NQO1_CAVPO
ID NQO1_CAVPO Reviewed; 275 AA.
AC Q8CHK7;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=NAD(P)H dehydrogenase [quinone] 1;
DE EC=1.6.5.2 {ECO:0000250|UniProtKB:P15559};
DE AltName: Full=Azoreductase;
DE AltName: Full=DT-diaphorase {ECO:0000250|UniProtKB:P15559};
DE Short=DTD;
DE AltName: Full=Menadione reductase;
DE AltName: Full=NAD(P)H:quinone oxidoreductase 1 {ECO:0000250|UniProtKB:P15559};
DE AltName: Full=Phylloquinone reductase;
DE AltName: Full=Quinone reductase 1;
DE Short=QR1;
GN Name=NQO1;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Hartley;
RA Itoh K., Takahashi Y., Kitagawa M., Kamataki T.;
RT "Inhibition of the transcription of the guinea pig NAD(P)H: quinone
RT oxidoreductase1 (NQO1) gene by specificity protein 1 (Sp1).";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Flavin-containing quinone reductase that catalyzes two-
CC electron reduction of quinones to hydroquinones using either NADH or
CC NADPH as electron donors. In a ping-pong kinetic mechanism, the
CC electrons are sequentially transferred from NAD(P)H to flavin cofactor
CC and then from reduced flavin to the quinone, bypassing the formation of
CC semiquinone and reactive oxygen species (By similarity). Regulates
CC cellular redox state primarily through quinone detoxification. Reduces
CC components of plasma membrane redox system such as coenzyme Q and
CC vitamin quinones, producing antioxidant hydroquinone forms. In the
CC process may function as superoxide scavenger to prevent hydroquinone
CC oxidation and facilitate excretion (By similarity). Alternatively, can
CC activate quinones and their derivatives by generating redox reactive
CC hydroquinones with DNA cross-linking antitumor potential (By
CC similarity). Acts as a gatekeeper of the core 20S proteasome known to
CC degrade proteins with unstructured regions. Upon oxidative stress,
CC interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way
CC and inhibits their ubiquitin-independent degradation by the 20S
CC proteasome (By similarity). {ECO:0000250|UniProtKB:P05982,
CC ECO:0000250|UniProtKB:P15559}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADH = a quinol + NAD(+);
CC Xref=Rhea:RHEA:46160, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132124; EC=1.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46161;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADPH = a quinol + NADP(+);
CC Xref=Rhea:RHEA:46164, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132124; EC=1.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46165;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADH + ubiquinone-10 = NAD(+) + ubiquinol-10;
CC Xref=Rhea:RHEA:61984, ChEBI:CHEBI:15378, ChEBI:CHEBI:46245,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:64183;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61985;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + menadione + NADH = menadiol + NAD(+);
CC Xref=Rhea:RHEA:69695, ChEBI:CHEBI:6746, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28869, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69696;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- SUBUNIT: Homodimer. Interacts with PDLIM4 isoform 2; this interaction
CC stabilizes PDLIM4 isoform 2 in response to oxidative stress and
CC protects it from ubiquitin-independent degradation by the core 20S
CC proteasome. Interacts with TP73 (via SAM domain); this interaction is
CC NADH-dependent, stabilizes TP73 in response to oxidative stress and
CC protects it from ubiquitin-independent degradation by the 20S
CC proteasome. Interacts with TP53; this interaction is NADH-dependent,
CC stabilizes TP53 in response to oxidative stress and protects it from
CC ubiquitin-independent degradation by the 20S proteasome.
CC {ECO:0000250|UniProtKB:P15559}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P05982}.
CC -!- SIMILARITY: Belongs to the NAD(P)H dehydrogenase (quinone) family.
CC {ECO:0000305}.
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DR EMBL; AB055403; BAC53985.1; -; mRNA.
DR RefSeq; NP_001166457.1; NM_001172986.1.
DR AlphaFoldDB; Q8CHK7; -.
DR SMR; Q8CHK7; -.
DR STRING; 10141.ENSCPOP00000011185; -.
DR GeneID; 100135582; -.
DR KEGG; cpoc:100135582; -.
DR CTD; 1728; -.
DR eggNOG; ENOG502QQMI; Eukaryota.
DR HOGENOM; CLU_058643_2_0_1; -.
DR InParanoid; Q8CHK7; -.
DR OMA; WFERVLV; -.
DR OrthoDB; 1394543at2759; -.
DR TreeFam; TF300296; -.
DR BRENDA; 1.6.5.2; 1225.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0050136; F:NADH dehydrogenase (quinone) activity; ISS:UniProtKB.
DR GO; GO:0008753; F:NADPH dehydrogenase (quinone) activity; IEA:RHEA.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0019430; P:removal of superoxide radicals; ISS:UniProtKB.
DR GO; GO:0006743; P:ubiquinone metabolic process; ISS:UniProtKB.
DR GO; GO:0042360; P:vitamin E metabolic process; ISS:UniProtKB.
DR GO; GO:0042373; P:vitamin K metabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.50.360; -; 1.
DR InterPro; IPR003680; Flavodoxin_fold.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR Pfam; PF02525; Flavodoxin_2; 1.
DR SUPFAM; SSF52218; SSF52218; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; FAD; Flavoprotein; Isopeptide bond; NAD; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..275
FT /note="NAD(P)H dehydrogenase [quinone] 1"
FT /id="PRO_0000071621"
FT REGION 226..275
FT /note="Important for apoenzyme conformational stability"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 13
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q64669"
FT BINDING 19..20
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q64669"
FT BINDING 68
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q64669"
FT BINDING 105..108
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q64669"
FT BINDING 127..129
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 149..152
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q64669"
FT BINDING 157
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q64669"
FT BINDING 202
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q64669"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT CROSSLNK 252
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P15559"
SQ SEQUENCE 275 AA; 31086 MW; 15C475E39A7176C0 CRC64;
MAALRRALII LAHSEKTSFN YAMKEAAVEA LQRKGWEVAV SDLYAMKFDP IISRKDITGA
LKDPENFQYP AESALAYKES RLSPDIVTEQ KKVEEADLLI FQFPLQWFGV PAILKGWFER
VFTGGFAYTY AAMYDKGPFQ NKKAVLSITT GGSESMYSLK GIHGDMNIIL WPIQSGTLHF
CGFQVLEPQL TYGIGHTPPD VRTEILAGWK KRLENIWDET PLYFAPSSLF DLNFQAGFLL
KKEIEDEQKN NKYGLSVGHH LGKPIPTDNQ IKARK
