P15559 (NQO1_HUMAN) 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):
Quinone reductase 1
Short name=QR1
NAD(P)H:quinone oxidoreductase 1
DT-diaphorase
Short name=DTD
Azoreductase
Phylloquinone reductase
Menadione reductase

Gene names

Name:	NQO1
Synonyms:	DIA4, NMOR1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	274 AA.
Sequence status	Complete.
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.
Enzyme regulation	Inhibited by dicoumarol.
Subunit structure	Homodimer. Ref.9 Ref.12
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.11

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	FAD Flavoprotein NAD NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome
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 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...

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

2

FAD

Nucleotide binding

104 – 107

4

FAD

Nucleotide binding

148 – 151

4

FAD

Region

126 – 128

3

Substrate binding

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

59

1

N6-acetyllysine Ref.8

Modified residue

262

1

N6-acetyllysine Ref.8

Natural variations

Natural variant

139

1

R → W. [dbSNP:rs1131341]

VAR_016170

Natural variant

187

1

P → S Lack of activity. [dbSNP:rs1800566] Ref.3 Ref.14 Ref.15

VAR_008384

Natural variant

269

1

Q → H. [dbSNP:rs34447156]

VAR_050220

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

124 – 126

3

Helix

133 – 135

3

Turn

137 – 140

4

Beta strand

142 – 148

7

Helix

154 – 156

3

Helix

165 – 173

9

Turn

174 – 177

4

Helix

178 – 180

3

Beta strand

188 – 190

3

Helix

193 – 195

3

Helix

198 – 212

15

Helix

213 – 217

5

Helix

226 – 228

3

Helix

233 – 235

3

Helix

241 – 248

8

Beta strand

254 – 256

3

Turn

266 – 270

5

Sequences

	Sequence		Length	Mass (Da)
	P15559-1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: A4010462AD00F3FE	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

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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-59 AND LYS-262, MASS SPECTROMETRY.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03934 mRNA. Translation: AAA59940.1.
M81600 , M81596, M81597, M81598, M81599 Genomic DNA. Translation: AAB60701.1.
AY281093 Genomic DNA. Translation: AAP20940.1. Sequence problems.
AK312368 mRNA. Translation: BAG35286.1.
CH471092 Genomic DNA. Translation: EAW83284.1.
BC007659 mRNA. Translation: AAH07659.1.

IPI

IPI00012069.

PIR

A30879. A41135.

RefSeq

NP_000894.1.
NP_001020604.1.

UniGene

Hs.406515.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3JSX	X-ray	2.45	A/B/C/D/E/F/G/H	2-274	[»]

ProteinModelPortal

P15559.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24210N.

MINT

MINT-231407.

STRING

P15559.

PTM databases

PhosphoSite

P15559.

Proteomic databases

PRIDE

P15559.

Genome annotation databases

Ensembl

ENST00000320623; ENSP00000319788; ENSG00000181019; Homo sapiens. [Genome view]

GeneID

1728.

KEGG

hsa:1728.

NMPDR

fig|9606.3.peg.12483.

UCSC

uc002exp.1. human.

Organism-specific databases

CTD

1728.

GeneCards

GC16M069744.

HGNC

HGNC:2874. NQO1.

HPA

CAB012421.
HPA007308.

MIM

125860. gene.

PharmGKB

PA31744.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08081.

HOGENOM

HBG532247.

HOVERGEN

HBG029104.

InParanoid

P15559.

OMA

YDVLPPF.

OrthoDB

EOG9R26DS.

PhylomeDB

P15559.

Enzyme and pathway databases

BRENDA

1.6.5.2. 247.

Reactome

REACT_13. Metabolism of amino acids and derivatives.

Gene expression databases

ArrayExpress

P15559.

Bgee

P15559.

CleanEx

HS_NQO1.

Genevestigator

P15559.

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...

Entry information

Entry name

NQO1_HUMAN

Accession

Primary (citable) accession number: P15559
Secondary accession number(s): B2R5Y9, Q86UK1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	August 10, 2010
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.