LZ-FYVE: a novel developmental stage-specific leucine zipper, FYVE-finger protein.

We describe the molecular cloning and characterization of LZ-FYVE, a novel embryonic factor that possesses two leucine zipper motifs and a FYVE-finger domain. A partial clone of LZ-FYVE, encoding a functional leucine zipper domain, was initially isolated from a mouse embryo cDNA library by virtue of its interaction in the yeast two-hybrid system with the transcription factor ATF-2. The LZ-FYVE protein demonstrated mouse embryo-specific expression by Northern blot analysis and was detected as a nuclear protein at very restricted periods (12--14 days post-coitus) in specific tissues during embryogenesis. In particular, LZ-FYVE protein was notable in embryonic lung, cartilage, and otic capsule. Structural analysis of the deduced, full-length LZ-FYVE amino acid sequence revealed two N-terminal leucine zipper domains as well as a C-terminal FYVE-finger domain. The FYVE-finger domains specifically recognized phosphatidylinositol 3-phosphate and have been previously described only in cytoplasmic proteins involved in endosomal membrane fusion, vesicular trafficking, or organelle-specific targeting. While LZ-FYVE may have endosomal functions in the cytoplasm, because LZ-FYVE is present in the nucleus at early stages of embryonic development, it is likely that LZ-FYVE has a nuclear function.