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Entry: A7KW97_9HIV1
LinkDB: A7KW97_9HIV1
Original site: A7KW97_9HIV1 
ID   A7KW97_9HIV1            Unreviewed;        81 AA.
AC   A7KW97;
DT   11-SEP-2007, integrated into UniProtKB/TrEMBL.
DT   11-SEP-2007, sequence version 1.
DT   24-JAN-2024, entry version 62.
DE   RecName: Full=Protein Vpu {ECO:0000256|ARBA:ARBA00018094, ECO:0000256|HAMAP-Rule:MF_04082};
DE   AltName: Full=U ORF protein {ECO:0000256|ARBA:ARBA00031215, ECO:0000256|HAMAP-Rule:MF_04082};
DE   AltName: Full=Viral protein U {ECO:0000256|ARBA:ARBA00030659, ECO:0000256|HAMAP-Rule:MF_04082};
GN   Name=vpu {ECO:0000256|HAMAP-Rule:MF_04082,
GN   ECO:0000256|RuleBase:RU364058, ECO:0000313|EMBL:ABS76358.1};
OS   Human immunodeficiency virus 1.
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11676 {ECO:0000313|EMBL:ABS76358.1};
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1] {ECO:0000313|EMBL:ABS76358.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=Zp62615.p31 {ECO:0000313|EMBL:ABS76358.1};
RA   Jiang C., Kirchherr J., Haynes B., Gao F.;
RL   Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|EMBL:ACE66046.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=62615.03_p1 {ECO:0000313|EMBL:ACE66046.1}, 62615.03_p31
RC   {ECO:0000313|EMBL:ACE66054.1}, 62615.03_p33
RC   {ECO:0000313|EMBL:ACE66056.1}, 62615.03_p4
RC   {ECO:0000313|EMBL:ACE66074.1}, 62615.03_p42
RC   {ECO:0000313|EMBL:ACE66068.1}, 62615.03_p49
RC   {ECO:0000313|EMBL:ACE66072.1}, 62615.03_p50
RC   {ECO:0000313|EMBL:ACE66076.1}, and 62615.03_p8
RC   {ECO:0000313|EMBL:ACE66092.1};
RX   PubMed=18490657; DOI=10.1073/pnas.0802203105;
RA   Keele B.F., Giorgi E.E., Salazar-Gonzalez J.F., Decker J.M., Pham K.T.,
RA   Salazar M.G., Sun C., Grayson T., Wang S., Li H., Wei X., Jiang C.,
RA   Kirchherr J.L., Gao F., Anderson J.A., Ping L.H., Swanstrom R.,
RA   Tomaras G.D., Blattner W.A., Goepfert P.A., Kilby J.M., Saag M.S.,
RA   Delwart E.L., Busch M.P., Cohen M.S., Montefiori D.C., Haynes B.F.,
RA   Gaschen B., Athreya G.S., Lee H.Y., Wood N., Seoighe C., Perelson A.S.,
RA   Bhattacharya T., Korber B.T., Hahn B.H., Shaw G.M.;
RT   "Identification and characterization of transmitted and early founder virus
RT   envelopes in primary HIV-1 infection.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:7552-7557(2008).
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:0000256|RuleBase:RU364058}.
CC   -!- FUNCTION: Enhances virion budding, by targeting human 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:0000256|HAMAP-Rule:MF_04082}.
CC   -!- ACTIVITY REGULATION: Ion channel activity is inhibited by hexamethylene
CC       amiloride in vitro. {ECO:0000256|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:0000256|HAMAP-Rule:MF_04082}.
CC   -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000256|HAMAP-Rule:MF_04082,
CC       ECO:0000256|RuleBase:RU364058}; Single-pass type I membrane protein
CC       {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058}.
CC       Membrane {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane
CC       protein {ECO:0000256|ARBA:ARBA00004479}.
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.
CC       {ECO:0000256|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:0000256|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:0000256|HAMAP-Rule:MF_04082}.
CC   -!- SIMILARITY: Belongs to the HIV-1 VPU protein family.
CC       {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058}.
CC   -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC       feature annotation. {ECO:0000256|HAMAP-Rule:MF_04082}.
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DR   EMBL; EF593303; ABS76358.1; -; Genomic_DNA.
DR   EMBL; EU575596; ACE66046.1; -; Genomic_RNA.
DR   EMBL; EU575600; ACE66054.1; -; Genomic_RNA.
DR   EMBL; EU575601; ACE66056.1; -; Genomic_RNA.
DR   EMBL; EU575607; ACE66068.1; -; Genomic_RNA.
DR   EMBL; EU575610; ACE66072.1; -; Genomic_RNA.
DR   EMBL; EU575611; ACE66074.1; -; Genomic_RNA.
DR   EMBL; EU575612; ACE66076.1; -; Genomic_RNA.
DR   EMBL; EU575619; ACE66092.1; -; Genomic_RNA.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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   Apoptosis {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058};
KW   Host membrane {ECO:0000256|HAMAP-Rule:MF_04082,
KW   ECO:0000256|RuleBase:RU364058};
KW   Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04082,
KW   ECO:0000256|RuleBase:RU364058};
KW   Inhibition of host innate immune response by virus {ECO:0000256|HAMAP-
KW   Rule:MF_04082};
KW   Inhibition of host interferon signaling pathway by virus
KW   {ECO:0000256|HAMAP-Rule:MF_04082};
KW   Inhibition of host tetherin by virus {ECO:0000256|HAMAP-Rule:MF_04082};
KW   Ion channel {ECO:0000256|HAMAP-Rule:MF_04082,
KW   ECO:0000256|RuleBase:RU364058};
KW   Ion transport {ECO:0000256|HAMAP-Rule:MF_04082,
KW   ECO:0000256|RuleBase:RU364058};
KW   Membrane {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058};
KW   Phosphoprotein {ECO:0000256|HAMAP-Rule:MF_04082};
KW   Transmembrane {ECO:0000256|HAMAP-Rule:MF_04082,
KW   ECO:0000256|RuleBase:RU364058};
KW   Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04082,
KW   ECO:0000256|RuleBase:RU364058};
KW   Transport {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058};
KW   Viral immunoevasion {ECO:0000256|HAMAP-Rule:MF_04082}.
FT   TOPO_DOM        1..6
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04082"
FT   TRANSMEM        6..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU364058"
FT   TOPO_DOM        28..81
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04082"
SQ   SEQUENCE   81 AA;  9117 MW;  3E906F124B2E138A CRC64;
     MQPLAIAGIV ALVVAAIIAI VVWTIVIIEY RKILRQKKID RLLDRIRERA EDSGNESEGD
     QEELSALVER GHLAPWDVND L
//
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