HGNC Approved Gene Symbol: DDT
Cytogenetic location: 22q11.23 Genomic coordinates (GRCh38): 22:23,971,370-23,980,504 (from NCBI)
D-dopachrome tautomerase (DDT) converts D-dopachrome into 5,6-dihydroxyindole (summary by Nishihira et al., 1998).
By screening a liver library with a rat D-dopachrome tautomerase cDNA, Nishihira et al. (1998) identified cDNAs encoding human DDT. The sequence of the predicted 118-amino acid DDT protein is 80% identical to that of the rat protein. The molecular mass of recombinant DDT expressed in bacterial cells was 13 kD by SDS-PAGE. Northern blot analysis revealed that DDT was expressed as a 0.6-kb mRNA in all tissues tested, with the strongest expression in liver.
Using site-directed mutagenesis, Nishihira et al. (1998) showed that the N-terminal proline is essential for D-dopachrome tautomerization.
Esumi et al. (1998) found that the DDT gene in human and mouse is identical in exon structure to the MIF gene (153620). Both genes have 2 introns that are located at equivalent positions relative to a 2-fold repeat in protein structure. Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this superfamily exist in nematodes and a plant, and a related gene in C. elegans shares an intron position with MIF and DDT.
In addition to similarities in structure, the genes for DDT and MIF are closely linked on human chromosome 22 and mouse chromosome 10. Esumi et al. (1998) demonstrated the close linkage by anaphase fluorescence in situ hybridization in the human. The DDT gene was mapped in the mouse by interspecific backcross analysis.
Esumi, N., Budarf, M., Ciccarelli, L., Sellinger, B., Kozak, C. A., Wistow, G. Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF. Mammalian Genome 9: 753-757, 1998. [PubMed: 9716662] [Full Text: https://doi.org/10.1007/s003359900858]
Nishihira, J., Fujinaga, M., Kuriyama, T., Suzuki, M., Sugimoto, H., Nakagawa, A., Tanaka, I., Sakai, M. Molecular cloning of human D-dopachrome tautomerase cDNA: N-terminal proline is essential for enzyme activation. Biochem. Biophys. Res. Commun. 243: 538-544, 1998. [PubMed: 9480844] [Full Text: https://doi.org/10.1006/bbrc.1998.8123]