P05925 (VPU_HV1EL) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 90. History...
Names and origin
|Protein names||Recommended name:|
U ORF protein
Viral protein U
|Organism||Human immunodeficiency virus type 1 group M subtype D (isolate ELI) (HIV-1) [Complete proteome]|
|Taxonomic identifier||11689 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
|Sequence length||81 AA.|
|Protein existence||Inferred from homology|
General annotation (Comments)
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.
Ion channel activity is inhibited by hexamethylene amiloride in vitro By similarity.
May form pentamers or hexamers. Forms ternary complexes, by interacting with human CD4 and BTRC, and with human BST2 and BTRC By similarity.
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.
Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4 By similarity.
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).
Belongs to the HIV-1 VPU protein family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 81||81||Protein Vpu||PRO_0000085420|
|Topological domain||1 – 5||5||Extracellular Potential|
|Transmembrane||6 – 26||21||Helical; Potential|
|Topological domain||27 – 81||55||Cytoplasmic Potential|
Amino acid modifications
|Modified residue||53||1||Phosphoserine; by host CK2 By similarity|
|Modified residue||57||1||Phosphoserine; by host CK2 By similarity|
|||"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].
|||"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.
|K03454 Genomic DNA. Translation: AAA44328.1.|
3D structure databases
|SMR||P05925. Positions 38-81. |
Protocols and materials databases
Family and domain databases
|Gene3D||220.127.116.11. 1 hit. |
|InterPro||IPR008187. Vpu. |
|Pfam||PF00558. Vpu. 1 hit. |
|SUPFAM||SSF57647. SSF57647. 1 hit. |
|Accession||Primary (citable) accession number: P05925|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families