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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 (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi167 – 1748ATPCurated

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. hydrolase activity Source: UniProtKB-KW
  3. protein C-terminus binding Source: MGI
  4. protein domain specific binding Source: MGI

GO - Biological processi

  1. abscission Source: UniProtKB
  2. cell division Source: UniProtKB-KW
  3. cytokinesis checkpoint Source: UniProtKB
  4. endosomal transport Source: MGI
  5. negative regulation of cytokinesis Source: UniProtKB
  6. positive regulation of exosomal secretion Source: MGI
  7. protein transport Source: UniProtKB-KW
  8. ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: MGI
  9. ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway Source: MGI
  10. vacuole organization Source: GO_Central
  11. vesicle-mediated transport Source: UniProtKB
  12. viral budding via host ESCRT complex Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cell cycle, Cell division, Protein transport, Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_198518. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:1890520. Vps4a.

Subcellular locationi

Prevacuolar compartment membrane 1 Publication; Peripheral membrane protein 1 Publication. Late endosome membrane By similarity; Peripheral membrane protein By similarity. Midbody By similarity
Note: Membrane-associated in the prevacuolar endosomal compartment. Localizes to the midbody of dividing cells. Localizes to the midbody of dividing cells, interaction with ZFYVE19/ANCHR mediates retention at midbody. Localized in two distinct rings on either side of the Fleming body (By similarity).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular vesicular exosome Source: MGI
  3. late endosome membrane Source: UniProtKB-SubCell
  4. midbody Source: UniProtKB
  5. nucleus Source: GO_Central
  6. perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi228 – 2281E → Q: Perinuclear localization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 437436Vacuolar protein sorting-associated protein 4APRO_0000084766Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonineBy similarity
Modified residuei8 – 81N6-acetyllysineBy similarity
Modified residuei97 – 971PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ8VEJ9.
PaxDbiQ8VEJ9.
PRIDEiQ8VEJ9.

PTM databases

PhosphoSiteiQ8VEJ9.

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

BgeeiQ8VEJ9.
CleanExiMM_VPS4A.
ExpressionAtlasiQ8VEJ9. baseline and differential.
GenevestigatoriQ8VEJ9.

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

Protein-protein interaction databases

IntActiQ8VEJ9. 1 interaction.
MINTiMINT-4120125.

Structurei

3D structure databases

ProteinModelPortaliQ8VEJ9.
SMRiQ8VEJ9. Positions 3-101, 116-436.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 8079MITAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili15 – 3723Sequence AnalysisAdd
BLAST

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
Contains 1 MIT domain.Sequence Analysis

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG0464.
GeneTreeiENSGT00550000074466.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiQ8VEJ9.
KOiK12196.
OMAiAVGQTPC.
OrthoDBiEOG74BJS2.
PhylomeDBiQ8VEJ9.
TreeFamiTF105012.

Family and domain databases

Gene3Di1.20.58.280. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR007330. MIT.
IPR027417. P-loop_NTPase.
IPR015415. Vps4_C.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF04212. MIT. 1 hit.
PF09336. Vps4_C. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
SM00745. MIT. 1 hit.
[Graphical view]
SUPFAMiSSF116846. SSF116846. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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.

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. Positions 3-101, 116-436.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8VEJ9. 1 interaction.
MINTiMINT-4120125.

PTM databases

PhosphoSiteiQ8VEJ9.

Proteomic databases

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

eggNOGiCOG0464.
GeneTreeiENSGT00550000074466.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiQ8VEJ9.
KOiK12196.
OMAiAVGQTPC.
OrthoDBiEOG74BJS2.
PhylomeDBiQ8VEJ9.
TreeFamiTF105012.

Enzyme and pathway databases

ReactomeiREACT_198518. Endosomal Sorting Complex Required For Transport (ESCRT).

Miscellaneous databases

NextBioi369058.
PROiQ8VEJ9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VEJ9.
CleanExiMM_VPS4A.
ExpressionAtlasiQ8VEJ9. baseline and differential.
GenevestigatoriQ8VEJ9.

Family and domain databases

Gene3Di1.20.58.280. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR007330. MIT.
IPR027417. P-loop_NTPase.
IPR015415. Vps4_C.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF04212. MIT. 1 hit.
PF09336. Vps4_C. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
SM00745. MIT. 1 hit.
[Graphical view]
SUPFAMiSSF116846. SSF116846. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Comparative sequence and expression analyses of four mammalian VPS4 genes."
    Beyer A., Scheuring S., Mueller S., Mincheva A., Lichter P., Koehrer K.
    Gene 305:47-59(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF GLU-228, INTERACTION WITH VPS4B.
    Strain: 129/SvEvTacfBrImported.
    Tissue: SpleenImported.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Head.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/NImported.
    Tissue: Mammary glandImported.

Entry informationi

Entry nameiVPS4A_MOUSE
AccessioniPrimary (citable) accession number: Q8VEJ9
Secondary accession number(s): Q3TXT2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: March 1, 2002
Last modified: March 4, 2015
This is version 109 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.