NAD(P)H dehydrogenase [quinone] 1 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P15559 (NQO1_HUMAN)

Last modified June 16, 2009. Version 102. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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:	DIA4, NMOR1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	274 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.
Enzyme regulation	Inhibited by dicoumarol.
Subunit structure	Homodimer. Ref.6 Ref.9
Subcellular location	Cytoplasm.
Induction	By dioxin.
Polymorphism	The Ser-187 polymorphism may be linked to susceptibility to forms of cancers.
Miscellaneous	Quinone reductase accepts electrons from both NADH and NADPH with equal efficiency.
Sequence similarities	Belongs to the NAD(P)H dehydrogenase (quinone) family.
Mass spectrometry	Molecular mass is 30864±6 Da from positions 1 - 274. Determined by ESI. Ref.8

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Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	FAD Flavoprotein NAD NADP
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	nitric oxide biosynthetic process Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to toxin Traceable author statement. Source: ProtInc synaptic transmission, cholinergic Traceable author statement. Source: ProtInc xenobiotic metabolic process Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.1 Inferred from direct assay. Source: HPA
Molecular function	NAD(P)H dehydrogenase (quinone) activity Traceable author statement. Source: ProtInc coenzyme binding Inferred from electronic annotation. Source: InterPro cytochrome-b5 reductase activity Traceable author statement. Source: ProtInc electron carrier activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 274

274

NAD(P)H dehydrogenase [quinone] 1

PRO_0000071622

Regions

Nucleotide binding

18 – 19

FAD

Nucleotide binding

104 – 107

FAD

Nucleotide binding

148 – 151

FAD

Region

126 – 128

Substrate binding

Sites

Binding site

FAD

Binding site

FAD

Binding site

156

FAD

Binding site

201

FAD

Natural variations

Natural variant

139

R → W: dbSNP rs1131341.

VAR_016170

Natural variant

187

P → S Lack of activity. dbSNP rs1800566. Ref.3 Ref.11 Ref.12

VAR_008384

Natural variant

269

Q → H: dbSNP rs34447156.

VAR_050220

Secondary structure

274

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P15559-1 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: A4010462AD00F3FE
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FASTA

274

30,868

        10         20         30         40         50         60 
MVGRRALIVL AHSERTSFNY AMKEAAAAAL KKKGWEVVES DLYAMNFNPI ISRKDITGKL 

        70         80         90        100        110        120 
KDPANFQYPA ESVLAYKEGH LSPDIVAEQK KLEAADLVIF QFPLQWFGVP AILKGWFERV 

       130        140        150        160        170        180 
FIGEFAYTYA AMYDKGPFRS KKAVLSITTG GSGSMYSLQG IHGDMNVILW PIQSGILHFC 

       190        200        210        220        230        240 
GFQVLEPQLT YSIGHTPADA RIQILEGWKK RLENIWDETP LYFAPSSLFD LNFQAGFLMK 

       250        260        270 
KEVQDEEKNK KFGLSVGHHL GKSIPTDNQI KARK

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human dioxin-inducible cytosolic NAD(P)H:menadione oxidoreductase. cDNA sequence and localization of gene to chromosome 16." Jaiswal A.K., McBride O.W., Adesnik M., Nebert D.W. J. Biol. Chem. 263:13572-13578(1988) [PubMed: 2843525] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxin." Jaiswal A.K. Biochemistry 30:10647-10653(1991) [PubMed: 1657151] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	NIEHS SNPs program Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-187.
[4]	"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: Colon.
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"Crystal structure of human DT-diaphorase: a model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)." Skelly J.V., Sanderson M.R., Suter D.A., Baumann U., Read M.A., Gregory D.S.J., Bennett M., Hobbs S.M., Neidle S. J. Med. Chem. 42:4325-4330(1999) [PubMed: 10543876] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 4-274 IN COMPLEX WITH FAD, SUBUNIT.
[7]	"Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release." Faig M., Bianchet M.A., Talalay P., Chen S., Winski S., Ross D., Amzel L.M. Proc. Natl. Acad. Sci. U.S.A. 97:3177-3182(2000) [PubMed: 10706635] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH FAD AND DUROQUINONE.
[8]	"Characterization of a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches." Winski S.L., Faig M., Bianchet M.A., Siegel D., Swann E., Fung K., Duncan M.W., Moody C.J., Amzel L.M., Ross D. Biochemistry 40:15135-15142(2001) [PubMed: 11735396] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH FAD AND THE INHIBITOR ES936, MASS SPECTROMETRY.
[9]	"Structure-based development of anticancer drugs: complexes of NAD(P)H:quinone oxidoreductase 1 with chemotherapeutic quinones." Faig M., Bianchet M.A., Winski S., Hargreaves R., Moody C.J., Hudnott A.R., Ross D., Amzel L.M. Structure 9:659-667(2001) [PubMed: 11587640] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEXES WITH FAD AND INHIBITORS, ACTIVE SITE, SUBUNIT.
[10]	"The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its potent inhibitor dicoumarol." Asher G., Dym O., Tsvetkov P., Adler J., Shaul Y. Biochemistry 45:6372-6378(2006) [PubMed: 16700548] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR DICOUMAROL.
[11]	"NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity." Traver R.D., Horikoshi T., Danenberg K.D., Stadlbauer T.H., Danenberg P.V., Ross D., Gibson N.W. Cancer Res. 52:797-802(1992) [PubMed: 1737339] [Abstract] Cited for: VARIANT SER-187.
[12]	"No linkage of P187S polymorphism in NAD(P)H: quinone oxidoreductase (NQO1/DIA4) and type 1 diabetes in the Danish population." Kristiansen O.P., Larsen Z.M., Johannesen J., Nerup J., Mandrup-Poulsen T., Pociot F. Hum. Mutat. 14:67-70(1999) [PubMed: 10447260] [Abstract] Cited for: VARIANT SER-187.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

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Cross-references

Sequence databases

J03934 mRNA. Translation: AAA59940.1.
M81600

M81599 Genomic DNA. Translation: AAB60701.1.
AY281093 Genomic DNA. Translation: AAP20940.1. Sequence problems.
BC007659 mRNA. Translation: AAH07659.1.

IPI

IPI00012069.

PIR

A30879. A41135.

RefSeq

NP_000894.1.
NP_001020604.1.

UniGene

Hs.406515

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D4A	X-ray	1.70	A/B/C/D	2-274	[»]
1DXO	X-ray	2.50	A/B/C/D	2-274	[»]
1GG5	X-ray	2.50	A/B/C/D	2-274	[»]
1H66	X-ray	2.00	A/B/C/D	3-274	[»]
1H69	X-ray	1.86	A/B/C/D	3-274	[»]
1KBO	X-ray	2.30	A/B/C/D	2-274	[»]
1KBQ	X-ray	1.80	A/B/C/D	2-274	[»]
1QBG	X-ray	2.30	A/B/C/D	4-274	[»]
2F1O	X-ray	2.75	A/B/C/D/E/F/G/H	2-274	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24210N.

PTM databases

PhosphoSite

P15559.

Proteomic databases

PRIDE

P15559.

Genome annotation databases

Ensembl

ENSG00000181019. Homo sapiens. [Contig view]

GeneID

1728.

KEGG

hsa:1728.

NMPDR

fig|9606.3.peg.12483.

Organism-specific databases

GeneCards

GC16M068300.

H-InvDB

HIX0013192.

HGNC

HGNC:2874. NQO1.

HPA

CAB012421.
HPA007308.

MIM

125860. gene.

PharmGKB

PA31744.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P15559.

HOVERGEN

P15559.

OMA

P15559. VERVYAY.

Enzyme and pathway databases

BRENDA

1.6.5.2. 247.

Reactome

REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

P15559.

Bgee

P15559.

CleanEx

HS_NQO1.

GermOnline

ENSG00000181019. Homo sapiens.

Family and domain databases

InterPro

IPR003680. Flavodoxin_fold.
[Graphical view]

Pfam

PF02525. Flavodoxin_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00266. Dicumarol.
DB00170. Menadione.

NextBio

6989.

SOURCE

Search...

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Entry information

Entry name

NQO1_HUMAN

Accession

Primary (citable) accession number: P15559
Secondary accession number(s): Q86UK1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	June 16, 2009
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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