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HAMAP rule MF_04082

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General rule information [?]

Accession MF_04082
Dates 6-JUN-2017 (Created)
7-FEB-2023 (Last updated, Version 9)
Viruses; Lentivirus
Template P05919 (VPU_HV1H2)

Propagated annotation [?]

Identifier, protein and gene names [?]

Protein name
RecName: Full=Protein Vpu;
AltName: Full=U ORF protein;
AltName: Full=Viral protein U;
Gene name

Comments [?]

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. Ion channel activity has also been suggested, however, formation of cation-selective channel has been reconstituted ex-vivo in lipid bilayers. It is thus unsure that this activity plays a role in vivo.
Activity regulation Ion channel activity is inhibited by hexamethylene amiloride in vitro.
Subunit Forms pentamers or hexamers. 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.
Subcellular location Host membrane; Single-pass type I membrane protein.
Domain The N-terminal and transmembrane domains are required for proper virion budding, whereas the cytoplasmic domain is required for CD4 degradation. The cytoplasmic domain is composed of 2 amphipathic alpha helix.
Ptm Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4.
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).
Similarity Belongs to the HIV-1 VPU protein family.

Keywords [?]

Gene Ontology [?]

GO:0033644; Cellular component: host cell membrane.
GO:0016020; Cellular component: membrane.
GO:0005261; Molecular function: monoatomic cation channel activity.
GO:0042609; Molecular function: CD4 receptor binding.
GO:0032801; Biological process: receptor catabolic process.
GO:0039587; Biological process: suppression by virus of host tetherin activity.
GO:0039502; Biological process: suppression by virus of host type I interferon-mediated signaling pathway.
GO:0019076; Biological process: viral release from host cell.

Cross-references [?]

Pfam PF00558; Vpu; 1;

Computed features [?]

General Transmembrane; -; 1;

Features [?]

From: VPU_HV1H2 (P05919)
Key     From     To       Description   Tag   Condition   FTGroup
TOPO_DOM     Nter     6       Extracellular        
TRANSMEM     7     27       Helical        
TOPO_DOM     28     Cter       Cytoplasmic        
MOD_RES     52     52       Phosphoserine; by host CK2     S  
MOD_RES     56     56       Phosphoserine; by host CK2     S  

Additional information [?]

Size range 74-86 amino acids
Related rules None
Fusion None