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Protein

Protein Vpu

Gene

vpu

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate SF162) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-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 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

Enzyme 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

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 SF162) (HIV-1)
Taxonomic identifieri11691 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

  • Host membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7ExtracellularUniRule annotation7
Transmembranei8 – 28HelicalUniRule annotationAdd BLAST21
Topological domaini29 – 81CytoplasmicUniRule annotationAdd BLAST53

GO - Cellular componenti

Keywords - Cellular componenti

Host membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000854211 – 81Protein VpuAdd BLAST81

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53Phosphoserine; by host CK2UniRule annotation1
Modified residuei57Phosphoserine; by host CK2UniRule annotation1

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

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.UniRule annotation

GO - Molecular functioni

Protein-protein interaction databases

IntActiP19554. 7 interactors.
MINTiMINT-8389678.

Structurei

Secondary structure

181
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi39 – 48Combined sources10
Helixi52 – 55Combined sources4
Turni56 – 59Combined sources4
Helixi61 – 63Combined sources3
Beta strandi64 – 67Combined sources4
Helixi70 – 72Combined sources3
Helixi75 – 78Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VPUNMR-A39-81[»]
2K7YNMR-A39-81[»]
4P6ZX-ray3.00V29-81[»]
ProteinModelPortaliP19554.
SMRiP19554.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19554.

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

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.
PfamiView protein in Pfam
PF00558. Vpu. 1 hit.
SUPFAMiSSF57647. SSF57647. 1 hit.

Sequencei

Sequence statusi: Complete.

P19554-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPLQILAIV ALVVAAIIAI VVWTIVYIEY RKILRQRKID RLIDRITERA
60 70 80
EDSGNESEGD QEELSALVER GHLAPWDVDD L
Length:81
Mass (Da):9,254
Last modified:February 1, 1991 - v1
Checksum:iE571E3E160928D60
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M65024 Genomic RNA. Translation: AAA45071.1.

Similar proteinsi

Entry informationi

Entry nameiVPU_HV1S1
AccessioniPrimary (citable) accession number: P19554
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: August 30, 2017
This is version 115 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

Documents

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