ID M1L269_9HIV1 Unreviewed; 853 AA. AC M1L269; DT 01-MAY-2013, integrated into UniProtKB/TrEMBL. DT 01-MAY-2013, sequence version 1. DT 23-MAY-2018, entry version 39. DE RecName: Full=Envelope glycoprotein gp160 {ECO:0000256|HAMAP-Rule:MF_04083}; DE AltName: Full=Env polyprotein {ECO:0000256|HAMAP-Rule:MF_04083}; DE Contains: DE RecName: Full=Surface protein gp120 {ECO:0000256|HAMAP-Rule:MF_04083}; DE Short=SU {ECO:0000256|HAMAP-Rule:MF_04083}; DE AltName: Full=Glycoprotein 120 {ECO:0000256|HAMAP-Rule:MF_04083}; DE Short=gp120 {ECO:0000256|HAMAP-Rule:MF_04083}; DE Contains: DE RecName: Full=Transmembrane protein gp41 {ECO:0000256|HAMAP-Rule:MF_04083}; DE Short=TM {ECO:0000256|HAMAP-Rule:MF_04083}; DE AltName: Full=Glycoprotein 41 {ECO:0000256|HAMAP-Rule:MF_04083}; DE Short=gp41 {ECO:0000256|HAMAP-Rule:MF_04083}; GN Name=env {ECO:0000256|HAMAP-Rule:MF_04083, GN ECO:0000313|EMBL:AGF34672.1}; OS Human immunodeficiency virus 1. OC Viruses; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae; OC Lentivirus; Primate lentivirus group. OX NCBI_TaxID=11676 {ECO:0000313|EMBL:AGF34672.1, ECO:0000313|Proteomes:UP000106273}; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] {ECO:0000313|EMBL:AGF34672.1, ECO:0000313|Proteomes:UP000106273} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=2011.ANHUI.WH69 {ECO:0000313|EMBL:AGF34672.1}; RX PubMed=23372706; DOI=10.1371/journal.pone.0054322; RA Wu J., Meng Z., Xu J., Lei Y., Jin L., Zhong P., Han R., Su B.; RT "New Emerging Recombinant HIV-1 Strains and Close Transmission Linkage RT of HIV-1 Strains in the Chinese MSM Population Indicate a New Epidemic RT Risk."; RL PLoS ONE 8:E54322-E54322(2013). CC -!- FUNCTION: Envelope glycoprotein gp160: Oligomerizes in the host CC endoplasmic reticulum into predominantly trimers. In a second CC time, gp160 transits in the host Golgi, where glycosylation is CC completed. The precursor is then proteolytically cleaved in the CC trans-Golgi and thereby activated by cellular furin or furin-like CC proteases to produce gp120 and gp41. {ECO:0000256|HAMAP- CC Rule:MF_04083}. CC -!- FUNCTION: Surface protein gp120: Attaches the virus to the host CC lymphoid cell by binding to the primary receptor CD4. This CC interaction induces a structural rearrangement creating a high CC affinity binding site for a chemokine coreceptor like CXCR4 and/or CC CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, CC which are respectively found on dendritic cells (DCs), and on CC endothelial cells of liver sinusoids and lymph node sinuses. These CC interactions allow capture of viral particles at mucosal surfaces CC by these cells and subsequent transmission to permissive cells. CC HIV subverts the migration properties of dendritic cells to gain CC access to CD4+ T-cells in lymph nodes. Virus transmission to CC permissive T-cells occurs either in trans (without DCs infection, CC through viral capture and transmission), or in cis (following DCs CC productive infection, through the usual CD4-gp120 interaction), CC thereby inducing a robust infection. In trans infection, bound CC virions remain infectious over days and it is proposed that they CC are not degraded, but protected in non-lysosomal acidic organelles CC within the DCs close to the cell membrane thus contributing to the CC viral infectious potential during DCs' migration from the CC periphery to the lymphoid tissues. On arrival at lymphoid tissues, CC intact virions recycle back to DCs' cell surface allowing virus CC transmission to CD4+ T-cells. {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- FUNCTION: Transmembrane protein gp41: Acts as a class I viral CC fusion protein. Under the current model, the protein has at least CC 3 conformational states: pre-fusion native state, pre-hairpin CC intermediate state, and post-fusion hairpin state. During fusion CC of viral and target intracellular membranes, the coiled coil CC regions (heptad repeats) assume a trimer-of-hairpins structure, CC positioning the fusion peptide in close proximity to the C- CC terminal region of the ectodomain. The formation of this structure CC appears to drive apposition and subsequent fusion of viral and CC target cell membranes. Complete fusion occurs in host cell CC endosomes and is dynamin-dependent, however some lipid transfer CC might occur at the plasma membrane. The virus undergoes clathrin- CC dependent internalization long before endosomal fusion, thus CC minimizing the surface exposure of conserved viral epitopes during CC fusion and reducing the efficacy of inhibitors targeting these CC epitopes. Membranes fusion leads to delivery of the nucleocapsid CC into the cytoplasm. {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- SUBUNIT: The mature envelope protein (Env) consists of a CC homotrimer of non-covalently associated gp120-gp41 heterodimers. CC The resulting complex protrudes from the virus surface as a spike. CC There seems to be as few as 10 spikes on the average virion. CC Surface protein gp120 interacts with host CD4, CCR5 and CXCR4. CC Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CC CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R)). Gp120 CC and gp41 interact with GalCer. Gp120 interacts with host CC ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction results in CC rapid activation of integrin ITGAL/LFA-1, which facilitates CC efficient cell-to-cell spreading of HIV-1. Gp120 interacts with CC cell-associated heparan sulfate; this interaction increases virus CC infectivity on permissive cells and may be involved in infection CC of CD4- cells. {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- SUBCELLULAR LOCATION: Host cell membrane CC {ECO:0000256|SAAS:SAAS00937286}; Peripheral membrane protein CC {ECO:0000256|SAAS:SAAS00937286}. Host cell membrane CC {ECO:0000256|SAAS:SAAS00936930}; Single-pass type I membrane CC protein {ECO:0000256|SAAS:SAAS00936930}. Host endosome membrane CC {ECO:0000256|SAAS:SAAS00937040}; Single-pass type I membrane CC protein {ECO:0000256|SAAS:SAAS00937040}. Virion membrane CC {ECO:0000256|SAAS:SAAS00796993}; Single-pass type I membrane CC protein {ECO:0000256|SAAS:SAAS00796993}. CC -!- SUBCELLULAR LOCATION: Surface protein gp120: Virion membrane CC {ECO:0000256|HAMAP-Rule:MF_04083}; Peripheral membrane protein CC {ECO:0000256|HAMAP-Rule:MF_04083}. Host cell membrane CC {ECO:0000256|HAMAP-Rule:MF_04083}; Peripheral membrane protein CC {ECO:0000256|HAMAP-Rule:MF_04083}. Host endosome membrane CC {ECO:0000256|HAMAP-Rule:MF_04083}; Single-pass type I membrane CC protein {ECO:0000256|HAMAP-Rule:MF_04083}. Note=The surface CC protein is not anchored to the viral envelope, but associates with CC the extravirion surface through its binding to TM. It is probably CC concentrated at the site of budding and incorporated into the CC virions possibly by contacts between the cytoplasmic tail of Env CC and the N-terminus of Gag. {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- SUBCELLULAR LOCATION: Transmembrane protein gp41: Virion membrane CC {ECO:0000256|HAMAP-Rule:MF_04083}; Single-pass type I membrane CC protein {ECO:0000256|HAMAP-Rule:MF_04083}. Host cell membrane CC {ECO:0000256|HAMAP-Rule:MF_04083}; Single-pass type I membrane CC protein {ECO:0000256|HAMAP-Rule:MF_04083}. Host endosome membrane CC {ECO:0000256|HAMAP-Rule:MF_04083}; Single-pass type I membrane CC protein {ECO:0000256|HAMAP-Rule:MF_04083}. Note=It is probably CC concentrated at the site of budding and incorporated into the CC virions possibly by contacts between the cytoplasmic tail of Env CC and the N-terminus of Gag. {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- DOMAIN: Some of the most genetically diverse regions of the viral CC genome are present in Env. They are called variable regions 1 CC through 5 (V1 through V5). Coreceptor usage of gp120 is determined CC mainly by the primary structure of the third variable region (V3) CC in the outer domain of gp120. The sequence of V3 determines which CC coreceptor, CCR5 and/or CXCR4 (corresponding to R5/macrophage, CC X4/T cell and R5X4/T cell and macrophage tropism), is used to CC trigger the fusion potential of the Env complex, and hence which CC cells the virus can infect. Binding to CCR5 involves a region CC adjacent in addition to V3. {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- DOMAIN: The 17 amino acids long immunosuppressive region is CC present in many retroviral envelope proteins. Synthetic peptides CC derived from this relatively conserved sequence inhibit immune CC function in vitro and in vivo. {ECO:0000256|HAMAP-Rule:MF_04083, CC ECO:0000256|RuleBase:RU363095}. CC -!- DOMAIN: The CD4-binding region is targeted by the antibody b12. CC {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- DOMAIN: The YXXL motif is involved in determining the exact site CC of viral release at the surface of infected mononuclear cells and CC promotes endocytosis. YXXL and di-leucine endocytosis motifs CC interact directly or indirectly with the clathrin adapter CC complexes, opperate independently, and their activities are not CC additive. {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- DOMAIN: The membrane proximal external region (MPER) present in CC gp41 is a tryptophan-rich region recognized by the antibodies 2F5, CC Z13, and 4E10. MPER seems to play a role in fusion. CC {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- PTM: Highly glycosylated by host. The high number of glycan on the CC protein is reffered to as 'glycan shield' because it contributes CC to hide protein sequence from adaptive immune system. CC {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- PTM: Palmitoylation of the transmembrane protein and of Env CC polyprotein (prior to its proteolytic cleavage) is essential for CC their association with host cell membrane lipid rafts. CC Palmitoylation is therefore required for envelope trafficking to CC classical lipid rafts, but not for viral replication. CC {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. CC Envelope glycoproteins are synthesized as a inactive precursor CC that is heavily N-glycosylated and processed likely by host cell CC furin in the Golgi to yield the mature SU and TM proteins. The CC cleavage site between SU and TM requires the minimal sequence CC [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are CC reduced by P4HB/PDI, following binding to CD4 receptor. CC {ECO:0000256|HAMAP-Rule:MF_04083}. 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_04083}. CC -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins CC are used as antiretroviral drugs. Attachment of virions to the CC cell surface via non-specific interactions and CD4 binding can be CC blocked by inhibitors that include cyanovirin-N, CC cyclotriazadisulfonamide analogs, PRO 2000, TNX 355 and PRO 542. CC In addition, BMS 806 can block CD4-induced conformational changes. CC Env interactions with the coreceptor molecules can be targeted by CC CCR5 antagonists including SCH-D, maraviroc (UK 427857) and CC aplaviroc (GW 873140), and the CXCR4 antagonist AMD 070. Fusion of CC viral and cellular membranes can be inhibited by peptides such as CC enfuvirtide and tifuvirtide (T 1249). Resistance to inhibitors CC associated with mutations in Env are observed. Most of the time, CC single mutations confer only a modest reduction in drug CC susceptibility. Combination of several mutations is usually CC required to develop a high-level drug resistance. CC {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- SIMILARITY: Belongs to the HIV-1 env protein family. CC {ECO:0000256|HAMAP-Rule:MF_04083}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation CC of feature annotation. {ECO:0000256|HAMAP-Rule:MF_04083, CC ECO:0000256|RuleBase:RU363095}. 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; KC183781; AGF34672.1; -; Genomic_RNA. DR Proteomes; UP000106273; Genome. DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule. DR GO; GO:0090527; P:actin filament reorganization; IEA:UniProtKB-UniRule. DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule. DR GO; GO:0030683; P:evasion or tolerance by virus of host immune response; IEA:UniProtKB-UniRule. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule. DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule. DR GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule. DR GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule. DR GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule. DR GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule. DR CDD; cd09909; HIV-1-like_HR1-HR2; 1. DR Gene3D; 2.170.40.20; -; 2. DR HAMAP; MF_04083; HIV_ENV; 1. DR InterPro; IPR036377; Gp120_core_sf. DR InterPro; IPR037527; Gp160. DR InterPro; IPR000328; GP41-like. DR InterPro; IPR000777; HIV1_Gp120. DR Pfam; PF00516; GP120; 2. DR Pfam; PF00517; GP41; 1. DR SUPFAM; SSF56502; SSF56502; 2. PE 3: Inferred from homology; KW Apoptosis {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00936854}; KW Clathrin-mediated endocytosis of virus by host {ECO:0000256|HAMAP- KW Rule:MF_04083}; KW Cleavage on pair of basic residues {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095}; KW Coiled coil {ECO:0000256|HAMAP-Rule:MF_04083}; KW Complete proteome {ECO:0000313|Proteomes:UP000106273}; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|SAAS:SAAS00487956}; KW Fusion of virus membrane with host endosomal membrane KW {ECO:0000256|HAMAP-Rule:MF_04083}; KW Fusion of virus membrane with host membrane {ECO:0000256|HAMAP- KW Rule:MF_04083, ECO:0000256|RuleBase:RU363095, KW ECO:0000256|SAAS:SAAS00487637}; KW Glycoprotein {ECO:0000256|HAMAP-Rule:MF_04083}; KW Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00936840}; KW Host endosome {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00936869}; KW Host membrane {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00937255}; KW Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00797036}; KW Lipoprotein {ECO:0000256|HAMAP-Rule:MF_04083}; KW Membrane {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00797370}; KW Palmitate {ECO:0000256|HAMAP-Rule:MF_04083}; KW Signal {ECO:0000256|HAMAP-Rule:MF_04083}; KW Transmembrane {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00797262}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00797734}; KW Viral attachment to host cell {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00797747}; KW Viral envelope protein {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00797156, KW ECO:0000313|EMBL:AGF34672.1}; KW Viral immunoevasion {ECO:0000256|HAMAP-Rule:MF_04083}; KW Viral penetration into host cytoplasm {ECO:0000256|HAMAP- KW Rule:MF_04083, ECO:0000256|RuleBase:RU363095, KW ECO:0000256|SAAS:SAAS00132213}; KW Virion {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00796948}; KW Virus endocytosis by host {ECO:0000256|HAMAP-Rule:MF_04083}; KW Virus entry into host cell {ECO:0000256|HAMAP-Rule:MF_04083, KW ECO:0000256|RuleBase:RU363095, ECO:0000256|SAAS:SAAS00797206}. FT TRANSMEM 12 34 Helical. {ECO:0000256|RuleBase:RU363095}. FT TRANSMEM 502 525 Helical. {ECO:0000256|RuleBase:RU363095}. FT TRANSMEM 668 695 Helical. {ECO:0000256|RuleBase:RU363095}. FT TOPO_DOM 696 853 Cytoplasmic. {ECO:0000256|HAMAP-Rule: FT MF_04083}. FT DOMAIN 32 145 GP120. {ECO:0000259|Pfam:PF00516}. FT DOMAIN 137 501 GP120. {ECO:0000259|Pfam:PF00516}. FT DOMAIN 520 711 GP41. {ECO:0000259|Pfam:PF00517}. FT REGION 358 368 CD4-binding loop. {ECO:0000256|HAMAP- FT Rule:MF_04083}. FT REGION 451 461 V5. {ECO:0000256|HAMAP-Rule:MF_04083}. FT REGION 502 522 Fusion peptide. {ECO:0000256|HAMAP-Rule: FT MF_04083}. FT REGION 564 582 Immunosuppression. {ECO:0000256|HAMAP- FT Rule:MF_04083}. FT REGION 652 673 MPER; binding to GalCer. FT {ECO:0000256|HAMAP-Rule:MF_04083}. FT COILED 623 657 {ECO:0000256|HAMAP-Rule:MF_04083}. FT MOTIF 702 705 YXXL motif; contains endocytosis signal. FT {ECO:0000256|HAMAP-Rule:MF_04083}. FT SITE 501 502 Cleavage; by host furin. FT {ECO:0000256|HAMAP-Rule:MF_04083}. FT LIPID 754 754 S-palmitoyl cysteine; by host. FT {ECO:0000256|HAMAP-Rule:MF_04083}. FT DISULFID 52 72 {ECO:0000256|HAMAP-Rule:MF_04083}. FT DISULFID 214 243 {ECO:0000256|HAMAP-Rule:MF_04083}. FT DISULFID 224 235 {ECO:0000256|HAMAP-Rule:MF_04083}. FT DISULFID 588 594 {ECO:0000256|HAMAP-Rule:MF_04083}. FT UNSURE 272 272 D or N. {ECO:0000313|EMBL:AGF34672.1}. SQ SEQUENCE 853 AA; 96371 MW; 08A2E3C1825E45EC CRC64; MRVTGIKKNW PLWKWGTMLL GMLMICSAEG NLWVTVYYGV PVWKEATTTL FCASDAKAYN AEAHNVWATH ACVPTDPDPQ EVVLENVTEN FNMWKNEMVN QMHEDVISLW DQSLKPCVKL TPLCVTLNCT NVTSNSNSVN NNSSLENTQE MKNCSFNTTT VVRDKKQQVY ALFYRLDIVP LTNSSEYRLI NCNTSAITQA CPKVSFDPIP IHYCTPAGYA LLKCNDERFN GTGPCHNVSS VQCTHGIKPV VSTQLLLNGS LAEKEIIVRS EDLTNNAKTI IVQLNKSVEI VCIRPGNNTR KSIRIGPGQT FYATGEIIGD IRQAHCNISG KDWEETLRNV SKKLAEHFQN KTIQFASSSG GDLEITTHSF NCRGEFFYCN TSGLFNKTYM HNDTLNSTEN WPXITIPCRI KQIINMWQEV GRAMYAPPIA GNITCKSNIT GLLLVRDGGA GSNDTEIFRP GGGDMRDNWR SELYKYKVVE IKPLGVAPTD AKRRVVEREK RAVGIGAVFL GFLGVAGSTM GAASLTLTVQ ARQLLSGIVQ QQSNLLRAIE AQQHMLQLTV WGIKQLQTRV LAIERYLKDQ QLLGIWGCSG KLICTTAVPW NSSWSNKSQK EIWDNMTWMQ WDKEISNYTD TIYRLLEVSQ NQQERNEKDL LALDSWKNLW NWFDITNWLW YIKIFIMIVG GLIGLRIIFA VLSIVKRVRE GYSPLSFQTP SHHQREPDRP EGIEEGGGEQ GRDRSVRLVS GFLAIVWDDL RSLCLFSYHR LRDFILIATR TVELLGHSSL KGLRRGWEGL KYLGNLLLYW GQELKISAIS LIDATAIATA GWTDRVIEAA QRAWLALLHI PRRIRQGFER ALV //