ID U3LJT6_9HIV1 Unreviewed; 81 AA. AC U3LJT6; DT 11-DEC-2013, integrated into UniProtKB/TrEMBL. DT 11-DEC-2013, sequence version 1. DT 10-OCT-2018, entry version 23. DE RecName: Full=Protein Vpu {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058}; DE AltName: Full=U ORF protein {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058}; DE AltName: Full=Viral protein U {ECO:0000256|HAMAP-Rule:MF_04082, ECO:0000256|RuleBase:RU364058}; 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; 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., RA Michael N., Kim J., O'Connell R., Scott P., Brett-Major D., RA 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 RT the 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 CC prevents any unwanted premature interactions between viral Env and CC its host receptor CD4 in the endoplasmic reticulum. Degradation of CC antiretroviral protein Tetherin/BST2 is important for virion CC budding, as BST2 tethers new viral particles to the host cell CC membrane. Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, CC a substrate recognition subunit of the Skp1/Cullin/F-box protein CC E3 ubiquitin ligase, induces their ubiquitination and subsequent CC proteasomal degradation. The alteration of the E3 ligase CC specificity by Vpu seems to promote the degradation of host IKBKB, CC leading to NF-kappa-B down-regulation and subsequent apoptosis. CC Ion channel activity has also been suggested, however, formation CC of cation-selective channel has been reconstituted ex-vivo in CC lipid bilayers. It is thus unsure that this activity plays a role CC in vivo. {ECO:0000256|HAMAP-Rule:MF_04082, CC ECO:0000256|RuleBase:RU364058}. CC -!- ACTIVITY REGULATION: Ion channel activity is inhibited by CC hexamethylene amiloride in vitro. {ECO:0000256|HAMAP- CC Rule:MF_04082}. CC -!- SUBUNIT: Forms pentamers or hexamers. Interacts with host CD4 and CC BRTC; these interactions induce proteasomal degradation of CD4. CC Interacts with host BST2; this interaction leads to the CC degradation of host BST2. Interacts with host FBXW11. Interacts CC with host AP1M1; this interaction plays a role in the CC mistrafficking and subsequent degradation of host BST2. CC {ECO:0000256|HAMAP-Rule:MF_04082}. CC -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000256|HAMAP- CC Rule:MF_04082, ECO:0000256|RuleBase:RU364058}; Single-pass type I CC membrane protein {ECO:0000256|HAMAP-Rule:MF_04082, CC ECO:0000256|RuleBase:RU364058}. CC -!- DOMAIN: The N-terminal and transmembrane domains are required for CC proper virion budding, whereas the cytoplasmic domain is required CC for CD4 degradation. The cytoplasmic domain is composed of 2 CC amphipathic alpha helix. {ECO:0000256|HAMAP-Rule:MF_04082}. CC -!- PTM: Phosphorylated by host CK2. This phosphorylation is necessary CC for interaction with human BTRC and degradation of CD4. CC {ECO:0000256|HAMAP-Rule:MF_04082}. CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M CC (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). CC The vast majority of strains found worldwide belong to the group CC M. Group O seems to be endemic to and largely confined to Cameroon CC and neighboring countries in West Central Africa, where these CC viruses represent a small minority of HIV-1 strains. The group N CC is represented by a limited number of isolates from Cameroonian CC persons. The group M is further subdivided in 9 clades or subtypes CC (A to D, F to H, J and K). {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 --------------------------------------------------------------------------- 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: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:UniProtKB-UniRule. 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 3: Inferred from homology; KW Apoptosis {ECO:0000256|HAMAP-Rule:MF_04082, KW 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- KW 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, KW 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, KW ECO:0000256|RuleBase:RU364058}; KW Viral immunoevasion {ECO:0000256|HAMAP-Rule:MF_04082}. FT TOPO_DOM 1 4 Extracellular. {ECO:0000256|HAMAP-Rule: FT MF_04082}. FT TRANSMEM 6 28 Helical. {ECO:0000256|RuleBase:RU364058}. FT TOPO_DOM 29 81 Cytoplasmic. {ECO:0000256|HAMAP-Rule: FT MF_04082}. FT MOD_RES 53 53 Phosphoserine; by host CK2. FT {ECO:0000256|HAMAP-Rule:MF_04082}. FT MOD_RES 57 57 Phosphoserine; by host CK2. FT {ECO:0000256|HAMAP-Rule:MF_04082}. SQ SEQUENCE 81 AA; 9235 MW; E7638D28F224EC76 CRC64; MQSLQIAAII ALVVVAIIAI VVWSIILIEY RKILRQRKID RLIDRIRERA EDSGNESDGD QEELSGLVER GHLAPWDIDD L //