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Protein

Vacuolar protein sorting-associated protein 4A

Gene

Vps4a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 Expressed in 288 organ(s), highest expression level in seminiferous tubule of testis
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

BioGridi227970, 2 interactors
ComplexPortaliCPX-340 VPS4A/B complex
IntActiQ8VEJ9, 1 interactor
MINTiQ8VEJ9
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
OMAiVKQLFTM
OrthoDBiEOG091G0Q8J
PhylomeDBiQ8VEJ9
TreeFamiTF105012

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR003959 ATPase_AAA_core
IPR003960 ATPase_AAA_CS
IPR007330 MIT
IPR036181 MIT_dom_sf
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

Cross-referencesi

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

3D structure databases

ProteinModelPortaliQ8VEJ9
SMRiQ8VEJ9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi227970, 2 interactors
ComplexPortaliCPX-340 VPS4A/B complex
IntActiQ8VEJ9, 1 interactor
MINTiQ8VEJ9
STRINGi10090.ENSMUSP00000034388

PTM databases

iPTMnetiQ8VEJ9
PhosphoSitePlusiQ8VEJ9

Proteomic databases

EPDiQ8VEJ9
MaxQBiQ8VEJ9
PaxDbiQ8VEJ9
PRIDEiQ8VEJ9

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi27183
MGIiMGI:1890520 Vps4a

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:Q8VEJ9
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031913 Expressed in 288 organ(s), highest expression level in seminiferous tubule of testis
CleanExiMM_VPS4A
GenevisibleiQ8VEJ9 MM

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR003959 ATPase_AAA_core
IPR003960 ATPase_AAA_CS
IPR007330 MIT
IPR036181 MIT_dom_sf
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
ProtoNetiSearch...

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: November 7, 2018
This is version 140 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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