VPS28: A Core Component of the ESCRT-I Complex Involved in Endosomal Sorting and Cytokinetic Abscission
Essential regulator of multivesicular body biogenesis, receptor downregulation, and cell division; implicated in cancer and viral pathogenesis.
Gene Information Card
| Symbol | VPS28 |
|---|---|
| Full Name | VPS28 subunit of ESCRT-I |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 51160 ncbi.nlm.nih.gov/gene/51160 |
| Ensembl ID | ENSG00000160948 |
| UniProt ID | Q9UK41 |
| OMIM ID | 611952 |
| HGNC ID | 18178 |
| Aliases | ESCRT-I subunit VPS28, hVPS28, CGI-86 |
Description
VPS28 encodes a core component of the endosomal sorting complex required for transport I (ESCRT-I). This complex is essential for the sorting of ubiquitinated membrane proteins into intraluminal vesicles of multivesicular bodies, leading to lysosomal degradation. VPS28 directly interacts with TSG101 and VPS37 to form the ESCRT-I complex. Beyond endosomal trafficking, ESCRT-I functions in cytokinetic abscission, HIV-1 budding, and nuclear envelope reformation. VPS28 is ubiquitously expressed and its dysregulation is linked to cancer progression and viral replication.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Altered VPS28 expression disrupts receptor downregulation (e.g., EGFR), promoting oncogenic signaling | NCBI Gene, COSMIC |
| HIV-1 infection | VPS28 is hijacked by HIV-1 Gag for viral budding; depletion blocks virus release | UniProt, PubMed |
| Neurodegenerative disorders | Impaired endosomal sorting may contribute to protein aggregation (e.g., tau, APP) | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 10.5 | Medium |
| Kidney | 14.1 | Medium |
| Testis | 18.6 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 16.3 | Cervical cancer cell line |
| HEK293 | 14.7 | Embryonic kidney cells |
| A549 | 13.2 | Lung carcinoma |
| K562 | 11.9 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; predicted loss of function |
| c.205C>T (p.Arg69Trp) | Missense | Rare | Unknown significance; reported in COSMIC |
| c.340G>A (p.Glu114Lys) | Missense | Rare | Unknown significance; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Complete loss of VPS28 is likely embryonic lethal in model organisms; hypomorphic mutations impair ESCRT-I assembly and endosomal sorting.
Gain of Function (GOF)
No documented gain-of-function mutations; overexpression may enhance viral budding or receptor degradation.
Dominant Negative (DN)
Truncating mutations that disrupt TSG101 binding could act as dominant negatives, inhibiting ESCRT-I function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ESCRT-mediated multivesicular body sorting (Reactome: R-HSA-917729)
• Cytokinetic abscission (Reactome: R-HSA-2467813)
• HIV-1 budding (Reactome: R-HSA-162585)
Protein Summary
VPS28 is a 221-amino-acid protein (25 kDa) that contains a conserved N-terminal domain required for TSG101 binding and a C-terminal region that interacts with VPS37. It is a stable component of the ESCRT-I complex, which adopts a rod-like structure. VPS28 is essential for the recruitment of downstream ESCRT-III components. Post-translational modifications include ubiquitination, which may regulate its stability.
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