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-MAY-2023, entry version 95.
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   OrthoDB; 5471423at2759; -.
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   PANTHER; PTHR10204; NAD P H OXIDOREDUCTASE-RELATED; 1.
DR   PANTHER; PTHR10204:SF1; NAD(P)H DEHYDROGENASE [QUINONE] 1; 1.
DR   Pfam; PF02525; Flavodoxin_2; 1.
DR   SUPFAM; SSF52218; Flavoproteins; 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
//