Human
NAD(P)H:
quinone oxidoreductase2 (
NQO2) gene, 1336 base pairs (bp) of the 5'-flanking region and 165 bp of the 3'-flanking region, have been sequenced.
NQO2 gene is 20 kilobase pairs in length and have seven exons interrupted by six introns as compared to the previously cloned NQO1 gene which contains six exons. 187 bp of the first exon in the
NQO2 gene are noncoding and are absent in the NQO1 gene. 92 bp of the second exon in the
NQO2 gene corresponded to the first exon of the NQO1 gene and so on. The sizes and nucleotide sequences of exons 3-6 are highly conserved between
NQO2 and NQO1 genes. The last exon in the
NQO2 gene is 1603 bp shorter than the last exon of the NQO1 gene and encodes for 58
amino acids as compared to 101
amino acids encoded by the NQO1 gene. This makes
NQO2 protein 43
amino acids shorter than the NQO1
protein. The high degree of conservation between
NQO2 and NQO1 gene organization and sequence confirmed that
NQO2 gene encodes for a second member of the NQO gene family in human. Nucleotide sequence analysis of the 5'-flanking region of the
NQO2 gene revealed presence of four SP1 binding sites at positions -214, -170, -106, and -75, a single copy of the antioxidant response element (ARE) at
nucleotide -936, and three copies of
xenobiotic response element (XRE) at positions -708, -557, and -51. ARE and XRE elements have previously been found in the promoters of the NQO1 and
glutathione S-transferase Ya subunit genes and mediate increases in their expression in response to polycyclic aromatic compounds, phenolic
antioxidants, and
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD), respectively. The
NQO2 cDNA-derived
protein in monkey kidney COS1 cells efficiently catalyzed nitroreduction of anti-
tumor compound CB10-200, an analog of nitrophenylaziridine. Northern blot analysis indicates that
NQO2 gene is expressed in human heart, brain, lung, liver, and skeletal muscle but does not express in placenta. In contrast, the NQO1 gene was expressed in all human tissues. Large variations were noticed for expression of the
NQO2 and NQO1 genes among various tissues, 1336 bp of the 5'-flanking region of the
NQO2 gene containing ARE and XRE was found sufficient to increase expression of the CAT gene in response to
beta-naphthoflavone and
tCDD in transfected human
hepatoblastoma (Hep-G2) cells.