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Protein

Protein Vpu

Gene

vpu

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

Functioni

Enhances virion budding by targeting host CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its host receptor 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. 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.UniRule annotation6 Publications

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).UniRule annotation

Activity regulationi

Ion channel activity is inhibited by hexamethylene amiloride in vitro.UniRule annotation

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel
Biological processApoptosis, 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 VpuUniRule annotation
Alternative name(s):
U ORF proteinUniRule annotation
Viral protein UUniRule annotation
Gene namesi
Name:vpuUniRule annotation
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesOrterviralesRetroviridaeOrthoretrovirinaeLentivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000002241 Componenti: Genome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6ExtracellularUniRule annotation6
Transmembranei7 – 27HelicalUniRule annotationAdd BLAST21
Topological domaini28 – 81CytoplasmicUniRule annotationAdd BLAST54

GO - Cellular componenti

Keywords - Cellular componenti

Host membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000854331 – 81Protein VpuAdd BLAST81

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52Phosphoserine; by host CK2UniRule annotation1 Publication1
Modified residuei56Phosphoserine; by host CK2UniRule annotation1 Publication1

Post-translational modificationi

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

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 degradation 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.UniRule annotation7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD4P017303EBI-6248147,EBI-353826From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

IntActiP05919, 56 interactors

Structurei

Secondary structure

181
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP05919
SMRiP05919
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.UniRule annotation

Sequence similaritiesi

Belongs to the HIV-1 VPU protein family.UniRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG09000203

Family and domain databases

Gene3Di1.10.195.10, 1 hit
HAMAPiMF_04082 HIV_VPU, 1 hit
InterProiView protein in InterPro
IPR008187 Vpu
IPR009032 Vpu_cyt_dom_sf
PfamiView protein in Pfam
PF00558 Vpu, 1 hit
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.

Similar proteinsi

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N29NMR-A28-81[»]
ProteinModelPortaliP05919
SMRiP05919
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP05919, 56 interactors

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...

Phylogenomic databases

OrthoDBiVOG09000203

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
HAMAPiMF_04082 HIV_VPU, 1 hit
InterProiView protein in InterPro
IPR008187 Vpu
IPR009032 Vpu_cyt_dom_sf
PfamiView protein in Pfam
PF00558 Vpu, 1 hit
SUPFAMiSSF57647 SSF57647, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiVPU_HV1H2
AccessioniPrimary (citable) accession number: P05919
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: October 10, 2018
This is version 119 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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