A NOVEL SH3-CONTAINING HUMAN GENE FAMILY PREFERENTIALLY EXPRESSED IN THE CENTRAL-NERVOUS-SYSTEM

The Src-homology-3 domain (SH3) is an evolutionarily conserved, 50- to 60-amino-acid module carried by intracellular proteins involved in th e transduction of signals for cell polarization, motility, enzymatic a ctivation, and transcriptional regulation. The SH3 drives protein-prot ein interactions through binding to proline-rich ligands, This functio n relies on the conserved secondary structure, whereas the SH3 primary structure is highly diverse. Taking advantage of the fact that the fe w conserved amino acids are clustered near the N- and C-terminal ends, we designed degenerate oligonucleotides spanning these two regions an d screened by PCR a variety of normal and tumor tissues for the expres sion of SH3-containing transcripts. Using this strategy, we have ident ified a novel SH3-containing human gene family of six related transcri pts that map to four different chromosomes. The SH3 domain lies at the C-terminal end and shows 56-50% amino acid homology to the C-terminal SH3 of Sem-5/Drk/GRB2. The N-terminal segment of this novel SH3GL (fr om SR3-containing Grb2-Iike) gene family does not resemble any known p rotein. Three of these transcripts are in-frame and show a peculiar ti ssue distribution: SH3GL2 is preferentially expressed in the brain, SH 3GL3 in brain and testis, and SH3GL1 is ubiquitous. (C) 1997 Academic Press.