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P05925

- VPU_HV1EL

UniProt

P05925 - VPU_HV1EL

Protein

Protein Vpu

Gene

vpu

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

    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: Genome

    Subcellular locationi

    GO - Cellular componenti

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

    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.By similarity

    Keywords - PTMi

    Phosphoprotein

    Interactioni

    Subunit structurei

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

    Structurei

    3D structure databases

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

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei6 – 2621HelicalSequence AnalysisAdd
    BLAST

    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.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

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

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K03454 Genomic DNA. Translation: AAA44328.1.
    PIRiS06409.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K03454 Genomic DNA. Translation: AAA44328.1 .
    PIRi S06409.

    3D structure databases

    ProteinModelPortali P05925.
    SMRi P05925. Positions 38-81.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    Gene3Di 1.10.195.10. 1 hit.
    InterProi IPR008187. Vpu.
    IPR009032. Vpu_cyt.
    [Graphical view ]
    Pfami PF00558. Vpu. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57647. SSF57647. 1 hit.
    ProtoNeti Search...

    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(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.

    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: October 1, 2014
    This is version 91 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