PUBLICATION
The IA-2 gene family: Homologs in C. elegans, Drosophila and zebrafish
- Authors
- Notkins, A.L., Krause, M., Odenwald, W.F., Toyama, R., and Cai, T.
- ID
- ZDB-PUB-010815-2
- Date
- 2000
- Source
- Diabetologia 43(1): (Abstract)
- Registered Authors
- Cai, Tao, Toyama, Reiko
- Keywords
- none
- MeSH Terms
- none
- PubMed
- none
Citation
Notkins, A.L., Krause, M., Odenwald, W.F., Toyama, R., and Cai, T. (2000) The IA-2 gene family: Homologs in C. elegans, Drosophila and zebrafish. Diabetologia. 43(1).
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping