ID   VPU_SIVCZ               Reviewed;          88 AA.
AC   P17286;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   23-FEB-2022, entry version 106.
DE   RecName: Full=Protein Vpu;
DE   AltName: Full=U ORF protein;
DE   AltName: Full=Viral protein U;
GN   Name=vpu;
OS   Simian immunodeficiency virus (isolate CPZ GAB1) (SIV-cpz) (Chimpanzee
OS   immunodeficiency virus).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=402771;
OH   NCBI_TaxID=9596; Pan (chimpanzees).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2188136; DOI=10.1038/345356a0;
RA   Huet T., Cheynier R., Meyerhans A., Roelants G., Wain-Hobson S.;
RT   "Genetic organization of a chimpanzee lentivirus related to HIV-1.";
RL   Nature 345:356-359(1990).
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 receptor
CC       human CD4 in the endoplasmic reticulum. Degradation of antiretroviral
CC       protein Tetherin/BST2 is important for virion budding, as BST2 tethers
CC       new viral particles to the host cell membrane. Mechanistically, Vpu
CC       bridges either CD4 or BST2 to BTRC, a substrate recognition subunit of
CC       the Skp1/Cullin/F-box protein E3 ubiquitin ligase, induces their
CC       ubiquitination and subsequent proteasomal degradation. The alteration
CC       of the E3 ligase specificity by Vpu seems to interfere with the
CC       degradation of host IKBKB, leading to NF-kappa-B down-regulation and
CC       subsequent apoptosis. Ion channel activity has also been suggested,
CC       however, formation of cation-selective channel has been reconstituted
CC       ex-vivo in lipid bilayers. It is thus unsure that this activity plays a
CC       role in vivo (By similarity). {ECO:0000250}.
CC   -!- ACTIVITY REGULATION: Ion channel activity is inhibited by hexamethylene
CC       amiloride in vitro. {ECO:0000250}.
CC   -!- SUBUNIT: May form pentamers or hexamers. Forms a ternary complex by
CC       interacting with host CD4 and host BTRCP (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}.
CC   -!- DOMAIN: The N-terminal and transmembrane domains are required for
CC       proper virion budding, whereas the cytoplasmic domain is required for
CC       CD4 degradation. The cytoplasmic domain is composed of 2 amphipathic
CC       alpha helix (By similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated by host CK2. This phosphorylation is necessary for
CC       interaction with host BRCP and degradation of CD4, but not for
CC       enhancement of virion budding (By similarity). {ECO:0000250}.
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DR   EMBL; X52154; CAA36406.1; -; Genomic_RNA.
DR   PIR; S09989; ASLJSK.
DR   Proteomes; UP000009153; Genome.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005261; F:cation channel activity; IEA:InterPro.
DR   GO; GO:0042609; F:CD4 receptor binding; IEA:InterPro.
DR   GO; GO:0032801; P:receptor catabolic process; IEA:InterPro.
DR   GO; GO:0019076; P:viral release from host cell; IEA:InterPro.
DR   Gene3D; 1.10.195.10; -; 1.
DR   InterPro; IPR008187; Vpu.
DR   InterPro; IPR009032; Vpu_cyt_dom_sf.
DR   Pfam; PF00558; Vpu; 1.
DR   SUPFAM; SSF57647; SSF57647; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Host membrane; Host-virus interaction; Ion channel;
KW   Ion transport; Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..88
FT                   /note="Protein Vpu"
FT                   /id="PRO_0000085434"
FT   TOPO_DOM        1..2
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        3..23
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        24..88
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         56
FT                   /note="Phosphoserine; by host CK2"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         60
FT                   /note="Phosphoserine; by host CK2"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   88 AA;  10565 MW;  5EF8772AD64B6055 CRC64;
     MTLLVGLVLI LVGLIAWNIC IWGYIIKWGY RRYKRHRLET EIERLNLILR ERAEDSGNES
     NGEEEERLEQ LIHNYNHNNH FANPMFDL