Reviewed, UniProtKB/Swiss-Prot P05982 (NQO1_RAT)

Names and origin

Protein names

Recommended name:
    NAD(P)H dehydrogenase [quinone] 1
    EC=1.6.5.2
Alternative name(s):
    Quinone reductase 1
    NAD(P)H:quinone oxidoreductase 1
      Short name=QR1
    DT-diaphorase
      Short name=DTD
    Azoreductase
    Phylloquinone reductase
    Menadione reductase

Gene names

Name:	Nqo1
Synonyms:	Nmor1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	FAD Flavoprotein NAD NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of neuron apoptosis Inferred from mutant phenotype. Source: RGD response to oxidative stress Inferred from expression pattern. Source: RGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NAD(P)H dehydrogenase (quinone) activity Inferred from direct assay. Source: RGD coenzyme binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro
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

1

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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

Beta strand

237 – 239

3

Helix

241 – 247

7

Beta strand

254 – 256

3

Turn

266 – 270

5

Sequences

	Sequence		Length	Mass (Da)
	P05982-1 [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: 3536915] [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: 3100515] [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: 2480957] [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: 15489334] [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: 3143406] [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: 2963593] [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: 1703398] [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: 3144286] [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: 2504488] [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: 2499768] [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: 2141979] [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: 7568029] [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

EMBLGenBankDDBJ

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.

UniGene

Rn.11234

3D structure databases

PDBPDBe

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

ModBase

Search...

Proteomic databases

PRIDE

P05982.

Genome annotation databases

Ensembl

ENSRNOG00000012772. Rattus norvegicus. [Contig view]

GeneID

24314.

KEGG

rno:24314.

NMPDR

fig|10116.3.peg.14965.

Organism-specific databases

RGD

2503. Nqo1.

Phylogenomic databases

HOVERGEN

P05982.

Enzyme and pathway databases

BRENDA

1.6.5.2. 248.

Gene expression databases

ArrayExpress

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 Resources

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:	June 16, 2009
This is version 96 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)