AC   MF_04082;
DC   Protein; auto
TR   HAMAP; MF_04082; -; 1; level=0
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Names: HIV_VPU
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ID   VPU
DE   RecName: Full=Protein Vpu;
DE   AltName: Full=U ORF protein;
DE   AltName: Full=Viral protein U;
GN   Name=vpu;
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CC   -!- FUNCTION: Enhances virion budding, by targeting human CD4 and
CC       Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents
CC       any unwanted premature interactions between viral Env and its host
CC       receptor CD4 in the endoplasmic reticulum. Degradation of
CC       antiretroviral protein Tetherin/BST2 is important for virion budding,
CC       as BST2 tethers new viral particles to the host cell membrane.
CC       Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, a substrate
CC       recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin
CC       ligase, induces their ubiquitination and subsequent proteasomal
CC       degradation. The alteration of the E3 ligase specificity by Vpu seems
CC       to promote the degradation of host IKBKB, leading to NF-kappa-B down-
CC       regulation and subsequent apoptosis. Acts as a viroporin that forms an
CC       oligomeric ion channel in membranes. Modulates the host DNA repair
CC       mechanisms to promote degradation of nuclear viral cDNA in cells that
CC       are already productively infected in order to suppress immune sensing
CC       and proviral hyper-integration (superinfection). Manipulates PML-NBs
CC       and modulates SUMOylation of host BLM protein thereby enhancing its
CC       DNA-end processing activity toward viral unintegrated linear DNA. Also
CC       inhibits RAD52-mediated homologous repair of viral cDNA, preventing the
CC       generation of dead-end circular forms of single copies of the long
CC       terminal repeat and permitting sustained nucleolytic attack.
CC   -!- ACTIVITY REGULATION: Ion channel activity is inhibited by hexamethylene
CC       amiloride in vitro.
CC   -!- SUBUNIT: Homopentamer. Interacts with host CD4 and BRTC; these
CC       interactions induce proteasomal degradation of CD4. Interacts with host
CC       BST2; this interaction leads to the degradation of host BST2. Interacts
CC       with host FBXW11. Interacts with host AP1M1; this interaction plays a
CC       role in the mistrafficking and subsequent degradation of host BST2.
CC       Interacts with host RANBP2; this interaction allows Vpu to down-
CC       regulate host BLM sumoylation.
CC   -!- SUBCELLULAR LOCATION: Host membrane; Single-pass type I membrane
CC       protein.
CC   -!- DOMAIN: The N-terminus and transmembrane domains are required for self-
CC       oligomerization and proper virion budding, whereas the cytoplasmic
CC       domain is required for CD4 degradation. The cytoplasmic domain is
CC       composed of 2 amphipathic alpha helix that form a U-shape.
CC   -!- PTM: Phosphorylated by host CK2. This phosphorylation is necessary for
CC       interaction with human BTRC and degradation of CD4.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC   -!- SIMILARITY: Belongs to the HIV-1 VPU protein family.
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DR   Pfam; PF00558; Vpu; 1; trigger=no
DR   General; Transmembrane; -; 1; trigger=no
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KW   Apoptosis
KW   Host membrane
KW   Host-virus interaction
KW   Inhibition of host innate immune response by virus
KW   Inhibition of host interferon signaling pathway by virus
KW   Inhibition of host tetherin by virus
KW   Ion channel
KW   Ion transport
KW   Membrane
KW   Phosphoprotein
KW   Transmembrane
KW   Transmembrane helix
KW   Transport
KW   Viral immunoevasion
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GO   GO:0033644; C:host cell membrane
GO   GO:0016020; C:membrane
GO   GO:0005261; F:monoatomic cation channel activity
GO   GO:0042609; F:CD4 receptor binding
GO   GO:0032801; P:receptor catabolic process
GO   GO:0039587; P:suppression by virus of host tetherin activity
GO   GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway
GO   GO:0019076; P:viral release from host cell
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FT   From: VPU_HV1H2 (P05919)
FT   TOPO_DOM        Nter..6
FT                   /note="Extracellular"
FT   TRANSMEM        7..27
FT                   /note="Helical"
FT   TOPO_DOM        28..Cter
FT                   /note="Cytoplasmic"
FT   MOD_RES         52
FT                   /note="Phosphoserine; by host CK2"
FT   Condition: S
FT   MOD_RES         56
FT                   /note="Phosphoserine; by host CK2"
FT   Condition: S
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Size: 74-86;
Related: None;
Template: P05919;
Scope:
 Viruses; Lentivirus
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
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# Revision 1.10 2023/06/07
//