Alternative titles; symbols
HGNC Approved Gene Symbol: CHMP4A
Cytogenetic location: 14q12 Genomic coordinates (GRCh38): 14:24,209,615-24,213,488 (from NCBI)
CHMP4A 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 the N-terminal region of ALIX (PDCD6IP; 608074) as bait in a yeast 2-hybrid screen of a HeLa cell cDNA library, Katoh et al. (2003) cloned CHMP4A. The deduced 223-amino acid protein has 3 coiled-coil regions, a basic N-terminal half, and an acidic C-terminal half.
By Northern blot analysis, Katoh et al. (2004) detected a 1-kb CHMP4A transcript in all tissues examined, with highest expression in heart and moderate expression in skeletal muscle, kidney, and liver.
By PCR of a human melanoma cDNA library, Lin et al. (2005) cloned CHMP4A, which they designated SNF7-1. They identified 2 PxxP motifs near the C terminus of CHMP4A. Northern blot analysis detected CHMP4A expression in all tissues examined, with highest levels in kidney, liver, skeletal muscle, and heart.
By yeast 2-hybrid analysis, Katoh et al. (2003) found that CHMP4A interacted with ALIX.
Lin et al. (2005) found that overexpressed SNF7-1 associated with COS-7 cell membranes and perturbed normal multivesicular body biogenesis. The N-terminal half of SNF7-1 localized to membranes and formed detergent-resistant polymers, whereas the C-terminal half associated with the ESCRT-III component SKD1 (VPS4B; 609983).
Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of human ESCRT-III components, including CHMP4A. CHMP4A interacted with the ESCRT-III protein VPS4A (609982) and with the signal transduction molecule CC2D1A (610055).
In S. cerevisiae, ESCRT-III consists of Vps20 (610901), Snf7, Vps24 (610052), and Vps2 (610893), which assemble in that order and require the ATPase Vps4 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.
By genomic sequence analysis, Katoh et al. (2003) mapped the CHMP4A gene to chromosome 14q11.2.
Katoh, K., Shibata, H., Hatta, K., Maki, M. CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms. Arch. Biochem. Biophys. 421: 159-165, 2004. [PubMed: 14678797] [Full Text: https://doi.org/10.1016/j.abb.2003.09.038]
Katoh, K., Shibata, H., Suzuki, H., Nara, A., Ishidoh, K., Kominami, E., Yoshimori, T., Maki, M. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J. Biol. Chem. 278: 39104-39113, 2003. [PubMed: 12860994] [Full Text: https://doi.org/10.1074/jbc.M301604200]
Lin, Y., Kimpler, L. A., Naismith, T. V., Lauer, J. M., Hanson, P. I. Interaction of the mammalian endosomal sorting complex required for transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1. J. Biol. Chem. 280: 12799-12809, 2005. Note: Erratum: J. Biol. Chem. 281: 38966 only, 2006. [PubMed: 15632132] [Full Text: https://doi.org/10.1074/jbc.M413968200]
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]