HAMAP rule MF_04082

Accession	MF_04082
Dates	6-JUN-2017 (Created) 7-FEB-2023 (Last updated, Version 9)

Name

HIV_VPU

Scope

Viruses; Lentivirus

Template

P05919 (VPU_HV1H2)

Triggered by

HAMAP; MF_04082 (Get profile general information and statistics)

Identifier

VPU

Protein name

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

Gene name

vpu

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.

Apoptosis
Host membrane
Host-virus interaction
Inhibition of host innate immune response by virus
Inhibition of host interferon signaling pathway by virus
Inhibition of host tetherin by virus
Ion channel
Ion transport
Membrane
Phosphoprotein
Transmembrane
Transmembrane helix
Transport
Viral immunoevasion

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.

Pfam	PF00558; Vpu; 1;

General

Transmembrane; -; 1;

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

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

View rule in raw text format (no links)