Distinct inositol and phosphatidylinositol polyphosphates B-phosphatases have recently been cloned. Primers have been designed coding for highly conserved amino acid regions that are shared between sequences of B-phosphatases. One of the PCR fragment referred to as 51 C, shows 99 % identity to a previously reported sequence (INPPL-1) present in the database. We report here the identification of cDNAs for a new SH2-domain-containing protein showing homology to the inositol B-phosphatase SHIP and therefore referred to as SHIPS. SHIPS differs at both N- and C-terminal ends with the sequence of INPPL-1. The translated sequence of SHIPS encodes a 1258 amino acid protein with a predicted molecular mass of 142 kDa. Particularly high levels of SHIPS were found in human heart, skeletal muscle and placenta as shown by Northern blot analysis. SHIPS was also expressed in dog thyroid cells in primary culture where the expression was enhanced in TSH and EGF-stimulated cells. (C) 1997 Academic Press.