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Protein

Vacuolar protein sorting-associated protein 4B

Gene

Vps4b

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. 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

Keywordsi

Molecular functionHydrolase
Biological processCell cycle, Cell division, Protein transport, Transport
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1100499 Vps4b

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
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 residuei102PhosphoserineCombined sources1
Modified residuei108PhosphoserineBy similarity1
Modified residuei410PhosphoserineBy similarity1

Keywords - PTMi

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 Expressed in 288 organ(s), highest expression level in conjunctival fornix
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
ComplexPortaliCPX-340 VPS4A/B complex
IntActiP46467, 60 interactors
MINTiP46467
STRINGi10090.ENSMUSP00000092230

Structurei

Secondary structure

1444
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

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

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

Similar proteinsi

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
ComplexPortaliCPX-340 VPS4A/B complex
IntActiP46467, 60 interactors
MINTiP46467
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
OMAiTHFKKVK
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
PROiPR:P46467
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000009907 Expressed in 288 organ(s), highest expression level in conjunctival fornix
CleanExiMM_VPS4B
ExpressionAtlasiP46467 baseline and differential
GenevisibleiP46467 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 nameiVPS4B_MOUSE
AccessioniPrimary (citable) accession number: P46467
Secondary accession number(s): Q91W22, Q9R1C9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 16, 2004
Last modified: September 12, 2018
This is version 163 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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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