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Protein Vpu



Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (HIV-1)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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 annotation9 Publications


The infectious clone pNL4-3 is a chimeric provirus that consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).
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 annotation1 Publication

GO - Molecular functioni

GO - Biological processi


Molecular functionIon channel
Biological processApoptosis, 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 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 annotation
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (HIV-1)
Taxonomic identifieri11686 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
  • UP000007692 Componenti: Genome

Subcellular locationi

  • Host membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6ExtracellularUniRule annotation6
Transmembranei7 – 27HelicalUniRule annotationAdd BLAST21
Topological domaini28 – 81CytoplasmicUniRule annotationAdd BLAST54

GO - Cellular componenti

Keywords - Cellular componenti

Host membrane, Membrane

Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi52S → N: Complete loss of interaction with human BTRC, and of CD4 degradation activity; when associated with N-56. 1 Publication1
Mutagenesisi56S → N: Complete loss of interaction with human BTRC, and of CD4 degradation activity; when associated with N-52. 1 Publication1

Keywords - Diseasei


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000854171 – 81Protein VpuAdd BLAST81

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52Phosphoserine; by host CK2UniRule annotation1 Publication1
Modified residuei56Phosphoserine; by host CK2UniRule annotation1 Publication1

Post-translational modificationi

Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4.UniRule annotation1 Publication

Keywords - PTMi


PTM databases



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 annotation3 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiP05923. 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 annotation1 Publication

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases


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.

P05923-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
60 70 80
Mass (Da):9,160
Last modified:November 1, 1988 - v1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti5 – 6QI → IV in strain: Clone pNL4-3. 2
Natural varianti9A → V in strain: Clone pNL4-3. 1
Natural varianti60I → V in strain: Clone pNL4-3. 1

Sequence databases

Select the link destinations:
Links Updated
K02013 Genomic RNA. Translation: AAB59750.1.
M19921 Genomic RNA. Translation: AAA44991.1.

Similar proteinsi

Entry informationi

Entry nameiVPU_HV1BR
AccessioniPrimary (citable) accession number: P05923
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: February 28, 2018
This is version 116 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program


Keywords - Technical termi

Complete proteome