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FLASH GENE

Symbol

NQO1

contributors: mct/npt - updated : 04-07-2023

HGNC name	NAD(P)H dehydrogenase, quinone 1
HGNC id	2874

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	17.16 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000903 6 - 2601 NP_000894 - 274 - 2000 10908561 NM_001025433 5 - 2499 NP_001020604 - 240 - 2000 10908561 NM_001025434 5 - 2487 NP_001020605 - 236 - 2000 10908561 NM_001286137 4 - 2305 NP_001273066 - 202 - 200 10908561

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   liver       highly   mouth       highly Lymphoid/Immune lymph node         Respiratory lung         Skin/Tegument skin       highly Urinary kidney         Visual eye anterior segment

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

four potential polyadenylation sites

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY

NAD(P)H dehydrogenase (quinone) family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus
text	is primarily located in the cytosol, however, lower levels of NQO1 have also been found in the nucleus, and also associated with mitotic spindles in cells undergoing division

basic FUNCTION	involved in detoxification pathways as well as in biosynthetic processes such as the vitamin k-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis
	may be involved in nitric oxide biosynthesis, response to toxin, synaptic transmission, cholinergic, xenobiotic metabolism
	plays a role in suppressing inflammatory response and in attenuation of macrophage migration induced by LPS
	belongs to the phase II detoxifying enzymes that are induced to protect against electrophilic insults, oxidative stress, and ionizing radiation
	original role in the regulation of mRNA translation via the control of EIF4GI stability by the proteasome
	rescue proteins containing intrinsically unstructured domains, such as TP53 and TP73, from degradation by the 20S proteasome
	FAD containing quinone reductase that catalyzes the 2-electron reduction of a broad range of quinones
	NQO1, a cellular redox sensor, is linked to the metabolite-sensing network that tunes PPARGC1A expression and activity in regulating energy metabolism
	plays a key role in suppressing ionizing radiation (IR)-induced centrosome amplification and aneuploidy through a direct interaction with Aurora-A
	xenobiotic metabolizing enzyme that detoxifies chemical stressors and antioxidants, providing cytoprotection in normal tissues
	NQO1 may likely function as a redox-dependent molecular switch
	NQO1/SREBF1 axis promoted the progression and metastasis of Hepatocellular carcinoma (HCC)
	novel regulatory role of NQO1 in the mechanism of cell cycle progression at the G2/M phase in cancer through effects on FOS/CKS1 signaling
	NQO1 protects cells from oxidative stress and damage caused by toxic quinones

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

detoxification

text	dependent two-electrons reduction of quinones derived from the oxidation of phenolic metabolites of benzene

PATHWAY

metabolism

drug

signaling

a component

SQSTM1-NFE2L2-NQO1 cascade functions to assure mammalian longevity by stabilizing mitochondrial integrity

INTERACTION

DNA

RNA

small molecule	cofactor,
	FAD

protein	REXO4 is involved in the activation of NQO1 gene activity, enhanced in the presence of ESR2
	interacting with PDLIM4
	NQO1 binds and protects PPARGC1A from degradation in an NADH-dependent manner
	function of NQO1 in the oxygen-sensing mechanism that regulates HIF1A stability in cancers
	NQO1 interacts with and activates SIRT2 in an NAD-dependent manner
	SIRT1 and NQO1 form likely a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress
	NQO1 directly interacts with the unstructured DNA-binding domain of FOS, which has been implicated in cancer proliferation, differentiation, and development as well as patient survival
	NQO1 alleviates diabetes-induced renal inflammation and fibrosis by regulating the TLR4/NFKB1 and TGFB1/Smad signaling pathways

cell & other

REGULATION

induced by	dioxine
		dicoumarol

repressed by

TCF7L1

Other

regulated by NFE2L2

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in tardive dyskinesia tumoral     --over   associated with breast cancer progression constitutional     --over   in the early and intermediate stages of Parkinson's disease (PD) and disappeared in the end-stage PD

Susceptibility

to benzene toxicity modifying the susceptibility to acute myeloid leukemia to various forms of cancer to breast cancer with poor survival to artery plaques in type 2 diabetic patients

Variant & Polymorphism other	Cb09T TT phenotype with no NQO1 activity (susceptible)
	allele 2 and 3 increases the risk of ALL
	an increased risk of hematotoxicity after exposure to benzene
	homozygote missense variant increasing the risk of breast cancer with poor survival
	C609T polymorphism is associated with carotid artery plaques in type 2 diabetic patients (Han 2009)

Candidate gene	prognostic and predictive marker for breast cancer
Marker	may be a potential biomarker for poor prognostic evaluation of breast cancers
Therapy target
	System Type Disorder Pubmed cancer digestive liver might be a potential therapeutic target for HCC neurology neurodegenerative Parkinson/dementia Parkinsonism blockade of AKT1-mediated NQO1 degradation may ameliorate PD pathogenesis

ANIMAL & CELL MODELS