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Protein

Vacuolar protein sorting-associated protein 4A

Gene

Vps4a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. 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. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi167 – 174ATPCurated8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processCell cycle, Cell division, Protein transport, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar protein sorting-associated protein 4A (EC:3.6.4.6)
Gene namesi
Name:Vps4aImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1890520. Vps4a.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi228E → Q: Perinuclear localization. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000847661 – 437Vacuolar protein sorting-associated protein 4AAdd BLAST437

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8N6-acetyllysineBy similarity1
Modified residuei95PhosphoserineBy similarity1
Modified residuei97PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8VEJ9.
MaxQBiQ8VEJ9.
PaxDbiQ8VEJ9.
PRIDEiQ8VEJ9.

PTM databases

iPTMnetiQ8VEJ9.
PhosphoSitePlusiQ8VEJ9.

Expressioni

Tissue specificityi

Highly expressed in testis and moderately in heart and brain. Not detected in spleen, lung, liver, skeletal muscle or kidney.1 Publication

Gene expression databases

BgeeiENSMUSG00000031913.
CleanExiMM_VPS4A.
GenevisibleiQ8VEJ9. MM.

Interactioni

Subunit structurei

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. 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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ8VEJ9. 1 interactor.
MINTiMINT-4120125.
STRINGi10090.ENSMUSP00000034388.

Structurei

3D structure databases

ProteinModelPortaliQ8VEJ9.
SMRiQ8VEJ9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 80MITAdd BLAST79

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili15 – 37Sequence analysisAdd BLAST23

Domaini

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) (By similarity).By similarity

Sequence similaritiesi

Belongs to the AAA ATPase family.Sequence analysis

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0739. Eukaryota.
ENOG410XRHN. LUCA.
GeneTreeiENSGT00550000074466.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiQ8VEJ9.
KOiK12196.
OMAiVRWNDVA.
OrthoDBiEOG091G0Q8J.
PhylomeDBiQ8VEJ9.
TreeFamiTF105012.

Family and domain databases

InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR007330. MIT.
IPR027417. P-loop_NTPase.
IPR015415. Vps4_C.
PfamiView protein in Pfam
PF00004. AAA. 1 hit.
PF04212. MIT. 1 hit.
PF09336. Vps4_C. 1 hit.
SMARTiView protein in SMART
SM00382. AAA. 1 hit.
SM00745. MIT. 1 hit.
SUPFAMiSSF116846. SSF116846. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS00674. AAA. 1 hit.

Sequencei

Sequence statusi: Complete.

Q8VEJ9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTSTLQKAI DLVTKATEED KAKNYEEALR LYQHAVEYFL HAIKYEAHSD
60 70 80 90 100
KAKESIRAKC MQYLDRAEKL KDYLRNKEKH GKKPVKENQS EGKGSDSDSE
110 120 130 140 150
GDNPEKKKLQ EQLMGAVVME KPNIRWNDVA GLEGAKEALK EAVILPIKFP
160 170 180 190 200
HLFTGKRTPW RGILLFGPPG TGKSYLAKAV ATEANNSTFF SVSSSDLMSK
210 220 230 240 250
WLGESEKLVK NLFELARQHK PSIIFIDEVD SLCGSRNENE SEAARRIKTE
260 270 280 290 300
FLVQMQGVGN NNDGTLVLGA TNIPWVLDSA IRRRFEKRIY IPLPEEAARA
310 320 330 340 350
QMFRLHLGST PHNLTDANIH ELARKTEGYS GADISIIVRD SLMQPVRKVQ
360 370 380 390 400
SATHFKKVCG PSRTNPSVMI DDLLTPCSPG DPGAIEMTWM DVPGDKLLEP
410 420 430
VVCMSDMLRS LATTRPTVNA DDLLKVKKFS EDFGQES
Length:437
Mass (Da):48,907
Last modified:March 1, 2002 - v1
Checksum:iB67CF13F7AFD9129
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF530161 Genomic DNA. Translation: AAM94861.1.
AK047821 mRNA. Translation: BAC33165.1.
AK159117 mRNA. Translation: BAE34833.1.
BC018368 mRNA. Translation: AAH18368.1.
CCDSiCCDS40463.1.
RefSeqiNP_569053.1. NM_126165.1.
UniGeneiMm.236004.

Genome annotation databases

EnsembliENSMUST00000034388; ENSMUSP00000034388; ENSMUSG00000031913.
GeneIDi116733.
KEGGimmu:116733.
UCSCiuc009ngv.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiVPS4A_MOUSE
AccessioniPrimary (citable) accession number: Q8VEJ9
Secondary accession number(s): Q3TXT2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: March 1, 2002
Last modified: September 27, 2017
This is version 132 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families