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Reviewed, UniProtKB/Swiss-Prot P05949 (VPU_HV1A2)

Last modified February 9, 2010. Version 57. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Protein Vpu
Alternative name(s):
    Viral protein U
    U ORF protein
Gene names
Name: vpu
OrganismHuman immunodeficiency virus type 1 (isolate ARV2/SF2 group M subtype B) (HIV-1)
Taxonomic identifier11685 [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 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_0000085416

Regions

Topological domain1 – 55Extracellular Potential
Transmembrane6 – 2621 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
P05949-1 [UniParc].

Last modified January 9, 2007. Version 2.
Checksum: 22612B1B1C2D917C

FASTA819,373
        10         20         30         40         50         60 
MQSLQILAIV SLVVVAIIAI VVWTIVLIEY RKILRQRKID RLFDRIREKA EDSGNESERD 

        70         80 
QEELSALVEM GHLAPWDVDD L 

« Hide

References

[1]"Host range, replicative, and cytopathic properties of human immunodeficiency virus type 1 are determined by very few amino acid changes in tat and gp120."
Cheng-Mayer C., Shioda T., Levy J.A.
J. Virol. 65:6931-6941(1991) [PubMed: 1658383] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Isolate SF13.
[2]"Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2)."
Sanchez-Pescador R., Power M.D., Barr P.J., Steimer K.S., Stempien M.M., Brown-Shimer S.L., Gee W.W., Renard A., Randolph A., Levy J.A., Dina D., Luciw P.A.
Science 227:484-492(1985) [PubMed: 2578227] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-38.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L07422 Genomic RNA. Translation: AAA80323.1.
K02007 Genomic RNA. Translation: AAB59881.1. Different termination.

3D structure databases

SMRP05949. Positions 38-81.
ModBaseSearch...

Enzyme and pathway databases

ReactomeREACT_6185. HIV Infection.

Family and domain databases

InterProIPR008187. Vpu.
IPR009032. Vpu_cyt.
[Graphical view]
Gene3DG3DSA:1.10.195.10. Vpu_cyt. 1 hit.
PfamPF00558. Vpu. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameVPU_HV1A2
AccessionPrimary (citable) accession number: P05949
Secondary accession number(s): Q80160
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: January 9, 2007
Last modified: February 9, 2010
This is version 57 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectVirus (Virus annotation project)

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents