Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein Vpu

Gene

vpu

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Enhances virion budding, by targeting human CD4 and Tetherin/BST2 to proteasome degradation (PubMed:24498878). 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 (PubMed:11696595). 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.6 Publications

GO - Molecular functioni

GO - Biological processi

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

Enzyme and pathway databases

ReactomeiR-HSA-162585. Uncoating of the HIV Virion.
R-HSA-162588. Budding and maturation of HIV virion.
R-HSA-162592. Integration of provirus.
R-HSA-162594. Early Phase of HIV Life Cycle.
R-HSA-164516. Minus-strand DNA synthesis.
R-HSA-164525. Plus-strand DNA synthesis.
R-HSA-164843. 2-LTR circle formation.
R-HSA-171286. Synthesis and processing of ENV and VPU.
R-HSA-173107. Binding and entry of HIV virion.
R-HSA-175474. Assembly Of The HIV Virion.
R-HSA-175567. Integration of viral DNA into host genomic DNA.
R-HSA-177539. Autointegration results in viral DNA circles.
R-HSA-180534. Vpu mediated degradation of CD4.
R-HSA-180689. APOBEC3G mediated resistance to HIV-1 infection.
R-HSA-180910. Vpr-mediated nuclear import of PICs.

Protein family/group databases

TCDBi1.A.40.1.1. the human immunodeficiency virus type i, hiv-1 (retrovirdiac) vpu channel (vpu-c) family.

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 B (isolate HXB2) (HIV-1)
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000002241 Componenti: Genome

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66ExtracellularSequence analysis1 Publication
Transmembranei7 – 2721HelicalSequence analysisAdd
BLAST
Topological domaini28 – 8154CytoplasmicSequence analysis1 PublicationAdd
BLAST

GO - Cellular componenti

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_0000085433Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei52 – 521Phosphoserine; by host CK21 Publication
Modified residuei56 – 561Phosphoserine; by host CK21 Publication

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

PTM databases

iPTMnetiP05919.

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 BST2.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD4P017303EBI-6248147,EBI-353826From a different organism.

Protein-protein interaction databases

IntActiP05919. 56 interactions.

Structurei

Secondary structure

1
81
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi36 – 405Combined sources
Helixi41 – 5010Combined sources
Helixi57 – 6913Combined sources
Turni73 – 764Combined sources
Beta strandi77 – 793Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2N29NMR-A28-81[»]
ProteinModelPortaliP05919.
SMRiP05919. Positions 37-81.
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.

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.

P05919-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
QPIPIVAIVA LVVAIIIAIV VWSIVIIEYR KILRQRKIDR LIDRLIERAE
60 70 80
DSGNESEGEI SALVEMGVEM GHHAPWDVDD L
Length:81
Mass (Da):9,111
Last modified:November 1, 1988 - v1
Checksum:i53A951D6240556EA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03455 Genomic RNA. No translation available.

Cross-referencesi

Web resourcesi

BioAfrica HIV proteomics resource

Vpu entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03455 Genomic RNA. No translation available.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2N29NMR-A28-81[»]
ProteinModelPortaliP05919.
SMRiP05919. Positions 37-81.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP05919. 56 interactions.

Protein family/group databases

TCDBi1.A.40.1.1. the human immunodeficiency virus type i, hiv-1 (retrovirdiac) vpu channel (vpu-c) family.

PTM databases

iPTMnetiP05919.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

ReactomeiR-HSA-162585. Uncoating of the HIV Virion.
R-HSA-162588. Budding and maturation of HIV virion.
R-HSA-162592. Integration of provirus.
R-HSA-162594. Early Phase of HIV Life Cycle.
R-HSA-164516. Minus-strand DNA synthesis.
R-HSA-164525. Plus-strand DNA synthesis.
R-HSA-164843. 2-LTR circle formation.
R-HSA-171286. Synthesis and processing of ENV and VPU.
R-HSA-173107. Binding and entry of HIV virion.
R-HSA-175474. Assembly Of The HIV Virion.
R-HSA-175567. Integration of viral DNA into host genomic DNA.
R-HSA-177539. Autointegration results in viral DNA circles.
R-HSA-180534. Vpu mediated degradation of CD4.
R-HSA-180689. APOBEC3G mediated resistance to HIV-1 infection.
R-HSA-180910. Vpr-mediated nuclear import of PICs.

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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Human immunodeficiency virus type 1 Vpu protein is an oligomeric type I integral membrane protein."
    Maldarelli F., Chen M.Y., Willey R.L., Strebel K.
    J. Virol. 67:5056-5061(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY, SUBUNIT, SUBCELLULAR LOCATION.
  3. "The human immunodeficiency virus type 1 encoded Vpu protein is phosphorylated by casein kinase-2 (CK-2) at positions Ser52 and Ser56 within a predicted alpha-helix-turn-alpha-helix-motif."
    Schubert U., Henklein P., Boldyreff B., Wingender E., Strebel K., Porstmann T.
    J. Mol. Biol. 236:16-25(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-52 AND SER-56.
  4. "The human immunodeficiency virus type 1 Vpu protein specifically binds to the cytoplasmic domain of CD4: implications for the mechanism of degradation."
    Bour S., Schubert U., Strebel K.
    J. Virol. 69:1510-1520(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST CD4.
  5. "The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels."
    Ewart G.D., Sutherland T., Gage P.W., Cox G.B.
    J. Virol. 70:7108-7115(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif."
    Margottin F., Bour S.P., Durand H., Selig L., Benichou S., Richard V., Thomas D., Strebel K., Benarous R.
    Mol. Cell 1:565-574(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST BTRC.
  7. "The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappaB-dependent expression of antiapoptotic factors."
    Akari H., Bour S., Kao S., Adachi A., Strebel K.
    J. Exp. Med. 194:1299-1311(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation."
    Mangeat B., Gers-Huber G., Lehmann M., Zufferey M., Luban J., Piguet V.
    PLoS Pathog. 5:E1000574-E1000574(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HOST FBXW11.
  9. "HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes."
    Iwabu Y., Fujita H., Kinomoto M., Kaneko K., Ishizaka Y., Tanaka Y., Sata T., Tokunaga K.
    J. Biol. Chem. 284:35060-35072(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HOST BST2.
  10. "Molecular dynamics simulations reveal the HIV-1 Vpu transmembrane protein to form stable pentamers."
    Padhi S., Khan N., Jameel S., Priyakumar U.D.
    PLoS ONE 8:E79779-E79779(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  11. "Mechanisms underlying HIV-1 Vpu-mediated viral egress."
    Roy N., Pacini G., Berlioz-Torrent C., Janvier K.
    Front. Microbiol. 5:177-177(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  12. "Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1."
    Jia X., Weber E., Tokarev A., Lewinski M., Rizk M., Suarez M., Guatelli J., Xiong Y.
    Elife 3:E02362-E02362(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HOST AP1M1.
  13. "HIV Nef and Vpu protect HIV-infected CD4+ T cells from antibody-mediated cell lysis through down-modulation of CD4 and BST2."
    Pham T.N., Lukhele S., Hajjar F., Routy J.P., Cohen E.A.
    Retrovirology 11:15-15(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiVPU_HV1H2
AccessioniPrimary (citable) accession number: P05919
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: June 8, 2016
This is version 105 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.