M4QBY5 · M4QBY5_9HIV1

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).

Caution

Lacks conserved residue(s) required for the propagation of feature annotation.

Activity regulation

Ion channel activity is inhibited by hexamethylene amiloride in vitro.

GO annotations

AspectTerm
Cellular Componenthost cell membrane
Cellular Componentmembrane
Molecular FunctionCD4 receptor binding
Molecular Functionmonoatomic cation channel activity
Biological Processapoptotic process
Biological Processreceptor catabolic process
Biological Processsuppression by virus of host tetherin activity
Biological Processsymbiont-mediated suppression of host innate immune response
Biological Processsymbiont-mediated suppression of host type I interferon-mediated signaling pathway
Biological Processviral release from host cell

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Protein Vpu
  • Alternative names
    • U ORF protein
    • Viral protein U

Gene names

    • Name
      vpu

Organism names

Accessions

  • Primary accession
    M4QBY5

Subcellular Location

Host membrane
; Single-pass type I membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-6Extracellular
Transmembrane6-28Helical
Topological domain28-79Cytoplasmic

Keywords

PTM/Processing

Post-translational modification

Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4.

Keywords

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.

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

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    79
  • Mass (Da)
    8,882
  • Last updated
    2013-05-29 v1
  • Checksum
    E9409EEC6F8E7156
MSSLYALGVGALIIALIIAIIVWTIVFIEIKKWVRQKKIDRLIERIRQGSGNESEGDVEELSAMVDVGHHLRLLDVNDL

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KC332917
EMBL· GenBank· DDBJ
AGH25476.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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