P05982 · NQO1_RAT
- ProteinNAD(P)H dehydrogenase [quinone] 1
- GeneNqo1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids274 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons are sequentially transferred from NAD(P)H to flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species (PubMed:1703398, PubMed:7862630, PubMed:8999809).
Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion (By similarity).
Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential (By similarity).
Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome (By similarity).
Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion (By similarity).
Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential (By similarity).
Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome (By similarity).
Miscellaneous
Quinone reductase accepts electrons from both NADH and NADPH with equal efficiency.
This protein is inhibited by dicoumarol.
Catalytic activity
- a quinone + H+ + NADH = a quinol + NAD+This reaction proceeds in the forward direction.
- H+ + NADH + ubiquinone-10 = NAD+ + ubiquinol-10This reaction proceeds in the forward direction.
- H+ + menadione + NADH = menadiol + NAD+This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
85 μM | NADH | |||||
39 μM | NADPH | |||||
110 μM | NADH | |||||
2.5 μM | menadione | |||||
840 μM | 5-(aziridin-1-yl)-2,4-dinitrobenzamide |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
2400 μmol/min/mg | toward menadione | ||||
140 nmol/min/mg | toward 5-(aziridin-1-yl)-2,4-dinitrobenzamide |
kcat is 0.075 min-1 NADH with as substrate. kcat is 0.074 min-1 with NADPH as substrate.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 12 | FAD (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 18-19 | FAD (UniProtKB | ChEBI) | ||||
Sequence: FN | ||||||
Binding site | 67 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 104-107 | FAD (UniProtKB | ChEBI) | ||||
Sequence: LYWF | ||||||
Binding site | 126-128 | substrate | ||||
Sequence: AYT | ||||||
Binding site | 148-151 | FAD (UniProtKB | ChEBI) | ||||
Sequence: TTGG | ||||||
Binding site | 156 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 201 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNAD(P)H dehydrogenase [quinone] 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP05982
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 105 | Decreases the catalytic efficiency toward menadione and nitrobenzene substrates. | ||||
Sequence: Y → Q | ||||||
Mutagenesis | 117-118 | Destroys enzyme activity. | ||||
Sequence: FE → KK | ||||||
Mutagenesis | 131 | Decreases the catalytic efficiency toward menadione. Has no effect on the catalytic efficiency toward nitrobenzene substrate. | ||||
Sequence: T → A | ||||||
Mutagenesis | 161 | Destroys enzyme activity. | ||||
Sequence: V → D | ||||||
Mutagenesis | 164 | Destroys enzyme activity. | ||||
Sequence: D → Q | ||||||
Mutagenesis | 195 | Induces a very low catalytic efficiency. | ||||
Sequence: H → A | ||||||
Mutagenesis | 204 | Has no effect on the catalytic efficiency toward menadione and nitrobenzene substrates. | ||||
Sequence: V → I | ||||||
Mutagenesis | 219 | Has no effect on the catalytic efficiency toward menadione and nitrobenzene substrates. | ||||
Sequence: S → T | ||||||
Mutagenesis | 239 | Has no effect on the catalytic efficiency toward menadione. Slightly decreases the catalytic efficiency toward nitrobenzene substrate. | ||||
Sequence: L → M |
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000071625 | 2-274 | NAD(P)H dehydrogenase [quinone] 1 | |||
Sequence: AVRRALIVLAHAERTSFNYAMKEAAVEALKKKGWEVVESDLYAMNFNPLISRNDITGEPKDSENFQYPVESSLAYKEGRLSPDIVAEQKKLEAADLVIFQFPLYWFGVPAILKGWFERVLVAGFAYTYATMYDKGPFQNKKTLLSITTGGSGSMYSLQGVHGDMNVILWPIQSGILRFCGFQVLEPQLVYSIGHTPPDARVQVLEGWKKRLETVWEESPLYFAPSSLFDLNFQAGFLLKKEVQEEQKKNKFGLSVGHHLGKSIPADNQIKARK | ||||||
Modified residue | 82 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 251 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
By polycyclic hydrocarbons (Governed by the aromatic hydrocarbon-responsive (AH) locus).
Gene expression databases
Interaction
Subunit
Homodimer (PubMed:7568029).
Interacts with PDLIM4 isoform 2; this interaction stabilizes PDLIM4 isoform 2 in response to oxidative stress and protects it from ubiquitin-independent degradation by the core 20S proteasome (By similarity).
Interacts with TP73 (via SAM domain); this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity).
Interacts with TP53; this interaction is NADH-dependent, stabilizes TP53 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity).
Interacts with PDLIM4 isoform 2; this interaction stabilizes PDLIM4 isoform 2 in response to oxidative stress and protects it from ubiquitin-independent degradation by the core 20S proteasome (By similarity).
Interacts with TP73 (via SAM domain); this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity).
Interacts with TP53; this interaction is NADH-dependent, stabilizes TP53 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity).
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 225-274 | Important for apoenzyme conformational stability | ||||
Sequence: PSSLFDLNFQAGFLLKKEVQEEQKKNKFGLSVGHHLGKSIPADNQIKARK |
Sequence similarities
Belongs to the NAD(P)H dehydrogenase (quinone) family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length274
- Mass (Da)30,947
- Last updated2007-01-23 v4
- Checksum40E8801320A20F09
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8L2UJ69 | A0A8L2UJ69_RAT | Nqo1 | 256 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 31 | in Ref. 9; AA sequence | ||||
Sequence: Missing | ||||||
Sequence conflict | 80 | in Ref. 10; X17464 | ||||
Sequence: R → G | ||||||
Sequence conflict | 135 | in Ref. 3; AAA41988 | ||||
Sequence: K → Q | ||||||
Sequence conflict | 216 | in Ref. 9; AA sequence | ||||
Sequence: W → E | ||||||
Sequence conflict | 227 | in Ref. 9; AA sequence | ||||
Sequence: S → E | ||||||
Sequence conflict | 263 | in Ref. 9; AA sequence | ||||
Sequence: S → I | ||||||
Sequence conflict | 269 | in Ref. 11; AA sequence | ||||
Sequence: Q → E |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
J02608 EMBL· GenBank· DDBJ | AAA41716.1 EMBL· GenBank· DDBJ | mRNA | ||
J02679 EMBL· GenBank· DDBJ | AAA41715.1 EMBL· GenBank· DDBJ | mRNA | ||
M36660 EMBL· GenBank· DDBJ | AAA39829.1 EMBL· GenBank· DDBJ | mRNA | ||
J02640 EMBL· GenBank· DDBJ | AAA41988.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
M31805 EMBL· GenBank· DDBJ | AAA41989.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M31801 EMBL· GenBank· DDBJ | AAA41989.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M31802 EMBL· GenBank· DDBJ | AAA41989.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M31804 EMBL· GenBank· DDBJ | AAA41989.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M33039 EMBL· GenBank· DDBJ | AAA41990.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M33038 EMBL· GenBank· DDBJ | AAA41990.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC083542 EMBL· GenBank· DDBJ | AAH83542.1 EMBL· GenBank· DDBJ | mRNA | ||
X17464 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |