ID   VPU_HV1N5               Reviewed;          45 AA.
AC   P08804;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   23-FEB-2022, entry version 100.
DE   RecName: Full=Protein Vpu;
DE   AltName: Full=U ORF protein;
DE   AltName: Full=Viral protein U;
DE   Flags: Fragment;
GN   Name=vpu;
OS   Human immunodeficiency virus type 1 group M subtype B (isolate NY5)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11698;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3014529; DOI=10.1073/pnas.83.14.5038;
RA   Willey R.W., Rutledge R.A., Dias S., Folks T., Theodore T., Buckler C.E.,
RA   Martin M.A.;
RT   "Identification of conserved and divergent domains within the envelope gene
RT   of the acquired immunodeficiency syndrome retrovirus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:5038-5042(1986).
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 ternary complexes, by
CC       interacting with human CD4 and BTRC, and with human BST2 and BTRC (By
CC       similarity). {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 human BRCP and degradation of CD4 (By similarity).
CC       {ECO:0000250}.
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   -!- SIMILARITY: Belongs to the HIV-1 VPU protein family. {ECO:0000305}.
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DR   EMBL; K03346; AAB02406.1; -; Genomic_DNA.
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; Transmembrane; Transport.
FT   CHAIN           <1..45
FT                   /note="Protein Vpu"
FT                   /id="PRO_0000085428"
FT   REGION          1..45
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..18
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         17
FT                   /note="Phosphoserine; by host CK2"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         21
FT                   /note="Phosphoserine; by host CK2"
FT                   /evidence="ECO:0000250"
FT   NON_TER         1
SQ   SEQUENCE   45 AA;  5167 MW;  2AA46D116BB624F7 CRC64;
     RKVDRIIDRI RERAEDSGNE SEGDQEELSA LVEMGHDAPW DVNDL