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MGP004989

UniProt Annotations

Entry Information
Gene Namecharged multivesicular body protein 4A
Protein EntryCHM4A_HUMAN
UniProt IDQ9BY43
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9BY43-1; Sequence=Displayed; Name=2; IsoId=Q9BY43-2; Sequence=VSP_056264; Note=No experimental confirmation available.;
DomainThe 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). {ECO:0000250}.
FunctionProbable 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. {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:14583093, ECO:0000269|PubMed:18209100}.
Sequence CautionSequence=AAH10893.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAI07700.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAD61949.1; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityBelongs to the SNF7 family. {ECO:0000305}.
Subcellular LocationCytoplasmic vesicle membrane. Late endosome membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=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.
SubunitProbable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentally. Self-associates; overexpression leads to the assembly of filaments that curve and associate to create circular rings. Interacts with CHMP2A. Interacts with CHMP3; the interaction requires the release of CHMP4A autoinhibition. Interacts with CHMP4B. Interacts with CHMP4C. Interacts with CHMP6. Interacts with VPS4A. Interacts with PDCD6IP; the interaction is direct. {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:14583093, ECO:0000269|PubMed:14678797, ECO:0000269|PubMed:17547705, ECO:0000269|PubMed:18511562}.
Tissue SpecificityWidely expressed. Expressed at higher level in heart, kidney, liver and skeletal muscle. Also expressed in brain, placenta, lung and pancreas. {ECO:0000269|PubMed:14678797}.
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