Alternative titles; symbols
HGNC Approved Gene Symbol: CHMP6
Cytogenetic location: 17q25.3 Genomic coordinates (GRCh38): 17:80,991,841-81,000,133 (from NCBI)
CHMP6 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006).
Using PCR, Yorikawa et al. (2005) cloned CHMP6 from a human fetus cDNA library. The deduced 201-amino acid protein contains 2 coiled-coil domains, an N-myristoylation site, and clusters of basic and acidic residues in its N- and C-terminal regions, respectively. Metabolic labeling confirmed that CHMP6 is myristoylated. Fluorescence-tagged CHMP6 localized in a punctate distribution in HeLa cells, mostly in the perinuclear area. It colocalized with an early endosomal marker and partially colocalized with a marker of both late endosomes and lysosomes.
By coimmunoprecipitation of epitope-tagged proteins expressed in HEK293 cells, Yorikawa et al. (2005) showed that CHMP6 interacted with CHMP4B (610897) and EAP20 (VPS25; 610907). In vitro pull-down assays using recombinant proteins demonstrated direct physical interaction that was mediated by the N-terminal basic half of CHMP6. In transfected HeLa cells, CHMP6 colocalized with lysobisphosphatidic acid, a major phospholipid of internal vesicles of the MVB. Immunoelectron microscopy showed that CHMP6 localized in internal membranes of MVB-like structures, as well as on limiting membranes. Overexpression of CHMP6 interfered with transferrin receptor (TFRC; 190010) recycling from the plasma membrane and caused it to accumulate in the cytoplasm. Ubiquitinated proteins and endocytosed EGF (131530) also accumulated in CHMP6-expressing cells. Yorikawa et al. (2005) concluded that CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting.
In S. cerevisiae, ESCRT-III consists of Vps20, Snf7 (610051), Vps24 (610052), and Vps2 (610893), which assemble in that order and require the ATPase Vps4 (see 609982) for their disassembly. Wollert et al. (2009) reconstituted and visualized by fluorescence microscopy the ESCRT-III-dependent budding and scission of intralumenal vesicles into giant unilamellar vesicles. Wollert et al. (2009) showed that 3 subunits of ESCRT-III, Vps20, Snf7, and Vps24, are sufficient to detach intralumenal vesicles. Vps2, the ESCRT-III subunit responsible for recruiting Vps4, and the ATPase activity of Vps4 were required for ESCRT-III recycling and supported additional rounds of budding. The minimum set of ESCRT-III and Vps4 proteins capable of multiple cycles of vesicle detachment corresponds to the ancient set of ESCRT proteins conserved from archaea to animals.
The International Radiation Hybrid Mapping Consortium mapped the CHMP6 gene to chromosome 17 (RH102270).
Tsang, H. T. H., Connell, J. W., Brown, S. E., Thompson, A., Reid, E., Sanderson, C. M. A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. Genomics 88: 333-346, 2006. [PubMed: 16730941] [Full Text: https://doi.org/10.1016/j.ygeno.2006.04.003]
Wollert, T., Wunder, C., Lippincott-Schwartz, J., Hurley, J. H. Membrane scission by the ESCRT-III complex. Nature 458: 172-177, 2009. [PubMed: 19234443] [Full Text: https://doi.org/10.1038/nature07836]
Yorikawa, C., Shibata, H., Waguri, S., Hatta, K., Horii, M., Katoh, K., Kobayashi, T., Uchiyama, Y., Maki, M. Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting. Biochem. J. 387: 17-26, 2005. [PubMed: 15511219] [Full Text: https://doi.org/10.1042/BJ20041227]