Alternative titles; symbols
HGNC Approved Gene Symbol: STX12
Cytogenetic location: 1p35.3 Genomic coordinates (GRCh38): 1:27,773,219-27,824,443 (from NCBI)
STX12 functions with the VPS16B (VIPAS39; 613401)/VPS33B (608552) complex in the biogenesis of platelet alpha-granules (Ambrosio et al., 2022).
By database analysis, Advani et al. (1998) identified syntaxin-12, which they called syntaxin-13. They cloned STX12 cDNA from a rat brainstem and spinal cord cDNA library using a human brain cDNA clone as probe. Rat STX12 shares 53% sequence identity with STX7 (603217). Northern blot analysis detected expression of a 2.9-kb transcript in rat brain, with very little expression in other tissues. Western blot analysis detected a 33-kD band in brain, a faint signal in pancreas, and barely detectable signals in other tissues. Cell fractionation studies of rat brain showed that STX12 is an integral membrane protein, and immunolocalization studies localized STX12 to the cell body of cultured rat hippocampal neurons. Tang et al. (1998) independently cloned rat STX12 from a rat brain cDNA library. Northern blot analysis detected highest expression in brain, lung, and kidney. Immunolocalization studies showed compact perinuclear staining, and experimental manipulation revealed specific localization of STX12 to the endosomal compartment.
Using immunocytochemistry, fluorescence, and confocal microscopy, Collins et al. (2002) showed that STX7 and STX12 are involved in the ordered fusion of endosomes and lysosomes with the phagosome, where phagocytic cells kill and degrade internalized foreign particles. STX12 is localized to the recycling endosome compartment, while STX7 is found in late endosomes and lysosomes and both are recruited to the phagosome. However, STX12 is acquired earlier before rapidly recycling off the phagosome, while STX7 is recruited later and continues to accumulate throughout the phagosome maturation process.
Using purified recombinant proteins, Ambrosio et al. (2022) showed that the SNARE protein STX12 interacted with the VPS16B/VPS33B complex that mediates transport of newly synthesized alpha-granule proteins through megakaryocyte endosomal compartments. Deletion analysis indicated that the STX12 SNARE domain mediated the interactions with VPS16B/VPS33B, while the N-terminal region of STX12, likely the Habc domain, inhibited it. STX12 was localized to sorting endosomes in stem cell-derived immortalized megakaryocyte cells (imMKCL), and STX12 deficiency caused alpha-granule defects in imMKCL. These results demonstrated that STX12 is another component needed for alpha-granule biogenesis in addition to VPS16B and VPS33B. CCDC22 (300859), a component of the CCC complex working at endosome exit sites, competed with STX12 for binding to the same region of the VPS16B/VPS33B complex, and competition between the 2 proteins appeared to have functional significance in alpha-granule biogenesis in imMKCL. STX12 deficiency caused less severe alpha-granule defects than VPS16B/VPS33B deficiency, suggesting that STX12 assists but is less important than VPS16B/VPS33B in alpha-granule biogenesis.
Advani, R. J., Bae, H.-R., Bock, J. B., Chao, D. S., Doung, Y.-C., Prekeris, R., Yoo, J.-S., Scheller, R. H. Seven novel mammalian SNARE proteins localize to distinct membrane compartments. J. Biol. Chem. 273: 10317-10324, 1998. [PubMed: 9553086] [Full Text: https://doi.org/10.1074/jbc.273.17.10317]
Ambrosio, A. L., Febvre, H. P., Di Pietro, S. M. Syntaxin 12 and COMMD3 are new factors that function with VPS33B in the biogenesis of platelet alpha-granules. Blood 139: 922-935, 2022. [PubMed: 34905616] [Full Text: https://doi.org/10.1182/blood.2021012056]
Collins, R. F., Schreiber, A. D., Grinstein, S., Trimble, W. S. Syntaxins 13 and 7 function at distinct steps during phagocytosis. J. Immun. 169: 3250-3256, 2002. [PubMed: 12218144] [Full Text: https://doi.org/10.4049/jimmunol.169.6.3250]
Tang, B. L., Tan, A. E. H., Lim, L. K., Lee, S. S., Low, D. Y. H., Hong, W. Syntaxin 12, a member of the syntaxin family localized to the endosome. J. Biol. Chem. 273: 6944-6950, 1998. [PubMed: 9507000] [Full Text: https://doi.org/10.1074/jbc.273.12.6944]