Alternative titles; symbols
HGNC Approved Gene Symbol: BLOC1S1
Cytogenetic location: 12q13.2 Genomic coordinates (GRCh38): 12:55,716,046-55,719,703 (from NCBI)
BLOC1S1 is 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).
Inoue et al. (1996) described the isolation and characterization of a human gene with homology to yeast GCN5. The 545-bp cDNA, termed GCN5L1, encodes a 126-amino acid polypeptide having 23.5% identity to yeast GCN5. Northern blot analysis revealed transcription of this gene in all human tissues examined.
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 BLOC1S1, which they called BLOS1. The deduced BLOS1 protein contains coiled-coil regions and has a calculated molecular mass of 14.3 kD. Western blot analysis detected endogenous HeLa cell BLOS1 at an apparent molecular mass of 13 kD.
By mass spectrometry of BLOC1 proteins purified from bovine liver, mouse liver, and HeLa cells, Starcevic and Dell'Angelica (2004) identified BLOS1 as a subunit of BLOC1. Other BLOC1 subunits identified were pallidin, muted (607289), dysbindin (DTNBP1; 607145), cappuccino (605695), snapin (SNAPAP; 607007), 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.
Inoue et al. (1996) mapped the BLOC1S1 gene to 12q13-q14 by fluorescence in situ hybridization. Gross (2015) mapped the BLOC1S1 gene to chromosome 12q13.2 based on an alignment of the BLOC1S1 sequence (GenBank BC132795) with the genomic sequence (GRCh38).
Cheli et al. (2010) generated a fly model of BLOC1 deficiency. Mutant flies lacking the conserved Blos1 subunit displayed eye pigmentation defects due to abnormal pigment granules (lysosome-related organelles), as well as abnormal glutamatergic transmission and behavior. Epistatic analyses revealed that BLOC1 function in pigment granule biogenesis requires the activities of BLOC2 and a putative Rab guanine nucleotide exchange factor named Claret. The eye pigmentation phenotype was modified by misexpression of proteins involved in intracellular protein trafficking; in particular, the phenotype was partially ameliorated by Rab11 (605570) and strongly enhanced by the clathrin-disassembly factor auxilin (DNAJC6; 608375).
Cheli, V. T., Daniels, R. W., Godoy, R., Hoyle, D. J., Kandachar, V., Starcevic, M., Martinez-Agosto, J. A., Poole, S., DiAntonio, A., Lloyd, V, K., Chang, H. C., Krantz, D. E., Dell-Angelica, E. C. Genetic modifiers of abnormal organelle biogenesis in a Drosophila model of BLOC-1 deficiency. Hum. Molec. Genet. 19: 861-878, 2010. [PubMed: 20015953] [Full Text: https://doi.org/10.1093/hmg/ddp555]
Gross, M. B. Personal Communication. Baltimore, Md. 12/28/2015.
Inoue, M., Isomura, M., Ikegawa, S., Fujiwara, T., Shin, S., Moriya, H., Nakamura, Y. Isolation and characterization of a human cDNA clone (GCN5L1) homologous to GCN5, a yeast transcription factor. Cytogenet. Cell Genet. 73: 134-136, 1996. [PubMed: 8646881] [Full Text: https://doi.org/10.1159/000134324]
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]