NQO1_PONAB
ID NQO1_PONAB Reviewed; 274 AA.
AC Q5RD31;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 94.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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; CR858087; CAH90326.1; -; mRNA.
DR RefSeq; NP_001125152.1; NM_001131680.1.
DR AlphaFoldDB; Q5RD31; -.
DR SMR; Q5RD31; -.
DR STRING; 9601.ENSPPYP00000008478; -.
DR Ensembl; ENSPPYT00000036450; ENSPPYP00000034498; ENSPPYG00000007508.
DR GeneID; 100172039; -.
DR KEGG; pon:100172039; -.
DR CTD; 1728; -.
DR eggNOG; ENOG502QQMI; Eukaryota.
DR GeneTree; ENSGT00940000159150; -.
DR HOGENOM; CLU_058643_2_0_1; -.
DR InParanoid; Q5RD31; -.
DR OMA; WFERVLV; -.
DR OrthoDB; 1394543at2759; -.
DR TreeFam; TF300296; -.
DR Proteomes; UP000001595; Chromosome 16.
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..274
FT /note="NAD(P)H dehydrogenase [quinone] 1"
FT /id="PRO_0000071624"
FT REGION 225..274
FT /note="Important for apoenzyme conformational stability"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 12
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 18..19
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 67
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 104..107
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 126..128
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 148..151
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 156
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 201
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT CROSSLNK 250
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT CROSSLNK 251
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P15559"
SQ SEQUENCE 274 AA; 30940 MW; 87588D65B8E92A67 CRC64;
MVGRRALIVL AHSERTSFNY AMKEAAVAAL KKKGWEVVES DLYAMNFNPI ISRKDITGKL
KDPENFQYPA ESVLAYKEGH LSPDIVAEQK KLEAADLVIF QFPLQWFGVP AILKGWFERV
FVGEFAYTYA AMYDKGPFRS KKAVLSITTG GSGSMYSLQG IHGDMNVILW PIQSGILHFC
GFQVLEPQLT YSIGHTPADA RIQILEGWKK RLENIWDETP LYFAPSSLFD LNFQAGFLMK
KEVQDEEKNK KFGLSVGHHL GKSIPTDNQI KARK
