TY - JOUR

T1 - A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage

AU - Andersen, Jannik N

AU - Jansen, Peter G

AU - Echwald, Søren M

AU - Mortensen, Ole H

AU - Fukada, Toshiyuki

AU - Del Vecchio, Robert

AU - Tonks, Nicholas K

AU - Møller, Niels Peter H

N1 - Keywords: Amino Acid Sequence; Animals; Chromosome Mapping; Exons; Gene Components; Genetic Predisposition to Disease; Genome, Human; Humans; Linkage (Genetics); Molecular Sequence Data; Protein Tyrosine Phosphatases; Pseudogenes; Sequence Alignment

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1096/fj.02-1212rev

DO - 10.1096/fj.02-1212rev

M3 - Journal article

C2 - 14718383

VL - 18

SP - 8

EP - 30

JO - F A S E B Journal

JF - F A S E B Journal

SN - 0892-6638

IS - 1

ER -