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Protein

Protein Vpu

Gene

vpu

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

Functioni

Enhances 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 receptor human 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 (PubMed:11696595). 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.9 Publications

Miscellaneous

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).

Enzyme regulationi

Ion channel activity is inhibited by hexamethylene amiloride in vitro.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

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 Vpu
Alternative name(s):
U ORF protein
Viral protein U
Gene namesi
Name:vpu
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]
Proteomesi
  • UP000007692 Componenti: Genome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7ExtracellularSequence analysis7
Transmembranei8 – 25HelicalSequence analysisAdd BLAST18
Topological domaini26 – 81CytoplasmicSequence analysisAdd BLAST56

GO - Cellular componenti

Keywords - Cellular componenti

Host membrane, Membrane

Pathology & Biotechi

Mutagenesis

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

AIDS

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 CK21 Publication1
Modified residuei56Phosphoserine; by host CK21 Publication1

Post-translational modificationi

Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4.1 Publication

Keywords - PTMi

Phosphoprotein

PTM databases

iPTMnetiP05923.

Interactioni

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 BST2.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiP05923. 1 interactor.
MINTiMINT-8402293.

Structurei

3D structure databases

ProteinModelPortaliP05923.
SMRiP05923.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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.1 Publication

Sequence similaritiesi

Belongs to the HIV-1 VPU protein family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG09000203.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

P05923-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPIQIAIAA LVVAIIIAIV VWSIVIIEYR KILRQRKIDR LIDRLIERAE
60 70 80
DSGNESEGEI SALVEMGVEM GHHAPWDIDD L
Length:81
Mass (Da):9,160
Last modified:November 1, 1988 - v1
Checksum:iB9F588F7C6654B51
GO

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:
EMBLi
GenBanki
DDBJi
Links Updated
K02013 Genomic RNA. Translation: AAB59750.1.
M19921 Genomic RNA. Translation: AAA44991.1.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: July 5, 2017
This is version 112 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families