ID NCPR_RABIT Reviewed; 679 AA. AC P00389; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 24-JAN-2024, entry version 157. 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=POR {ECO:0000255|HAMAP-Rule:MF_03212}; OS Oryctolagus cuniculus (Rabbit). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus. OX NCBI_TaxID=9986; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=3029050; DOI=10.1093/oxfordjournals.jbchem.a121807; RA Katagiri M., Murakami H., Yabusaki Y., Sugiyama T., Okamoto M., Yamano T., RA Ohkawa H.; RT "Molecular cloning and sequence analysis of full-length cDNA for rabbit RT liver NADPH-cytochrome P-450 reductase mRNA."; RL J. Biochem. 100:945-954(1986). RN [2] RP PROTEIN SEQUENCE OF 12-81. RC TISSUE=Liver; RX PubMed=6802823; DOI=10.1016/s0021-9258(19)83868-1; RA Black S.D., Coon M.J.; RT "Structural features of liver microsomal NADPH-cytochrome P-450 reductase. RT Hydrophobic domain, hydrophilic domain, and connecting region."; RL J. Biol. Chem. 257:5929-5938(1982). 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. {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}. 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 --------------------------------------------------------------------------- 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; D00101; BAA00063.1; -; mRNA. DR EMBL; X04610; CAA28279.1; -; mRNA. DR PIR; A25505; A25505. DR RefSeq; NP_001153762.1; NM_001160290.1. DR AlphaFoldDB; P00389; -. DR SMR; P00389; -. DR STRING; 9986.ENSOCUP00000040187; -. DR PaxDb; 9986-ENSOCUP00000020921; -. DR GeneID; 100301554; -. DR KEGG; ocu:100301554; -. DR CTD; 5447; -. DR eggNOG; KOG1158; Eukaryota. DR InParanoid; P00389; -. DR OrthoDB; 276396at2759; -. DR BioCyc; MetaCyc:MONOMER-14302; -. DR Proteomes; UP000001811; Unplaced. DR GO; GO:0005789; C:endoplasmic reticulum 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 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 Direct protein sequencing; Endoplasmic reticulum; FAD; Flavoprotein; FMN; KW Membrane; NADP; Oxidoreductase; Phosphoprotein; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..679 FT /note="NADPH--cytochrome P450 reductase" FT /id="PRO_0000167599" FT TOPO_DOM 1..21 FT /note="Lumenal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT TRANSMEM 22..42 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT TOPO_DOM 43..679 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT DOMAIN 81..225 FT /note="Flavodoxin-like" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT DOMAIN 280..522 FT /note="FAD-binding FR-type" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 87..92 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 139..142 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 174..183 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 209 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 299 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 425 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 455..458 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 473..475 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 479 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 489..492 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 536 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 597..598 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 603..607 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 640 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT BINDING 678 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212" FT MOD_RES 64 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P16435" FT CONFLICT 40..41 FT /note="YW -> NY (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 53 FT /note="E -> N (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 679 AA; 76588 MW; B1A163FA53A5988B CRC64; MADSHGDTGA TMPEAAAQEA SVFSMTDVVL FSLIVGLITY WFLFRKKKEE VPEFTKIQAP TSSSVKESSF VEKMKKTGRN IVVFYGSQTG TAEEFANRLS KDAHRYGMRG MAADPEEYDL ADLSSLPEIN NALAVFCMAT YGEGDPTDNA QDFYDWLQET DVDLSGVKYA VFGLGNKTYE HFNAMGKYVD QRLEQLGAQR IFELGMGDDD ANLEEDFITW REQFWPAVCE HFGVEATGEE SSIRQYELVL HTDIDVAKVY QGEMGRLKSY ENQKPPFDAK NPFLATVTTN RKLNQGTERH LMHLELDISD SKIRYESGDH VAVYPANDSA LVNQLGEILG ADLDVVMSLN NLDEESNKKH PFPCPTSYRT ALTYYLDITN PPRTNVLYEL AQYAADPAEQ EQLRKMASSS GEGKELYLSW VVEARRHILA ILQDYPSLRP PIDHLCELLP RLQARYYSIA SSSKVHPNSV HICAVAVEYE TKAGRLNKGV ATSWLRAKEP AGENGGRALV PMFVRKSQFR LPFKATTPVI MVGPGTGVAP FIGFIQERAW LRQQGKEVGE TLLYYGCRRA AEDYLYREEL AGFQKDGTLS QLNVAFSREQ AQKVYVQHLL RRDKEHLWRL IHEGGAHIYV CGDARNMARD VQNTFYDIVA ELGAMEHAQA VDYVKKLMTK GRYSLDVWS //