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,1
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA;
* Scientific Computing, Novo Nordisk, DK-2760 Måløv, Denmark;
Exiqon, DK-2950 Vedbæk, Denmark; and
Signal transduction, Novo Nordisk, DK-2880 Bagsværd, Denmark
1Correspondence: N.P.H.M., Novo Nordisk, Bldg. 6A1.086, Signal Transduction, DK-2880 Bagsværd, Denmark; E-mail: nphm{at}novonordisk.com and N.K.T., Cold Spring Harbor Laboratory, Demerec Bldg., 1 Bungtown Rd., Cold Spring Harbor, NY 11724-2208, USA; E-mail: tonks{at}cshl.edu
The protein tyrosine phosphatases (PTPs) are now recognized as critical regulators of signal transduction under normal and pathophysiological conditions. In this analysis we have explored the sequence of the human genome to define the composition of the PTP family. Using public and proprietary sequence databases, we discovered one novel human PTP gene and defined chromosomal loci and exon structure of the additional 37 genes encoding known PTP transcripts. Direct orthologs were present in the mouse genome for all 38 human PTP genes. In addition, we identified 12 PTP pseudogenes unique to humans that have probably contaminated previous bioinformatics analysis of this gene family. PCR amplification and transcript sequencing indicate that some PTP pseudogenes are expressed, but their function (if any) is unknown. Furthermore, we analyzed the enhanced diversity generated by alternative splicing and provide predicted amino acid sequences for four human PTPs that are currently defined by fragments only. Finally, we correlated each PTP locus with genetic disease markers and identified 4 PTPs that map to known susceptibility loci for type 2 diabetes and 19 PTPs that map to regions frequently deleted in human cancers. We have made our analysis available at http://ptp.cshl.edu or http://science.novonordisk.com/ptp and we hope this resource will facilitate the functional characterization of these key enzymes.—Andersen, J. N., Jansen, P. G., Echwald, S. M., Mortensen, O. H., Fukada, T., Del Vecchio, R., Tonks, N. K., Møller, N. P. H. A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage.
Key Words: genome analysis • protein classification • PTP exon structure • PTP gene family • processed pseudogenes • PTPs and cancer • alternative splicing
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