Cloning, chromosomal localization, and characterization of cDNA from a novel gene, SH3BP4, expressed by human corneal fibroblasts

The cornea contains, as a major element, a transparent stroma produced and maintained by keratocytes (fibroblasts). Through molecular biology studies using cultured human corneal fibroblasts, a cDNA that was shown to be novel was isolated and sequenced. This novel gene product, named SH3-domain bind ing protein 4 (SH3BP4), contains a 5.6-kb message that is present in normal human corneal fibroblasts and all tissues examined, with higher levels in pancreas, placenta, heart, and kidney. SH3BP4 was localized by FISH analysi s to human chromosome 2q37.1-q37.2 near the telomere. The deduced sequence for SH3BP4 was found to contain a 963-amino-acid open reading frame that ha s homology to a 479-amino-acid protein in GenBank called EH-binding protein . Although the entire sequence of EH-binding protein aligns with SH3BP4, th e alignment is not complete or contiguous. Therefore, SH3BP4 has an additio nal 73 amino acids at the N-terminus and an additional 411 amino acids near the C-terminus that are not present in EH-binding protein. Consensus seque nce domains identified in SH3BP4 include a SH3 domain, three N-P-F motifs, a P-X-X-P motif noted for binding to SH3 domains, a bipartite nuclear targe ting signal, and a tyrosine phosphorylation site. SH3BP4 homologies and con sensus sequence sites indicate that it may be involved in a newly identifie d cascade of proteins involved in endocytosis, intracellular sorting, and t he cell cycle. (C) 1999 Academic Press.