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: 73.69   (req: < 5)

Gene RIFs: 44   (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: 73.69   (req: >= 5)

Gene RIFs: 44   (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