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P05925 (VPU_HV1EL) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein Vpu
Alternative name(s):
U ORF protein
Viral protein U
Gene names
Name:vpu
OrganismHuman immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1) [Complete proteome]
Taxonomic identifier11689 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length81 AA.
Sequence statusComplete.
Protein existenceInferred from homology

General annotation (Comments)

Function

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 interfere with 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 regulation

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

Subunit structure

May form pentamers or hexamers. Forms ternary complexes, by interacting with human CD4 and BTRC, and with human BST2 and BTRC By similarity.

Subcellular location

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

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 By similarity.

Post-translational modification

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

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).

Sequence similarities

Belongs to the HIV-1 VPU protein family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 8181Protein Vpu
PRO_0000085420

Regions

Topological domain1 – 55Extracellular Potential
Transmembrane6 – 2621Helical; Potential
Topological domain27 – 8155Cytoplasmic Potential

Amino acid modifications

Modified residue531Phosphoserine; by host CK2 By similarity
Modified residue571Phosphoserine; by host CK2 By similarity

Sequences

Sequence LengthMass (Da)Tools
P05925 [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: 757F366D4267E5F5

FASTA819,268
        10         20         30         40         50         60 
MQPLGIIAIA ALVVAIILAI VVWTIVFIEY RRIKKQRRID CLLDRITERA EDSGNESEGD 

        70         80 
REKLSKLVEM GHHAPWDIDD L 

« Hide

References

[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(1986) [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(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K03454 Genomic DNA. Translation: AAA44328.1.
PIRS06409.

3D structure databases

ProteinModelPortalP05925.
SMRP05925. Positions 38-81.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D1.10.195.10. 1 hit.
InterProIPR008187. Vpu.
IPR009032. Vpu_cyt.
[Graphical view]
PfamPF00558. Vpu. 1 hit.
[Graphical view]
SUPFAMSSF57647. SSF57647. 1 hit.
ProtoNetSearch...

Entry information

Entry nameVPU_HV1EL
AccessionPrimary (citable) accession number: P05925
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: April 16, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families