Alternative titles; symbols
HGNC Approved Gene Symbol: VTA1
Cytogenetic location: 6q24.1-q24.2 Genomic coordinates (GRCh38): 6:142,147,263-142,224,685 (from NCBI)
C6ORF55 encodes a protein involved in trafficking of the multivesicular body, an endosomal compartment involved in sorting membrane proteins for degradation in lysosomes (Ward et al., 2005).
Using subtractive hybridization to identify genes upregulated by dopamine in rat cerebral astrocytes, followed by screening a human fetal brain cDNA library, Shi et al. (2001) cloned C6ORF55. The transcript contains a novel (CAG)n repeat that encodes polyglutamines.
Using yeast 2-hybrid analysis to screen human cDNA libraries for genes encoding LYST (606897)-interacting proteins, Tchernev et al. (2002) cloned C6ORF55, which they called LIP5.
Using Skd1 (VPS4B; 609983) as bait in a yeast 2-hybrid screen of a mouse brain cDNA library, Fujita et al. (2004) cloned C6orf55, which they called Sbp1. By database analysis, they identified multiple human cDNAs corresponding to SBP1, including 2 that encode 307- and 282-amino acid proteins, designated DRG1 and LIP5, respectively, that are identical in their first 157 amino acids but differ in their C termini. Fujita et al. (2004) suggested that these cDNAs encode distinct proteins due to small sequence alterations rather than alternative splicing. The deduced 309-amino acid mouse protein contains N- and C-terminal coiled-coil domains. The N-terminal region of SBP1 is rich in basic amino acids, whereas the C-terminal region is acidic. Northern blot analysis detected Sbp1 expression in most mouse tissues examined, with highest levels in heart, brain, liver, and kidney. Immunofluorescence analysis of HeLa cells showed that endogenous human SBP1 localized to the cytosol.
By sequence analysis, Ward et al. (2005) determined that the LIP5 cDNA encoding the 282-amino acid protein contains a frameshift, and that the full-length LIP5 protein contains 307 amino acids. Cell fractionation of COS-7 cells followed by Western blot analysis showed that epitope-tagged LIP5 was primarily cytosolic.
By yeast 2-hybrid analysis and pull-down assays, Fujita et al. (2004) showed that the C-terminal region of mouse Sbp1 bound Skd1. Expression of an ATPase-negative mouse Skd1 mutant in HeLa cells redirected endogenous SBP1 and SKD1 from the cytosol to an aberrant endosomal structure derived from early and late endosomes and lysosomes. In control HeLa cells, SKD1 existed as a monomer, and SBP1 formed an oligomer protein complex. The ATPase-negative Skd1 mutant formed large heterooligomers with endogenous SBP1 and SKD1 when expressed in HeLa cells, suggesting that the ATPase activity of SKD1 is required for disassembly of the SBP1/SKD1 complex.
Using affinity purification experiments, Ward et al. (2005) showed that LIP5 specifically interacted with CHMP5 (610900). Depletion of LIP5 by small-interfering RNA did not alter the distribution of early or late endocytic markers in HeLa and 293T cells, but it altered EGFR (131550) trafficking and reduced EGFR degradation in lysosomes. Depletion of LIP5 in 293T cells infected with human immunodeficiency virus (HIV)-1 reduced release of infectious particles.
By genomic sequence analysis, Fujita et al. (2004) mapped the C6ORF55 gene to chromosome 6.
Fujita, H., Umezuki, Y., Imamura, K., Ishikawa, D., Uchimura, S., Nara, A., Yoshimori, T., Hayashizaki, Y., Kawai, J., Ishidoh, K., Tanaka, Y., Himeno, M. Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B. J. Cell Sci. 117: 2997-3009, 2004. [PubMed: 15173323] [Full Text: https://doi.org/10.1242/jcs.01170]
Shi, J., Cai, W., Chen, X., Ying, K., Zhang, K., Xie, Y. Identification of dopamine responsive mRNAs in glial cells by suppression subtractive hybridization. Brain Res. 910: 29-37, 2001. [PubMed: 11489251] [Full Text: https://doi.org/10.1016/s0006-8993(01)02393-9]
Tchernev, V. T., Mansfield, T. A., Giot, L., Kumar, A. M., Nandabalan, K., Li, Y., Mishra, V. S., Detter, J. C., Rothberg, J. M., Wallace, M. R., Southwick, F. S., Kingsmore, S. F. The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins. Molec. Med. 8: 56-64, 2002. [PubMed: 11984006]
Ward, D. M., Vaughn, M. B., Shiflett, S. L., White, P. L., Pollock, A. L., Hill, J., Schnegelberger, R., Sundquist, W. I., Kaplan, J. The role of LIP5 and CHMP5 in multivesicular body formation and HIV-1 budding in mammalian cells. J. Biol. Chem. 280: 10548-10555, 2005. [PubMed: 15644320] [Full Text: https://doi.org/10.1074/jbc.M413734200]