Q02837 · ENV_SIVG1
- ProteinEnvelope glycoprotein gp160
- Geneenv
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids854 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
function
The surface protein gp120 (SU) attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CCR5. This peculiar 2 stage receptor-interaction strategy allows gp120 to maintain the highly conserved coreceptor-binding site in a cryptic conformation, protected from neutralizing antibodies. These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide (By similarity).
Surface protein gp120 (SU) may target the virus to gut-associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7 (alpha-4/beta-7 integrins), a complex that mediates T-cell migration to the GALT. Interaction between gp120 and ITGA4/ITGB7 would allow the virus to enter GALT early in the infection, infecting and killing most of GALT's resting CD4+ T-cells. This T-cell depletion is believed to be the major insult to the host immune system leading to AIDS (By similarity).
The surface protein gp120 is a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they take up antigen, process it, and present it to T-cells following migration to lymphoid organs. SIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. Virion capture also seems to lead to MHC-II-restricted viral antigen presentation, and probably to the activation of SIV-specific CD4+ cells (By similarity).
The transmembrane protein gp41 (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm (By similarity).
The envelope glycoprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface.
The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).
Miscellaneous
This is an African green monkey isolate.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 522-523 | Cleavage; by host furin | ||||
Sequence: RV |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell endosome membrane | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane | |
Cellular Component | viral envelope | |
Cellular Component | virion membrane | |
Molecular Function | structural molecule activity | |
Biological Process | apoptotic process | |
Biological Process | membrane fusion involved in viral entry into host cell | |
Biological Process | symbiont entry into host cell | |
Biological Process | virion attachment to host cell |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameEnvelope glycoprotein gp160
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Taxonomic lineageViruses > Riboviria > Pararnavirae > Artverviricota > Revtraviricetes > Ortervirales > Retroviridae > Orthoretrovirinae > Lentivirus > Simian immunodeficiency virus
- Virus hosts
Accessions
- Primary accessionQ02837
Subcellular Location
UniProt Annotation
GO Annotation
Transmembrane protein gp41
Virion membrane ; Single-pass type I membrane protein
Host cell membrane ; Single-pass type I membrane protein
Host endosome membrane ; Single-pass type I membrane protein
Note: It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
Surface protein gp120
Virion membrane ; Peripheral membrane protein
Host cell membrane ; Peripheral membrane protein
Host endosome membrane ; Peripheral membrane protein
Note: The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 21-705 | Extracellular | ||||
Sequence: NLYVTVFYGIPVWKNSTVQAFCMTPNTNMWATTNCIPDDHDNTEVPLNITEAFEAWDNPLVKQAESNIHLLFEQTMRPCVKLSPICIKMSCVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASNCTFAIAGYQRDVKKNYSMTWYDQELVCNNKTGSEKGSKDCYMIHCNDSVIKEACDKTYWDTLRVRYCAPAGYALLKCNDKDYRGFAPKCKNVSVVHCTRLINTTITTGIGLNGSRSENRTEIWQKGGNDNDTVIIKLNKFYNLTVRCRRPGNKTVLPVTIMAGLVFHSQKYNTRLKQAWCHFQGDWKGAWKEVREEVKKVKNLTEVSIENIHLRRIWGDPESANFWFNCQGEFFYCKMDWFINYLNNRTEDAEGTNRTCDKGKPGPGPCVQRTYVACHIRQVVNDWYTVSKKVYAPPREGHLECNSSVTALYVAIDYNNKSGPINVTLSPQVRSIWAYELGDYKLVEITPIGFAPTDVRRYTGPTREKRVPFVLGFLGFLGAAGTAMGAAATTLTVQSRHLLAGILQQQKNLLAAVEQQQQLLKLTIWGVKNLNARVTALEKYLEDQARLNSWGCAWKQVCHTTVPWKYNNTPKWDNMTWLEWERQINALEGNITQLLEEAQNQESKNLDLYQKLDDWSGFWSWFSLSTWLGYVKIGFLVIVIILGLRFAWV | ||||||
Transmembrane | 706-726 | Helical | ||||
Sequence: LWGCIRNIRQGYNPLPQIHIH | ||||||
Topological domain | 727-854 | Cytoplasmic | ||||
Sequence: SSAERPDNGGGQDRGGESSSSKLIRLQEESSTPSRINNWWLNFKSCSLRIRTWCYNICLTLLIFIRTAVGYLQYGLQQLQEAATGLAQALARAAREAWGRLGAIVRSAYRAVINSPRRVRQGLEKVLG |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MGRLLIKILIIAIGISIGIG | ||||||
Chain | PRO_0000038460 | 21-522 | Surface protein gp120 | |||
Sequence: NLYVTVFYGIPVWKNSTVQAFCMTPNTNMWATTNCIPDDHDNTEVPLNITEAFEAWDNPLVKQAESNIHLLFEQTMRPCVKLSPICIKMSCVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASNCTFAIAGYQRDVKKNYSMTWYDQELVCNNKTGSEKGSKDCYMIHCNDSVIKEACDKTYWDTLRVRYCAPAGYALLKCNDKDYRGFAPKCKNVSVVHCTRLINTTITTGIGLNGSRSENRTEIWQKGGNDNDTVIIKLNKFYNLTVRCRRPGNKTVLPVTIMAGLVFHSQKYNTRLKQAWCHFQGDWKGAWKEVREEVKKVKNLTEVSIENIHLRRIWGDPESANFWFNCQGEFFYCKMDWFINYLNNRTEDAEGTNRTCDKGKPGPGPCVQRTYVACHIRQVVNDWYTVSKKVYAPPREGHLECNSSVTALYVAIDYNNKSGPINVTLSPQVRSIWAYELGDYKLVEITPIGFAPTDVRRYTGPTREKR | ||||||
Chain | PRO_0000239507 | 21-854 | Envelope glycoprotein gp160 | |||
Sequence: NLYVTVFYGIPVWKNSTVQAFCMTPNTNMWATTNCIPDDHDNTEVPLNITEAFEAWDNPLVKQAESNIHLLFEQTMRPCVKLSPICIKMSCVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASNCTFAIAGYQRDVKKNYSMTWYDQELVCNNKTGSEKGSKDCYMIHCNDSVIKEACDKTYWDTLRVRYCAPAGYALLKCNDKDYRGFAPKCKNVSVVHCTRLINTTITTGIGLNGSRSENRTEIWQKGGNDNDTVIIKLNKFYNLTVRCRRPGNKTVLPVTIMAGLVFHSQKYNTRLKQAWCHFQGDWKGAWKEVREEVKKVKNLTEVSIENIHLRRIWGDPESANFWFNCQGEFFYCKMDWFINYLNNRTEDAEGTNRTCDKGKPGPGPCVQRTYVACHIRQVVNDWYTVSKKVYAPPREGHLECNSSVTALYVAIDYNNKSGPINVTLSPQVRSIWAYELGDYKLVEITPIGFAPTDVRRYTGPTREKRVPFVLGFLGFLGAAGTAMGAAATTLTVQSRHLLAGILQQQKNLLAAVEQQQQLLKLTIWGVKNLNARVTALEKYLEDQARLNSWGCAWKQVCHTTVPWKYNNTPKWDNMTWLEWERQINALEGNITQLLEEAQNQESKNLDLYQKLDDWSGFWSWFSLSTWLGYVKIGFLVIVIILGLRFAWVLWGCIRNIRQGYNPLPQIHIHSSAERPDNGGGQDRGGESSSSKLIRLQEESSTPSRINNWWLNFKSCSLRIRTWCYNICLTLLIFIRTAVGYLQYGLQQLQEAATGLAQALARAAREAWGRLGAIVRSAYRAVINSPRRVRQGLEKVLG | ||||||
Glycosylation | 35 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 42↔55 | |||||
Sequence: CMTPNTNMWATTNC | ||||||
Glycosylation | 68 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 99↔207 | |||||
Sequence: CVKLSPICIKMSCVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASNCTFAIAGYQRDVKKNYSMTWYDQELVCNNKTGSEKGSKDCYMIHCNDSVIKEAC | ||||||
Disulfide bond | 106↔198 | |||||
Sequence: CIKMSCVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASNCTFAIAGYQRDVKKNYSMTWYDQELVCNNKTGSEKGSKDCYMIHC | ||||||
Disulfide bond | 111↔154 | |||||
Sequence: CVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASNC | ||||||
Glycosylation | 115 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 136 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 153 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 168 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 182 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 199 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 220↔250 | |||||
Sequence: CAPAGYALLKCNDKDYRGFAPKCKNVSVVHC | ||||||
Disulfide bond | 230↔242 | |||||
Sequence: CNDKDYRGFAPKC | ||||||
Glycosylation | 244 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 255 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 265 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 271 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 283 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 295 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 300↔333 | |||||
Sequence: CRRPGNKTVLPVTIMAGLVFHSQKYNTRLKQAWC | ||||||
Glycosylation | 305 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 355 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 382↔457 | |||||
Sequence: CQGEFFYCKMDWFINYLNNRTEDAEGTNRTCDKGKPGPGPCVQRTYVACHIRQVVNDWYTVSKKVYAPPREGHLEC | ||||||
Disulfide bond | 389↔430 | |||||
Sequence: CKMDWFINYLNNRTEDAEGTNRTCDKGKPGPGPCVQRTYVAC | ||||||
Glycosylation | 400 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 409 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 458 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 472 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 478 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Chain | PRO_0000038461 | 523-854 | Transmembrane protein gp41 | |||
Sequence: VPFVLGFLGFLGAAGTAMGAAATTLTVQSRHLLAGILQQQKNLLAAVEQQQQLLKLTIWGVKNLNARVTALEKYLEDQARLNSWGCAWKQVCHTTVPWKYNNTPKWDNMTWLEWERQINALEGNITQLLEEAQNQESKNLDLYQKLDDWSGFWSWFSLSTWLGYVKIGFLVIVIILGLRFAWVLWGCIRNIRQGYNPLPQIHIHSSAERPDNGGGQDRGGESSSSKLIRLQEESSTPSRINNWWLNFKSCSLRIRTWCYNICLTLLIFIRTAVGYLQYGLQQLQEAATGLAQALARAAREAWGRLGAIVRSAYRAVINSPRRVRQGLEKVLG | ||||||
Glycosylation | 630 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 646 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N |
Post-translational modification
Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R (By similarity).
Keywords
- PTM
PTM databases
Interaction
Subunit
Surface protein gp120
The mature envelope protein (Env) consists of a homotrimer of non-covalently associated gp120-gp41 heterodimers. The resulting complex protrudes from the virus surface as a spike. Interacts with host CD4 and CCR5 (By similarity).
Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R))
Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R))
Transmembrane protein gp41
The mature envelope protein (Env) consists of a homotrimer of non-covalently associated gp120-gp41 heterodimers. The resulting complex protrudes from the virus surface as a spike.
Family & Domains
Features
Showing features for region, coiled coil, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 111-153 | V1 | ||||
Sequence: CVELNGTATTKATTTATTTMTTPCQNCSTEQIEGEMAEEPASN | ||||||
Region | 154-198 | V2 | ||||
Sequence: CTFAIAGYQRDVKKNYSMTWYDQELVCNNKTGSEKGSKDCYMIHC | ||||||
Region | 300-332 | V3 | ||||
Sequence: CRRPGNKTVLPVTIMAGLVFHSQKYNTRLKQAW | ||||||
Region | 389-430 | V4 | ||||
Sequence: CKMDWFINYLNNRTEDAEGTNRTCDKGKPGPGPCVQRTYVAC | ||||||
Region | 473-481 | V5 | ||||
Sequence: KSGPINVTL | ||||||
Region | 523-543 | Fusion peptide | ||||
Sequence: VPFVLGFLGFLGAAGTAMGAA | ||||||
Region | 586-602 | Immunosuppression | ||||
Sequence: LNARVTALEKYLEDQAR | ||||||
Coiled coil | 633-672 | |||||
Sequence: WLEWERQINALEGNITQLLEEAQNQESKNLDLYQKLDDWS | ||||||
Region | 667-688 | MPER; binding to GalCer | ||||
Sequence: KLDDWSGFWSWFSLSTWLGYVK | ||||||
Motif | 717-720 | YXXL motif; contains endocytosis signal | ||||
Sequence: YNPL |
Domain
Some of the most genetically diverse regions of the viral genome are present in Env. They are called variable regions 1 through 5 (V1 through V5) (By similarity).
The YXXL motif is involved in determining the exact site of viral release at the surface of infected mononuclear cells and promotes endocytosis.
The 17 amino acids long immunosuppressive region is present in many retroviral envelope proteins. Synthetic peptides derived from this relatively conserved sequence inhibit immune function in vitro and in vivo (By similarity).
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length854
- Mass (Da)96,856
- Last updated1993-07-01 v1
- Checksum5919CA6C9622912F
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M66437 EMBL· GenBank· DDBJ | AAA91928.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M58410 EMBL· GenBank· DDBJ | AAA47591.1 EMBL· GenBank· DDBJ | Genomic RNA |