ID   NCPR_ASPNG              Reviewed;         694 AA.
AC   Q00141;
DT   01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   08-FEB-2011, sequence version 2.
DT   24-JAN-2024, entry version 137.
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};
OS   Aspergillus niger.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=5061 {ECO:0000312|EMBL:CAA81550.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, AND INDUCTION.
RC   STRAIN=ATCC 9029 / NRRL 3 / CBS 120.49 / DSM 2466 / N400 / FGSC 732;
RX   PubMed=7646819; DOI=10.1089/dna.1995.14.719;
RA   van den Brink H.J.M., van Zeijl C.M.J., Brons J.F.,
RA   van den Hondel C.A.M.J.J., van Gorcom R.F.M.;
RT   "Cloning and characterization of the NADPH cytochrome P450 oxidoreductase
RT   gene from the filamentous fungus Aspergillus niger.";
RL   DNA Cell Biol. 14:719-729(1995).
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] {ECO:0000305}
RP   CATALYTIC ACTIVITY.
RC   STRAIN=T18.5;
RX   PubMed=11594739; DOI=10.1006/abbi.2001.2534;
RA   Faber B.W., van Gorcom R.F.M., Duine J.A.;
RT   "Purification and characterization of benzoate-para-hydroxylase, a
RT   cytochrome P450 (CYP53A1), from Aspergillus niger.";
RL   Arch. Biochem. Biophys. 394:245-254(2001).
RN   [4]
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, ECO:0000269|PubMed:11594739,
CC         ECO:0000269|PubMed:7646819};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03212, ECO:0000269|PubMed:11594739,
CC         ECO:0000269|PubMed:7646819};
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, ECO:0000269|PubMed:11594739,
CC         ECO:0000269|PubMed:7646819};
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:7646819, PubMed:10852481, Ref.4). Expression regulation is
CC       particularly complex, involving regulatory promoter elements,
CC       differential promoter use and regulation at the post-transcriptional
CC       level (PubMed:10852481). {ECO:0000269|PubMed:10852481,
CC       ECO:0000269|PubMed:7646819, ECO:0000269|Ref.4}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA81550.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; Z26938; CAA81550.1; ALT_FRAME; Genomic_DNA.
DR   PIR; S38427; S38427.
DR   AlphaFoldDB; Q00141; -.
DR   SMR; Q00141; -.
DR   PaxDb; 5061-CADANGAP00006979; -.
DR   VEuPathDB; FungiDB:An08g07840; -.
DR   VEuPathDB; FungiDB:ASPNIDRAFT2_1148233; -.
DR   VEuPathDB; FungiDB:ATCC64974_100340; -.
DR   VEuPathDB; FungiDB:M747DRAFT_344448; -.
DR   eggNOG; KOG1158; Eukaryota.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0009055; F:electron transfer activity; IDA:UniProtKB.
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:0016491; F:oxidoreductase activity; IDA:UniProtKB.
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; Steroid biosynthesis;
KW   Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..694
FT                   /note="NADPH--cytochrome P450 reductase"
FT                   /id="PRO_0000167604"
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..694
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   DOMAIN          66..220
FT                   /note="Flavodoxin-like"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   DOMAIN          276..537
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         168..177
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         203
FT                   /ligand="FMN"
FT                   /ligand_id="ChEBI:CHEBI:58210"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         295
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         450..453
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         468..470
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         485..488
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         551
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         613..614
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         619..623
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         655
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT   BINDING         693
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
SQ   SEQUENCE   694 AA;  76807 MW;  BA3E7867ACB1D810 CRC64;
     MAQLDTLDLV VLAVLLVGSV AYFTKGTYWA VAKDPYASTG PAMNGAAKAG KTRNIIEKME
     ETGKNCVIFY GSQTGTAEDY ASRLAKEGSQ RFGLKTMVAD LEEYDYENLD QFPEDKVAFF
     VLATYGEGEP TDNAVEFYQF FTGDDVAFES ASADEKPLSK LKYVAFGLGN NTYEHYNAMV
     RQVDAAFQKL GPQRIGSAGE GDDGAGTMEE DFLAWKEPMW AALSESMDLE EREAVYEPVF
     CVTENESLSP EDETVYLGEP TQSHLQGTPK GPYSAHNPFI APIAESRELF TVKDRNCLHM
     EISIAGSNLS YQTGDHIAVW PTNAGAEVDR FLQVFGLEGK RDSVINIKGI DVTAKVPIPT
     PTTYDAAVRY YMEVCAPVSR QFVATLAAFA PDEESKAEIV RLGSHKDYFH EKVTNQCFNM
     AQALQSITSK PFSAVPFSLL IEGITKLQPR YYSISSSSLV QKDKISITAV VESVRLPGAS
     HMVKGVTTNY LLALKQKQNG DPSPDPHGLT YSITGPRNKY DGIHVPVHVR HSNFKLPSDP
     SRPIIMVGPG TGVAPFRGFI QERAALAAKG EKVGPTVLFF GCRKSDEDFL YKDEWKTYQD
     QLGDNLKIIT AFSREGPQKV YVQHRLREHS ELVSDLLKQK ATFYVCGDAA NMAREVNLVL
     GQIIAAQRGL PAEKGEEMVK HMRRRGRYQE DVWS
//