PUBLICATION
The IA-2 gene family: homologs in Caenorhabditis elegans, Drosophila and zebrafish
- Authors
- Cai, T., Krause, M.W., Odenwald, W.F., Toyama, R., and Notkins, A.L.
- ID
- ZDB-PUB-010213-2
- Date
- 2001
- Source
- Diabetologia 44(1): 81-88 (Journal)
- Registered Authors
- Cai, Tao, Toyama, Reiko
- Keywords
- C. elegans; Drosophila; zebrafish; IA-2; insulin-dependent diabetes mellitus
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Autoantigens
- Caenorhabditis elegans/genetics*
- Drosophila/genetics*
- Gene Expression
- Green Fluorescent Proteins
- Humans
- In Situ Hybridization
- Luminescent Proteins/analysis
- Luminescent Proteins/genetics
- Membrane Proteins/analysis
- Membrane Proteins/chemistry
- Membrane Proteins/genetics*
- Molecular Sequence Data
- Nerve Tissue/immunology
- Neurons/chemistry
- Phylogeny
- Protein Tyrosine Phosphatases/analysis
- Protein Tyrosine Phosphatases/chemistry
- Protein Tyrosine Phosphatases/genetics*
- RNA, Messenger/analysis
- Receptor-Like Protein Tyrosine Phosphatases, Class 8
- Sequence Alignment
- Tissue Distribution
- Transfection
- Zebrafish/genetics*
- PubMed
- 11206415 Full text @ Diabetologia
Citation
Cai, T., Krause, M.W., Odenwald, W.F., Toyama, R., and Notkins, A.L. (2001) The IA-2 gene family: homologs in Caenorhabditis elegans, Drosophila and zebrafish. Diabetologia. 44(1):81-88.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping