Biology:NAPA (gene)

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

N-ethylmaleimide-sensitive factor Attachment Protein Alpha, also known as SNAP-α, is a SNAP protein that is involved in the intra-cellular trafficking and fusing of vesicles to target membranes in cells.

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.

Further reading

• "A multisubunit particle implicated in membrane fusion". J. Cell Biol. 117 (3): 531–8. 1992. doi:10.1083/jcb.117.3.531. PMID 1315316. 
• "Soluble N-ethylmaleimide-sensitive fusion attachment proteins (SNAPs) bind to a multi-SNAP receptor complex in Golgi membranes". J. Biol. Chem. 267 (17): 12239–43. 1992. doi:10.1016/S0021-9258(19)49830-X. PMID 1601890. 
• "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin". J. Biol. Chem. 270 (28): 16955–61. 1995. doi:10.1074/jbc.270.28.16955. PMID 7622514. 
• "SNAP family of NSF attachment proteins includes a brain-specific isoform". Nature 362 (6418): 353–5. 1993. doi:10.1038/362353a0. PMID 8455721. Bibcode: 1993Natur.362..353W. 
• "Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein". Biochem. J. 320 (Pt 2): 429–36. 1997. doi:10.1042/bj3200429. PMID 8973549. 
• "Regulated secretion in platelets: identification of elements of the platelet exocytosis machinery". Blood 90 (4): 1490–500. 1997. doi:10.1182/blood.V90.4.1490. PMID 9269766. 
• "N-Ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment proteins (SNAP) mediate dissociation of GS28-syntaxin 5 Golgi SNAP receptors (SNARE) complex". J. Biol. Chem. 272 (41): 25441–4. 1997. doi:10.1074/jbc.272.41.25441. PMID 9325254. 
• "A SNARE involved in protein transport through the Golgi apparatus". Nature 389 (6653): 881–4. 1997. doi:10.1038/39923. PMID 9349823. Bibcode: 1997Natur.389..881L. 
• "Stimulation of NSF ATPase Activity by α-SNAP Is Required for SNARE Complex Disassembly and Exocytosis". J. Cell Biol. 139 (4): 875–83. 1997. doi:10.1083/jcb.139.4.875. PMID 9362506. 
• "Syntaxin 7, a novel syntaxin member associated with the early endosomal compartment". J. Biol. Chem. 273 (1): 375–80. 1998. doi:10.1074/jbc.273.1.375. PMID 9417091. 
• "Syntaxin 12, a member of the syntaxin family localized to the endosome". J. Biol. Chem. 273 (12): 6944–50. 1998. doi:10.1074/jbc.273.12.6944. PMID 9507000. 
• "Endobrevin, a Novel Synaptobrevin/VAMP-Like Protein Preferentially Associated with the Early Endosome". Mol. Biol. Cell 9 (6): 1549–63. 1998. doi:10.1091/mbc.9.6.1549. PMID 9614193. 
• "The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs". Neuron 21 (1): 99–110. 1998. doi:10.1016/S0896-6273(00)80518-8. PMID 9697855. 
• "Syntaxin 13 Mediates Cycling of Plasma Membrane Proteins via Tubulovesicular Recycling Endosomes". J. Cell Biol. 143 (4): 957–71. 1998. doi:10.1083/jcb.143.4.957. PMID 9817754. 
• "alpha-soluble N-ethylmaleimide-sensitive factor attachment protein is expressed in pancreatic beta cells and functions in insulin but not gamma-aminobutyric acid secretion". J. Biol. Chem. 274 (12): 8053–60. 1999. doi:10.1074/jbc.274.12.8053. PMID 10075705. 
• "Preferential association of syntaxin 8 with the early endosome". J. Cell Sci. 113 (6): 997–1008. 2000. doi:10.1242/jcs.113.6.997. PMID 10683148. https://eprints.qut.edu.au/99885/1/99885.pdf. 
• "Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi". EMBO J. 23 (6): 1267–78. 2005. doi:10.1038/sj.emboj.7600135. PMID 15029241. 
• "VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx". Mol. Cell 15 (4): 635–46. 2004. doi:10.1016/j.molcel.2004.07.010. PMID 15327778.