ID   NCPR_ASPNC              Reviewed;         695 AA.
AC   A2QS05;
DT   08-FEB-2011, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   27-MAR-2024, entry version 91.
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=An08g07840;
OS   Aspergillus niger (strain ATCC MYA-4892 / CBS 513.88 / FGSC A1513).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=425011;
RN   [1] {ECO:0000312|EMBL:CAK45677.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC MYA-4892 / CBS 513.88 / FGSC A1513;
RX   PubMed=17259976; DOI=10.1038/nbt1282;
RA   Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA   Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA   Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA   Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA   Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA   d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA   Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA   van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA   Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA   van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA   Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA   Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA   Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA   Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT   "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT   niger CBS 513.88.";
RL   Nat. Biotechnol. 25:221-231(2007).
RN   [2]
RP   INDUCTION.
RX   PubMed=10852481; DOI=10.1007/s004380051207;
RA   van den Brink J.M., Punt P.J., van Gorcom R.F., van den Hondel C.A.;
RT   "Regulation of expression of the Aspergillus niger benzoate para-
RT   hydroxylase cytochrome P450 system.";
RL   Mol. Gen. Genet. 263:601-609(2000).
RN   [3]
RP   INDUCTION.
RX   DOI=10.1021/acssuschemeng.9b04918;
RA   Lubbers R.J.M., Dilokpimol A., Peng M., Visser J., Makela M.R.,
RA   Hilden K.S., de Vries R.P.;
RT   "Discovery of novel p-hydroxybenzoate-m-hydroxylase, protocatechuate 3,4
RT   ring-cleavage dioxygenase, and hydroxyquinol 1,2 ring-cleavage dioxygenase
RT   from the filamentous fungus Aspergillus niger.";
RL   ACS Sustain. Chem. Eng. 7:19081-19089(2019).
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};
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   -!- INDUCTION: Expression is induced in the presence of benzoic acid
CC       (PubMed:10852481, Ref.3). Expression regulation is particularly
CC       complex, involving regulatory promoter elements, differential promoter
CC       use and regulation at the post-transcriptional level (PubMed:10852481).
CC       {ECO:0000269|PubMed:10852481, ECO:0000269|Ref.3}.
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; AM270176; CAK45677.1; -; Genomic_DNA.
DR   RefSeq; XP_001392901.1; XM_001392864.2.
DR   AlphaFoldDB; A2QS05; -.
DR   SMR; A2QS05; -.
DR   GeneID; 4983103; -.
DR   KEGG; ang:An08g07840; -.
DR   VEuPathDB; FungiDB:An08g07840; -.
DR   HOGENOM; CLU_001570_17_3_1; -.
DR   OrthoDB; 2786000at2759; -.
DR   Proteomes; UP000006706; Chromosome 8R.
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; IEA:UniProtKB-UniRule.
DR   GO; GO:0010181; F:FMN binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0050661; F:NADP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003958; F:NADPH-hemoprotein reductase activity; IEA:UniProtKB-UniRule.
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   2: Evidence at transcript 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_5000220324"
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;  76589 MW;  835324930A8A62F3 CRC64;
     MAQLDTLDLV VLAVLLVGSV AYFTKGTYWA VAKDPYASTG PAMNGAAKAG KTRNIIEKME
     ETGKNCVIFY GSQTGTAEDY ASRLAKEGSQ RFGLKTMVAD LEEYDYENLD QFPEDKVAFF
     VLATYGEGEP TDNAVEFYQF FTGDDVAFES GASADEKPLS KLKYVAFGLG NNTYEHYNAM
     VRQVDAAFQK LGAQRIGSAG EGDDGAGTME EDFLAWKEPM WAALSESMDL QEREAVYEPV
     FCVTENESLS PEDETVYLGE PTQSHLQGTP KGPYSAHNPF IAPIAESREL FTVKDRNCLH
     MEISIAGSNL SYQTGDHIAV WPTNAGAEVD RFLQVFGLEG KRDSVINIKG IDVTAKVPIP
     TPTTYDAAVR YYMEVCAPVS RQFVATLAAF APDEESKAEI VRLGSDKDYF HEKVTNQCFN
     IAQALQSITS KPFSAVPFSL LIEGITKLQP RYYSISSSSL VQKDKISITA VVESVRLPGA
     SHMVKGVTTN YLLALKQKQN GDPSPDPHGL TYSITGPRNK YDGIHVPVHV RHSNFKLPSD
     PSRPIIMVGP GTGVAPFRGF IQERAALAAK GEKVGPTVLF FGCRKSDEDF LYKDEWKTYQ
     DQLGDNLKII TAFSREGPQK VYVQHRLREH SELVSDLLKQ KATFYVCGDA ANMAREVNLV
     LGQIIAAQRG LPAEKGEEMV KHMRSSGSYQ EDVWS
//