIHSLMRK VKNPMPVPGT PYVVPADHVL LASPGVTALS DEYFPNASRW DPHRWENRVE
KEDEEDIVDY GYGTVSKGTS SPYLPFGAGR HRCIGEKFAY VNLGVIVATM ARHMKLFNVD
GKKGVPATDY SSMFSGPSKP AIIGWERRFP EKS
