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P46467 (VPS4B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Vps4b
Synonyms:Skd1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length444 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.6

Catalytic activity

ATP + H2O = ADP + phosphate.

Subunit structure

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. Ref.4 Ref.7 Ref.9

Subcellular location

Prevacuolar compartment membrane; Peripheral membrane protein. Late endosome membrane; Peripheral membrane protein By similarity. Note: Membrane-associated in the prevacuolar endosomal compartment. Ref.4 Ref.5

Tissue specificity

High level expression seen in the kidney. It is also expressed in the heart, brain, spleen, lung, liver, skeletal muscle, and testis. Ref.1 Ref.4

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).

Sequence similarities

Belongs to the AAA ATPase family.

Contains 1 MIT domain.

Ontologies

Keywords
   Biological processCell cycle
Cell division
Protein transport
Transport
   Cellular componentEndosome
Membrane
   DomainCoiled coil
   LigandATP-binding
Nucleotide-binding
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

cholesterol transport

Inferred from mutant phenotype Ref.5. Source: MGI

endosomal transport

Inferred from sequence orthology PubMed 11563910. Source: MGI

endosome organization

Inferred from mutant phenotype Ref.5. Source: MGI

endosome to lysosome transport via multivesicular body sorting pathway

Inferred from electronic annotation. Source: Ensembl

intracellular cholesterol transport

Inferred from electronic annotation. Source: Ensembl

potassium ion transport

Inferred from direct assay Ref.1. Source: MGI

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

response to lipid

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from direct assay Ref.5Ref.7PubMed 16757520. Source: MGI

early endosome

Inferred from electronic annotation. Source: Ensembl

endosome

Inferred from sequence orthology PubMed 11563910. Source: MGI

late endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosome

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

vacuolar membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATPase activity

Inferred from sequence orthology PubMed 11563910. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 444444Vacuolar protein sorting-associated protein 4B
PRO_0000084768

Regions

Domain4 – 8279MIT
Nucleotide binding174 – 1818ATP Potential
Coiled coil19 – 8264 Potential

Amino acid modifications

Modified residue1021Phosphoserine Ref.8
Modified residue1081Phosphoserine By similarity

Experimental info

Mutagenesis1801K → Q: Defective in ATP-binding. Causes membrane association. Induces vacuolation of endosomal compartments and impairs cholesterol sorting. Ref.5
Mutagenesis2351E → Q: Defective in ATP-hydrolysis. Causes membrane-association. Induces vacuolation of endosomal compartments and impairs cholesterol and protein sorting. Increased perinuclear localization. Ref.4 Ref.5 Ref.6 Ref.9
Mutagenesis290 – 2912RR → AA: Abolishes ATP-dependent oligomerization.
Sequence conflict901E → A in AAA50497. Ref.1
Sequence conflict3391A → V in AAA50497. Ref.1

Secondary structure

...................................................................... 444
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P46467 [UniParc].

Last modified January 16, 2004. Version 2.
Checksum: AA95B607DF8706A1

FASTA44449,419
        10         20         30         40         50         60 
MASTNTNLQK AIDLASKAAQ EDKAGNYEEA LQLYQHAVQY FLHVVKYEAQ GDKAKQSIRA 

        70         80         90        100        110        120 
KCTEYLDRAE KLKEYLKKKE KKPQKPVKEE QSGPVDEKGN DSDGEAESDD PEKKKLQNQL 

       130        140        150        160        170        180 
QGAIVIERPN VKWSDVAGLE GAKEALKEAV ILPIKFPHLF TGKRTPWRGI LLFGPPGTGK 

       190        200        210        220        230        240 
SYLAKAVATE ANNSTFFSIS SSDLVSKWLG ESEKLVKNLF QLARENKPSI IFIDEIDSLC 

       250        260        270        280        290        300 
GSRSENESEA ARRIKTEFLV QMQGVGVDND GILVLGATNI PWVLDSAIRR RFEKRIYIPL 

       310        320        330        340        350        360 
PEAHARAAMF RLHLGSTQNS LTEADFQELG RKTDGYSGAD ISIIVRDALM QPVRKVQSAT 

       370        380        390        400        410        420 
HFKKVRGPSR ADPNCIVNDL LTPCSPGDPG AIEMTWMDVP GDKLLEPVVS MWDMLRSLSS 

       430        440 
TKPTVNEQDL LKLKKFTEDF GQEG 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U10119 mRNA. Translation: AAA50497.1.
AF134119 Genomic DNA. Translation: AAD47570.1.
BC003799 mRNA. Translation: AAH03799.1.
PIRS48696.
RefSeqNP_033216.2. NM_009190.2.
UniGeneMm.18705.
Mm.483448.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZAMX-ray3.50A1-444[»]
2ZANX-ray3.00A1-444[»]
2ZAOX-ray3.20A1-444[»]
ProteinModelPortalP46467.
SMRP46467. Positions 7-108, 123-444.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203266. 2 interactions.
IntActP46467. 2 interactions.
MINTMINT-4134751.

PTM databases

PhosphoSiteP46467.

Proteomic databases

PaxDbP46467.
PRIDEP46467.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000094646; ENSMUSP00000092230; ENSMUSG00000009907.
ENSMUST00000112736; ENSMUSP00000108356; ENSMUSG00000009907.
GeneID20479.
KEGGmmu:20479.
UCSCuc007cgz.2. mouse.

Organism-specific databases

CTD9525.
MGIMGI:1100499. Vps4b.

Phylogenomic databases

eggNOGCOG0464.
HOGENOMHOG000225146.
HOVERGENHBG057074.
InParanoidP46467.
KOK12196.
OMARADPNKI.
OrthoDBEOG74BJS2.
PhylomeDBP46467.
TreeFamTF105012.

Gene expression databases

ArrayExpressP46467.
BgeeP46467.
CleanExMM_VPS4B.
GenevestigatorP46467.

Family and domain databases

Gene3D1.20.58.280. 1 hit.
3.40.50.300. 1 hit.
InterProIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR007330. MIT.
IPR027417. P-loop_NTPase.
IPR015415. Vps4_C.
[Graphical view]
PfamPF00004. AAA. 1 hit.
PF04212. MIT. 1 hit.
PF09336. Vps4_C. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
SM00745. MIT. 1 hit.
[Graphical view]
SUPFAMSSF116846. SSF116846. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEPS00674. AAA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP46467.
NextBio298605.
PROP46467.
SOURCESearch...

Entry information

Entry nameVPS4B_MOUSE
AccessionPrimary (citable) accession number: P46467
Secondary accession number(s): Q91W22, Q9R1C9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 16, 2004
Last modified: April 16, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot