P05982 (NQO1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NAD(P)H dehydrogenase [quinone] 1
EC=1.6.5.2

Alternative name(s):
Azoreductase
DT-diaphorase
Short name=DTD
Menadione reductase
NAD(P)H:quinone oxidoreductase 1
Phylloquinone reductase
Quinone reductase 1
Short name=QR1

Gene names

Name:	Nqo1
Synonyms:	Nmor1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	274 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Catalytic activity	NAD(P)H + a quinone = NAD(P)+ + a hydroquinone.
Cofactor	FAD.
Subunit structure	Homodimer. Ref.13
Subcellular location	Cytoplasm.
Induction	By polycyclic hydrocarbons (Governed by the aromatic hydrocarbon-responsive (AH) locus).
Miscellaneous	Quinone reductase accepts electrons from both NADH and NADPH with equal efficiency. This protein is inhibited by dicoumarol.
Sequence similarities	Belongs to the NAD(P)H dehydrogenase (quinone) family.
Caution	Ref.4 sequence seems incorrectly to be attributed to a mouse sequence while it really seems to correspond to the rat sequence.
Sequence caution	The sequence AAA41988.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	FAD Flavoprotein NAD NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from expression pattern PubMed 21602469. Source: RGD negative regulation of catalytic activity Inferred from electronic annotation. Source: Compara positive regulation of neuron apoptotic process Inferred from mutant phenotype PubMed 12603827. Source: RGD response to estradiol stimulus Inferred from expression pattern PubMed 14672740. Source: RGD response to ethanol Inferred from expression pattern PubMed 20833713. Source: RGD response to nutrient Inferred from expression pattern PubMed 21092375. Source: RGD response to oxidative stress Inferred from expression pattern PubMed 12011483. Source: RGD superoxide metabolic process Inferred from mutant phenotype PubMed 17901563. Source: RGD
Cellular_component	cytosol Inferred from direct assay PubMed 14991562. Source: RGD neuronal cell body Inferred from direct assay PubMed 14991562. Source: RGD
Molecular_function	NAD(P)H dehydrogenase (quinone) activity Inferred from direct assay PubMed 12603827. Source: RGD superoxide dismutase activity Inferred from mutant phenotype PubMed 17901563. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6 Ref.8

Chain

2 – 274

273

NAD(P)H dehydrogenase [quinone] 1

PRO_0000071625

Regions

Nucleotide binding

18 – 19

2

FAD

Nucleotide binding

104 – 107

4

FAD

Nucleotide binding

148 – 151

4

FAD

Region

126 – 128

3

Substrate binding By similarity

Sites

Binding site

12

1

FAD

Binding site

67

1

FAD

Binding site

156

1

FAD

Binding site

201

1

FAD

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Experimental info

Mutagenesis

117 – 118

2

FE → KK: Destroys enzyme activity.

Mutagenesis

161

1

V → D: Destroys enzyme activity.

Mutagenesis

164

1

D → Q: Destroys enzyme activity.

Sequence conflict

31

1

Missing AA sequence Ref.9

Sequence conflict

80

1

R → G in X17464. Ref.10

Sequence conflict

135

1

K → Q in AAA41988. Ref.3

Sequence conflict

216

1

W → E AA sequence Ref.9

Sequence conflict

227

1

S → E AA sequence Ref.9

Sequence conflict

263

1

S → I AA sequence Ref.9

Sequence conflict

269

1

Q → E AA sequence Ref.11

Secondary structure

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274

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Helix

18 – 32

15

Beta strand

36 – 41

6

Turn

42 – 46

5

Helix

53 – 55

3

Helix

68 – 78

11

Helix

83 – 94

12

Beta strand

96 – 103

8

Helix

111 – 120

10

Turn

123 – 125

3

Helix

133 – 135

3

Turn

137 – 140

4

Beta strand

142 – 148

7

Helix

153 – 156

4

Helix

165 – 173

9

Helix

174 – 178

5

Turn

179 – 181

3

Beta strand

188 – 190

3

Helix

193 – 195

3

Helix

198 – 212

15

Helix

215 – 217

3

Helix

226 – 228

3

Turn

233 – 236

4

Helix

241 – 247

7

Beta strand

254 – 256

3

Turn

266 – 270

5

Sequences

	Sequence		Length	Mass (Da)
	P05982 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 40E8801320A20F09	FASTA	274	30,947
	10 20 30 40 50 60 MAVRRALIVL AHAERTSFNY AMKEAAVEAL KKKGWEVVES DLYAMNFNPL ISRNDITGEP 70 80 90 100 110 120 KDSENFQYPV ESSLAYKEGR LSPDIVAEQK KLEAADLVIF QFPLYWFGVP AILKGWFERV 130 140 150 160 170 180 LVAGFAYTYA TMYDKGPFQN KKTLLSITTG GSGSMYSLQG VHGDMNVILW PIQSGILRFC 190 200 210 220 230 240 GFQVLEPQLV YSIGHTPPDA RVQVLEGWKK RLETVWEESP LYFAPSSLFD LNFQAGFLLK 250 260 270 KEVQEEQKKN KFGLSVGHHL GKSIPADNQI KARK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NAD(P)H:menadione oxidoreductase. Novel purification of enzyme cDNA and complete amino acid sequence, and gene regulation." Robertson J.A., Chen H.-C., Nebert D.W. J. Biol. Chem. 261:15794-15799(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Autoregulation plus positive and negative elements controlling transcription of genes in the [Ah] battery." Robertson J.A., Nebert D.W., Hankinson O. Chem. Scr. 27:83-87(1987) Cited for: NUCLEOTIDE SEQUENCE.
[3]	"Rat liver NAD(P)H: quinone reductase nucleotide sequence analysis of a quinone reductase cDNA clone and prediction of the amino acid sequence of the corresponding protein." Bayney R.M., Rodkey J.A., Bennett C.D., Lu A.Y.H., Pickett C.B. J. Biol. Chem. 262:572-575(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[4]	"Rat liver NAD(P)H:quinone reductase. Regulation of quinone reductase gene expression by planar aromatic compounds and determination of the exon structure of the quinone reductase structural gene." Bayney R.M., Morton M.R., Favreau L.V., Pickett C.B. J. Biol. Chem. 264:21793-21797(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Tissue: Liver.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[6]	"Structure-function relationship of NAD(P)H:quinone reductase: characterization of NH2-terminal blocking group and essential tyrosine and lysine residues." Haniu M., Yuan H., Chen S.A., Iyanagi T., Lee T.D., Shively J.E. Biochemistry 27:6877-6883(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-274.
[7]	"Rat liver NAD(P)H:quinone reductase: isolation of a quinone reductase structural gene and prediction of the NH2 terminal sequence of the protein by double-stranded sequencing of exons 1 and 2." Bayney R.M., Pickett C.B. Arch. Biochem. Biophys. 260:847-850(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-57.
[8]	"Expression of mammalian DT-diaphorase in Escherichia coli: purification and characterization of the expressed protein." Ma Q., Wang R., Yang C.S., Lu A.Y.H. Arch. Biochem. Biophys. 283:311-317(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-21.
[9]	"The nitroreductase enzyme in Walker cells that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) to 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2)." Knox R.J., Boland M.P., Friedlos F., Coles B., Southan C., Roberts J.J. Biochem. Pharmacol. 37:4671-4677(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-131 AND 156-270.
[10]	"Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells." Dear T.N., McDonald D.A., Kefford R.F. Cancer Res. 49:5323-5328(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 80-274.
[11]	"Reaction of rat liver DT-diaphorase (NAD(P)H:quinone acceptor reductase) with 5'-[p-(fluorosulfonyl)benzoyl]-adenosine." Liu X.F., Yuan H., Haniu M., Iyanagi T., Shively J.E., Chen S.A. Mol. Pharmacol. 35:818-822(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 147-156 AND 263-271.
[12]	"Rat liver NAD(P)H:quinone oxidoreductase: cDNA expression and site-directed mutagenesis." Forrest G.L., Qian J., Ma J.-X., Kaplan W.D., Akman S., Doroshow J., Chen S.A. Biochem. Biophys. Res. Commun. 169:1087-1093(1990) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[13]	"The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction." Li R., Bianchet M.A., Talalay P., Amzel L.M. Proc. Natl. Acad. Sci. U.S.A. 92:8846-8850(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FAD AND DUROQUINONE, SUBUNIT. Tissue: Liver.
[14]	Erratum Li R., Bianchet M.A., Talalay P., Amzel L.M. Proc. Natl. Acad. Sci. U.S.A. 92:10815-10815(1995)
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02608 mRNA. Translation: AAA41716.1.
J02679 mRNA. Translation: AAA41715.1.
M36660 mRNA. Translation: AAA39829.1.
J02640 mRNA. Translation: AAA41988.1. Different initiation.
M31805 , M31801, M31802, M31804 Genomic DNA. Translation: AAA41989.1.
M33039, M33038 Genomic DNA. Translation: AAA41990.1.
BC083542 mRNA. Translation: AAH83542.1.
X17464 mRNA. No translation available.

IPI

IPI00231595.

PIR

A34162.

RefSeq

NP_058696.2. NM_017000.3.

UniGene

Rn.11234.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QRD	X-ray	2.40	A/B	2-274	[»]

ProteinModelPortal

P05982.

SMR

P05982. Positions 2-274.

ModBase

Search...

Protein-protein interaction databases

IntAct

P05982. 1 interaction.

STRING

10116.ENSRNOP00000017175.

PTM databases

PhosphoSite

P05982.

2D gel databases

World-2DPAGE

0004:P05982.

Proteomic databases

PaxDb

P05982.

PRIDE

P05982.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000017174; ENSRNOP00000017175; ENSRNOG00000012772.

GeneID

24314.

KEGG

rno:24314.

UCSC

RGD:2503. rat.

Organism-specific databases

CTD

1728.

RGD

2503. Nqo1.

Phylogenomic databases

eggNOG

COG2249.

GeneTree

ENSGT00440000033410.

HOGENOM

HOG000149970.

HOVERGEN

HBG029104.

InParanoid

P05982.

KO

K00355.

OrthoDB

EOG44BB36.

Gene expression databases

Genevestigator

P05982.

GermOnline

ENSRNOG00000012772. Rattus norvegicus.

Family and domain databases

InterPro

IPR003680. Flavodoxin_fold.
[Graphical view]

Pfam

PF02525. Flavodoxin_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P05982.

NextBio

602959.

Entry information

Entry name

NQO1_RAT

Accession

Primary (citable) accession number: P05982
Secondary accession number(s): Q63478

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 123 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program