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Details on Person UniProt:Q9UN37 VPS4A

Class:IdReferenceGeneProduct:184262
_chainChangeLoginitiator methionine:1 added on Sat February 7 2015;chain:2-437 added on Sat February 7 2015;initiator methionine:1 removed on Tue November 3 2015;chain:2-437 removed on Tue November 3 2015;chain:1-437 added on Tue November 3 2015
_displayNameUniProt:Q9UN37 VPS4A
_timestamp2025-02-21 19:24:14
chainchain:1-437
checksumC3CC556FB84F105C
commentFUNCTION 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. It is required for proper accomplishment of various processes including the regulation of endosome size, primary cilium organization, mitotic spindle organization, chromosome segregation, and nuclear envelope sealing and spindle disassembly during anaphase (PubMed:33186545). Involved in cytokinesis: retained at the midbody by ZFYVE19/ANCHR and CHMP4C until abscission checkpoint signaling is terminated at late cytokinesis. It is then released following dephosphorylation of CHMP4C, leading to abscission (PubMed:24814515). VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). Critical for normal erythroblast cytokinesis and correct erythropoiesis (PubMed:33186543).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 (HIV-1 and other lentiviruses).CATALYTIC ACTIVITY ATP + H2O = ADP + phosphate + H(+)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 (By similarity). Interacts with CHMP1A, CHMP1B, CHMP2A, CHMP2B, CHMP3, CHMP4A, CHMP4B, CHMP4C and CHMP6. Interacts with VPS4B; the interaction suggests a heteromeric assembly with VPS4B. Interacts with SPAST. Interacts with IST1. Interacts with ZFYVE19/ANCHR; leading to retain it at midbody.INTERACTION Membrane-associated in the prevacuolar endosomal compartment. Localizes to the midbody of dividing cells, interaction with ZFYVE19/ANCHR mediates retention at midbody (PubMed:24814515). Localized in two distinct rings on either side of the Flemming body.TISSUE SPECIFICITY Ubiquitously expressed.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).DISEASE The disease may be caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the AAA ATPase family.
created[InstanceEdit:184440] D'Eustachio, P, 2006-07-27 16:05:42
descriptionrecommendedName: fullName evidence="28"Vacuolar protein sorting-associated protein 4A ecNumber evidence="2"3.6.4.6 alternativeName: Protein SKD2 alternativeName: VPS4-1 shortName: hVPS4
geneNameVPS4A
VPS4
identifierQ9UN37
isSequenceChangedFALSE
keyword3D-structure
Acetylation
ATP-binding
Cataract
Cell cycle
Cell division
Congenital dyserythropoietic anemia
Cytoplasm
Cytoskeleton
Disease variant
Endosome
Hereditary hemolytic anemia
Hydrolase
Intellectual disability
Membrane
Nucleotide-binding
Phosphoprotein
Protein transport
Proteomics identification
Reference proteome
Transport
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameVPS4A
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8992822] ENSEMBL:ENSG00000132612 VPS4A [Homo sapiens]
secondaryIdentifierVPS4A_HUMAN
B2RCB7
Q8TF07
Q9UI03
Q9Y582
sequenceLength437
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:917732] VPS4A [cytosol] [Homo sapiens]
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