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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. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).By similarity2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi174 – 181ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

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

BRENDAi3.6.4.6. 3474.
ReactomeiR-MMU-917729. 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
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1100499. Vps4b.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi180K → Q: Defective in ATP-binding. Causes membrane association. Induces vacuolation of endosomal compartments and impairs cholesterol sorting. 1 Publication1
Mutagenesisi235E → Q: Defective in ATP-hydrolysis. Causes membrane-association. Induces vacuolation of endosomal compartments and impairs cholesterol and protein sorting. Increased perinuclear localization. 4 Publications1
Mutagenesisi290 – 291RR → AA: Abolishes ATP-dependent oligomerization. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000847681 – 444Vacuolar protein sorting-associated protein 4BAdd BLAST444

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10N6-acetyllysineBy similarity1
Modified residuei102PhosphoserineCombined sources1
Modified residuei108PhosphoserineBy similarity1
Modified residuei410PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP46467.
PaxDbiP46467.
PeptideAtlasiP46467.
PRIDEiP46467.

PTM databases

iPTMnetiP46467.
PhosphoSitePlusiP46467.

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

BgeeiENSMUSG00000009907.
CleanExiMM_VPS4B.
ExpressionAtlasiP46467. baseline and differential.
GenevisibleiP46467. 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. In vitro, associates on the inside of a helical tubular structure formed by a CHMP2A-CHMP3 polymer. Interacts with CHMP1A, CHMP1B, CHMP4B and CHMP6. Interacts with CHMP2A (PubMed:15173323). Interacts with VPS4A; the interaction suggests a heteromeric assembly with VPS4A (PubMed:12594041). Interacts with VTA1 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203266. 60 interactors.
IntActiP46467. 60 interactors.
MINTiMINT-4134751.
STRINGi10090.ENSMUSP00000092230.

Structurei

Secondary structure

1444
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi133 – 135Combined sources3
Helixi140 – 150Combined sources11
Helixi152 – 155Combined sources4
Turni157 – 160Combined sources4
Helixi162 – 164Combined sources3
Beta strandi168 – 173Combined sources6
Helixi180 – 190Combined sources11
Beta strandi193 – 199Combined sources7
Turni203 – 205Combined sources3
Helixi216 – 225Combined sources10
Beta strandi228 – 234Combined sources7
Turni236 – 239Combined sources4
Helixi249 – 251Combined sources3
Helixi252 – 259Combined sources8
Turni260 – 263Combined sources4
Beta strandi265 – 267Combined sources3
Beta strandi273 – 279Combined sources7
Helixi281 – 283Combined sources3
Helixi286 – 289Combined sources4
Beta strandi294 – 297Combined sources4
Helixi303 – 314Combined sources12
Beta strandi317 – 319Combined sources3
Helixi323 – 332Combined sources10
Turni333 – 335Combined sources3
Helixi338 – 349Combined sources12
Helixi351 – 358Combined sources8
Beta strandi360 – 365Combined sources6
Beta strandi373 – 376Combined sources4
Beta strandi380 – 384Combined sources5
Beta strandi386 – 388Combined sources3
Beta strandi391 – 393Combined sources3
Turni396 – 398Combined sources3
Helixi401 – 403Combined sources3
Helixi411 – 419Combined sources9
Helixi427 – 436Combined sources10
Turni441 – 443Combined sources3

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP46467.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 82MITAdd BLAST79

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili19 – 82Sequence analysisAdd BLAST64

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

Sequence similaritiesi

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0739. Eukaryota.
ENOG410XRHN. LUCA.
GeneTreeiENSGT00550000074466.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiP46467.
KOiK12196.
OMAiPNCIVND.
OrthoDBiEOG091G0Q8J.
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)DescriptionActionsGraphical viewLength
Sequence conflicti90E → A in AAA50497 (PubMed:8082782).Curated1
Sequence conflicti339A → V in AAA50497 (PubMed:8082782).Curated1

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZAMX-ray3.50A1-444[»]
2ZANX-ray3.00A1-444[»]
2ZAOX-ray3.20A1-444[»]
ProteinModelPortaliP46467.
SMRiP46467.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203266. 60 interactors.
IntActiP46467. 60 interactors.
MINTiMINT-4134751.
STRINGi10090.ENSMUSP00000092230.

PTM databases

iPTMnetiP46467.
PhosphoSitePlusiP46467.

Proteomic databases

EPDiP46467.
PaxDbiP46467.
PeptideAtlasiP46467.
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

eggNOGiKOG0739. Eukaryota.
ENOG410XRHN. LUCA.
GeneTreeiENSGT00550000074466.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiP46467.
KOiK12196.
OMAiPNCIVND.
OrthoDBiEOG091G0Q8J.
PhylomeDBiP46467.
TreeFamiTF105012.

Enzyme and pathway databases

BRENDAi3.6.4.6. 3474.
ReactomeiR-MMU-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Miscellaneous databases

EvolutionaryTraceiP46467.
PROiP46467.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000009907.
CleanExiMM_VPS4B.
ExpressionAtlasiP46467. baseline and differential.
GenevisibleiP46467. MM.

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...

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: November 2, 2016
This is version 153 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

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 one 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.