*602750
D-DOPACHROME TAUTOMERASE; DDT

HGNC Approved Gene Symbol: DDT

Cytogenetic location: 22q11.23     Genomic coordinates (GRCh37): 22:24,313,553 - 24,322,018 (from NCBI)

TEXT
In melanocytes, dopachrome tautomerase (TYRP2; 191275) converts L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid. D-dopachrome tautomerase converts D-dopachrome into 5,6-dihydroxyindole. 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 weight of recombinant DDT expressed in bacterial cells was 13 kD by SDS-PAGE. Using site-directed mutagenesis, Nishihira et al. (1998) showed that the N-terminal proline is essential for D-dopachrome tautomerization. Northern blot analysis revealed that DDT was expressed as a 0.6-kb mRNA in all tissues tested, with the strongest expression in liver.

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.

REFERENCES
1. 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, related citations] [Full Text: Springer, Pubget]

2. 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, related citations] [Full Text: Elsevier Science, Pubget]

Contributors: Victor A. McKusick - updated : 9/18/1998
Creation Date: Rebekah S. Rasooly : 6/24/1998
Edit History: carol : 09/23/1998
dkim : 9/23/1998
terry : 9/18/1998
alopez : 6/24/1998