Alternative titles; symbols
HGNC Approved Gene Symbol: SNAPIN
Cytogenetic location: 1q21.3 Genomic coordinates (GRCh38): 1:153,658,654-153,661,852 (from NCBI)
SNAPAP is a component of the SNARE complex of proteins that is required for synaptic vesicle docking and fusion (Ilardi et al., 1999). SNAPAP is also a component of the ubiquitously expressed BLOC1 multisubunit protein complex. BLOC1 is required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules (Starcevic and Dell'Angelica, 2004).
Ilardi et al. (1999) identified SNAPAP, which they called Snapin, using mouse Snap25 (600322) as bait in a yeast 2-hybrid screen of a human brain cDNA library. The deduced 136-amino acid protein has a calculated molecular mass of 15 kD. It contains an N-terminal hydrophobic segment characteristic of a transmembrane domain and a coiled-coil C-terminal region. SNAPAP shares 98% sequence identity with the mouse homolog. Western blot analysis of various rat tissues showed SNAPAP almost exclusively in brain and synaptosome preparations. Further analysis indicated SNAPAP in all 12 rat brain areas examined; fractionation of rat cerebral synaptosomes indicated that SNAPAP partitions with the synaptic vesicle fraction and not with cytosolic or plasma membrane fractions.
Using the BLOC1 subunit pallidin (PLDN; 604310) as bait in a yeast 2-hybrid screen of a HeLa cell cDNA library, Starcevic and Dell'Angelica (2004) cloned SNAPAP. The deduced SNAPAP protein contains coiled-coil regions. Western blot analysis detected endogenous HeLa cell SNAPAP at an apparent molecular mass of 15 kD.
With the use of recombinant mouse proteins and deletion mutants in in vitro binding assays, Ilardi et al. (1999) determined that binding between Snapin and Snap25 shows a 1:1 stoichiometry. All of the SNARE components, including syntaxin (see 186590), SNAP25, VAMP2 (185881), and synaptotagmin (see 185605), were coprecipitated by the anti-Snapin antibody. With the use of truncation mutants, Ilardi et al. (1999) identified the SNAP25-interacting region in the final 20 amino acids of the C terminus; 3 point mutations in this region, designed to destabilize the coiled-coil structure, interfered with SNAP25 binding. The introduction of exogenous C-terminal Snapin or the SNAP25-binding region to rat presynaptic superior cervical ganglion neurons in culture reversibly inhibited synaptic transmission between the cells.
By mass spectrometry of BLOC1 proteins purified from bovine liver, mouse liver, and HeLa cells, Starcevic and Dell'Angelica (2004) identified SNAPAP as a subunit of BLOC1. Other BLOC1 subunits identified were pallidin, muted (607289), dysbindin (DTNBP1; 607145), cappuccino (605695), BLOC1S1 (601444), BLOC1S2 (609768), and BLOC1S3 (609762). Coimmunoprecipitation and yeast 2-hybrid analyses confirmed that these proteins interact within the BLOC1 complex.
Pu et al. (2015) determined that BLOC1S1, BLOC1S2, snapin, and, possibly, KXD1 (615178) were subunits of 2 protein complexes, BLOC1 and BLOC1-related complex (BORC). BORC recruited the small GTPase ARL8B (616596) and mediated kinesin-dependent movement of lysosomes along the plus ends of microtubules toward the cell periphery. Interference with BORC or other components of this pathway resulted in collapse of lysosomes into the pericentriolar region and reduced cell spreading and cell migration.
Gross (2015) mapped the SNAPIN gene to chromosome 1q21.3 based on an alignment of the SNAPIN sequence (GenBank AF086837) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 12/28/2015.
Ilardi, J. M., Mochida, S., Sheng, Z.-H. Snapin: a SNARE-associated protein implicated in synaptic transmission. Nature Neurosci. 2: 119-124, 1999. [PubMed: 10195194] [Full Text: https://doi.org/10.1038/5673]
Pu, J., Schindler, C., Jia, R., Jarnik, M., Backlund, P., Bonifacino, J. S. BORC, a multisubunit complex that regulates lysosome positioning. Dev. Cell 33: 176-188, 2015. [PubMed: 25898167] [Full Text: https://doi.org/10.1016/j.devcel.2015.02.011]
Starcevic, M., Dell'Angelica, E. C. Identification of Snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1). J. Biol. Chem. 279: 28393-28401, 2004. [PubMed: 15102850] [Full Text: https://doi.org/10.1074/jbc.M402513200]