ID   NCPR_ASPFU              Reviewed;         695 AA.
AC   Q4WM67;
DT   08-FEB-2011, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 1.
DT   24-JAN-2024, entry version 106.
DE   RecName: Full=NADPH--cytochrome P450 reductase {ECO:0000255|HAMAP-Rule:MF_03212};
DE            Short=CPR {ECO:0000255|HAMAP-Rule:MF_03212};
DE            Short=P450R {ECO:0000255|HAMAP-Rule:MF_03212};
DE            EC=1.6.2.4 {ECO:0000255|HAMAP-Rule:MF_03212};
GN   Name=cprA {ECO:0000255|HAMAP-Rule:MF_03212}; ORFNames=AFUA_6G10990;
OS   Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 /
OS   Af293) (Neosartorya fumigata).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Fumigati.
OX   NCBI_TaxID=330879;
RN   [1] {ECO:0000312|EMBL:EAL88947.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293;
RX   PubMed=16372009; DOI=10.1038/nature04332;
RA   Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA   Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA   Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA   Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA   Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA   Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA   Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA   Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA   Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA   Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA   O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA   Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA   Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA   Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA   Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA   Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA   Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA   Barrell B.G., Denning D.W.;
RT   "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT   Aspergillus fumigatus.";
RL   Nature 438:1151-1156(2005).
RN   [2] {ECO:0000305}
RP   CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=8912168;
RA   Baillie G.S., Hitchcock C.A., Burnet F.R.;
RT   "Increased cytochrome P-450 activity in Aspergillus fumigatus after
RT   xenobiotic exposure.";
RL   J. Med. Vet. Mycol. 34:341-347(1996).
CC   -!- FUNCTION: This enzyme is required for electron transfer from NADP to
CC       cytochrome P450 in microsomes. It can also provide electron transfer to
CC       heme oxygenase and cytochrome B5. Involved in ergosterol biosynthesis.
CC       {ECO:0000255|HAMAP-Rule:MF_03212}.
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:0000255|HAMAP-
CC         Rule:MF_03212, ECO:0000269|PubMed:8912168};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03212};
CC       Note=Binds 1 FAD per monomer. {ECO:0000255|HAMAP-Rule:MF_03212};
CC   -!- COFACTOR:
CC       Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03212};
CC       Note=Binds 1 FMN per monomer. {ECO:0000255|HAMAP-Rule:MF_03212};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000255|HAMAP-Rule:MF_03212}; Single-pass membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_03212}; Cytoplasmic side {ECO:0000255|HAMAP-
CC       Rule:MF_03212}. Mitochondrion outer membrane {ECO:0000255|HAMAP-
CC       Rule:MF_03212}; Single-pass membrane protein {ECO:0000255|HAMAP-
CC       Rule:MF_03212}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_03212}.
CC       Cell membrane {ECO:0000255|HAMAP-Rule:MF_03212}; Single-pass membrane
CC       protein {ECO:0000255|HAMAP-Rule:MF_03212}; Cytoplasmic side
CC       {ECO:0000255|HAMAP-Rule:MF_03212}.
CC   -!- SIMILARITY: Belongs to the NADPH--cytochrome P450 reductase family.
CC       {ECO:0000255|HAMAP-Rule:MF_03212}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the flavodoxin
CC       family. {ECO:0000255|HAMAP-Rule:MF_03212}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the flavoprotein
CC       pyridine nucleotide cytochrome reductase family. {ECO:0000255|HAMAP-
CC       Rule:MF_03212}.
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DR   EMBL; AAHF01000006; EAL88947.1; -; Genomic_DNA.
DR   RefSeq; XP_750985.1; XM_745892.1.
DR   AlphaFoldDB; Q4WM67; -.
DR   SMR; Q4WM67; -.
DR   STRING; 330879.Q4WM67; -.
DR   EnsemblFungi; EAL88947; EAL88947; AFUA_6G10990.
DR   GeneID; 3508290; -.
DR   KEGG; afm:AFUA_6G10990; -.
DR   VEuPathDB; FungiDB:Afu6g10990; -.
DR   eggNOG; KOG1158; Eukaryota.
DR   HOGENOM; CLU_001570_17_3_1; -.
DR   InParanoid; Q4WM67; -.
DR   OMA; QKRYQRD; -.
DR   OrthoDB; 2786000at2759; -.
DR   Proteomes; UP000002530; Chromosome 6.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR   GO; GO:0010181; F:FMN binding; IBA:GO_Central.
DR   GO; GO:0050661; F:NADP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003958; F:NADPH-hemoprotein reductase activity; IBA:GO_Central.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IEA:UniProtKB-UniRule.
DR   CDD; cd06204; CYPOR; 1.
DR   Gene3D; 3.40.50.360; -; 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   HAMAP; MF_03212; NCPR; 1.
DR   InterPro; IPR003097; CysJ-like_FAD-binding.
DR   InterPro; IPR017927; FAD-bd_FR_type.
DR   InterPro; IPR001094; Flavdoxin-like.
DR   InterPro; IPR008254; Flavodoxin/NO_synth.
DR   InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
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; IPR023208; P450R.
DR   InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR   PANTHER; PTHR19384:SF17; NADPH--CYTOCHROME 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   PIRSF; PIRSF000208; P450R; 1.
DR   PRINTS; PR00369; FLAVODOXIN.
DR   PRINTS; PR00371; FPNCR.
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; PS51384; FAD_FR; 1.
DR   PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Endoplasmic reticulum; FAD; Flavoprotein; FMN;
KW   Lipid biosynthesis; Lipid metabolism; Membrane; Mitochondrion;
KW   Mitochondrion outer membrane; NADP; Oxidoreductase; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transmembrane; Transmembrane helix.
FT   CHAIN           1..695
FT                   /note="NADPH--cytochrome P450 reductase"
FT                   /id="PRO_0000404329"
FT   TOPO_DOM        1..8
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   TRANSMEM        9..31
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   TOPO_DOM        32..695
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   DOMAIN          66..221
FT                   /note="Flavodoxin-like"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   DOMAIN          277..538
FT                   /note="FAD-binding FR-type"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         72..77
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         123..126
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         169..178
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         204
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         296
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         451..454
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         469..471
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         486..489
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         552
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         614..615
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         620..624
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         656
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         694
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
SQ   SEQUENCE   695 AA;  76783 MW;  AB6C6208F70E9112 CRC64;
     MAQLDTLDIV VLVVLLVGSV AYFTKGSYWA VPKDPYAAAN SAMNGAAKTG KTRDIIQKME
     ETGKNCVIFY GSQTGTAEDY ASRLAKEGSQ RFGLKTMVAD LEDYDYENLD KFPEDKIAFF
     VLATYGEGEP TDNAVEFYQF ITGEDVAFES GASAEEKPLS SLKYVAFGLG NNTYEHYNAM
     VRHVDAALTK LGAQRIGTAG EGDDGAGTME EDFLAWKEPM WAALSESMNL QEREAVYEPV
     FSVIEDESLS PEDDSVYLGE PTQGHLSGSP KGPYSAHNPY IAPIVESREL FTAKDRNCLH
     MEIGIAGSNL TYQTGDHIAI WPTNAGVEVD RFLEVFGIEK KRHTVINIKG LDVTAKVPIP
     TPTTYDAAVR FYMEICAPVS RQFVSSLVPF APDEESKAEI VRLGNDKDYF HEKISNQCFN
     IAQALQNITS KPFSAVPFSL LIEGLNRLQP RYYSISSSSL VQKDKISITA VVESVRLPGA
     SHIVKGVTTN YLLALKQKQN GDPSPDPHGL TYAITGPRNK YDGIHVPVHV RHSNFKLPSD
     PSKPIIMVGP GTGVAPFRGF IQERAALAES GKDVGPTILF FGCRNRNEDF LYKEEWKVYQ
     EKLGDKLKII TAFSRETAKK VYVQHRLQEH ADLVSDLLKQ KATFYVCGDA ANMAREVNLV
     LGQIIAKSRG LPAEKGEEMV KHMRSSGSYQ EDVWS
//