ID ENV_HV2CA Reviewed; 859 AA. AC P24105; DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-1992, sequence version 1. DT 10-JUN-2026, entry version 130. DE RecName: Full=Envelope glycoprotein gp160; DE AltName: Full=Env polyprotein; DE Contains: DE RecName: Full=Surface protein gp120; DE Short=SU; DE AltName: Full=Glycoprotein 120; DE Short=gp120; DE Contains: DE RecName: Full=Transmembrane protein gp41; DE Short=TM; DE AltName: Full=Glycoprotein 41; DE Short=gp41; DE Flags: Precursor; GN Name=env; OS Human immunodeficiency virus type 2 subtype A (isolate CAM2) (HIV-2). OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus; OC Lentivirus humimdef2; Human immunodeficiency virus 2. OX NCBI_TaxID=11715; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2005437; DOI=10.1099/0022-1317-72-3-721; RA Tristem M., Hill F., Karpas A.; RT "Nucleotide sequence of a Guinea-Bissau-derived human immunodeficiency RT virus type 2 proviral clone (HIV-2CAM2)."; RL J. Gen. Virol. 72:721-724(1991). RN [2] RP REVIEW. RX PubMed=12029140; DOI=10.1099/0022-1317-83-6-1253; RA Reeves J.D., Doms R.W.; RT "Human immunodeficiency virus type 2."; RL J. Gen. Virol. 83:1253-1265(2002). CC -!- FUNCTION: The surface protein gp120 (SU) 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. This peculiar 2 CC stage receptor-interaction strategy allows gp120 to maintain the highly CC conserved coreceptor-binding site in a cryptic conformation, protected CC from neutralizing antibodies. Since CD4 also displays a binding site CC for the disulfide-isomerase P4HB/PDI, a P4HB/PDI-CD4-CXCR4-gp120 CC complex may form. In that complex, P4HB/PDI could reach and reduce CC gp120 disulfide bonds, causing major conformational changes in gp120. CC TXN, another PDI family member could also be involved in disulfide CC rearrangements in Env during fusion. These changes are transmitted to CC the transmembrane protein gp41 and are thought to activate its CC fusogenic potential by unmasking its fusion peptide (By similarity). CC {ECO:0000250}. CC -!- FUNCTION: The surface protein gp120 is a ligand for CD209/DC-SIGN and CC CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), CC and on endothelial cells of liver sinusoids and lymph node sinuses. CC These interactions allow capture of viral particles at mucosal surfaces CC by these cells and subsequent transmission to permissive cells. DCs are CC professional antigen presenting cells, critical for host immunity by CC inducing specific immune responses against a broad variety of CC pathogens. They act as sentinels in various tissues where they take up CC antigen, process it, and present it to T-cells following migration to CC lymphoid organs. HIV subverts the migration properties of dendritic CC cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission CC to 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), thereby CC inducing a robust infection. In trans infection, bound virions remain CC infectious over days and it is proposed that they are not degraded, but CC protected in non-lysosomal acidic organelles within the DCs close to CC the cell membrane thus contributing to the viral infectious potential CC during DCs' migration from the periphery to the lymphoid tissues. On CC arrival at lymphoid tissues, intact virions recycle back to DCs' cell CC surface allowing virus transmission to CD4+ T-cells. Virion capture CC also seems to lead to MHC-II-restricted viral antigen presentation, and CC probably to the activation of HIV-specific CD4+ cells (By similarity). CC {ECO:0000250}. CC -!- FUNCTION: The transmembrane protein gp41 (TM) acts as a class I viral CC fusion 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 (By similarity). {ECO:0000250}. CC -!- FUNCTION: The envelope glycoprotein gp160 precursor down-modulates cell CC surface CD4 antigen by interacting with it in the endoplasmic reticulum CC and blocking its transport to the cell surface. {ECO:0000250}. CC -!- FUNCTION: The gp120-gp41 heterodimer seems to contribute to T-cell CC depletion during HIV-1 infection. The envelope glycoproteins expressed CC on the surface of infected cells induce apoptosis through an CC interaction with uninfected cells expressing the receptor (CD4) and the CC coreceptors CXCR4 or CCR5. This type of bystander killing may be CC obtained by at least three distinct mechanisms. First, the interaction CC between the 2 cells can induce cellular fusion followed by nuclear CC fusion within the syncytium. Syncytia are condemned to die from CC apoptosis. Second, the 2 interacting cells may not fuse entirely and CC simply exchange plasma membrane lipids, after a sort of hemifusion CC process, followed by rapid death. Third, it is possible that virus- CC infected cells, on the point of undergoing apoptosis, fuse with CD4- CC expressing cells, in which case apoptosis is rapidly transmitted from CC one cell to the other and thus occurs in a sort of contagious fashion CC (By similarity). {ECO:0000250}. CC -!- FUNCTION: The gp120-gp41 heterodimer allows rapid transcytosis of the CC virus through CD4 negative cells such as simple epithelial monolayers CC of the intestinal, rectal and endocervical epithelial barriers. Both CC gp120 and gp41 specifically recognize glycosphingolipids galactosyl- CC ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the CC lipid rafts structures of epithelial cells. Binding to these CC alternative receptors allows the rapid transcytosis of the virus CC through the epithelial cells. This transcytotic vesicle-mediated CC transport of virions from the apical side to the basolateral side of CC the epithelial cells does not involve infection of the cells themselves CC (By similarity). {ECO:0000250}. 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 human CD4, CCR5 and CXCR4, to form a P4HB/PDI-CD4-CXCR4- CC gp120 complex. Gp120 also interacts with the C-type lectins CD209/DC- CC SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R)). CC Gp120 and gp41 interact with GalCer (By similarity). {ECO:0000250}. 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:0000250}. CC -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane CC {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host CC cell membrane {ECO:0000250}; Single-pass type I membrane protein CC {ECO:0000250}. Host endosome membrane {ECO:0000305}; Single-pass type I CC membrane protein {ECO:0000305}. Note=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:0000250}. CC -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Host cell CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Host CC endosome membrane {ECO:0000305}; Peripheral membrane protein CC {ECO:0000305}. Note=The surface protein is not anchored to the viral CC envelope, but associates with the extravirion surface through its CC binding to TM. It is probably concentrated at the site of budding and CC incorporated into the virions possibly by contacts between the CC cytoplasmic tail of Env and the N-terminus of Gag (By similarity). CC {ECO:0000250}. 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. Binding to CCR5 involves a region adjacent in addition to V3 CC (By similarity). {ECO:0000250}. 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 (By similarity). {ECO:0000250}. 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 (By similarity). CC {ECO:0000250}. 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 (By similarity). {ECO:0000250}. CC -!- MISCELLANEOUS: Some HIV-2 isolates have been described that can infect CC cells independently of CD4, using CXCR4 as primary receptor. These CC isolates may have an exposed coreceptor binding site. 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; D00835; BAA00716.1; -; Genomic_DNA. DR PIR; F38475; VCLJCT. DR SMR; P24105; -. DR GlyCosmos; P24105; 26 sites, No reported glycans. 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 InterPro; IPR036377; Gp120_core_sf. 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 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: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:InterPro. DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0052170; P:symbiont-mediated suppression of host innate immune response; IEA:UniProtKB-KW. DR GO; GO:0039587; P:symbiont-mediated-mediated suppression of host tetherin activity; IEA:UniProtKB-KW. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. PE 3: Inferred from homology; KW AIDS; Apoptosis; 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 Inhibition of host innate immune response by virus; KW Inhibition of host tetherin by virus; Lipoprotein; Membrane; Palmitate; KW Signal; Transmembrane; Transmembrane helix; Viral attachment to host cell; KW Viral envelope protein; Viral immunoevasion; KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host; KW Virus entry into host cell. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..859 FT /note="Envelope glycoprotein gp160" FT /id="PRO_0000239497" FT CHAIN 25..512 FT /note="Surface protein gp120" FT /evidence="ECO:0000250" FT /id="PRO_0000038437" FT CHAIN 513..859 FT /note="Transmembrane protein gp41" FT /evidence="ECO:0000250" FT /id="PRO_0000038438" FT TOPO_DOM 25..680 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 681..701 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 702..859 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 114..159 FT /note="V1" FT REGION 160..204 FT /note="V2" FT REGION 304..337 FT /note="V3" FT REGION 397..420 FT /note="V4" FT REGION 463..470 FT /note="V5" FT REGION 513..533 FT /note="Fusion peptide" FT /evidence="ECO:0000255" FT REGION 576..592 FT /note="Immunosuppression" FT /evidence="ECO:0000250" FT REGION 658..679 FT /note="MPER; binding to GalCer" FT /evidence="ECO:0000250" FT REGION 726..745 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 625..646 FT /evidence="ECO:0000255" FT MOTIF 708..711 FT /note="YXXV motif; contains endocytosis signal" FT /evidence="ECO:0000250" FT MOTIF 858..859 FT /note="Di-leucine internalization motif" FT /evidence="ECO:0000250" FT SITE 512..513 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000250" FT LIPID 774 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000250" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 71 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 115 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 148 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 163 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 176 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 188 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 195 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 205 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 237 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 247 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 271 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 277 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 288 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 299 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 309 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 343 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 366 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 398 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 411 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 448 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 463 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 467 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 612 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 621 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 637 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT DISULFID 45..58 FT /evidence="ECO:0000250" FT DISULFID 102..213 FT /evidence="ECO:0000250" FT DISULFID 109..204 FT /evidence="ECO:0000250" FT DISULFID 114..160 FT /evidence="ECO:0000250" FT DISULFID 226..256 FT /evidence="ECO:0000250" FT DISULFID 236..248 FT /evidence="ECO:0000250" FT DISULFID 304..338 FT /evidence="ECO:0000250" FT DISULFID 390..447 FT /evidence="ECO:0000250" FT DISULFID 397..420 FT /evidence="ECO:0000250" SQ SEQUENCE 859 AA; 99018 MW; 6F54913F206B26C3 CRC64; MERGRNQLLI AILLASACLI YCRQQYVTVF YGVPAWKNAS IPLFCATKNR DTWGTIQCLP DNDDYQEIPL NVTEAFDAWD NTITEQAIED VWNLFETSIK PCVKLTPLCV AMKCNISTSD TTMIRTTTPS TAKEAPISDN SPCIRTNNCS GLEEEKIVKC HFNMTGLERD KKKQYNETWY SSDVVCDNST DQTTNETTCY MNHCNTSVIT ESCDKHYWDA MRFRYCAPPG FAILRCNDTK YSGFAPNCSK VVASTCTRMM ETQTSTWFGF NGTRAENRTY IYWHGKDNRT IISLNKHYNL SMYCRRPGNK TVVPITLMSG QRFHSRPIIN KRPRQAWCWF KGNWTEAMQE VKQTLAEHPR YKGTKNITDI TFKAPERGSD PEVTYMWSNC RGEFFYCNMT WFLNWVENKP NTTKRNYAPC HIRQIINTWH KVGKNVYLPP REGELTCNST VTSIIANIDE RDNQTTNITF SADVAELYRL ELGDYKLVEI TPIGFAPTSQ KRYSPAHGRP KRGAFVLGFL GFLTTAGVAM GTASLTLSAQ SRTLLAGIVQ QQQQLLDVVK RQQELLRLTV WGTKILQARV TAIEKYLKDQ AQLNSWGCAF RQVCHTTVPW ANESLTPDWN NMTWQEWEQK VRYLEANISQ SLEEAQLQQE KNMYELQKLN NWDVFTNWFD LTSWISYIQY GVYIVVGIIV LRIVIYVVQM LSRLRKGYRP VFSSSPGYIQ QIHIHKDPEQ PASEETEEDV GGNGGDRSWP WQIEYIHFLI RQLIRLLTGL YNICRNLLSR IFQTLQPILQ NLRDWLRPKV AFLQYGCEWI QEAFQAAARA ARETLAGACR DVWGMLQRIG RGILAVPRRI RQGAELALL //