UniProt functional annotation for P46467



	UniProt functional annotation for P46467

UniProt code: P46467.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. 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. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (By similarity). {ECO:0000250|UniProtKB:O75351, ECO:0000269|PubMed:10393249, ECO:0000269|PubMed:10679028}.

Function: (Microbial infection) In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (lentiviruses). {ECO:0000250|UniProtKB:O75351}.

Catalytic activity: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6;

Subunit: Proposed to be monomeric or homodimeric in nucleotide-free form and to oligomerize upon binding to ATP to form two stacked hexameric or heptameric rings with a central pore through which ESCRT- III substrates are translocated in an ATP-dependent manner. In vitro, associates on the inside of a helical tubular structure formed by a CHMP2A-CHMP3 polymer. Interacts with CHMP1A, CHMP1B, CHMP4B and CHMP6. Interacts with CHMP2A (PubMed:15173323). Interacts with VPS4A; the interaction suggests a heteromeric assembly with VPS4A (PubMed:12594041). Interacts with VTA1 (By similarity). {ECO:0000250|UniProtKB:O75351, ECO:0000269|PubMed:12594041, ECO:0000269|PubMed:15173323}.

Subcellular location: Late endosome membrane {ECO:0000269|PubMed:12594041}; Peripheral membrane protein {ECO:0000305}. Note=Membrane-associated in the prevacuolar endosomal compartment.

Tissue specificity: High level expression seen in the kidney. It is also expressed in the heart, brain, spleen, lung, liver, skeletal muscle, and testis. {ECO:0000269|PubMed:12594041, ECO:0000269|PubMed:8082782}.

Domain: The MIT domain serves as an adapter for ESCRT-III proteins. It forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT interacting motif) helices along the groove between MIT helices 2 and 3 present in a subset of ESCRT-III proteins thus establishing the canonical MIM-MIT interaction. In an extended conformation along the groove between helices 1 and 3, also binds to a type-2 MIT interacting motif (MIM2). {ECO:0000250|UniProtKB:O75351}.

Similarity: Belongs to the AAA ATPase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. 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. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (By similarity). {ECO:0000250\|UniProtKB:O75351, ECO:0000269\|PubMed:10393249, ECO:0000269\|PubMed:10679028}.



Function:		(Microbial infection) In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (lentiviruses). {ECO:0000250\|UniProtKB:O75351}.


Catalytic activity:		Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6;
Subunit:		Proposed to be monomeric or homodimeric in nucleotide-free form and to oligomerize upon binding to ATP to form two stacked hexameric or heptameric rings with a central pore through which ESCRT- III substrates are translocated in an ATP-dependent manner. In vitro, associates on the inside of a helical tubular structure formed by a CHMP2A-CHMP3 polymer. Interacts with CHMP1A, CHMP1B, CHMP4B and CHMP6. Interacts with CHMP2A (PubMed:15173323). Interacts with VPS4A; the interaction suggests a heteromeric assembly with VPS4A (PubMed:12594041). Interacts with VTA1 (By similarity). {ECO:0000250\|UniProtKB:O75351, ECO:0000269\|PubMed:12594041, ECO:0000269\|PubMed:15173323}.
Subcellular location:		Late endosome membrane {ECO:0000269\|PubMed:12594041}; Peripheral membrane protein {ECO:0000305}. Note=Membrane-associated in the prevacuolar endosomal compartment.
Tissue specificity:		High level expression seen in the kidney. It is also expressed in the heart, brain, spleen, lung, liver, skeletal muscle, and testis. {ECO:0000269\|PubMed:12594041, ECO:0000269\|PubMed:8082782}.
Domain:		The MIT domain serves as an adapter for ESCRT-III proteins. It forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT interacting motif) helices along the groove between MIT helices 2 and 3 present in a subset of ESCRT-III proteins thus establishing the canonical MIM-MIT interaction. In an extended conformation along the groove between helices 1 and 3, also binds to a type-2 MIT interacting motif (MIM2). {ECO:0000250\|UniProtKB:O75351}.
Similarity:		Belongs to the AAA ATPase family. {ECO:0000305}.