NCPR_ASPNG
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 03-AUG-2022, entry version 132.
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;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03212,
CC ECO:0000269|PubMed:11594739, 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;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03212,
CC ECO:0000269|PubMed:11594739, 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 STRING; 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.40.50.80; -; 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 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; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 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
