Protein tyrosine phosphatases: counting the trees in the forest

The recent identification of many different protein tyrosine phosphatases (PTPs) has led to the recognition that these enzymes match protein tyrosine kinases (PTKs) in importance for intracellular signalling. The total number of PTPs encoded by the mammalian genome has been estimated at between 500 and approx. 2000. These estimates are imprecise due to the large number of sequence database entries that represent different splice forms, or duplicates of the same PTP sequence. A careful analysis of these entries, grouped by identical catalytic domain shows that no more than 48 full-length PTP sequences are currently known, and that their total number in the human genome may not exceed 100. An alignment of all catalytic domains also suggests that during evolution intragenic catalytic domain duplication, as seen in most membrane-bound PTPs, preceded gene duplication.