HIP12 is a non-proapoptotic member of a gene family including HIP1, an interacting protein with huntingtin

Huntingtin-interacting protein 1 (HIP1) is a membrane-associated protein th at interacts with huntingtin, the protein altered in Huntington disease. HI P1 shows homology to S1a2p, a protein essential for the assembly and functi on of the cytoskeleton and endocytosis in Saccharomyces cerevisiae. We have determined that the HIP1 gene comprises 32 exons spanning approximately 21 5 kb of genomic DNA and gives rise to two alternate splice forms termed HIP 1-1 and HIP1-2. Additionally, we have identified a novel protein termed HIP 12 with significant sequence and biochemical similarities to HIP1 and high sequence similarity to S1a2p. HIP12 differs from HIP1 in its pattern of exp ression both at the mRNA and protein level. However, HIP1 and HIP12 are bot h found within the brain and show a similar subcellular distribution patter n. In contrast to HIP1, which is toxic in cell culture, HIP12 does not conf er toxicity in the same assay systems. Interestingly, HIP12 does not intera ct with huntingtin but can interact with HIP 1, suggesting a potential inte raction in vivo that may influence the function of each respective protein.