SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein.

Abstract

The function of the Fanconi anemia complementation group A (FANCA) protein remains unclear. To investigate possible protein-protein interactions, we performed yeast two-hybrid screening using a FANCA fragment as bait. Sorting nexin 5 (SNX5), a new member of the human SNX family, was identified as a putative FANCA-binding protein. The interaction between FANCA and SNX5 was confirmed by immunoprecipitation studies. All members of the SNX family have a characteristic amino acid region termed the phox homology (PX) domain. Deletion mutant analysis indicated that the PX domain is not required for binding to FANCA. The SNX proteins are thought to play an important role in receptor trafficking between organelles. We found that overexpression of SNX5 increased FANCA protein levels. Northern blot analysis of SNX5 showed the presence of alternatively spliced transcripts and different expression patterns in various human cancer cell lines and normal tissues. Further studies are needed to elucidate the functional significance of FANCA and SNX5 binding; however, we speculate that FANCA may affect SNX5 traffic with cell surface receptors.