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
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
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping