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Uncovering the Protein Tyrosine Phosphatome in Cattle A Uncovering the Protein Tyrosine Phosphatome in Cattle A. Priest, Dr. S. Rodriguez-Zas Department of Animal Sciences, University of Illinois, Urbana, Illinois 61801 Table 1. Similarity between homologue PTP genes in humans and cattle UniProt Bos taurus Bos taurus Entrez % % Prohormone Extended Name E Valuea % Gapsd Predicted? Entrez Number Gene Name Identityb Positivec Name protein tyrosine phosphatase, Introduction PTPRD 532751 PTPRD 0.00E+00 98 99 0 predicted • Protein tyrosine phosphatases (PTPs), receptor type, D protein tyrosine phosphatase, are enzymes involved in signal PTPRK 509657 PTPRK 0.00E+00 98 99 0 predicted receptor type, K transduction, cellular signaling, protein tyrosine phosphatase, PTPN11 533590 PTPN11 0.00E+00 98 99 0 predicted regulation of cellular growth, non-receptor type 11 mitogenesis, motility, cell to cell a. Indicator of the statistical probability that the two sequences aligned are true homologues and not similar by chance interactions, metabolism, gene b. Alignment locations with the same amino acids in both sequences transcription, and the immune response c. Alignment locations with similar amino acids in both sequences 1,2 d. Insertions or deletions of nucleotides during the evolutionary process that differentiated cattle from humans • Improper functioning of PTPs can play a Materials and Methods Results Conclusion role in diabetes, obesity, cancers, and • This comprehensive survey suggests • First, a master list of PTP sequences • A total of 37 human PTP protein sequences immune dysfunctions3 that many PTP genes have been was created using the human protein were found in the GenBank and UniProt • Due to their association with numerous conserved between the human and cattle tyrosine phosphatome as a guide searches from the first three search steps cellular processes, PTPs have the genomes and provided information • Second, the protein and gene • Of these 37 sequences, only 31 had a potential to significantly impact the describing the various tissues and age sequences of the human PTPs were counterpart in the cattle genome, and sustainability of the dairy and beef cattle groups where PTP genes are expressed retrieved from the NCBI GenBank and UniProt contained information on only 12 industries in cattle UniProt databases PTPs • The PTP encompasses three • Further basic and applied research holds (http://www.ncbi.nlm.nih.gov • The alignment of the 37 human sequences evolutionarily unrelated classes of the possibility to improve cattle http://www.uniprot.org/uniprot), and a against the cattle RefSeq sequences using proteins: PTPs, Cdc25, and low production and health lies in the search for the human PTP protein on BLASTP uncovered 26 predicted sequences molecular weight phosphatases4 application of this information cattle was undertaken and confirmed 11 known sequences • The PTP class includes more than 100 • The results from this work will help in the • Third, cattle PTP protein sequences that • The best human-cattle matches were for genes in humans, and these can be design of follow-up functional studies to had been automatically annotated as PTPRD, PTPRK, and PTPN11 – this further divided into classical PTPs, characterize the role of PTPs in the PTPs by GenBank or UniProt were indicates that they are very-well conserved which dephosphorylate only tyrosine, physiology of cattle found across these species (Table 1) and dual specificity phosphatases, • Fourth, the remaining human PTP • The less reliable human-cattle matches were which can dephosphorylate tyrosine, sequences that were not found in the the sequences for PTPRH, PTPRC, and References serine, and threonine residues5 • 1. Ostman, A. and Böhmer, F.D. (2001). previous step were searched for in the LOC616515, which may be due to lesser • A total of 38 classical PTP genes have Regulation of receptor tyrosine kinase NCBI Cattle Genome RefSeq repository evolutionary conservation or to limitations on been identified in the human and mouse signaling by protein tyrosine phosphatases. (http://www.ncbi.nlm.nih.gov/RefSeq) the cattle genome sequence genomes5 Trends in Cell Biology. 11:258-266. using BLASTP, a bioinformatics tool to • The search in UniProt for PTPs in other • 2. Burke Jr., T.R. and Zhang ZY. (1998). • These classical PTPs can be divided align sequences to a database of livestock mammals uncovered two Protein-tyrosine phosphatases: Structure, into receptor type and non-receptor 6 sequences sequences in the pig for PTPN11 and mechanism, and inhibitor discovery. Peptide type5 • Fifth, PTP sequences that were not PTPRG. For these sequences, the pig Science. 47.3: 225-241. • 3. PTP gene family. (2007). Retrieved on May found in the fourth step were searched genes is more similar than the human to the against PTP proteins of other livestock 11, 2009, from cattle genes http://ghr.nlm.nih.gov/geneFamily=ptp. Objectives mammals available in UniProt to • To assemble the first protein tyrosine • The gene expression profiles from the EST • 4. Andreeva, A.V. and Kutuzov, M.A. (2008). uncover potentially between matches phosphatome in cattle and GEO databases indicated that three Protozoan protein tyrosine phosphatases. between non-human sequences and the • To study the expression patterns of PTP most common sites of PTP gene expression International Journal for Parasitology. 38:1279- cattle genome 1295. genes across tissues and ages, which are the brain, intestine and liver. In terms of • Sixth, a survey of the Expressed • 5. Andersen, J. N. et al. (2004). A genomic will facilitate uncovering potential development, the calf expresses the most Sequence Tagged and Gene Expression perspective on protein tyrosine phosphatases: differences in function and pathways PTP genes, followed by the fetus, and then Omnibus profiles summarized in the gene structure, pseudogenes, and genetic across the PTPs the adult disease linkage. FASEB Journal. 18:8–13 UniGene database was performed • The most commonly expressed PTP genes • 6. BLAST. (2009). Retrieved on May 11, 2009, (http://www.ncbi.nlm.nih.gov/ unigene) included PTPN2, PTPRA, and PTPN11 from http://blast.ncbi.nlm.nih.gov/Blast.cgi.
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