Tbio VPS4A 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

Protein Classes

PANTHER Classes

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

DTO Classes

Protein / Cellular Structure / Microtubule Family Cytoskeletal Protein / Non-motor Microtubule Binding Protein / Vacuolar Protein Sorting-associated Protein 4a

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: 68.71   (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: 68.71   (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 Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (75)

Explore Interacting Targets

1 – 10 of 75

• See Interactions on String-DB

ZFYVE19

Tbio

Novelty:  0.32587685

p_int:  0.999999991

p_wrong:  9e-9

Score:  0.761

Data Source:  BioPlex,STRINGDB

VPS4B

Tchem

Novelty:  0.00788708

p_int:  0.999998837

p_ni:  0.000001163

Score:  0.986

Data Source:  BioPlex,Reactome,STRINGDB

VTA1

Tbio

Novelty:  0.01697854

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:  0.06939851

p_int:  0.798036505

p_ni:  0.201778462

p_wrong:  0.000185033

Score:  0.238

Data Source:  BioPlex,STRINGDB

CHMP6

Tbio

Novelty:  0.02931

Score:  0.999

Data Source:  STRINGDB

CHMP1A

Tbio

Novelty:  0.03969333

Score:  0.999

Data Source:  STRINGDB

CHMP2A

Tbio

Novelty:  0.00169253

Score:  0.999

Data Source:  STRINGDB

CHMP2B

Tbio

Novelty:  0.01116381

Score:  0.995

Data Source:  STRINGDB

CHMP4B

Tbio

Novelty:  0.01391352

Score:  0.994

Data Source:  STRINGDB

CHMP1B

Tbio

Novelty:  0.06982523

Score:  0.993

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (57)

Functions (6)

Components (17)

Processes (34)

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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

Disease Associations ()

No disease associations found

GWAS Traits (8)

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1 – 5 of 8

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
high density lipoprotein cholesterol measurement	EFO_0004612	4	2	4		80.6
daytime rest measurement	EFO_0007828	1	1	1		55.2
telomere length	EFO_0004505	1	1	1		38.8
apolipoprotein A 1 measurement	EFO_0004614	1	1	1		35
total cholesterol measurement	EFO_0004574	1	1	1		33.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 8

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
high density lipoprotein cholesterol measurement	EFO_0004612	4		80.6
daytime rest measurement	EFO_0007828	1		55.2
telomere length	EFO_0004505	1		38.8
apolipoprotein A 1 measurement	EFO_0004614	1		35
total cholesterol measurement	EFO_0004574	1		33.1

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
ATP-binding
Cell cycle
Cell division
Complete proteome
Disease mutation
Endosome
Hydrolase
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
apolipoprotein A 1 measurement
biological sex
daytime rest measurement
heel bone mineral density
high density lipoprotein cholesterol measurement
telomere length
total cholesterol measurement
triglyceride measurement

MGI Phenotype Find Similar Targets

No Header	No Header
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
growth/size/body region phenotype
hematopoietic system phenotype
immune system phenotype
integument phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	vacuolar protein sorting 4 homolog A		743569
Macaque	vacuolar protein sorting 4 homolog A		705277
Mouse	vacuolar protein sorting 4A	MGI:1890520	116733
Rat	vacuolar protein sorting 4 homolog A	RGD:628810	246772
Dog	vacuolar protein sorting 4 homolog A		479674

Species	Name	OMA	EggNOG	Inparanoid
Chimp	vacuolar protein sorting 4 homolog A
Macaque	vacuolar protein sorting 4 homolog A
Mouse	vacuolar protein sorting 4A
Rat	vacuolar protein sorting 4 homolog A
Dog	vacuolar protein sorting 4 homolog A

Publication Statistics

PubMed Score 68.71

PubMed score by year

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PubTator Score 128.39

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Related Publications

Text Mined References (68)

GeneRif Annotations (33)

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PMID	Year	Title