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HAMAP rule MF_04082

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General rule information [?]

Accession MF_04082
Dates 6-JUN-2017 (Created)
7-JUN-2023 (Last updated, Version 10)
Scope(s) Viruses
Template(s) P05919 (VPU_HV1H2); [ Recover all ]
Triggered by HAMAP; MF_04082 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier VPU
Protein name RecName: Full=Protein Vpu;
AltName: Full=U ORF protein;
AltName: Full=Viral protein U;
Gene name Name=vpu;

Comments [?]

FUNCTIONEnhances 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.
ACTIVITY REGULATIONIon channel activity is inhibited by hexamethylene amiloride in vitro.
SUBUNITHomopentamer. 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.
SUBCELLULAR LOCATIONHost membrane; Single-pass type I membrane protein.
DOMAINThe 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.
PTMPhosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4.
MISCELLANEOUSHIV-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).
SIMILARITYBelongs 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;
General Transmembrane; -; 1;

Features [?]

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

Additional information [?]

Size range 74-86 amino acids
Related rules None
Fusion Nter: None Cter: None

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