CHMP4A

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 (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]

Full Name

Charged Multivesicular Body Protein 4A

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. When overexpressed, membrane-assembled circular arrays of CHMP4A filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).

Biological Process

Endosomal transport Source: Reactome
Late endosome to vacuole transport via multivesicular body sorting pathway Source: GO_Central
Macroautophagy Source: ParkinsonsUK-UCL
Membrane invagination Source: UniProtKB
Midbody abscission Source: UniProtKB
Mitotic metaphase plate congression Source: UniProtKB
Mitotic nuclear envelope reassembly Source: Reactome
Multivesicular body assembly Source: ParkinsonsUK-UCL
Negative regulation of autophagosome assembly Source: UniProtKB
Negative regulation of neuron death Source: UniProtKB
Nucleus organization Source: UniProtKB
Plasma membrane tubulation Source: UniProtKB
Posttranslational protein targeting to endoplasmic reticulum membrane Source: UniProtKB
Protein polymerization Source: UniProtKB
Vesicle budding from membrane Source: UniProtKB
Viral budding via host ESCRT complex Source: UniProtKB
Viral life cycle Source: Reactome

Cellular Location

Late endosome membrane; Cytoplasmic vesicle membrane. Membrane-associated. Localizes to large vesicle-like structures. Localizes to the midbody of dividing cells. Localized in two distinct rings on either side of the Fleming body.