ID   C505_FUSOX              Reviewed;        1066 AA.
AC   Q9Y8G7;
DT   30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 123.
DE   RecName: Full=Bifunctional cytochrome P450/NADPH--P450 reductase {ECO:0000305};
DE   AltName: Full=Cytochrome P450foxy {ECO:0000303|PubMed:11985584};
DE   AltName: Full=Fatty acid omega-hydroxylase;
DE   AltName: Full=P450foxy {ECO:0000303|PubMed:11985584};
DE   Includes:
DE     RecName: Full=Cytochrome P450 505;
DE              EC=1.14.14.1 {ECO:0000269|PubMed:11985584, ECO:0000269|PubMed:8830036};
DE   Includes:
DE     RecName: Full=NADPH--cytochrome P450 reductase;
DE              EC=1.6.2.4 {ECO:0000269|PubMed:11985584, ECO:0000269|PubMed:8830036};
GN   Name=CYP505 {ECO:0000303|PubMed:11985584};
OS   Fusarium oxysporum (Fusarium vascular wilt).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC   Fusarium oxysporum species complex.
OX   NCBI_TaxID=5507;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 82-99; 353-359;
RP   362-380; 518-538; 616-626 AND 1005-1009, AND SUBCELLULAR LOCATION.
RC   STRAIN=MT-811;
RX   PubMed=10995755; DOI=10.1074/jbc.m005617200;
RA   Kitazume T., Takaya N., Nakayama N., Shoun H.;
RT   "Fusarium oxysporum fatty-acid subterminal hydroxylase (CYP505) is a
RT   membrane-bound eukaryotic counterpart of Bacillus megaterium cytochrome
RT   P450BM3.";
RL   J. Biol. Chem. 275:39734-39740(2000).
RN   [2]
RP   FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY,
RP   AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=MT-811;
RX   PubMed=8830036; DOI=10.1093/oxfordjournals.jbchem.a021260;
RA   Nakayama N., Takemae A., Shoun H.;
RT   "Cytochrome P450foxy, a catalytically self-sufficient fatty acid
RT   hydroxylase of the fungus Fusarium oxysporum.";
RL   J. Biochem. 119:435-440(1996).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE SPECIFICITY.
RX   PubMed=11985584; DOI=10.1046/j.1432-1033.2002.02855.x;
RA   Kitazume T., Tanaka A., Takaya N., Nakamura A., Matsuyama S., Suzuki T.,
RA   Shoun H.;
RT   "Kinetic analysis of hydroxylation of saturated fatty acids by recombinant
RT   P450foxy produced by an Escherichia coli expression system.";
RL   Eur. J. Biochem. 269:2075-2082(2002).
CC   -!- FUNCTION: Functions as a fatty acid monooxygenase (PubMed:8830036,
CC       PubMed:11985584). Catalyzes hydroxylation of fatty acids at omega-1,
CC       omega-2 and omega-3 positions (PubMed:11985584). Shows activity toward
CC       fatty acids with a chain length of 9-18 carbons with optimum chain
CC       lengths of 12-14 carbons (lauric, tridecylic and myristic acids)
CC       (PubMed:8830036, PubMed:11985584). Can also use shorter saturated fatty
CC       acids with a chain length of 9 or 10 carbons as substrates
CC       (PubMed:11985584). Also displays a NADPH-dependent reductase activity
CC       in the C-terminal domain, which allows electron transfer from NADPH to
CC       the heme iron of the cytochrome P450 N-terminal domain (PubMed:8830036,
CC       PubMed:11985584). {ECO:0000269|PubMed:11985584,
CC       ECO:0000269|PubMed:8830036}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC         reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:142491; EC=1.14.14.1;
CC         Evidence={ECO:0000269|PubMed:11985584, ECO:0000269|PubMed:8830036};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=NADPH + 2 oxidized [cytochrome P450] = H(+) + NADP(+) + 2
CC         reduced [cytochrome P450]; Xref=Rhea:RHEA:24040, Rhea:RHEA-
CC         COMP:14627, Rhea:RHEA-COMP:14628, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:55376, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:60344; EC=1.6.2.4; Evidence={ECO:0000269|PubMed:11985584,
CC         ECO:0000269|PubMed:8830036};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000269|PubMed:11985584};
CC       Note=Binds 1 FAD. {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210;
CC         Evidence={ECO:0000269|PubMed:11985584};
CC       Note=Binds 1 FMN. {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000269|PubMed:11985584};
CC   -!- ACTIVITY REGULATION: Stimulated NADPH--cytochrome reductase activity in
CC       the presence of substrate. Inhibited by fatty acid substrates longer
CC       than 13 carbons and the degree of inhibition increases with increasing
CC       chain length. {ECO:0000269|PubMed:11985584}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.16 mM for NADH {ECO:0000269|PubMed:8830036};
CC         KM=0.15 mM for laurate {ECO:0000269|PubMed:8830036};
CC         KM=3200 uM for nonanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=260 uM for decanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=160 uM for undecanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=30 uM for laurate/dodecanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=36 uM for tridecanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=19 uM for tetradecanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=8 uM for pentadecanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=10 uM for hexadecanoic acid {ECO:0000269|PubMed:11985584};
CC         KM=74 uM for NADH {ECO:0000269|PubMed:11985584};
CC       pH dependence:
CC         Optimum pH is 6.5. {ECO:0000269|PubMed:8830036};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10995755,
CC       ECO:0000269|PubMed:8830036}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:10995755, ECO:0000269|PubMed:8830036}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the cytochrome P450
CC       family. {ECO:0000305}.
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; AB030037; BAA82526.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q9Y8G7; -.
DR   SMR; Q9Y8G7; -.
DR   VEuPathDB; FungiDB:FOC1_g10006735; -.
DR   VEuPathDB; FungiDB:FOC4_g10006868; -.
DR   VEuPathDB; FungiDB:FOIG_06751; -.
DR   VEuPathDB; FungiDB:FOMG_03037; -.
DR   VEuPathDB; FungiDB:FOXG_04152; -.
DR   VEuPathDB; FungiDB:FOZG_02961; -.
DR   VEuPathDB; FungiDB:HZS61_014270; -.
DR   BRENDA; 1.11.2.4; 2351.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR   GO; GO:0003958; F:NADPH-hemoprotein reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
DR   CDD; cd06206; bifunctional_CYPOR; 1.
DR   CDD; cd11068; CYP120A1; 1.
DR   Gene3D; 3.40.50.360; -; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1.
DR   Gene3D; 2.40.30.10; Translation factors; 1.
DR   InterPro; IPR023206; Bifunctional_P450_P450_red.
DR   InterPro; IPR003097; CysJ-like_FAD-binding.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   InterPro; IPR017927; FAD-bd_FR_type.
DR   InterPro; IPR008254; Flavodoxin/NO_synth.
DR   InterPro; IPR029039; Flavoprotein-like_sf.
DR   InterPro; IPR039261; FNR_nucleotide-bd.
DR   InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR   InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR   InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR   PANTHER; PTHR19384:SF127; BIFUNCTIONAL CYTOCHROME P450_NADPH--P450 REDUCTASE; 1.
DR   PANTHER; PTHR19384; NITRIC OXIDE SYNTHASE-RELATED; 1.
DR   Pfam; PF00667; FAD_binding_1; 1.
DR   Pfam; PF00258; Flavodoxin_1; 1.
DR   Pfam; PF00175; NAD_binding_1; 1.
DR   Pfam; PF00067; p450; 1.
DR   PIRSF; PIRSF000209; Bifunctional_P450_P450R; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1.
DR   SUPFAM; SSF52218; Flavoproteins; 1.
DR   SUPFAM; SSF63380; Riboflavin synthase domain-like; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   PROSITE; PS51384; FAD_FR; 1.
DR   PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Electron transport; FAD; Flavoprotein; FMN;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Multifunctional enzyme;
KW   NADP; Oxidoreductase; Transport.
FT   CHAIN           1..1066
FT                   /note="Bifunctional cytochrome P450/NADPH--P450 reductase"
FT                   /id="PRO_0000052210"
FT   DOMAIN          500..641
FT                   /note="Flavodoxin-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT   DOMAIN          676..904
FT                   /note="FAD-binding FR-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT   REGION          1..480
FT                   /note="Cytochrome P450"
FT   REGION          481..1066
FT                   /note="NADPH-P-450 reductase"
FT   BINDING         407
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:P14779"
FT   BINDING         506..511
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:P14779"
FT   BINDING         554..557
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:P14779"
FT   BINDING         588
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:P14779"
FT   BINDING         596
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000250|UniProtKB:P14779"
FT   SITE            270
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P14779"
SQ   SEQUENCE   1066 AA;  117926 MW;  6B8123698C223DBA CRC64;
     MAESVPIPEP PGYPLIGNLG EFTSNPLSDL NRLADTYGPI FRLRLGAKAP IFVSSNSLIN
     EVCDEKRFKK TLKSVLSQVR EGVHDGLFTA FEDEPNWGKA HRILVPAFGP LSIRGMFPEM
     HDIATQLCMK FARHGPRTPI DTSDNFTRLA LDTLALCAMD FRFYSYYKEE LHPFIEAMGD
     FLTESGNRNR RPPFAPNFLY RAANEKFYGD IALMKSVADE VVAARKASPS DRKDLLAAML
     NGVDPQTGEK LSDENITNQL ITFLIAGHET TSGTLSFAMY QLLKNPEAYS KVQKEVDEVV
     GRGPVLVEHL TKLPYISAVL RETLRLNSPI TAFGLEAIDD TFLGGKYLVK KGEIVTALLS
     RGHVDPVVYG NDADKFIPER MLDDEFARLN KEYPNCWKPF GNGKRACIGR PFAWQESLLA
     MVVLFQNFNF TMTDPNYALE IKQTLTIKPD HFYINATLRH GMTPTELEHV LAGNGATSSS
     THNIKAAANL DAKAGSGKPM AIFYGSNSGT CEALANRLAS DAPSHGFSAT TVGPLDQAKQ
     NLPEDRPVVI VTASYEGQPP SNAAHFIKWM EDLDGNDMEK VSYAVFACGH HDWVETFHRI
     PKLVDSTLEK RGGTRLVPMG SADAATSDMF SDFEAWEDIV LWPGLKEKYK ISDEESGGQK
     GLLVEVSTPR KTSLRQDVEE ALVVAEKTLT KSGPAKKHIE IQLPSAMTYK AGDYLAILPL
     NPKSTVARVF RRFSLAWDSF LKIQSEGPTT LPTNVAISAF DVFSAYVELS QPATKRNILA
     LAEATEDKDT IQELERLAGD AYQAEISPKR VSVLDLLEKF PAVALPISSY LAMLPPMRVR
     QYSISSSPFA DPSKLTLTYS LLDAPSLSGQ GRHVGVATNF LSHLTAGDKL HVSVRASSEA
     FHLPSDAEKT PIICVAAGTG LAPLRGFIQE RAAMLAAGRT LAPALLFFGC RNPEIDDLYA
     EEFERWEKMG AVDVRRAYSR ATDKSEGCKY VQDRVYHDRA DVFKVWDQGA KVFICGSREI
     GKAVEDVCVR LAIEKAQQNG RDVTEEMARA WFERSRNERF ATDVFD
//