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Protein Vpu



Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Unreviewed-Annotation score: Annotation score: 3 out of 5-Protein inferred from homologyi


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.UniRule annotation


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).UniRule annotation

Enzyme regulationi

Ion channel activity is inhibited by hexamethylene amiloride in vitro.UniRule annotation

GO - Molecular functioni

GO - Biological processi


Molecular functionIon channelUniRule annotation
Biological processApoptosisUniRule annotation, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host tetherin by virusUniRule annotation, Ion transport, Transport, Viral immunoevasion

Names & Taxonomyi

Protein namesi
Recommended name:
Protein VpuUniRule annotation
Alternative name(s):
U ORF proteinUniRule annotation
Viral protein UUniRule annotation
Gene namesi
Name:vpuUniRule annotationImported
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)Imported
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
  • UP000105453 Componenti: Genome

Subcellular locationi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 4ExtracellularUniRule annotation4
Transmembranei6 – 28HelicalUniRule annotationAdd BLAST23
Topological domaini29 – 82CytoplasmicUniRule annotationAdd BLAST54

GO - Cellular componenti

Keywords - Cellular componenti

Host membraneUniRule annotation, Membrane

PTM / Processingi

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53Phosphoserine; by host CK2UniRule annotation1
Modified residuei57Phosphoserine; by host CK2UniRule annotation1

Post-translational modificationi

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

Keywords - PTMi

PhosphoproteinUniRule annotation


Subunit structurei

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 degradadation 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.UniRule annotation

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9WB91. 1 interactor.


3D structure databases


Family & Domainsi


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.UniRule annotation

Sequence similaritiesi

Belongs to the HIV-1 VPU protein family.UniRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helixUniRule annotation

Family and domain databases

Gene3Di1.10.195.10. 1 hit.
HAMAPiMF_04082. HIV_VPU. 1 hit.
InterProiView protein in InterPro
IPR008187. Vpu.
IPR009032. Vpu_cyt_dom_sf.
PfamiView protein in Pfam
PF00558. Vpu. 1 hit.
SUPFAMiSSF57647. SSF57647. 1 hit.


Sequence statusi: Complete.

Q9WB91-1 [UniParc]FASTAAdd to basket

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        10         20         30         40         50
60 70 80
Mass (Da):9,242
Last modified:November 1, 1999 - v1

Sequence databases

Select the link destinations:
Links Updated
AF033819 Genomic RNA. Translation: AAD20388.1.
RefSeqiNP_057855.1. NC_001802.1.

Genome annotation databases


Similar proteinsi

Entry informationi

Entry nameiQ9WB91_HV1H2
AccessioniPrimary (citable) accession number: Q9WB91
Entry historyiIntegrated into UniProtKB/TrEMBL: November 1, 1999
Last sequence update: November 1, 1999
Last modified: January 31, 2018
This is version 59 of the entry and version 1 of the sequence. See complete history.
Entry statusiUnreviewed (UniProtKB/TrEMBL)


Keywords - Technical termi

Complete proteomeImported