I3XK15 · I3XK15_9PLVG
- ProteinProtein Vpu
- Genevpu
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids
- Protein existenceInferred from homology
- Annotation score4/5
Function
function
Enhances virion budding by targeting host CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its host receptor CD4 in the endoplasmic reticulum. Degradation of antiretroviral protein Tetherin/BST2 is important for virion budding, as BST2 tethers new viral particles to the host cell membrane. Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, a substrate recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin ligase, induces their ubiquitination and subsequent proteasomal degradation. The alteration of the E3 ligase specificity by Vpu seems to promote the degradation of host IKBKB, leading to NF-kappa-B down-regulation and subsequent apoptosis. Acts as a viroporin that forms an oligomeric ion channel in membranes. Modulates the host DNA repair mechanisms to promote degradation of nuclear viral cDNA in cells that are already productively infected in order to suppress immune sensing and proviral hyper-integration (superinfection). Manipulates PML-NBs and modulates SUMOylation of host BLM protein thereby enhancing its DNA-end processing activity toward viral unintegrated linear DNA. Also inhibits RAD52-mediated homologous repair of viral cDNA, preventing the generation of dead-end circular forms of single copies of the long terminal repeat and permitting sustained nucleolytic attack.
Enhances virion budding, by targeting human CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its host receptor CD4 in the endoplasmic reticulum. Degradation of antiretroviral protein Tetherin/BST2 is important for virion budding, as BST2 tethers new viral particles to the host cell membrane. Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, a substrate recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin ligase, induces their ubiquitination and subsequent proteasomal degradation. The alteration of the E3 ligase specificity by Vpu seems to promote the degradation of host IKBKB, leading to NF-kappa-B down-regulation and subsequent apoptosis. Acts as a viroporin that forms an oligomeric ion channel in membranes. Modulates the host DNA repair mechanisms to promote degradation of nuclear viral cDNA in cells that are already productively infected in order to suppress immune sensing and proviral hyper-integration (superinfection). Manipulates PML-NBs and modulates SUMOylation of host BLM protein thereby enhancing its DNA-end processing activity toward viral unintegrated linear DNA. Also inhibits RAD52-mediated homologous repair of viral cDNA, preventing the generation of dead-end circular forms of single copies of the long terminal repeat and permitting sustained nucleolytic attack.
Miscellaneous
HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
Activity regulation
Ion channel activity is inhibited by hexamethylene amiloride in vitro.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell membrane | |
Cellular Component | membrane | |
Molecular Function | CD4 receptor binding | |
Molecular Function | monoatomic cation channel activity | |
Biological Process | apoptotic process | |
Biological Process | receptor catabolic process | |
Biological Process | suppression by virus of host tetherin activity | |
Biological Process | symbiont-mediated suppression of host innate immune response | |
Biological Process | symbiont-mediated suppression of host type I interferon-mediated signaling pathway | |
Biological Process | viral release from host cell |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameProtein Vpu
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageViruses > Riboviria > Pararnavirae > Artverviricota > Revtraviricetes > Ortervirales > Retroviridae > Orthoretrovirinae > Lentivirus > Primate lentivirus group
Accessions
- Primary accessionI3XK15
Subcellular Location
UniProt Annotation
GO Annotation
Host membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-7 | Extracellular | ||||
Sequence: MIDLGYK | ||||||
Transmembrane | 6-29 | Helical | ||||
Sequence: YKLAVGAFIVALILAIVVWTIVFI | ||||||
Topological domain | 29-82 | Cytoplasmic | ||||
Sequence: IEYRKLLRQKKIDWLIKRIRERAEDSGNESEGDTEELSTMVDMGRLRLLDVNDL |
Keywords
- Cellular component
PTM/Processing
Post-translational modification
Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4.
Keywords
- PTM
Interaction
Subunit
Homopentamer. Interacts with host CD4 and BRTC; these interactions induce proteasomal degradation of CD4. Interacts with host BST2; this interaction leads to the degradation of host BST2. Interacts with host FBXW11. Interacts with host AP1M1; this interaction plays a role in the mistrafficking and subsequent degradation of host BST2. Interacts with host RANBP2; this interaction allows Vpu to down-regulate host BLM sumoylation.
Structure
Family & Domains
Domain
The N-terminus and transmembrane domains are required for self-oligomerization and proper virion budding, whereas the cytoplasmic domain is required for CD4 degradation. The cytoplasmic domain is composed of 2 amphipathic alpha helix that form a U-shape.
Sequence similarities
Belongs to the HIV-1 VPU protein family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length82
- Mass (Da)9,480
- Last updated2012-09-05 v1
- Checksum5526F1EFA4B54EC5