ID U3LJT6_9HIV1 Unreviewed; 81 AA. AC U3LJT6; DT 11-DEC-2013, integrated into UniProtKB/TrEMBL. DT 11-DEC-2013, sequence version 1. DT 24-JUL-2024, entry version 45. 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:AFZ63161.1}; OS Human immunodeficiency virus 1. OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus. OX NCBI_TaxID=11676 {ECO:0000313|EMBL:AFZ63161.1}; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] {ECO:0000313|EMBL:AFZ63161.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=306336_ENV {ECO:0000313|EMBL:AFZ63161.1}; RA Heipertz R.Jr., Sanders-Buell E., Kijak G., Howell S., Lazzaro M., RA Jagodzinski L., Eggleston J., Peel S., Malia J., Armstrong A., Michael N., RA Kim J., O'Connell R., Scott P., Brett-Major D., Tovanabutra S.; RL Submitted (SEP-2012) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:AFZ63161.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=306336_ENV {ECO:0000313|EMBL:AFZ63161.1}; RX PubMed=23972100; DOI=10.1089/AID.2013.0087; RA Heipertz R.A.Jr., Sanders-Buell E., Kijak G., Howell S., Lazzaro M., RA Jagodzinski L.L., Eggleston J., Peel S., Malia J., Armstrong A., RA Michael N.L., Kim J.H., O'Connell R.J., Scott P.T., Brett-Major D.M., RA Tovanabutra S.; RT "Molecular Epidemiology of Early and Acute HIV Type 1 Infections in the RT United States Navy and Marine Corps, 2005-2010."; RL AIDS Res. Hum. Retroviruses 29:1310-1320(2013). 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 -!- 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; JX863994; AFZ63161.1; -; Genomic_RNA. 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:0006915; P:apoptotic process; IEA:UniProtKB-KW. 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:0052170; P:symbiont-mediated suppression of host innate immune response; IEA:UniProtKB-KW. DR GO; GO:0039502; P:symbiont-mediated suppression 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 Interferon antiviral system evasion {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" FT REGION 50..81 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 63..81 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 81 AA; 9235 MW; E7638D28F224EC76 CRC64; MQSLQIAAII ALVVVAIIAI VVWSIILIEY RKILRQRKID RLIDRIRERA EDSGNESDGD QEELSGLVER GHLAPWDIDD L //