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Protein

Vacuolar protein sorting-associated protein 4B

Gene

VPS4B

Organism
Homo sapiens (Human)
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 and enveloped virus budding (HIV-1 and other lentiviruses). VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).4 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

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

GO - Molecular functioni

  • ATPase activity Source: MGI
  • ATPase activity, coupled Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • identical protein binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processCell cycle, Cell division, Protein transport, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-162588 Budding and maturation of HIV virion
R-HSA-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):
Cell migration-inducing gene 1 protein
Suppressor of K(+) transport growth defect 1
Short name:
Protein SKD1
Gene namesi
Name:VPS4B
Synonyms:SKD1, VPS42
ORF Names:MIG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000119541.9
HGNCiHGNC:10895 VPS4B
MIMi609983 gene
neXtProtiNX_O75351

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
Mutagenesisi15A → D: Reduces HIV-1 release 10-fold; when associated with D-66. 1 Publication1
Mutagenesisi15A → D: Reduces HIV-1 release 2-fold. 1 Publication1
Mutagenesisi66L → D: Reduces HIV-1 release 10-fold; when associated with D-15. 1 Publication1
Mutagenesisi66L → D: Reduces HIV-1 release 3-fold. 1 Publication1
Mutagenesisi208 – 209WL → AA: Strongly impairs HIV-1 release. 1 Publication2
Mutagenesisi210G → A: Impairs HIV-1 release. 1 Publication1
Mutagenesisi235E → Q: Defective in vacuolar protein sorting. 1 Publication1
Mutagenesisi390 – 396Missing : Abolishes interaction with VTA1. 1 Publication7

Organism-specific databases

DisGeNETi9525
MalaCardsiVPS4B
OpenTargetsiENSG00000119541
PharmGKBiPA35795

Chemistry databases

ChEMBLiCHEMBL2311229

Polymorphism and mutation databases

BioMutaiVPS4B

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000847671 – 444Vacuolar protein sorting-associated protein 4BAdd BLAST444

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei93PhosphoserineCombined sources1
Modified residuei102PhosphoserineCombined sources1
Modified residuei108PhosphoserineCombined sources1
Modified residuei410PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO75351
MaxQBiO75351
PaxDbiO75351
PeptideAtlasiO75351
PRIDEiO75351
ProteomicsDBi49918

PTM databases

iPTMnetiO75351
PhosphoSitePlusiO75351

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000119541 Expressed in 227 organ(s), highest expression level in esophagus squamous epithelium
CleanExiHS_VPS4B
ExpressionAtlasiO75351 baseline and differential
GenevisibleiO75351 HS

Organism-specific databases

HPAiCAB046445
HPA040393
HPA057649

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 VTA1.7 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114901, 49 interactors
ComplexPortaliCPX-338 VPS4A/B complex
DIPiDIP-53790N
IntActiO75351, 10 interactors
STRINGi9606.ENSP00000238497

Structurei

Secondary structure

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

3D structure databases

ProteinModelPortaliO75351
SMRiO75351
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75351

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).1 Publication

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0739 Eukaryota
ENOG410XRHN LUCA
GeneTreeiENSGT00550000074466
HOGENOMiHOG000225146
HOVERGENiHBG057074
InParanoidiO75351
KOiK12196
OMAiTHFKKVK
OrthoDBiEOG091G0Q8J
PhylomeDBiO75351
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.iShow all

O75351-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSSTSPNLQK AIDLASKAAQ EDKAGNYEEA LQLYQHAVQY FLHVVKYEAQ
60 70 80 90 100
GDKAKQSIRA KCTEYLDRAE KLKEYLKNKE KKAQKPVKEG QPSPADEKGN
110 120 130 140 150
DSDGEGESDD 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
PEPHARAAMF KLHLGTTQNS LTEADFRELG RKTDGYSGAD ISIIVRDALM
360 370 380 390 400
QPVRKVQSAT HFKKVRGPSR ADPNHLVDDL LTPCSPGDPG AIEMTWMDVP
410 420 430 440
GDKLLEPVVS MSDMLRSLSN TKPTVNEHDL LKLKKFTEDF GQEG
Length:444
Mass (Da):49,302
Last modified:January 16, 2004 - v2
Checksum:i9D565E4B20AF73FB
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EKZ3K7EKZ3_HUMAN
Vacuolar protein sorting-associated...
VPS4B
128Annotation score:
K7EL71K7EL71_HUMAN
Vacuolar protein sorting-associated...
VPS4B
111Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti114K → R in AAC39874 (PubMed:9653160).Curated1
Sequence conflicti127E → D in AAC39874 (PubMed:9653160).Curated1
Sequence conflicti342S → G in AAC39874 (PubMed:9653160).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02338558I → M Common polymorphism; induces thermal instability. 1 PublicationCorresponds to variant dbSNP:rs17688948Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF195514 mRNA Translation: AAG33022.1
AF282904 Genomic DNA Translation: AAG01471.1
AF038960 mRNA Translation: AAC39874.1
AY232629 mRNA Translation: AAP59551.1
CH471096 Genomic DNA Translation: EAW63143.1
BC039574 mRNA Translation: AAH39574.1
CCDSiCCDS11983.1
RefSeqiNP_004860.2, NM_004869.3
UniGeneiHs.126550

Genome annotation databases

EnsembliENST00000238497; ENSP00000238497; ENSG00000119541
GeneIDi9525
KEGGihsa:9525
UCSCiuc002lix.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiVPS4B_HUMAN
AccessioniPrimary (citable) accession number: O75351
Secondary accession number(s): Q69HW4, Q9GZS7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 16, 2004
Last modified: September 12, 2018
This is version 177 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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