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Protein

Vacuolar protein sorting-associated protein 4B

Gene

VPS4B

Organism
Homo sapiens (Human)
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 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)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi174 – 1818ATPSequence analysis

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

  • autophagy Source: ParkinsonsUK-UCL
  • cell separation after cytokinesis Source: UniProtKB
  • cholesterol transport Source: Ensembl
  • endosomal transport Source: MGI
  • endosome to lysosome transport via multivesicular body sorting pathway Source: UniProtKB
  • ESCRT III complex disassembly Source: ParkinsonsUK-UCL
  • late endosomal microautophagy Source: Ensembl
  • mitotic metaphase plate congression Source: UniProtKB
  • multivesicular body assembly Source: ParkinsonsUK-UCL
  • negative regulation of cell death Source: UniProtKB
  • negative regulation of exosomal secretion Source: UniProtKB
  • nucleus organization Source: UniProtKB
  • positive regulation of centriole elongation Source: UniProtKB
  • positive regulation of exosomal secretion Source: UniProtKB
  • positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
  • positive regulation of viral life cycle Source: UniProtKB
  • positive regulation of viral process Source: UniProtKB
  • positive regulation of viral release from host cell Source: UniProtKB
  • potassium ion transport Source: Ensembl
  • protein depolymerization Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of centrosome duplication Source: UniProtKB
  • regulation of mitotic spindle assembly Source: UniProtKB
  • regulation of viral process Source: UniProtKB
  • response to lipid Source: UniProtKB
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: UniProtKB
  • ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway Source: UniProtKB
  • vacuole organization Source: GO_Central
  • viral budding via host ESCRT complex Source: UniProtKB
  • viral life cycle Source: Reactome
  • viral release from host cell Source: UniProtKB
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

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

HGNCiHGNC:10895. VPS4B.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endosome Source: MGI
  • endosome membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • Flemming body Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • spindle pole Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi15 – 151A → D: Reduces HIV-1 release 10-fold; when associated with D-66. 1 Publication
Mutagenesisi15 – 151A → D: Reduces HIV-1 release 2-fold. 1 Publication
Mutagenesisi66 – 661L → D: Reduces HIV-1 release 10-fold; when associated with D-15. 1 Publication
Mutagenesisi66 – 661L → D: Reduces HIV-1 release 3-fold. 1 Publication
Mutagenesisi208 – 2092WL → AA: Strongly impairs HIV-1 release. 1 Publication
Mutagenesisi210 – 2101G → A: Impairs HIV-1 release. 1 Publication
Mutagenesisi235 – 2351E → Q: Defective in vacuolar protein sorting. 1 Publication
Mutagenesisi390 – 3967Missing : Abolishes interaction with VTA1. 1 Publication

Organism-specific databases

PharmGKBiPA35795.

Chemistry

ChEMBLiCHEMBL2311229.

Polymorphism and mutation databases

BioMutaiVPS4B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444Vacuolar protein sorting-associated protein 4BPRO_0000084767Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei10 – 101N6-acetyllysineBy similarity
Modified residuei93 – 931PhosphoserineCombined sources
Modified residuei102 – 1021PhosphoserineCombined sources
Modified residuei108 – 1081PhosphoserineCombined sources
Modified residuei410 – 4101PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO75351.
MaxQBiO75351.
PaxDbiO75351.
PeptideAtlasiO75351.
PRIDEiO75351.

PTM databases

iPTMnetiO75351.
PhosphoSiteiO75351.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000119541.
CleanExiHS_VPS4B.
ExpressionAtlasiO75351. baseline and differential.
GenevisibleiO75351. HS.

Organism-specific databases

HPAiCAB046445.
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

WithEntry#Exp.IntActNotes
CHMP5Q9NZZ33EBI-2514459,EBI-751303
ZFYVE19Q96K213EBI-2514459,EBI-6448240
ZFYVE19Q96K21-33EBI-2514459,EBI-10187928

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi114901. 47 interactions.
DIPiDIP-53790N.
IntActiO75351. 6 interactions.
STRINGi9606.ENSP00000238497.

Structurei

Secondary structure

444
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni1 – 33Combined sources
Helixi6 – 2419Combined sources
Helixi27 – 4721Combined sources
Helixi52 – 8130Combined sources
Beta strandi87 – 893Combined sources
Beta strandi125 – 1273Combined sources
Helixi133 – 1353Combined sources
Helixi140 – 15516Combined sources
Helixi157 – 1593Combined sources
Beta strandi168 – 17811Combined sources
Helixi180 – 19011Combined sources
Beta strandi195 – 2006Combined sources
Helixi213 – 22513Combined sources
Beta strandi227 – 2348Combined sources
Turni235 – 2373Combined sources
Helixi238 – 2403Combined sources
Beta strandi243 – 2453Combined sources
Helixi250 – 26314Combined sources
Beta strandi265 – 2673Combined sources
Beta strandi272 – 2798Combined sources
Turni281 – 2833Combined sources
Helixi286 – 2905Combined sources
Beta strandi294 – 2974Combined sources
Helixi303 – 31412Combined sources
Helixi323 – 3319Combined sources
Helixi338 – 34912Combined sources
Helixi351 – 3588Combined sources
Beta strandi360 – 3689Combined sources
Beta strandi375 – 3839Combined sources
Beta strandi386 – 3883Combined sources
Beta strandi391 – 3933Combined sources
Helixi396 – 3983Combined sources
Helixi401 – 4033Combined sources
Helixi411 – 4199Combined sources
Helixi427 – 43812Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WR0NMR-A1-77[»]
1XWIX-ray2.80A123-444[»]
2CPTNMR-A1-104[»]
2JQHNMR-A1-86[»]
2JQKNMR-A1-86[»]
4U7YX-ray2.50A1-89[»]
ProteinModelPortaliO75351.
SMRiO75351. Positions 1-108, 123-444.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75351.

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).1 Publication

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.
InParanoidiO75351.
KOiK12196.
OMAiPNNIVDD.
OrthoDBiEOG091G0Q8J.
PhylomeDBiO75351.
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.

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti114 – 1141K → R in AAC39874 (PubMed:9653160).Curated
Sequence conflicti127 – 1271E → D in AAC39874 (PubMed:9653160).Curated
Sequence conflicti342 – 3421S → G in AAC39874 (PubMed:9653160).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti58 – 581I → M Common polymorphism; induces thermal instability. 1 Publication
Corresponds to variant rs17688948 [ dbSNP | Ensembl ].
VAR_023385

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WR0NMR-A1-77[»]
1XWIX-ray2.80A123-444[»]
2CPTNMR-A1-104[»]
2JQHNMR-A1-86[»]
2JQKNMR-A1-86[»]
4U7YX-ray2.50A1-89[»]
ProteinModelPortaliO75351.
SMRiO75351. Positions 1-108, 123-444.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114901. 47 interactions.
DIPiDIP-53790N.
IntActiO75351. 6 interactions.
STRINGi9606.ENSP00000238497.

Chemistry

ChEMBLiCHEMBL2311229.

PTM databases

iPTMnetiO75351.
PhosphoSiteiO75351.

Polymorphism and mutation databases

BioMutaiVPS4B.

Proteomic databases

EPDiO75351.
MaxQBiO75351.
PaxDbiO75351.
PeptideAtlasiO75351.
PRIDEiO75351.

Protocols and materials databases

DNASUi9525.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9525.
GeneCardsiVPS4B.
HGNCiHGNC:10895. VPS4B.
HPAiCAB046445.
HPA057649.
MIMi609983. gene.
neXtProtiNX_O75351.
PharmGKBiPA35795.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0739. Eukaryota.
ENOG410XRHN. LUCA.
GeneTreeiENSGT00550000074466.
HOGENOMiHOG000225146.
HOVERGENiHBG057074.
InParanoidiO75351.
KOiK12196.
OMAiPNNIVDD.
OrthoDBiEOG091G0Q8J.
PhylomeDBiO75351.
TreeFamiTF105012.

Enzyme and pathway databases

ReactomeiR-HSA-162588. Budding and maturation of HIV virion.
R-HSA-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Miscellaneous databases

ChiTaRSiVPS4B. human.
EvolutionaryTraceiO75351.
GeneWikiiVPS4B.
GenomeRNAii9525.
PROiO75351.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119541.
CleanExiHS_VPS4B.
ExpressionAtlasiO75351. baseline and differential.
GenevisibleiO75351. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O75351
Secondary accession number(s): Q69HW4, Q9GZS7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 16, 2004
Last modified: September 7, 2016
This is version 162 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.