NCPR_RABIT
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 03-AUG-2022, entry version 152.
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;
CC Evidence={ECO:0000255|HAMAP-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;
CC Evidence={ECO:0000255|HAMAP-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.ENSOCUP00000020921; -.
DR PRIDE; P00389; -.
DR GeneID; 100301554; -.
DR KEGG; ocu:100301554; -.
DR CTD; 5447; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; P00389; -.
DR OrthoDB; 318396at2759; -.
DR BioCyc; MetaCyc:MON-14302; -.
DR Proteomes; UP000001811; Unplaced.
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: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 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 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
