NAPA (gene)

Function

The 'SNARE hypothesis' is a model explaining the process of docking and fusion of vesicles to their target membranes. According to this model, membrane proteins from the vesicle (v-SNAREs) and proteins from the target membrane (t-SNAREs) govern the specificity of vesicle targeting and docking through mutual recognition.

Once the 2 classes of SNAREs bind to each other, they form a complex that recruits the general elements of the fusion apparatus, namely NSF (N-ethylmaleimide-sensitive factor) and SNAPs (soluble NSF-attachment proteins), to the site of membrane fusion, thereby forming the 20S fusion complex.

Alpha- and gamma-SNAP are found in a wide range of tissues and act synergistically in intra-Golgi transport. The sequence of the predicted 295-amino acid human protein encoded by NAPA shares 37%, 60%, and 67% identity with the sequences of yeast, Drosophila, and squid alpha-SNAP, respectively. Platelets contain some of the same proteins, including NSF, p115/TAP, alpha-SNAP (this protein), gamma-SNAP, and the t-SNAREs syntaxin-2 and syntaxin-4, that are used in many vesicular transport processes in other cell types. Platelet exocytosis uses a molecular mechanism similar to that used by other secretory cells, such as neurons, although the proteins used by the platelet and their modes of regulation may be quite different.

Clinical significance

NAPA is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increased risk of birth defects in these methods of assisted reproductive technology (ART).

Interactions

NAPA has been shown to interact with:

• NSF,
• SNAP23,
• STX1A,
• STX4,
• STX5.
• ORAI1, STIM1.

References

References

1. (1990). "SNAPs, a family of NSF attachment proteins involved in intracellular membrane fusion in animals and yeast". Cell.
2. (September 2008). "Comparative proteomic analysis of human placenta derived from assisted reproductive technology". Proteomics.
3. (Nov 1997). "Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis". J. Cell Biol..
4. (Jul 1995). "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin". J. Biol. Chem..
5. (Oct 1995). "Complexins: cytosolic proteins that regulate SNAP receptor function". Cell.
6. (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature.
7. (Mar 1998). "Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro". Cell.
8. (July 2013). "An essential and NSF independent role for α-SNAP in store-operated calcium entry". eLife.