VPU_HV1BR
ID VPU_HV1BR Reviewed; 81 AA.
AC P05923;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 23-FEB-2022, entry version 130.
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 B (isolate BRU/LAI)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11686;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2981635; DOI=10.1016/0092-8674(85)90303-4;
RA Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.;
RT "Nucleotide sequence of the AIDS virus, LAV.";
RL Cell 40:9-17(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Clone pNL4-3;
RA Buckler C.E., Buckler-White A.J., Willey R.L., McCoy J.;
RL Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION AT SER-52 AND SER-56.
RX PubMed=1541298; DOI=10.1111/j.1432-1033.1992.tb16707.x;
RA Schubert U., Schneider T., Henklein P., Hoffmann K., Berthold E.,
RA Hauser H., Pauli G., Porstmann T.;
RT "Human-immunodeficiency-virus-type-1-encoded Vpu protein is phosphorylated
RT by casein kinase II.";
RL Eur. J. Biochem. 204:875-883(1992).
RN [4]
RP INTERACTION WITH HOST CD4.
RX PubMed=7853484; DOI=10.1128/jvi.69.3.1510-1520.1995;
RA Bour S., Schubert U., Strebel K.;
RT "The human immunodeficiency virus type 1 Vpu protein specifically binds to
RT the cytoplasmic domain of CD4: implications for the mechanism of
RT degradation.";
RL J. Virol. 69:1510-1520(1995).
RN [5]
RP FUNCTION.
RX PubMed=8946945; DOI=10.1016/s0014-5793(96)01146-5;
RA Schubert U., Ferrer-Montiel A.V., Oblatt-Montal M., Henklein P.,
RA Strebel K., Montal M.;
RT "Identification of an ion channel activity of the Vpu transmembrane domain
RT and its involvement in the regulation of virus release from HIV-1-infected
RT cells.";
RL FEBS Lett. 398:12-18(1996).
RN [6]
RP DOMAINS.
RX PubMed=8551619; DOI=10.1128/jvi.70.2.809-819.1996;
RA Schubert U., Bour S., Ferrer-Montiel A.V., Montal M., Maldarell F.,
RA Strebel K.;
RT "The two biological activities of human immunodeficiency virus type 1 Vpu
RT protein involve two separable structural domains.";
RL J. Virol. 70:809-819(1996).
RN [7]
RP INTERACTION WITH HOST BTRC, AND MUTAGENESIS OF SER-52 AND SER-56.
RX PubMed=9660940; DOI=10.1016/s1097-2765(00)80056-8;
RA Margottin F., Bour S.P., Durand H., Selig L., Benichou S., Richard V.,
RA Thomas D., Strebel K., Benarous R.;
RT "A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu
RT connects CD4 to the ER degradation pathway through an F-box motif.";
RL Mol. Cell 1:565-574(1998).
RN [8]
RP FUNCTION IN APOPTOSIS.
RX PubMed=11696595; DOI=10.1084/jem.194.9.1299;
RA Akari H., Bour S., Kao S., Adachi A., Strebel K.;
RT "The human immunodeficiency virus type 1 accessory protein Vpu induces
RT apoptosis by suppressing the nuclear factor kappaB-dependent expression of
RT antiapoptotic factors.";
RL J. Exp. Med. 194:1299-1311(2001).
RN [9]
RP FUNCTION.
RX PubMed=14657387; DOI=10.1073/pnas.2433165100;
RA Varthakavi V., Smith R.M., Bour S.P., Strebel K., Spearman P.;
RT "Viral protein U counteracts a human host cell restriction that inhibits
RT HIV-1 particle production.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15154-15159(2003).
RN [10]
RP REVIEW.
RX PubMed=12941395; DOI=10.1016/s1286-4579(03)00191-6;
RA Bour S., Strebel K.;
RT "The HIV-1 Vpu protein: a multifunctional enhancer of viral particle
RT release.";
RL Microbes Infect. 5:1029-1039(2003).
RN [11]
RP FUNCTION.
RX PubMed=16571793; DOI=10.1128/jvi.80.8.3765-3772.2006;
RA Harila K., Prior I., Sjoberg M., Salminen A., Hinkula J., Suomalainen M.;
RT "Vpu and Tsg101 regulate intracellular targeting of the human
RT immunodeficiency virus type 1 core protein precursor Pr55gag.";
RL J. Virol. 80:3765-3772(2006).
RN [12]
RP FUNCTION.
RX PubMed=16699598; DOI=10.1371/journal.ppat.0020039;
RA Neil S.J., Eastman S.W., Jouvenet N., Bieniasz P.D.;
RT "HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus
RT particles from the plasma membrane.";
RL PLoS Pathog. 2:354-367(2006).
RN [13]
RP INHIBITION BY HEXAMETHYLENE AMILORIDE.
RX PubMed=17082882; DOI=10.1007/s00216-006-0832-4;
RA Kim C.G., Lemaitre V., Watts A., Fischer W.B.;
RT "Drug-protein interaction with Vpu from HIV-1: proposing binding sites for
RT amiloride and one of its derivatives.";
RL Anal. Bioanal. Chem. 386:2213-2217(2006).
RN [14]
RP FUNCTION.
RX PubMed=18342597; DOI=10.1016/j.chom.2008.03.001;
RA Van Damme N., Goff D., Katsura C., Jorgenson R.L., Mitchell R.,
RA Johnson M.C., Stephens E.B., Guatelli J.;
RT "The interferon-induced protein BST-2 restricts HIV-1 release and is
RT downregulated from the cell surface by the viral Vpu protein.";
RL Cell Host Microbe 3:245-252(2008).
RN [15]
RP FUNCTION.
RX PubMed=18200009; DOI=10.1038/nature06553;
RA Neil S.J., Zang T., Bieniasz P.D.;
RT "Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu.";
RL Nature 451:425-430(2008).
RN [16]
RP FUNCTION.
RX PubMed=19286137; DOI=10.1016/j.chom.2009.01.009;
RA Goffinet C., Allespach I., Homann S., Tervo H.M., Habermann A., Rupp D.,
RA Oberbremer L., Kern C., Tibroni N., Welsch S., Krijnse-Locker J.,
RA Banting G., Krausslich H.G., Fackler O.T., Keppler O.T.;
RT "HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated
RT proteasomal degradation of the restriction factor.";
RL Cell Host Microbe 5:285-297(2009).
RN [17]
RP FUNCTION, AND INTERACTION WITH HOST BST2.
RX PubMed=19515779; DOI=10.1128/jvi.00242-09;
RA Douglas J.L., Viswanathan K., McCarroll M.N., Gustin J.K., Fruh K.,
RA Moses A.V.;
RT "Vpu directs the degradation of the human immunodeficiency virus
RT restriction factor BST2/Tetherin via a {beta}TrCP-dependent mechanism.";
RL J. Virol. 83:7931-7947(2009).
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. Ion channel activity has also been
CC suggested, however, formation of cation-selective channel has been
CC reconstituted ex-vivo in lipid bilayers. It is thus unsure that this
CC activity plays a role in vivo. {ECO:0000255|HAMAP-Rule:MF_04082,
CC ECO:0000269|PubMed:11696595, ECO:0000269|PubMed:14657387,
CC ECO:0000269|PubMed:16571793, ECO:0000269|PubMed:16699598,
CC ECO:0000269|PubMed:18200009, ECO:0000269|PubMed:18342597,
CC ECO:0000269|PubMed:19286137, ECO:0000269|PubMed:19515779,
CC ECO:0000269|PubMed:8946945}.
CC -!- ACTIVITY REGULATION: Ion channel activity is inhibited by hexamethylene
CC amiloride in vitro. {ECO:0000255|HAMAP-Rule:MF_04082,
CC ECO:0000269|PubMed:17082882}.
CC -!- SUBUNIT: Forms pentamers or hexamers. Interacts with host CD4 and BRTC;
CC these interactions induce proteasomal degradation of CD4. Interacts
CC with host BST2; this interaction leads to the degradation of host BST2.
CC Interacts with host FBXW11. Interacts with host AP1M1; this interaction
CC plays a role in the mistrafficking and subsequent degradation of host
CC BST2. {ECO:0000255|HAMAP-Rule:MF_04082, ECO:0000269|PubMed:19515779,
CC ECO:0000269|PubMed:7853484, ECO:0000269|PubMed:9660940}.
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-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. {ECO:0000255|HAMAP-Rule:MF_04082,
CC ECO:0000269|PubMed:8551619}.
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, ECO:0000269|PubMed:1541298}.
CC -!- MISCELLANEOUS: The infectious clone pNL4-3 is a chimeric provirus that
CC consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).
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; K02013; AAB59750.1; -; Genomic_RNA.
DR EMBL; M19921; AAA44991.1; -; Genomic_RNA.
DR IntAct; P05923; 1.
DR MINT; P05923; -.
DR iPTMnet; P05923; -.
DR Proteomes; UP000007692; Genome.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0005261; F:cation channel activity; IEA:UniProtKB-UniRule.
DR GO; GO:0042609; F:CD4 receptor binding; 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; IDA:CACAO.
DR Gene3D; 1.10.195.10; -; 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; SSF57647; 1.
PE 1: Evidence at protein level;
KW AIDS; Apoptosis; Host membrane; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway 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_0000085417"
FT TOPO_DOM 1..6
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
FT TOPO_DOM 28..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082"
FT MOD_RES 52
FT /note="Phosphoserine; by host CK2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082,
FT ECO:0000269|PubMed:1541298"
FT MOD_RES 56
FT /note="Phosphoserine; by host CK2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04082,
FT ECO:0000269|PubMed:1541298"
FT VARIANT 5..6
FT /note="QI -> IV (in strain: Clone pNL4-3)"
FT VARIANT 9
FT /note="A -> V (in strain: Clone pNL4-3)"
FT VARIANT 60
FT /note="I -> V (in strain: Clone pNL4-3)"
FT MUTAGEN 52
FT /note="S->N: Complete loss of interaction with human BTRC,
FT and of CD4 degradation activity; when associated with N-
FT 56."
FT /evidence="ECO:0000269|PubMed:9660940"
FT MUTAGEN 56
FT /note="S->N: Complete loss of interaction with human BTRC,
FT and of CD4 degradation activity; when associated with N-
FT 52."
FT /evidence="ECO:0000269|PubMed:9660940"
SQ SEQUENCE 81 AA; 9160 MW; B9F588F7C6654B51 CRC64;
MQPIQIAIAA LVVAIIIAIV VWSIVIIEYR KILRQRKIDR LIDRLIERAE DSGNESEGEI
SALVEMGVEM GHHAPWDIDD L
