SPIN90 (SH3 protein interacting with Nck, 90 kDa), an adaptor protein thatis developmentally regulated during cardiac myocyte differentiation

In the yeast two-hybrid screening, we have isolated a cDNA clone from a hum an heart library using Nck Src homology 3 (SH3) domains as bait. The full-l ength cDNA, which encoded 722 amino acids, was identified as a VIP54-relate d gene containing an SH3 domain, proline-rich motifs, a serine/threonine-ri ch region, and a long C-terminal hydrophobic region. We refer to this prote in as SPIN90 ((S) under bar H3 (P) under bar rotein (I) under bar nteractin g with (N) under bar ck, (90) under bar kDa), The amino acid sequence of th e SH3 domain has the highest homology with those of Fyn, Yes, and c-Src. SP IN90 was broadly expressed in human tissues; in particular, it was highly e xpressed in heart, brain, and skeletal muscle, and its expression was devel opmentally regulated during cardiac myocyte differentiation. SPIN90 is able to bind to the first and third SH3 domains of Nck, in vitro, and is coloca lized with Nck at sarcomere Z-discs within cardiac myocytes, Moreover, trea tment with antisera raised against SPIN90 disrupted sarcomere structure, su ggesting that this protein may play an important role in the maintenance of sarcomere structure and/or in the assembly of myofibrils into sarcomeres.