CHMP4A

Domain

The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components (By similarity).

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).

Sequence Similarities

Belongs to the SNF7 family.

Tissue Specificity

Widely expressed. Expressed at higher level in heart, kidney, liver and skeletal muscle. Also expressed in brain, placenta, lung and pancreas.

Cellular localization

• Cytoplasmic vesicle membrane
• Late endosome membrane
• Peripheral membrane protein
• 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.

Alternative names

C14orf123, SHAX2, CDA04, HSPC134, CHMP4A, Charged multivesicular body protein 4a, Chromatin-modifying protein 4a, SNF7 homolog associated with Alix-2, SNF7-1, Vacuolar protein sorting-associated protein 32-1, CHMP4a, hSnf-1, Vps32-1, hVps32-1

Database links

swissprot:Q9BY43 omim:BC010893 genbank:BC010893 entrezGene:29082