ID ENV_HV1Y2 Reviewed; 843 AA. AC P35961; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 176. 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 YU-2) OS (HIV-1). OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus; OC Human immunodeficiency virus 1. OX NCBI_TaxID=362651; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=1404605; DOI=10.1128/jvi.66.11.6587-6600.1992; RA Li Y., Hui H., Burgess C.J., Price R.W., Sharp P.M., Hahn B.H., Shaw G.M.; RT "Complete nucleotide sequence, genome organization, and biological RT properties of human immunodeficiency virus type 1 in vivo: evidence for RT limited defectiveness and complementation."; RL J. Virol. 66:6587-6600(1992). RN [2] RP INTERACTION OF SURFACE PROTEIN GP120 WITH HUMAN CCR5. RX PubMed=9632396; DOI=10.1126/science.280.5371.1949; RA Rizzuto C.D., Wyatt R., Hernandez-Ramos N., Sun Y., Kwong P.D., RA Hendrickson W.A., Sodroski J.; RT "A conserved HIV gp120 glycoprotein structure involved in chemokine RT receptor binding."; RL Science 280:1949-1953(1998). RN [3] 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 [4] 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 [5] 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 [6] 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 [7] 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 [8] 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 -!- 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}. 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 -!- 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/content/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; M93258; -; NOT_ANNOTATED_CDS; Genomic_RNA. DR PIR; H44001; H44001. DR PDB; 1G9N; X-ray; 2.90 A; G=82-126, G=191-293, G=325-479. DR PDB; 1RZK; X-ray; 2.90 A; G=82-479. DR PDB; 1YYL; X-ray; 2.75 A; G/P=82-126, G/P=191-293, G/P=325-483. DR PDB; 1YYM; X-ray; 2.20 A; G/P=82-126, G/P=191-296, G/P=325-483. DR PDB; 2I5Y; X-ray; 2.20 A; G/P=82-126, G/P=191-293, G/P=325-479. DR PDB; 2I60; X-ray; 2.40 A; G/P=82-126, G/P=191-293, G/P=325-479. DR PDB; 2NY7; X-ray; 2.30 A; G=158-479. DR PDB; 2QAD; X-ray; 3.30 A; A/E=88-120, A/E=195-479. DR PDB; 3HI1; X-ray; 2.90 A; G/J=89-122, G/J=195-479. DR PDB; 3TGQ; X-ray; 3.40 A; A/B/C/D=43-479. DR PDB; 4DVR; X-ray; 2.50 A; G=82-122, G=199-301, G=324-484. DR PDB; 4JO3; X-ray; 2.60 A; P/Q=313-327. DR PDB; 4JZW; X-ray; 1.78 A; A/G=43-479. DR PDB; 4JZZ; X-ray; 1.49 A; A=43-479. DR PDB; 4K0A; X-ray; 2.13 A; A=43-479. DR PDB; 4KA2; X-ray; 1.79 A; A=43-479. DR PDB; 4LAJ; X-ray; 2.14 A; A/B/F/J=43-479. DR PDB; 4R4F; X-ray; 3.51 A; A=43-479. DR PDB; 4RQS; X-ray; 4.49 A; G=82-126, G=191-293, G=325-479. DR PDB; 4RWY; X-ray; 2.13 A; A=43-479. DR PDB; 5A7X; EM; 17.00 A; A/E/I=82-479. DR PDB; 5A8H; EM; 23.00 A; A/G/M=82-479. DR PDBsum; 1G9N; -. DR PDBsum; 1RZK; -. DR PDBsum; 1YYL; -. DR PDBsum; 1YYM; -. DR PDBsum; 2I5Y; -. DR PDBsum; 2I60; -. DR PDBsum; 2NY7; -. DR PDBsum; 2QAD; -. DR PDBsum; 3HI1; -. DR PDBsum; 3TGQ; -. DR PDBsum; 4DVR; -. DR PDBsum; 4JO3; -. DR PDBsum; 4JZW; -. DR PDBsum; 4JZZ; -. DR PDBsum; 4K0A; -. DR PDBsum; 4KA2; -. DR PDBsum; 4LAJ; -. DR PDBsum; 4R4F; -. DR PDBsum; 4RQS; -. DR PDBsum; 4RWY; -. DR PDBsum; 5A7X; -. DR PDBsum; 5A8H; -. DR SMR; P35961; -. DR DIP; DIP-48439N; -. DR IntAct; P35961; 1. DR BindingDB; P35961; -. DR ChEMBL; CHEMBL6180; -. DR DrugBank; DB11854; Astodrimer. DR DrugBank; DB04639; Biphenylalanine. DR GlyCosmos; P35961; 27 sites, No reported glycans. DR ABCD; P35961; 6 sequenced antibodies. DR Reactome; R-HSA-5621480; Dectin-2 family. DR EvolutionaryTrace; P35961; -. DR Proteomes; UP000007419; 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: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: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: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 GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule. DR CDD; cd09909; HIV-1-like_HR1-HR2; 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; 2. DR SUPFAM; SSF58069; Virus ectodomain; 1. 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; Disulfide bond; KW 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..31 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CHAIN 32..843 FT /note="Envelope glycoprotein gp160" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT /id="PRO_0000239469" FT CHAIN 32..498 FT /note="Surface protein gp120" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT /id="PRO_0000038377" FT CHAIN 499..843 FT /note="Transmembrane protein gp41" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT /id="PRO_0000038378" FT TOPO_DOM 32..671 FT /note="Extracellular" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT TRANSMEM 672..692 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT TOPO_DOM 693..843 FT /note="Cytoplasmic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 130..154 FT /note="V1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 155..192 FT /note="V2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 292..325 FT /note="V3" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 359..369 FT /note="CD4-binding loop" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 380..405 FT /note="V4" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 448..458 FT /note="V5" FT REGION 450..458 FT /note="V5" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 499..519 FT /note="Fusion peptide" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 561..579 FT /note="Immunosuppression" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 649..670 FT /note="MPER; binding to GalCer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT REGION 706..731 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 620..654 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT MOTIF 699..702 FT /note="YXXL motif; contains endocytosis signal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT MOTIF 842..843 FT /note="Di-leucine internalization motif" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT COMPBIAS 714..731 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 498..499 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT LIPID 751 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 87 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 129 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 135 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 138 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 154 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 158 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 184 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 193 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 237 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 258 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 272 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 285 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 291 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 297 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 327 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 351 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 381 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 389 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 395 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 400 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 435 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 450 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 598 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 603 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 612 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT CARBOHYD 624 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 53..73 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 118..201 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 125..192 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 130..155 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 214..243 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 224..235 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 292..326 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 373..432 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 380..405 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT DISULFID 585..591 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04083" FT STRAND 52..55 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:3TGQ" FT HELIX 64..72 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 82..84 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 90..93 FT /evidence="ECO:0007829|PDB:4JZZ" FT HELIX 94..96 FT /evidence="ECO:0007829|PDB:4RWY" FT HELIX 98..114 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 118..122 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:1G9N" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 201..204 FT /evidence="ECO:0007829|PDB:3HI1" FT STRAND 211..214 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 219..224 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 231..243 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 252..258 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 267..269 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 276..278 FT /evidence="ECO:0007829|PDB:4DVR" FT STRAND 280..294 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 298..300 FT /evidence="ECO:0007829|PDB:2QAD" FT TURN 306..308 FT /evidence="ECO:0007829|PDB:1G9N" FT STRAND 323..329 FT /evidence="ECO:0007829|PDB:4JZZ" FT HELIX 330..348 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 350..352 FT /evidence="ECO:0007829|PDB:2QAD" FT STRAND 353..356 FT /evidence="ECO:0007829|PDB:4JZZ" FT HELIX 364..367 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 369..373 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 376..380 FT /evidence="ECO:0007829|PDB:4JZZ" FT HELIX 383..385 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 388..391 FT /evidence="ECO:0007829|PDB:1RZK" FT HELIX 392..394 FT /evidence="ECO:0007829|PDB:4LAJ" FT TURN 396..398 FT /evidence="ECO:0007829|PDB:2QAD" FT STRAND 400..412 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 414..421 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 426..429 FT /evidence="ECO:0007829|PDB:1YYM" FT STRAND 430..443 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 446..449 FT /evidence="ECO:0007829|PDB:2I5Y" FT STRAND 452..457 FT /evidence="ECO:0007829|PDB:4JZZ" FT HELIX 462..470 FT /evidence="ECO:0007829|PDB:4JZZ" FT STRAND 473..477 FT /evidence="ECO:0007829|PDB:4JZZ" SQ SEQUENCE 843 AA; 95648 MW; C69DFD971C918B71 CRC64; MRATEIRKNY QHLWKGGTLL LGMLMICSAA EQLWVTVYYG VPVWKEATTT LFCASDAKAY DTEVHNVWAT HACVPTDPNP QEVKLENVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK LTPLCVTLNC TDLRNATNTT SSSWETMEKG EIKNCSFNIT TSIRDKVQKE YALFYNLDVV PIDNASYRLI SCNTSVITQA CPKVSFEPIP IHYCAPAGFA ILKCNDKKFN GTGPCTNVST VQCTHGIRPV VSTQLLLNGS LAEEEIVIRS ENFTNNAKTI IVQLNESVVI NCTRPNNNTR KSINIGPGRA LYTTGEIIGD IRQAHCNLSK TQWENTLEQI AIKLKEQFGN NKTIIFNPSS GGDPEIVTHS FNCGGEFFYC NSTQLFTWND TRKLNNTGRN ITLPCRIKQI INMWQEVGKA MYAPPIRGQI RCSSNITGLL LTRDGGKDTN GTEIFRPGGG DMRDNWRSEL YKYKVVKIEP LGVAPTKAKR RVVQREKRAV GLGALFLGFL GAAGSTMGAA SITLTVQARQ LLSGIVQQQN NLLRAIEAQQ HLLQLTVWGI KQLQARVLAV ERYLRDQQLL GIWGCSGKLI CTTTVPWNTS WSNKSLNEIW DNMTWMKWER EIDNYTHIIY SLIEQSQNQQ EKNEQELLAL DKWASLWNWF DITKWLWYIK IFIMIVGGLI GLRIVFVVLS IVNRVRQGYS PLSFQTHLPA QRGPDRPDGI EEEGGERDRD RSGPLVDGFL AIIWVDLRSL CLFSYHRLRD LLLIVTRIVE LLGRRGWGVL KYWWNLLQYW IQELKNSAVS LLNATAIAVA EGTDRVIEIL QRAFRAVLHI PVRIRQGLER ALL //