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Protein

Vacuolar protein sorting-associated protein 4B

Gene

Vps4b

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 (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi174 – 1818ATPSequence Analysis

GO - Molecular functioni

  1. ATPase activity Source: MGI
  2. ATP binding Source: MGI
  3. protein C-terminus binding Source: MGI

GO - Biological processi

  1. ATP catabolic process Source: MGI
  2. cell cycle Source: UniProtKB-KW
  3. cell division Source: UniProtKB-KW
  4. cholesterol transport Source: MGI
  5. endosomal transport Source: MGI
  6. endosome organization Source: MGI
  7. endosome to lysosome transport via multivesicular body sorting pathway Source: MGI
  8. intracellular cholesterol transport Source: MGI
  9. negative regulation of exosomal secretion Source: MGI
  10. positive regulation of exosomal secretion Source: MGI
  11. positive regulation of viral release from host cell Source: MGI
  12. potassium ion transport Source: MGI
  13. protein transport Source: UniProtKB-KW
  14. regulation of viral process Source: MGI
  15. response to lipid Source: MGI
  16. ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: MGI
  17. vacuole organization Source: GO_Central
  18. 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 4B (EC:3.6.4.6)
Alternative name(s):
Suppressor of K(+) transport growth defect 1
Short name:
Protein SKD1
Gene namesi
Name:Vps4b
Synonyms:Skd1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 1

Organism-specific databases

MGIiMGI:1100499. Vps4b.

Subcellular locationi

Prevacuolar compartment membrane; Peripheral membrane protein. Late endosome membrane By similarity; Peripheral membrane protein By similarity
Note: Membrane-associated in the prevacuolar endosomal compartment.

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. cytosol Source: MGI
  3. early endosome Source: MGI
  4. endosome Source: MGI
  5. endosome membrane Source: MGI
  6. extracellular vesicular exosome Source: MGI
  7. late endosome Source: MGI
  8. late endosome membrane Source: UniProtKB-SubCell
  9. lysosome Source: MGI
  10. nucleus Source: MGI
  11. vacuolar membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi180 – 1801K → Q: Defective in ATP-binding. Causes membrane association. Induces vacuolation of endosomal compartments and impairs cholesterol sorting. 1 Publication
Mutagenesisi235 – 2351E → Q: Defective in ATP-hydrolysis. Causes membrane-association. Induces vacuolation of endosomal compartments and impairs cholesterol and protein sorting. Increased perinuclear localization. 4 Publications
Mutagenesisi290 – 2912RR → AA: Abolishes ATP-dependent oligomerization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444Vacuolar protein sorting-associated protein 4BPRO_0000084768Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei102 – 1021Phosphoserine1 Publication
Modified residuei108 – 1081PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP46467.
PaxDbiP46467.
PRIDEiP46467.

PTM databases

PhosphoSiteiP46467.

Expressioni

Tissue specificityi

High level expression seen in the kidney. It is also expressed in the heart, brain, spleen, lung, liver, skeletal muscle, and testis.2 Publications

Gene expression databases

BgeeiP46467.
CleanExiMM_VPS4B.
ExpressionAtlasiP46467. baseline and differential.
GenevestigatoriP46467.

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. In vitro, associates on the inside of a helical tubular structure formed by a CHMP2A-CHMP3 polymer. Interacts with CHMP1A, CHMP1B, CHMP2A, CHMP4B and CHMP6. Interacts with VPS4A; the interaction suggests a heteromeric assembly with VPS4A. Interacts with VTA1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi203266. 2 interactions.
IntActiP46467. 2 interactions.
MINTiMINT-4134751.

Structurei

Secondary structure

1
444
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi133 – 1353Combined sources
Helixi140 – 15011Combined sources
Helixi152 – 1554Combined sources
Turni157 – 1604Combined sources
Helixi162 – 1643Combined sources
Beta strandi168 – 1736Combined sources
Helixi180 – 19011Combined sources
Beta strandi193 – 1997Combined sources
Turni203 – 2053Combined sources
Helixi216 – 22510Combined sources
Beta strandi228 – 2347Combined sources
Turni236 – 2394Combined sources
Helixi249 – 2513Combined sources
Helixi252 – 2598Combined sources
Turni260 – 2634Combined sources
Beta strandi265 – 2673Combined sources
Beta strandi273 – 2797Combined sources
Helixi281 – 2833Combined sources
Helixi286 – 2894Combined sources
Beta strandi294 – 2974Combined sources
Helixi303 – 31412Combined sources
Beta strandi317 – 3193Combined sources
Helixi323 – 33210Combined sources
Turni333 – 3353Combined sources
Helixi338 – 34912Combined sources
Helixi351 – 3588Combined sources
Beta strandi360 – 3656Combined sources
Beta strandi373 – 3764Combined sources
Beta strandi380 – 3845Combined sources
Beta strandi386 – 3883Combined sources
Beta strandi391 – 3933Combined sources
Turni396 – 3983Combined sources
Helixi401 – 4033Combined sources
Helixi411 – 4199Combined sources
Helixi427 – 43610Combined sources
Turni441 – 4433Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZAMX-ray3.50A1-444[»]
2ZANX-ray3.00A1-444[»]
2ZAOX-ray3.20A1-444[»]
ProteinModelPortaliP46467.
SMRiP46467. Positions 7-108, 123-444.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46467.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 8279MITAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili19 – 8264Sequence 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).

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated
Contains 1 MIT domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG0464.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiP46467.
KOiK12196.
OMAiGECNENE.
OrthoDBiEOG74BJS2.
PhylomeDBiP46467.
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.

P46467-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MASTNTNLQK AIDLASKAAQ EDKAGNYEEA LQLYQHAVQY FLHVVKYEAQ
60 70 80 90 100
GDKAKQSIRA KCTEYLDRAE KLKEYLKKKE KKPQKPVKEE QSGPVDEKGN
110 120 130 140 150
DSDGEAESDD PEKKKLQNQL QGAIVIERPN VKWSDVAGLE GAKEALKEAV
160 170 180 190 200
ILPIKFPHLF TGKRTPWRGI LLFGPPGTGK SYLAKAVATE ANNSTFFSIS
210 220 230 240 250
SSDLVSKWLG ESEKLVKNLF QLARENKPSI IFIDEIDSLC GSRSENESEA
260 270 280 290 300
ARRIKTEFLV QMQGVGVDND GILVLGATNI PWVLDSAIRR RFEKRIYIPL
310 320 330 340 350
PEAHARAAMF RLHLGSTQNS LTEADFQELG RKTDGYSGAD ISIIVRDALM
360 370 380 390 400
QPVRKVQSAT HFKKVRGPSR ADPNCIVNDL LTPCSPGDPG AIEMTWMDVP
410 420 430 440
GDKLLEPVVS MWDMLRSLSS TKPTVNEQDL LKLKKFTEDF GQEG
Length:444
Mass (Da):49,419
Last modified:January 16, 2004 - v2
Checksum:iAA95B607DF8706A1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti90 – 901E → A in AAA50497. (PubMed:8082782)Curated
Sequence conflicti339 – 3391A → V in AAA50497. (PubMed:8082782)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10119 mRNA. Translation: AAA50497.1.
AF134119 Genomic DNA. Translation: AAD47570.1.
BC003799 mRNA. Translation: AAH03799.1.
CCDSiCCDS15211.1.
PIRiS48696.
RefSeqiNP_033216.2. NM_009190.2.
UniGeneiMm.18705.
Mm.483448.

Genome annotation databases

EnsembliENSMUST00000094646; ENSMUSP00000092230; ENSMUSG00000009907.
ENSMUST00000112736; ENSMUSP00000108356; ENSMUSG00000009907.
GeneIDi20479.
KEGGimmu:20479.
UCSCiuc007cgz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10119 mRNA. Translation: AAA50497.1.
AF134119 Genomic DNA. Translation: AAD47570.1.
BC003799 mRNA. Translation: AAH03799.1.
CCDSiCCDS15211.1.
PIRiS48696.
RefSeqiNP_033216.2. NM_009190.2.
UniGeneiMm.18705.
Mm.483448.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZAMX-ray3.50A1-444[»]
2ZANX-ray3.00A1-444[»]
2ZAOX-ray3.20A1-444[»]
ProteinModelPortaliP46467.
SMRiP46467. Positions 7-108, 123-444.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203266. 2 interactions.
IntActiP46467. 2 interactions.
MINTiMINT-4134751.

PTM databases

PhosphoSiteiP46467.

Proteomic databases

MaxQBiP46467.
PaxDbiP46467.
PRIDEiP46467.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000094646; ENSMUSP00000092230; ENSMUSG00000009907.
ENSMUST00000112736; ENSMUSP00000108356; ENSMUSG00000009907.
GeneIDi20479.
KEGGimmu:20479.
UCSCiuc007cgz.2. mouse.

Organism-specific databases

CTDi9525.
MGIiMGI:1100499. Vps4b.

Phylogenomic databases

eggNOGiCOG0464.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiP46467.
KOiK12196.
OMAiGECNENE.
OrthoDBiEOG74BJS2.
PhylomeDBiP46467.
TreeFamiTF105012.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiP46467.
NextBioi298605.
PROiP46467.
SOURCEiSearch...

Gene expression databases

BgeeiP46467.
CleanExiMM_VPS4B.
ExpressionAtlasiP46467. baseline and differential.
GenevestigatoriP46467.

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. "Identification of a novel mammalian member of the NSF/CDC48p/Pas1p/TBP-1 family through heterologous expression in yeast."
    Perier F., Coulter K.L., Liang H., Radeke C.M., Gaber R.F., Vandenberg C.A.
    FEBS Lett. 351:286-290(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: BALB/c.
  2. "Cloning, characterisation, and functional expression of the Mus musculus SKD1 gene in yeast demonstrates that the mouse SKD1 and the yeast VPS4 genes are orthologues and involved in intracellular protein trafficking."
    Scheuring S., Bodor O., Rohricht R.A., Muller S., Beyer A., Kohrer K.
    Gene 234:149-159(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
  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].
    Tissue: Mammary tumor.
  4. "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: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH VPS4A, MUTAGENESIS OF GLU-235.
  5. "ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking."
    Bishop N., Woodman P.
    Mol. Biol. Cell 11:227-239(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-180 AND GLU-235.
  6. "The mouse SKD1, a homologue of yeast Vps4p, is required for normal endosomal trafficking and morphology in mammalian cells."
    Yoshimori T., Yamagata F., Yamamoto A., Mizushima N., Kabeya Y., Nara A., Miwako I., Ohashi M., Ohsumi M., Ohsumi Y.
    Mol. Biol. Cell 11:747-763(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF GLU-235.
  7. "Mammalian class E Vps proteins, SBP1 and mVps2/CHMP2A, interact with and regulate the function of an AAA-ATPase SKD1/Vps4B."
    Fujita H., Umezuki Y., Imamura K., Ishikawa D., Uchimura S., Nara A., Yoshimori T., Hayashizaki Y., Kawai J., Ishidoh K., Tanaka Y., Himeno M.
    J. Cell Sci. 117:2997-3009(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CHMP2A.
  8. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "Nucleotide-dependent conformational changes and assembly of the AAA ATPase SKD1/VPS4B."
    Inoue M., Kamikubo H., Kataoka M., Kato R., Yoshimori T., Wakatsuki S., Kawasaki M.
    Traffic 9:2180-2189(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 123-444, SUBUNIT, MUTAGENESIS OF GLU-235 AND 290-ARG-ARG-291.

Entry informationi

Entry nameiVPS4B_MOUSE
AccessioniPrimary (citable) accession number: P46467
Secondary accession number(s): Q91W22, Q9R1C9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 16, 2004
Last modified: February 4, 2015
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.