Tbio VPS4A Vacuolar protein sorting-associated protein 4A

Protein Classes

PANTHER Classes

Protein / Cytoskeletal Protein / Microtubule Family Cytoskeletal Protein / Non-motor Microtubule Binding Protein / Vacuolar Protein Sorting-associated Protein 4A

Protein Summary

Description

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). Involved in cytokinesis: retained at the midbody by ZFYVE19/ANCHR and CHMP4C until abscission checkpoint signaling is terminated at late cytokinesis. It is then released following dephosphorylation of CHMP4C, leading to abscission (PubMed:24814515). VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really an yeast Vps4 ortholog. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9UN37
• B2RCB7
• Q8TF07
• Q9UI03
• Q9Y582

Gene Name

• VPS4A

Ensembl ID

• ENST00000254950
• ENSP00000254950
• ENSG00000132612

Symbol

• VPS4
• SKD1
• SKD2
• VPS4
• SKD1A
• VPS4-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	0.98
molecular function	0.96
biological process	0.86
histone modification site profile	0.85
interacting protein	0.85

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 51.26   (req: < 5)

Gene RIFs: 33   (req: <= 3)

Antibodies: 142   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 51.26   (req: >= 5)

Gene RIFs: 33   (req: > 3)

Antibodies: 142   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 40

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Data Bank (3)

1 – 3 of 3

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (202)

Reactome (9)

KEGG (2)

PathwayCommons (1)

WikiPathways (190)

Budding and maturation of HIV virion (R-HSA-162588)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Budding and maturation of HIV virion	28 targets	R-HSA-162588
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Endosomal Sorting Complex Required For Transport (ESCRT)	31 targets	R-HSA-917729
Reactome	HIV Infection	256 targets	R-HSA-162906
Reactome	HIV Life Cycle	153 targets	R-HSA-162587

Name	Explore in Pharos	Explore in Source
Budding and maturation of HIV virion	28 targets	R-HSA-162588
Disease	1105 targets	R-HSA-1643685
Endosomal Sorting Complex Required For Transport (ESCRT)	31 targets	R-HSA-917729
HIV Infection	256 targets	R-HSA-162906
HIV Life Cycle	153 targets	R-HSA-162587

Gene Ontology Terms (57)

Functions (6)

Components (17)

Processes (34)

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10

1 – 6 of 6

GO Term	Evidence	Assigned by
protein C-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein domain specific binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein-containing complex binding	Inferred from Physical Interaction (IPI)	UniProtKB
ATP binding	Inferred from Mutant Phenotype (IMP)	UniProtKB
ATPase activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
ATPase activity, coupled	Non-traceable Author Statement (NAS)	UniProtKB

Protein-Protein Interactions (75)

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1 – 10 of 75

• See Interactions on String-DB

ZFYVE19

Tbio

Novelty: 1.07142857

p_int: 0.999999991

p_wrong: 9e-9

Score: 0.761

Data Source: BioPlex,STRINGDB

VPS4B

Tbio

Novelty: 0.00983426

p_int: 0.999998837

p_ni: 0.000001163

Score: 0.986

Data Source: BioPlex,Reactome,STRINGDB

VTA1

Tbio

Novelty: 0.02244131

p_int: 0.826061018

p_ni: 0.173897874

p_wrong: 0.000041108

Score: 0.997

Data Source: BioPlex,Reactome,STRINGDB

ARL8B

Tbio

Family: Enzyme

Novelty: 0.08537963

p_int: 0.798036505

p_ni: 0.201778462

p_wrong: 0.000185033

Score: 0.238

Data Source: BioPlex,STRINGDB

CHMP6

Tbio

Novelty: 0.0478065

Score: 0.999

Data Source: STRINGDB

CHMP1A

Tbio

Novelty: 0.06086208

Score: 0.999

Data Source: STRINGDB

CHMP2A

Tbio

Novelty: 0.00337804

Score: 0.999

Data Source: STRINGDB

CHMP2B

Tbio

Novelty: 0.01676728

Score: 0.995

Data Source: STRINGDB

CHMP4B

Tbio

Novelty: 0.02197696

Score: 0.994

Data Source: STRINGDB

CHMP1B

Tbio

Novelty: 0.16112223

Score: 0.993

Data Source: STRINGDB

Publication Statistics

PubMed Score  51.26

PubMed score by year

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PubTator Score  128.39

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Acetylation
ATP-binding
Cell cycle
Cell division
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Endosome
Hydrolase
Membrane

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