UniProtKB - P69700 (VPU_HV1H3)
Protein
Protein Vpu
Gene
vpu
Organism
Human immunodeficiency virus type 1 group M subtype B (isolate HXB3) (HIV-1)
Status
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 annotation
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
- cation channel activity Source: UniProtKB-UniRule
- CD4 receptor binding Source: UniProtKB-UniRule
GO - Biological processi
- receptor catabolic process Source: UniProtKB-UniRule
- suppression by virus of host tetherin activity Source: UniProtKB-UniRule
- suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-UniRule
- viral release from host cell Source: UniProtKB-UniRule
Keywordsi
Names & Taxonomyi
Protein namesi | Recommended name: Protein VpuUniRule annotationAlternative name(s): U ORF proteinUniRule annotation Viral protein UUniRule annotation |
Gene namesi | Name:vpuUniRule annotation |
Organismi | Human immunodeficiency virus type 1 group M subtype B (isolate HXB3) (HIV-1) |
Taxonomic identifieri | 11707 [NCBI] |
Taxonomic lineagei | Viruses › Ortervirales › Retroviridae › Orthoretrovirinae › Lentivirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Subcellular locationi
- Host membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 6 | ExtracellularUniRule annotation | 6 | |
Transmembranei | 7 – 27 | HelicalUniRule annotationAdd BLAST | 21 | |
Topological domaini | 28 – 81 | CytoplasmicUniRule annotationAdd BLAST | 54 |
GO - Cellular componenti
- host cell membrane Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-UniRule
Keywords - Cellular componenti
Host membrane, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085409 | 1 – 81 | Protein VpuAdd BLAST | 81 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 52 | Phosphoserine; by host CK2UniRule annotation | 1 | |
Modified residuei | 56 | Phosphoserine; by host CK2UniRule annotation | 1 |
Post-translational modificationi
Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4.UniRule annotation
Keywords - PTMi
PhosphoproteinInteractioni
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 annotationGO - Molecular functioni
- CD4 receptor binding Source: UniProtKB-UniRule
Protein-protein interaction databases
MINTi | P69700 |
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 helixFamily and domain databases
Gene3Di | 1.10.195.10, 1 hit |
HAMAPi | MF_04082 HIV_VPU, 1 hit |
InterProi | View protein in InterPro IPR008187 Vpu IPR009032 Vpu_cyt_dom_sf |
Pfami | View protein in Pfam PF00558 Vpu, 1 hit |
SUPFAMi | SSF57647 SSF57647, 1 hit |
i Sequence
Sequence statusi: Complete.
P69700-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MQPIQIAIVA LVVAIIIAIV VWSIVIIEYR KILRQRKIDR LIDRLIERAE
60 70 80
DSGNESEGEI SALVEMGVEM GHHAPWDVDD L
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M14100 Genomic RNA Translation: AAA44678.1 |
PIRi | S33984 |
Similar proteinsi
Cross-referencesi
Web resourcesi
BioAfrica HIV proteomics resource Vpu entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M14100 Genomic RNA Translation: AAA44678.1 |
PIRi | S33984 |
3D structure databases
SMRi | P69700 |
ModBasei | Search... |
Protein-protein interaction databases
MINTi | P69700 |
Family and domain databases
Gene3Di | 1.10.195.10, 1 hit |
HAMAPi | MF_04082 HIV_VPU, 1 hit |
InterProi | View protein in InterPro IPR008187 Vpu IPR009032 Vpu_cyt_dom_sf |
Pfami | View protein in Pfam PF00558 Vpu, 1 hit |
SUPFAMi | SSF57647 SSF57647, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | VPU_HV1H3 | |
Accessioni | P69700Primary (citable) accession number: P69700 Secondary accession number(s): P05920 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 29, 2005 |
Last sequence update: | March 29, 2005 | |
Last modified: | September 18, 2019 | |
This is version 85 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |