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Protein

Protein Vpu

Gene

vpu

Organism
Human immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Protein inferred from homologyi

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. 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.By similarity

Enzyme regulationi

Ion channel activity is inhibited by hexamethylene amiloride in vitro.By similarity

GO - Molecular functioni

  1. cation channel activity Source: InterPro

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. receptor catabolic process Source: InterPro
  3. suppression by virus of host tetherin activity Source: UniProtKB-KW
  4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  5. viral release from host cell Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Apoptosis, 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 D (isolate ELI) (HIV-1)
Taxonomic identifieri11689 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000007693 Componenti: Genome

Subcellular locationi

Host membrane By similarity; Single-pass type I membrane protein By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 55ExtracellularSequence Analysis
Transmembranei6 – 2621HelicalSequence AnalysisAdd
BLAST
Topological domaini27 – 8155CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. host cell membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 8181Protein VpuPRO_0000085420Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei53 – 531Phosphoserine; by host CK2By similarity
Modified residuei57 – 571Phosphoserine; by host CK2By similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

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.By similarity

Structurei

3D structure databases

ProteinModelPortaliP05925.
SMRiP05925. Positions 38-81.
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.By similarity

Sequence similaritiesi

Belongs to the HIV-1 VPU protein family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di1.10.195.10. 1 hit.
InterProiIPR008187. Vpu.
IPR009032. Vpu_cyt.
[Graphical view]
PfamiPF00558. Vpu. 1 hit.
[Graphical view]
SUPFAMiSSF57647. SSF57647. 1 hit.

Sequencei

Sequence statusi: Complete.

P05925-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPLGIIAIA ALVVAIILAI VVWTIVFIEY RRIKKQRRID CLLDRITERA
60 70 80
EDSGNESEGD REKLSKLVEM GHHAPWDIDD L
Length:81
Mass (Da):9,268
Last modified:November 1, 1988 - v1
Checksum:i757F366D4267E5F5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03454 Genomic DNA. Translation: AAA44328.1.
PIRiS06409.

Cross-referencesi

Web resourcesi

BioAfrica HIV proteomics resource

Vpu entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03454 Genomic DNA. Translation: AAA44328.1.
PIRiS06409.

3D structure databases

ProteinModelPortaliP05925.
SMRiP05925. Positions 38-81.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

Gene3Di1.10.195.10. 1 hit.
InterProiIPR008187. Vpu.
IPR009032. Vpu_cyt.
[Graphical view]
PfamiPF00558. Vpu. 1 hit.
[Graphical view]
SUPFAMiSSF57647. SSF57647. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. "Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients."
    Alizon M., Wain-Hobson S., Montagnier L., Sonigo P.
    Cell 46:63-74(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Identification of a protein encoded by the vpu gene of HIV-1."
    Cohen E.A., Terwilliger E.F., Sodroski J.G., Haseltine W.A.
    Nature 334:532-534(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION.

Entry informationi

Entry nameiVPU_HV1EL
AccessioniPrimary (citable) accession number: P05925
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: March 4, 2015
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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).

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.