| First Author | Cai T | Year | 2001 |
| Journal | Diabetologia | Volume | 44 |
| Issue | 1 | Pages | 81-8 |
| PubMed ID | 11206415 | Mgi Jnum | J:67940 |
| Mgi Id | MGI:1931717 | Doi | 10.1007/s001250051583 |
| Citation | Cai T, et al. (2001) The IA-2 gene family: homologs in Caenorhabditis elegans, Drosophila and zebrafish. Diabetologia 44(1):81-8 |
| abstractText | AIMS/HYPOTHESIS: IA-2 and IA-2beta are major autoantigens in Type I (insulin-dependent) diabetes mellitus and are expressed in neuroendocrine tissues including the brain and pancreatic islets of Langerhans. Based on sequence analysis, IA-2 and IA-2beta are transmembrane protein tyrosine phosphatases but lack phosphatase activity because of critical amino acid substitutions in the catalytic domain. We studied the evolutionary conservation of IA-2 and IA-2beta genes and searched for homologs in non-mammalian vertebrates and invertebrates. METHODS: IA-2 from various species was identified from EST sequences or cloned from cDNA libraries or both. Expression in tissues was determined by transfection and in situ hybridization. RESULTS: We identified homologs of IA-2 in C. elegans, Drosophila, and zebrafish which showed 46, 58 and 82 % identity and 60, 65 and 87 % similarity, respectively, to the amino acids of the intracellular domain of human IA-2. Further studies showed that IA-2 was expressed in the neural tissues of the three species. Comparison of the genomic structure of the intracellular domain of human IA-2 with that of human IA-2beta showed that they were nearly identical and comparison of the intron-exon boundaries of Drosophila IA-2 with human IA-2 and IA-2beta showed a high degree of relatedness. CONCLUSION/INTERPRETATION: Based on these findings and sequence analysis of IA-2 homologs in mammals, we conclude that there is an IA-2 gene family which is a part of the larger protein tyrosine phosphatase superfamily. The IA-2 and IA-2beta genes represent two distinct subgroups within the IA-2 family which originated over 500 million years ago, long before the development of the pancreatic islets of Langerhans. |
