Reviewed, UniProtKB/Swiss-Prot P16083 (NQO2_HUMAN)

Names and origin

Protein names

Recommended name:
    Ribosyldihydronicotinamide dehydrogenase [quinone]
    EC=1.10.99.2
Alternative name(s):
    NRH dehydrogenase [quinone] 2
    NRH:quinone oxidoreductase 2
    Quinone reductase 2
      Short name=QR2

Gene names

Name:	NQO2
Synonyms:	NMOR2

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	231 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 hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. Ref.19
Catalytic activity	1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone = 1-(beta-D-ribofuranosyl)nicotinamide + a hydroquinone. Ref.20
Cofactor	Binds 1 zinc ion per subunit. FAD.
Enzyme regulation	Inhibited by melatonin, resveratrol and 5-hydroxytryptamine. Ref.19
Subunit structure	Homodimer. Ref.19
Subcellular location	Cytoplasm.
Miscellaneous	Uses dihydronicotinamide riboside (NRH) rather than NAD(P)H as an electron donor.
Sequence similarities	Belongs to the NAD(P)H dehydrogenase (quinone) family.
Biophysicochemical properties	Kinetic parameters: KM=28 µM for NRH KM=11.6 µM for menadione KM=252 µM for NADH

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	FAD Flavoprotein Metal-binding Zinc
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NADPH dehydrogenase (quinone) activity Ref.1 Traceable author statement. Source: ProtInc coenzyme binding Inferred from electronic annotation. Source: InterPro dihydronicotinamide riboside quinone reductase activity Inferred from electronic annotation. Source: EC electron carrier activity Ref.1 Traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 231

230

Ribosyldihydronicotinamide dehydrogenase [quinone]

PRO_0000071626

Regions

Nucleotide binding

18 – 21

4

FAD

Nucleotide binding

104 – 107

4

FAD

Nucleotide binding

148 – 151

4

FAD

Region

127 – 129

3

Substrate binding

Sites

Metal binding

174

1

Zinc

Metal binding

178

1

Zinc

Metal binding

223

1

Zinc

Binding site

12

1

FAD

Binding site

156

1

FAD

Binding site

194

1

FAD

Binding site

201

1

FAD

Amino acid modifications

Modified residue

31

1

Phosphoserine Ref.13

Modified residue

80

1

Phosphoserine

Modified residue

197

1

Phosphoserine

Natural variations

Natural variant

16

1

K → R: dbSNP rs28383623. Ref.4

VAR_021399

Natural variant

29

1

E → G: dbSNP rs17136117. Ref.4

VAR_021400

Natural variant

47

1

F → L: dbSNP rs1143684. Ref.4 Ref.6

VAR_021401

Natural variant

58

1

G → D: dbSNP rs17300141. Ref.4

VAR_021402

Natural variant

184

1

V → A: dbSNP rs28383651. Ref.4

VAR_021403

Experimental info

Mutagenesis

162

1

N → H: Loss of activity toward CB1954, no effect toward menadione. Ref.18

Sequence conflict

140

1

G → C in AAB60642. Ref.2

Secondary structure

1

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231

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Helix

18 – 32

15

Beta strand

36 – 41

6

Helix

42 – 45

4

Helix

53 – 55

3

Helix

68 – 77

10

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

Turn

153 – 156

4

Beta strand

160 – 162

3

Helix

165 – 173

9

Turn

174 – 177

4

Helix

178 – 180

3

Beta strand

188 – 190

3

Helix

193 – 195

3

Helix

198 – 213

16

Helix

214 – 217

4

Helix

225 – 229

5

Sequences

	Sequence		Length	Mass (Da)
	P16083-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: FAF549B991FDB978	FASTA	231	25,953
	10 20 30 40 50 60 MAGKKVLIVY AHQEPKSFNG SLKNVAVDEL SRQGCTVTVS DLYAMNFEPR ATDKDITGTL 70 80 90 100 110 120 SNPEVFNYGV ETHEAYKQRS LASDITDEQK KVREADLVIF QFPLYWFSVP AILKGWMDRV 130 140 150 160 170 180 LCQGFAFDIP GFYDSGLLQG KLALLSVTTG GTAEMYTKTG VNGDSRYFLW PLQHGTLHFC 190 200 210 220 230 GFKVLAPQIS FAPEIASEEE RKGMVAAWSQ RLQTIWKEEP IPCTAHWHFG Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide and deduced amino acid sequence of a human cDNA (NQO2) corresponding to a second member of the NAD(P)H:quinone oxidoreductase gene family. Extensive polymorphism at the NQO2 gene locus on chromosome 6." Jaiswal A.K., Burnett P., Adesnik M., McBride O.W. Biochemistry 29:1899-1906(1990) [PubMed: 1691923] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Human NAD(P)H:quinone oxidoreductase 2. Gene structure, activity, and tissue-specific expression." Jaiswal A.K. J. Biol. Chem. 269:14502-14508(1994) [PubMed: 8182056] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[3]	"Human NRH:quinone oxidoreductase 2, complete genomic sequence." Iida A., Osawa S., Kitamura Y., Kitamoto T., Koyama K., Nakamura Y. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-16; GLY-29; LEU-47; ASP-58 AND ALA-184.
[5]	"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: Cerebellum.
[6]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-47.
[7]	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].
[8]	"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: Brain.
[9]	"Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase." Wu K., Knox R., Sun X.Z., Joseph P., Jaiswal A.K., Zhang D., Deng P.S.-K., Chen S. Arch. Biochem. Biophys. 347:221-228(1997) [PubMed: 9367528] [Abstract] Cited for: CHARACTERIZATION, BIOPHYSICOCHEMICAL PROPERTIES.
[10]	"Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase)." Zhao Q., Yang X.L., Holtzclaw W.D., Talalay P. Proc. Natl. Acad. Sci. U.S.A. 94:1669-1674(1997) [PubMed: 9050836] [Abstract] Cited for: CHARACTERIZATION.
[11]	Erratum Zhao Q., Yang X.L., Holtzclaw W.D., Talalay P. Proc. Natl. Acad. Sci. U.S.A. 94:5979-5979(1997)
[12]	"Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines." Kwiek J.J., Haystead T.A.J., Rudolph J. Biochemistry 43:4538-4547(2004) [PubMed: 15078100] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[13]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, MASS SPECTROMETRY.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-197, MASS SPECTROMETRY.
[16]	"Crystal structure of human quinone reductase type 2, a metalloflavoprotein." Foster C.E., Bianchet M.A., Talalay P., Zhao Q., Amzel L.M. Biochemistry 38:9881-9886(1999) [PubMed: 10433694] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[17]	"Crystal structure of quinone reductase 2 in complex with resveratrol." Buryanovskyy L., Fu Y., Boyd M., Ma Y., Hsieh T.-C., Wu J.M., Zhang Z. Biochemistry 43:11417-11426(2004) [PubMed: 15350128] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH RESVERATROL.
[18]	"Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954." Fu Y., Buryanovskyy L., Zhang Z. Biochem. Biophys. Res. Commun. 336:332-338(2005) [PubMed: 16129418] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH CB1954, MUTAGENESIS OF ASN-162.
[19]	"Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2." Calamini B., Santarsiero B.D., Boutin J.A., Mesecar A.D. Biochem. J. 413:81-91(2008) [PubMed: 18254726] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MELATONIN AND FAD, FUNCTION, SUBUNIT, ENZYME REGULATION.
[20]	"Quinone reductase 2 is a catechol quinone reductase." Fu Y., Buryanovskyy L., Zhang Z. J. Biol. Chem. 283:23829-23835(2008) [PubMed: 18579530] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEXES WITH DOPAMINE AND ADRENOCHROME, ENZYME ACTIVITY.
[21]	"The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2)." Winger J.A., Hantschel O., Superti-Furga G., Kuriyan J. BMC Struct. Biol. 9:7-7(2009) [PubMed: 19236722] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH ZINC IONS; FAD AND IMATINIB.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02888 mRNA. Translation: AAA60239.1.
AY299456 Genomic DNA. Translation: AAB60642.3.
AB050248 Genomic DNA. Translation: BAB16974.1.
AY855291 Genomic DNA. Translation: AAW29945.1.
AK311746 mRNA. Translation: BAG34689.1.
AL133351 Genomic DNA. Translation: CAI23294.1.
CH471087 Genomic DNA. Translation: EAW55107.1.
BC006096 mRNA. Translation: AAH06096.1.

IPI

IPI00219129.

PIR

A32667.

RefSeq

NP_000895.2.

UniGene

Hs.533050

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QR2	X-ray	2.10	A/B	2-231	[»]
1SG0	X-ray	1.50	A/B	2-231	[»]
1XI2	X-ray	1.50	A/B	2-231	[»]
1ZX1	X-ray	2.16	A/B	1-231	[»]
2BZS	X-ray	2.00	A/B	2-230	[»]
2QMY	X-ray	2.50	A/B	2-231	[»]
2QMZ	X-ray	2.10	A/B	2-231	[»]
2QR2	X-ray	2.45	A/B	2-231	[»]
2QWX	X-ray	1.50	A/B	1-231	[»]
2QX4	X-ray	1.65	A/B	2-231	[»]
2QX6	X-ray	1.75	A/B	2-231	[»]
2QX8	X-ray	1.60	A/B	2-231	[»]
2QX9	X-ray	2.31	A/B	2-231	[»]
3FW1	X-ray	1.75	A	1-231	[»]
3G5M	X-ray	1.84	A/B	1-231	[»]
3GAM	X-ray	1.98	A/B	1-231	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P16083. 6 interactions.

STRING

P16083.

PTM databases

PhosphoSite

P16083.

Proteomic databases

PRIDE

P16083.

Genome annotation databases

Ensembl

ENST00000338130; ENSP00000337773; ENSG00000124588; Homo sapiens. [Genome view]
ENST00000380430; ENSP00000369795; ENSG00000124588; Homo sapiens. [Genome view]
ENST00000380455; ENSP00000369822; ENSG00000124588; Homo sapiens. [Genome view]

GeneID

4835.

KEGG

hsa:4835.

Organism-specific databases

CTD

4835.

GeneCards

GC06P002945.

H-InvDB

HIX0018967.

HGNC

HGNC:7856. NQO2.

HPA

HPA021283.
HPA021332.

MIM

160998. gene.

PharmGKB

PA31745.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG532247.

HOVERGEN

P16083.

InParanoid

P16083.

PhylomeDB

P16083.

Enzyme and pathway databases

BRENDA

1.10.99.2. 247.

Gene expression databases

ArrayExpress

P16083.

Bgee

P16083.

CleanEx

HS_NQO2.

Genevestigator

P16083.

GermOnline

ENSG00000124588. 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

DB00170. Menadione.
DB00157. NADH.

NextBio

18630.

SOURCE

Search...

Entry information

Entry name

NQO2_HUMAN

Accession

Primary (citable) accession number: P16083
Secondary accession number(s): B2R492, Q5TD04

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 112 of the entry and version 4 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.