CHMP2B

This gene encodes a component of the heteromeric ESCRT-III complex (Endosomal Sorting Complex Required for Transport III) that functions in the recycling or degradation of cell surface receptors. ESCRT-III functions in the concentration and invagination of ubiquitinated endosomal cargos into intralumenal vesicles. The protein encoded by this gene is found as a monomer in the cytosol or as an oligomer in ESCRT-III complexes on endosomal membranes. It is expressed in neurons of all major regions of the brain. Mutations in this gene result in one form of familial frontotemporal lobar degeneration. [provided by RefSeq, Jul 2008]

Full Name

Charged Multivesicular Body Protein 2B

Function

Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4.

Biological Process

Autophagy Source: ParkinsonsUK-UCL
Cognition Source: UniProtKB
Endosomal transport Source: Reactome
Endosome organization Source: UniProtKB
Endosome transport via multivesicular body sorting pathway Source: GO_Central
ESCRT III complex disassembly Source: ParkinsonsUK-UCL
Late endosome to vacuole transport Source: GO_Central
Macroautophagy Source: ParkinsonsUK-UCL
Midbody abscission Source: UniProtKB
Mitotic metaphase plate congression Source: UniProtKB
Mitotic nuclear envelope reassembly Source: Reactome
Multivesicular body assembly Source: ParkinsonsUK-UCL
Multivesicular body-lysosome fusion Source: ParkinsonsUK-UCL
Neuron cellular homeostasis Source: UniProtKB
Nucleus organization Source: UniProtKB
Positive regulation of viral release from host cell Source: UniProtKB
Protein transport Source: GO_Central
Regulation of centrosome duplication Source: UniProtKB
Regulation of mitotic spindle assembly Source: UniProtKB
Viral budding via host ESCRT complex Source: UniProtKB
Viral life cycle Source: Reactome

Cellular Location

Late endosome membrane; Cytosol

Involvement in disease

Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (FTDALS7): A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia (FTD) is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis (ALS) is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS7 is an autosomal dominant form characterized by onset of ALS or FTD in adulthood. A few patients may have both phenotypes.