ID ENV_HV1B1 Reviewed; 856 AA. AC P03375; P03376; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 02-SEP-2026, entry version 189. DE RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083}; DE AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083}; DE Contains: DE RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083}; DE Short=SU {ECO:0000255|HAMAP-Rule:MF_04083}; DE AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083}; DE Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083}; DE Contains: DE RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083}; DE Short=TM {ECO:0000255|HAMAP-Rule:MF_04083}; DE AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083}; DE Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083}; DE Flags: Precursor; GN Name=env {ECO:0000255|HAMAP-Rule:MF_04083}; OS Human immunodeficiency virus type 1 group M subtype B (isolate BH10) OS (HIV-1). OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus; OC Lentivirus humimdef1; Human immunodeficiency virus type 1. OX NCBI_TaxID=11678; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=2578615; DOI=10.1038/313277a0; RA Ratner L., Haseltine W.A., Patarca R., Livak K.J., Starcich B.R., RA Josephs S.F., Doran E.R., Rafalski J.A., Whitehorn E.A., Baumeister K., RA Ivanoff L., Petteway S.R. Jr., Pearson M.L., Lautenberger J.A., Papas T.S., RA Ghrayeb J., Chang N.T., Gallo R.C., Wong-Staal F.; RT "Complete nucleotide sequence of the AIDS virus, HTLV-III."; RL Nature 313:277-284(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Isolate PV22; RX PubMed=2982104; DOI=10.1038/313450a0; RA Muesing M.A., Smith D.H., Cabradilla C.D., Benton C.V., Lasky L.A., RA Capon D.J.; RT "Nucleic acid structure and expression of the human AIDS/lymphadenopathy RT retrovirus."; RL Nature 313:450-458(1985). RN [3] RP PROTEOLYTIC PROCESSING OF POLYPROTEIN. RX PubMed=2450679; DOI=10.1016/0092-8674(88)90487-4; RA McCune J.M., Rabin L.B., Feinberg M.B., Lieberman M., Kosek J.C., RA Reyes G.R., Weissman I.L.; RT "Endoproteolytic cleavage of gp160 is required for the activation of human RT immunodeficiency virus."; RL Cell 53:55-67(1988). RN [4] RP PROTEIN SEQUENCE OF C-TERMINUS, DISULFIDE BONDS, GLYCOSYLATION AT ASN-88; RP ASN-136; ASN-141; ASN-156; ASN-160; ASN-186; ASN-197; ASN-230; ASN-234; RP ASN-241; ASN-262; ASN-276; ASN-289; ASN-295; ASN-301; ASN-332; ASN-339; RP ASN-356; ASN-386; ASN-392; ASN-397; ASN-406; ASN-448 AND ASN-463, AND RP STRUCTURE OF CARBOHYDRATES. RX PubMed=2355006; DOI=10.1016/s0021-9258(18)86956-3; RA Leonard C.K., Spellman M.W., Riddle L., Harris R.J., Thomas J.N., RA Gregory T.J.; RT "Assignment of intrachain disulfide bonds and characterization of potential RT glycosylation sites of the type 1 recombinant human immunodeficiency virus RT envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells."; RL J. Biol. Chem. 265:10373-10382(1990). RN [5] RP INTERACTION OF GLYCOPROTEIN 120 WITH HOST CD4. RX PubMed=2214026; DOI=10.1128/jvi.64.11.5585-5593.1990; RA Crise B., Buonocore L., Rose J.K.; RT "CD4 is retained in the endoplasmic reticulum by the human immunodeficiency RT virus type 1 glycoprotein precursor."; RL J. Virol. 64:5585-5593(1990). RN [6] RP INTERACTION OF TRANSMEMBRANE PROTEIN GP41 WITH GALACTOSYL CERAMIDE. RX PubMed=11342649; DOI=10.4049/jimmunol.166.10.6257; RA Alfsen A., Iniguez P., Bouguyon E., Bomsel M.; RT "Secretory IgA specific for a conserved epitope on gp41 envelope RT glycoprotein inhibits epithelial transcytosis of HIV-1."; RL J. Immunol. 166:6257-6265(2001). RN [7] RP REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI. RX PubMed=11181151; DOI=10.1086/318823; RA Fenouillet E., Barbouche R., Courageot J., Miquelis R.; RT "The catalytic activity of protein disulfide isomerase is involved in human RT immunodeficiency virus envelope-mediated membrane fusion after CD4 cell RT binding."; RL J. Infect. Dis. 183:744-752(2001). RN [8] RP REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI. RX PubMed=12218052; DOI=10.1074/jbc.m205467200; RA Barbouche R., Miquelis R., Jones I.M., Fenouillet E.; RT "Protein-disulfide isomerase-mediated reduction of two disulfide bonds of RT HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for RT fusion."; RL J. Biol. Chem. 278:3131-3136(2003). RN [9] RP REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI. RX PubMed=14592831; DOI=10.1182/blood-2003-05-1390; RA Markovic I., Stantchev T.S., Fields K.H., Tiffany L.J., Tomic M., RA Weiss C.D., Broder C.C., Strebel K., Clouse K.A.; RT "Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 RT envelope-mediated T-cell fusion during viral entry."; RL Blood 103:1586-1594(2004). RN [10] RP REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI. RX PubMed=15644496; DOI=10.1124/mol.104.008276; RA Barbouche R., Lortat-Jacob H., Jones I.M., Fenouillet E.; RT "Glycosaminoglycans and protein disulfide isomerase-mediated reduction of RT HIV Env."; RL Mol. Pharmacol. 67:1111-1118(2005). RN [11] RP REVIEW. RX PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x; RA Geijtenbeek T.B., van Kooyk Y.; RT "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a RT pathogen receptor with broad specificity."; RL APMIS 111:698-714(2003). RN [12] RP REVIEW. RX PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5; RA Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S., RA Puri A., Durell S., Blumenthal R.; RT "The HIV Env-mediated fusion reaction."; RL Biochim. Biophys. Acta 1614:36-50(2003). RN [13] RP REVIEW. RX PubMed=15719026; DOI=10.1038/sj.cdd.4401584; RA Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R., RA Piacentini M., Kroemer G.; RT "Mechanisms of apoptosis induction by the HIV-1 envelope."; RL Cell Death Differ. 12:916-923(2005). RN [14] RP REVIEW. RX PubMed=15725757; DOI=10.1089/aid.2005.21.171; RA Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.; RT "V3: HIV's switch-hitter."; RL AIDS Res. Hum. Retroviruses 21:171-189(2005). RN [15] RP REVIEW. RX PubMed=16114975; DOI=10.2165/00003495-200565130-00002; RA Reeves J.D., Piefer A.J.; RT "Emerging drug targets for antiretroviral therapy."; RL Drugs 65:1747-1766(2005). RN [16] RP REVIEW. RX PubMed=16437164; DOI=10.1038/sj.emboj.7600947; RA Lusso P.; RT "HIV and the chemokine system: 10 years later."; RL EMBO J. 25:447-456(2006). CC -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host CC endoplasmic reticulum into predominantly trimers. In a second time, CC gp160 transits in the host Golgi, where glycosylation is completed. The CC precursor is then proteolytically cleaved in the trans-Golgi and CC thereby activated by cellular furin or furin-like proteases to produce CC gp120 and gp41. {ECO:0000255|HAMAP-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 interaction CC induces a structural rearrangement creating a high affinity binding CC site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a CC ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively CC found on dendritic cells (DCs), and on endothelial cells of liver CC sinusoids and lymph node sinuses. These interactions allow capture of CC viral particles at mucosal surfaces by these cells and subsequent CC transmission to permissive cells. HIV subverts the migration properties CC of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus CC transmission to permissive T-cells occurs either in trans (without DCs CC infection, through viral capture and transmission), or in cis CC (following DCs productive infection, through the usual CD4-gp120 CC interaction), thereby inducing a robust infection. In trans infection, CC bound 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 periphery to CC the lymphoid tissues. On arrival at lymphoid tissues, intact virions CC recycle back to DCs' cell surface allowing virus transmission to CD4+ CC T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}. CC -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion CC protein. Under the current model, the protein has at least 3 CC conformational states: pre-fusion native state, pre-hairpin CC intermediate state, and post-fusion hairpin state. During fusion of CC viral and target intracellular membranes, the coiled coil regions CC (heptad repeats) assume a trimer-of-hairpins structure, positioning the CC fusion peptide in close proximity to the C-terminal region of the CC ectodomain. The formation of this structure appears to drive apposition CC and subsequent fusion of viral and target cell membranes. Complete CC fusion occurs in host cell endosomes and is dynamin-dependent, however CC some lipid transfer might occur at the plasma membrane. The virus CC undergoes clathrin-dependent internalization long before endosomal CC fusion, thus minimizing the surface exposure of conserved viral CC epitopes during fusion and reducing the efficacy of inhibitors CC targeting these epitopes. Membranes fusion leads to delivery of the CC nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}. CC -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env) CC consists of a homotrimer of non-covalently associated gp120-gp41 CC heterodimers. The resulting complex protrudes from the virus surface as CC a spike. There seems to be as few as 10 spikes on the average virion. CC Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the CC C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred CC to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts CC with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction CC results in rapid activation of integrin ITGAL/LFA-1, which facilitates CC efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell- CC associated heparan sulfate; this interaction increases virus CC infectivity on permissive cells and may be involved in infection of CC CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083, CC ECO:0000269|PubMed:2214026}. CC -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein CC (Env) consists of a homotrimer of non-covalently associated gp120-gp41 CC heterodimers. The resulting complex protrudes from the virus surface as CC a spike. There seems to be as few as 10 spikes on the average virion. CC {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:2214026}. CC -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane CC {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane CC {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane CC {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not CC anchored to the viral envelope, but associates with the extravirion CC surface through its binding to TM. It is probably concentrated at the CC site of budding and incorporated into the virions possibly by contacts CC between the cytoplasmic tail of Env and the N-terminus of Gag. CC {ECO:0000255|HAMAP-Rule:MF_04083}. CC -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane CC {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane CC {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane CC {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at CC the site of budding and incorporated into the virions possibly by CC contacts between the cytoplasmic tail of Env and the N-terminus of Gag. CC {ECO:0000255|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 through 5 CC (V1 through V5). Coreceptor usage of gp120 is determined mainly by the CC primary structure of the third variable region (V3) in the outer domain CC of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or CC CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and CC macrophage tropism), is used to trigger the fusion potential of the Env CC complex, and hence which cells the virus can infect. Binding to CCR5 CC involves a region adjacent in addition to V3. {ECO:0000255|HAMAP- CC Rule:MF_04083}. CC -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is CC a tryptophan-rich region recognized by the antibodies 2F5, Z13, and CC 4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP- CC Rule:MF_04083}. CC -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in CC many retroviral envelope proteins. Synthetic peptides derived from this CC relatively conserved sequence inhibit immune function in vitro and in CC vivo. {ECO:0000255|HAMAP-Rule:MF_04083}. CC -!- DOMAIN: The YXXL motif is involved in determining the exact site of CC viral release at the surface of infected mononuclear cells and promotes CC endocytosis. YXXL and di-leucine endocytosis motifs interact directly CC or indirectly with the clathrin adapter complexes, opperate CC independently, and their activities are not additive. CC {ECO:0000255|HAMAP-Rule:MF_04083}. CC -!- DOMAIN: The CD4-binding region is targeted by the antibody b12. CC {ECO:0000255|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 to CC hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP- CC Rule:MF_04083}. CC -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein CC (prior to its proteolytic cleavage) is essential for their association CC with host cell membrane lipid rafts. Palmitoylation is therefore CC required for envelope trafficking to classical lipid rafts, but not for CC viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}. CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. CC Envelope glycoproteins are synthesized as an inactive precursor that is CC heavily N-glycosylated and processed likely by host cell furin in the CC Golgi to yield the mature SU and TM proteins. The cleavage site between CC SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 CC disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CC CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083, CC ECO:0000269|PubMed:12218052, ECO:0000269|PubMed:14592831, CC ECO:0000269|PubMed:15644496}. CC -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are CC used as antiretroviral drugs. Attachment of virions to the cell surface CC via non-specific interactions and CD4 binding can be blocked by CC inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs, CC PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4- CC induced conformational changes. Env interactions with the coreceptor CC molecules can be targeted by CCR5 antagonists including SCH-D, CC maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4 CC antagonist AMD 070. Fusion of viral and cellular membranes can be CC inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249). CC Resistance to inhibitors associated with mutations in Env are observed. CC Most of the time, single mutations confer only a modest reduction in CC drug susceptibility. Combination of several mutations is usually CC required to develop a high-level drug resistance. {ECO:0000255|HAMAP- CC Rule:MF_04083}. 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_04083}. CC -!- SIMILARITY: Belongs to the HIV-1 env protein family. CC {ECO:0000255|HAMAP-Rule:MF_04083}. CC -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database; CC URL="https://hivdb.stanford.edu"; CC -!- WEB RESOURCE: Name=HIV drug resistance mutations; CC URL="https://www.iasusa.org/hiv-drug-resistance/hiv-drug-resistance-mutations/"; 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; M15654; AAA44205.1; -; Genomic_RNA. DR EMBL; K02083; AAB59873.1; -; Genomic_DNA. DR EMBL; X01762; CAA25903.1; ALT_SEQ; Genomic_RNA. DR PIR; A03973; VCLJH3. DR PIR; A03974; VCLJVL. DR PDB; 2ARI; NMR; -; A=512-541. DR PDB; 3VGY; X-ray; 2.03 A; C=546-588. DR PDB; 3VH7; X-ray; 2.02 A; A/C/E=546-588. DR PDB; 3VU5; X-ray; 2.09 A; A=553-590. DR PDB; 3VU6; X-ray; 2.32 A; A=553-590. DR PDB; 3W19; X-ray; 1.28 A; C=553-590. DR PDB; 6ME1; X-ray; 1.97 A; E/F=512-521. DR BMRB; P03375; -. DR SMR; P03375; -. DR MINT; P03375; -. DR ChEMBL; CHEMBL5057; -. DR GlyCosmos; P03375; 29 sites, No reported glycans. DR iPTMnet; P03375; -. DR ABCD; P03375; 4 sequenced antibodies. DR Reactome; R-HSA-5621480; Dectin-2 family. DR EvolutionaryTrace; P03375; -. DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0044538; C:host cell periphery; IDA:UniProtKB. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C: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:0042609; F:CD4 receptor binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule. DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; 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: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:0052031; P:symbiont-mediated perturbation of host defense response; 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 FunFam; 1.10.287.210:FF:000001; Envelope glycoprotein gp160; 1. DR FunFam; 1.20.5.490:FF:000001; Envelope glycoprotein gp160; 1. DR FunFam; 2.170.40.20:FF:000001; Envelope glycoprotein gp160; 1. DR FunFam; 2.170.40.20:FF:000003; Envelope glycoprotein gp160; 1. DR Gene3D; 1.10.287.210; -; 1. DR Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2. DR Gene3D; 1.20.5.490; Single helix bin; 1. 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; 1. DR Pfam; PF00517; GP41; 1. DR SUPFAM; SSF56502; gp120 core; 1. DR SUPFAM; SSF58069; Virus ectodomain; 1. DR PDBsum; 2ARI; -. DR PDBsum; 3VGY; -. DR PDBsum; 3VH7; -. DR PDBsum; 3VU5; -. DR PDBsum; 3VU6; -. DR PDBsum; 3W19; -. DR PDBsum; 6ME1; -. PE 1: Evidence at protein level; KW 3D-structure; AIDS; Apoptosis; KW Clathrin-mediated endocytosis of virus by host; KW Cleavage on pair of basic residues; Coiled coil; Direct protein sequencing; KW Disulfide bond; Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; KW Host cell membrane; Host endosome; Host membrane; Host-virus interaction; KW Lipoprotein; Membrane; Palmitate; Signal; Transmembrane; KW Transmembrane helix; Viral attachment to host cell; Viral envelope protein; KW Viral immunoevasion; Viral penetration into host cytoplasm; Virion; KW Virus endocytosis by host; Virus entry into host cell. FT SIGNAL 1..32 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CHAIN 33..856 FT /note="Envelope glycoprotein gp160" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT /id="PRO_0000239239" FT CHAIN 33..511 FT /note="Surface protein gp120" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT /id="PRO_0000038371" FT CHAIN 512..856 FT /note="Transmembrane protein gp41" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT /id="PRO_0000038372" FT TOPO_DOM 33..684 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT TRANSMEM 685..705 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT TOPO_DOM 706..856 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 131..156 FT /note="V1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 157..196 FT /note="V2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 296..330 FT /note="V3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 364..374 FT /note="CD4-binding loop" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 385..418 FT /note="V4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 461..471 FT /note="V5" FT REGION 463..471 FT /note="V5" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 512..532 FT /note="Fusion peptide" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 574..592 FT /note="Immunosuppression" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 662..683 FT /note="MPER; binding to GalCer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 662..667 FT /note="Involved in GalCer binding" FT REGION 721..740 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 633..667 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT MOTIF 712..715 FT /note="YXXL motif; contains endocytosis signal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT MOTIF 855..856 FT /note="Di-leucine internalization motif" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT SITE 511..512 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT LIPID 764 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 88 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 136 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 141 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 156 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 186 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 197 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 234 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 241 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 262 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 276 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 289 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 295 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 301 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 332 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 339 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 356 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 386 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 392 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 397 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 406 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 448 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 463 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT CARBOHYD 611 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 616 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 625 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 637 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 674 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 54..74 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 119..205 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 126..196 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 131..157 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 218..247 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 228..239 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 296..331 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 378..445 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 385..418 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083, FT ECO:0000269|PubMed:2355006" FT DISULFID 598..604 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT VARIANT 403 FT /note="K -> E (in strain: Isolate PV22)" FT VARIANT 423 FT /note="I -> F (in strain: Isolate PV22)" FT VARIANT 461 FT /note="S -> N (in strain: Isolate PV22)" FT VARIANT 668 FT /note="S -> N (in strain: Isolate PV22)" FT VARIANT 673 FT /note="F -> L (in strain: Isolate PV22)" FT VARIANT 704 FT /note="V -> I (in strain: Isolate PV22)" FT VARIANT 723 FT /note="I -> T (in strain: Isolate PV22)" FT VARIANT 737 FT /note="G -> D (in strain: Isolate PV22)" FT HELIX 516..530 FT /evidence="ECO:0007829|PDB:2ARI" FT TURN 531..533 FT /evidence="ECO:0007829|PDB:2ARI" FT STRAND 536..538 FT /evidence="ECO:0007829|PDB:2ARI" FT HELIX 554..589 FT /evidence="ECO:0007829|PDB:3W19" SQ SEQUENCE 856 AA; 97225 MW; 0BFFB1A18931BB27 CRC64; MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLKNDTNT NSSSGRMIME KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD IIPIDNDTTS YTLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSANFTDN AKTIIVQLNQ SVEINCTRPN NNTRKSIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIDSKLR EQFGNNKTII FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW STKGSNNTEG SDTITLPCRI KQIINMWQEV GKAMYAPPIS GQIRCSSNIT GLLLTRDGGN SNNESEIFRP GGGDMRDNWR SELYKYKVVK IEPLGVAPTK AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ ARQLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG KLICTTAVPW NASWSNKSLE QIWNNMTWME WDREINNYTS LIHSLIEESQ NQQEKNEQEL LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA VLSVVNRVRQ GYSPLSFQTH LPIPRGPDRP EGIEEEGGER DRDRSIRLVN GSLALIWDDL RSLCLFSYHR LRDLLLIVTR IVELLGRRGW EALKYWWNLL QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGAYRAI RHIPRRIRQG LERILL //