ID VPU_HV1VI Reviewed; 81 AA.
AC Q9QSQ8;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 27-MAR-2024, entry version 100.
DE RecName: Full=Protein Vpu {ECO:0000255|HAMAP-Rule:MF_04082};
DE AltName: Full=U ORF protein {ECO:0000255|HAMAP-Rule:MF_04082};
DE AltName: Full=Viral protein U {ECO:0000255|HAMAP-Rule:MF_04082};
GN Name=vpu {ECO:0000255|HAMAP-Rule:MF_04082};
OS Human immunodeficiency virus type 1 group M subtype F1 (isolate VI850)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC Human immunodeficiency virus 1.
OX NCBI_TaxID=388813;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10725202; DOI=10.1006/viro.2000.0214;
RA Laukkanen T., Carr J.K., Janssens W., Liitsola K., Gotte D.,
RA McCutchan F.E., Op de Coul E., Cornelissen M., Heyndrickx L.,
RA van der Groen G., Salminen M.O.;
RT "Virtually full-length subtype F and F/D recombinant HIV-1 from Africa and
RT South America.";
RL Virology 269:95-104(2000).
CC -!- FUNCTION: Enhances virion budding by targeting host CD4 and
CC Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents
CC any unwanted premature interactions between viral Env and its host
CC receptor CD4 in the endoplasmic reticulum. Degradation of
CC antiretroviral protein Tetherin/BST2 is important for virion budding,
CC as BST2 tethers new viral particles to the host cell membrane.
CC Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, a substrate
CC recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin
CC ligase, induces their ubiquitination and subsequent proteasomal
CC degradation. The alteration of the E3 ligase specificity by Vpu seems
CC to promote the degradation of host IKBKB, leading to NF-kappa-B down-
CC regulation and subsequent apoptosis. Acts as a viroporin that forms an
CC oligomeric ion channel in membranes. Modulates the host DNA repair
CC mechanisms to promote degradation of nuclear viral cDNA in cells that
CC are already productively infected in order to suppress immune sensing
CC and proviral hyper-integration (superinfection). Manipulates PML-NBs
CC and modulates SUMOylation of host BLM protein thereby enhancing its
CC DNA-end processing activity toward viral unintegrated linear DNA. Also
CC inhibits RAD52-mediated homologous repair of viral cDNA, preventing the
CC generation of dead-end circular forms of single copies of the long
CC terminal repeat and permitting sustained nucleolytic attack.
CC {ECO:0000255|HAMAP-Rule:MF_04082}.
CC -!- ACTIVITY REGULATION: Ion channel activity is inhibited by hexamethylene
CC amiloride in vitro. {ECO:0000255|HAMAP-Rule:MF_04082}.
CC -!- SUBUNIT: Homopentamer. Interacts with host CD4 and BRTC; these
CC interactions induce proteasomal degradation of CD4. Interacts with host
CC BST2; this interaction leads to the degradation of host BST2. Interacts
CC with host FBXW11. Interacts with host AP1M1; this interaction plays a
CC role in the mistrafficking and subsequent degradation of host BST2.
CC Interacts with host RANBP2; this interaction allows Vpu to down-
CC regulate host BLM sumoylation. {ECO:0000255|HAMAP-Rule:MF_04082}.
CC -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000255|HAMAP-Rule:MF_04082};
CC Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04082}.
CC -!- DOMAIN: The N-terminus and transmembrane domains are required for self-
CC oligomerization and proper virion budding, whereas the cytoplasmic
CC domain is required for CD4 degradation. The cytoplasmic domain is
CC composed of 2 amphipathic alpha helix that form a U-shape.The N-
CC terminal and transmembrane domains are required for proper virion
CC budding, whereas the cytoplasmic domain is required for CD4
CC degradation. The cytoplasmic domain is composed of 2 amphipathic alpha
CC helix. {ECO:0000255|HAMAP-Rule:MF_04082}.
CC -!- PTM: Phosphorylated by host CK2. This phosphorylation is necessary for
CC interaction with human BTRC and degradation of CD4. {ECO:0000255|HAMAP-
CC Rule:MF_04082}.
CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC majority of strains found worldwide belong to the group M. Group O
CC seems to be endemic to and largely confined to Cameroon and neighboring
CC countries in West Central Africa, where these viruses represent a small
CC minority of HIV-1 strains. The group N is represented by a limited
CC number of isolates from Cameroonian persons. The group M is further
CC subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC {ECO:0000255|HAMAP-Rule:MF_04082}.
CC -!- SIMILARITY: Belongs to the HIV-1 VPU protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04082}.
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DR EMBL; AF077336; AAD46093.1; -; Genomic_DNA.
DR Proteomes; UP000007418; Segment.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0042609; F:CD4 receptor binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005261; F:monoatomic cation channel activity; IEA:UniProtKB-UniRule.
DR GO; GO:0032801; P:receptor catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0039587; P:suppression by virus of host tetherin activity; IEA:UniProtKB-UniRule.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-UniRule.
DR GO; GO:0019076; P:viral release from host cell; IEA:UniProtKB-UniRule.
DR Gene3D; 1.10.195.10; HIV-1 VPU cytoplasmic domain; 1.
DR HAMAP; MF_04082; HIV_VPU; 1.
DR InterPro; IPR008187; Vpu.
DR InterPro; IPR009032; Vpu_cyt_dom_sf.
DR Pfam; PF00558; Vpu; 1.
DR SUPFAM; SSF57647; HIV-1 VPU cytoplasmic domain; 1.
PE 3: Inferred from homology;
KW AIDS; Apoptosis; Host membrane; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host tetherin by virus; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport; Viral immunoevasion.
FT CHAIN 1..81
FT /note="Protein Vpu"
FT /id="PRO_0000244328"
FT TOPO_DOM 1..7
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
FT TOPO_DOM 29..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
FT MOD_RES 53
FT /note="Phosphoserine; by host CK2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
FT MOD_RES 57
FT /note="Phosphoserine; by host CK2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
SQ SEQUENCE 81 AA; 9062 MW; 74B5F473CE54F851 CRC64;
MSYLLAIGIA ALIVALIIAI VVWTIVYIEY KKLVRQRKIN KLYKRIRERA EDSGNESEGD
AEELAALGEM GPFIPGDINN L
//
