Alternative titles; symbols
HGNC Approved Gene Symbol: CHMP1B
Cytogenetic location: 18p11.21 Genomic coordinates (GRCh38): 18:11,851,413-11,854,444 (from NCBI)
CHMP1B 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).
By in silico gene trapping, Vuoristo et al. (2001) identified a novel gene, designated C18ORF2, embedded in exon 5 of the GNAL gene (139312) on chromosome 18p11. The C18ORF2 gene encodes a deduced 199-amino acid protein with a predicted molecular mass of 22.1 kD. The protein is highly conserved across several species and shares 55% sequence identity with the PRSM1 gene (CHMP1A). RT-PCR analysis detected moderate expression of C18ORF2 in all tissues tested.
Scott et al. (2005) found that the C-terminal half of the endosomal sorting complex protein CHMP1B bound the microtubule-interacting and transport (MIT) domain of VPS4A (609982).
Using a yeast 2-hybrid approach, Reid et al. (2005) identified CHMP1B as a binding partner of spastin (SPAST; 604277), mutations in which are the most common cause of hereditary spastic paraplegia, which results in degeneration of long axons. CHMP1B and spastin proteins showed clear cytoplasmic colocalization in transfected cells; CHMP1B and spastin proteins interacted specifically in vitro and in vivo in complementation assays, and spastin coimmunoprecipitated with CHMP1B. The interaction was mediated by a region of spastin lying between residues 80 and 196 and containing an MIT domain. Expression of epitope-tagged CHMP1B in mammalian cells prevented the development of the abnormal microtubule phenotype associated with expression of ATPase-defective spastin. The authors suggested a role for spastin in intracellular membrane traffic events, and proposed that defects in intracellular membrane traffic may be a significant cause of motor neuron pathology.
Tsang et al. (2006) performed a systematic yeast 2-hybrid analysis of human ESCRT-III components, including CHMP1B. The novel CHMP1B-binding partners included SSRP1 (604328), which may be involved in chromatin remodeling, TRAF4AF1, which may be involved in signal transduction, and AMSH (606247). Coimmunoprecipitation assays confirmed the interaction between CHMP1B and AMSH, and the 2 proteins partially colocalized with M6PR (154540) on late endosomal membranes.
Using yeast 2-hybrid screens, followed by coimmunoprecipitation and protein-binding assays, Bajorek et al. (2009) found that human IST1 (616434) interacted with several ESCRT proteins, including CHMP1A and CHMP1B, as well as with VPS4A and VPS4B (609983). IST1 bound CHMP1 directly, and like IST1, CHMP1 has a C-terminal MIM element that bound VPS4 MIT domains. Depletion of either IST1 or CHMP1 in HeLa cells blocked VPS4 recruitment to the midbody during cytokinesis and blocked cell division. Time-lapse imaging revealed that IST1 depletion caused dividing cells to arrest during the abscission stage. Cells remained tethered together through their midbodies before eventually recoalescing into a single cell with multiple nuclei. Bajorek et al. (2009) concluded that IST1 is specifically required for the cytokinesis function of ESCRT and that IST1 and CHMP1 recruit VPS4 to the midbody for abscission.
Vuoristo et al. (2001) determined that the C18ORF2 gene is intronless.
Cryoelectron Microscopy
McCullough et al. (2015) reported the 4-angstrom resolution of cryogenic electron microscopy reconstruction of a 1-start, double-stranded helical copolymer composed of 2 different human ESCRT-III subunits, CHMP1B and IST1. The inner strand comprises 'open' CHMP1B subunits that interlock in an elaborate domain-swapped architecture and is encircled by an outer strand of 'closed' IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively curved membranes in vitro and in vivo.
By genomic sequence analysis, Vuoristo et al. (2001) identified the C18ORF2 gene within intron 5 of the GNAL gene (139312) on chromosome 18p11.
Bajorek, M., Morita, E., Skalicky, J. J., Morham, S. G., Babst, M., Sundquist, W. I. Biochemical analyses of human IST1 and its function in cytokinesis. Molec. Biol. Cell 20: 1360-1373, 2009. [PubMed: 19129479] [Full Text: https://doi.org/10.1091/mbc.e08-05-0475]
McCullough, J., Clippinger, A. K., Talledge, N., Skowyra, M. L., Saunders, M. G., Naismith, T. V., Colf, L. A., Afonine, P., Arthur, C., Sundquist, W. I., Hanson, P. I., Frost, A. Structure and membrane remodeling activity of ESCRT-III helical polymers. Science 350: 1548-1551, 2015. [PubMed: 26634441] [Full Text: https://doi.org/10.1126/science.aad8305]
Reid, E., Connell, J., Edwards, T. L., Duley, S., Brown, S. E., Sanderson, C. M. The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III complex-associated endosomal protein CHMP1B. Hum. Molec. Genet. 14: 19-38, 2005. [PubMed: 15537668] [Full Text: https://doi.org/10.1093/hmg/ddi003]
Scott, A., Gaspar, J., Stuchell-Brereton, M. D., Alam, S. L., Skalicky, J. J., Sundquist, W. I. Structure and ESCRT-III protein interactions of the MIT domain of human VPS4A. Proc. Nat. Acad. Sci. 102: 13813-13818, 2005. [PubMed: 16174732] [Full Text: https://doi.org/10.1073/pnas.0502165102]
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]
Vuoristo, J. T., Berrettini, W. H., Ala-Kokko, L. C18orf2, a novel, highly conserved intronless gene within intron 5 of the GNAL gene on chromosome 18p11. Cytogenet. Cell Genet. 93: 19-22, 2001. [PubMed: 11474171] [Full Text: https://doi.org/10.1159/000056940]