UniProtKB - P05884 (ENV_SIVMK)
Envelope glycoprotein gp160
env
Functioni
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).
By similaritySurface 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).
By similarityThe 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).
By similarityThe 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).
By similarityThe 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.
By similarityThe 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).
By similarityMiscellaneous
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 736 | In-frame UAG termination codon | 1 |
GO - Molecular functioni
- structural molecule activity Source: InterPro
GO - Biological processi
- membrane fusion involved in viral entry into host cell Source: UniProtKB-KW
- virion attachment to host cell Source: UniProtKB-KW
Keywordsi
Biological process | Apoptosis, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Virus entry into host cell |
Names & Taxonomyi
Protein namesi | Recommended name: Envelope glycoprotein gp160Alternative name(s): Env polyprotein Cleaved into the following 2 chains: Alternative name(s): Glycoprotein 120 Short name: gp120 Alternative name(s): Glycoprotein 32 Short name: gp32 |
Gene namesi | Name:env |
Organismi | Simian immunodeficiency virus (isolate K6W) (SIV-mac) (Simian immunodeficiency virus rhesus monkey) |
Taxonomic identifieri | 11735 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Pararnavirae › Artverviricota › Revtraviricetes › Ortervirales › Retroviridae › Orthoretrovirinae › Lentivirus › |
Virus hosti | Cercopithecidae (Old World monkeys) [TaxID: 9527] |
Subcellular locationi
- Virion membrane By similarity; Single-pass type I membrane protein By similarity
- Host cell membrane By similarity; Single-pass type I membrane protein By similarity
- Host endosome membrane Curated; Single-pass type I membrane protein Curated 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.By similarity
- Virion membrane By similarity; Peripheral membrane protein By similarity
- Host cell membrane By similarity; Peripheral membrane protein By similarity
- Host endosome membrane Curated; Peripheral membrane protein Curated 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).By similarity
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 20 – 696 | ExtracellularSequence analysisAdd BLAST | 677 | |
Transmembranei | 697 – 717 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 718 – 881 | CytoplasmicSequence analysisAdd BLAST | 164 |
Keywords - Cellular componenti
Host cell membrane, Host endosome, Host membrane, Membrane, Viral envelope protein, VirionPathology & Biotechi
Chemistry databases
DrugBanki | DB04473, alpha-L-fucose DB03740, N-acetyl-alpha-D-glucosamine |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Sequence analysisAdd BLAST | 19 | |
ChainiPRO_0000239513 | 20 – 881 | Envelope glycoprotein gp160Add BLAST | 862 | |
ChainiPRO_0000038468 | 20 – 527 | Surface protein gp120By similarityAdd BLAST | 508 | |
ChainiPRO_0000038469 | 528 – 881 | Transmembrane protein gp41By similarityAdd BLAST | 354 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 37 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 44 ↔ 57 | By similarity | ||
Glycosylationi | 70 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 101 ↔ 222 | By similarity | ||
Disulfide bondi | 108 ↔ 213 | By similarity | ||
Disulfide bondi | 113 ↔ 170 | By similarity | ||
Glycosylationi | 114 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 148 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 158 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 186 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 200 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 204 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 214 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 235 ↔ 265 | By similarity | ||
Disulfide bondi | 245 ↔ 257 | By similarity | ||
Glycosylationi | 246 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 249 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 280 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 286 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 297 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 308 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 313 ↔ 346 | By similarity | ||
Glycosylationi | 318 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 373 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 379 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 397 ↔ 461 | By similarity | ||
Disulfide bondi | 404 ↔ 434 | By similarity | ||
Glycosylationi | 462 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 478 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 627 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 636 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Glycosylationi | 652 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Lipidationi | 789 | S-palmitoyl cysteine; by hostBy similarity | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 527 – 528 | Cleavage; by host furinSequence analysis | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, PalmitateInteractioni
Subunit structurei
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)).
By similarityThe 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.
By similarityStructurei
3D structure databases
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P05884 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 113 – 169 | V1Add BLAST | 57 | |
Regioni | 170 – 213 | V2Add BLAST | 44 | |
Regioni | 313 – 345 | V3Add BLAST | 33 | |
Regioni | 404 – 434 | V4Add BLAST | 31 | |
Regioni | 477 – 484 | V5 | 8 | |
Regioni | 528 – 548 | Fusion peptideSequence analysisAdd BLAST | 21 | |
Regioni | 591 – 607 | ImmunosuppressionBy similarityAdd BLAST | 17 | |
Regioni | 673 – 694 | MPER; binding to GalCerBy similarityAdd BLAST | 22 | |
Regioni | 732 – 761 | DisorderedSequence analysisAdd BLAST | 30 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 636 – 668 | Sequence analysisAdd BLAST | 33 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 723 – 726 | YXXV motif; contains endocytosis signalBy similarity | 4 | |
Motifi | 880 – 881 | Di-leucine internalization motifBy similarity | 2 |
Domaini
Keywords - Domaini
Coiled coil, Signal, Transmembrane, Transmembrane helixFamily and domain databases
CDDi | cd09909, HIV-1-like_HR1-HR2, 1 hit |
Gene3Di | 2.170.40.20, 2 hits |
InterProi | View protein in InterPro IPR036377, Gp120_core_sf IPR000328, GP41-like IPR000777, HIV1_Gp120 |
Pfami | View protein in Pfam PF00516, GP120, 1 hit PF00517, GP41, 1 hit |
SUPFAMi | SSF56502, SSF56502, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MGCLGNQLLI AILLLSVYGI YCTQYVTVFY GVPAWRNATI PLFCATKNRD
60 70 80 90 100
TWGTTQCLPD NGDYSELALN VTESFDAWEN TVTEQAIEDV WQLFETSIKP
110 120 130 140 150
CVKLSPLCIT MRCNKSETDR WGLTKSSTTI TTAAPTSAPV SEKIDMVNET
160 170 180 190 200
SSCIAQNNCT GLEQEQMISC KFTMTGLKRD KTKEYNETWY STDLVCEQGN
210 220 230 240 250
STDNESRCYM NHCNTSVIQE SCDKHYWDTI RFRYCAPPGY ALLRCNDTNY
260 270 280 290 300
SGFMPKCSKV VVSSCTRMME TQTSTWFGFN GTRAENRTYI YWHGRDNRTI
310 320 330 340 350
ISLNKYYNLT MKCRRPGNKT VLPVTIMSGL VFHSQPLTDR PKQAWCWFGG
360 370 380 390 400
KWKDAIKEVK QTIVKHPRYT GTNNTDKINL TAPGGGDPEV TFMWTNCRGE
410 420 430 440 450
FLYCKMNWFL NWVEDRDVTT QRPKERHRRN YVPCHIRQII NTWHKVGKNV
460 470 480 490 500
YLPPREGDLT CNSTVTSLIA NIDWTDGNQT SITMSAEVAE LYRLELGDYK
510 520 530 540 550
LVEITPIGLA PTDVKRYTTG GTSRNKRGVF VLGFLGFLAT AGSAMGAASF
560 570 580 590 600
RLTAQSRTLL AGIVQQQQQL LGVVKRQQEL LRLTVWGTKN LQTRVTAIEK
610 620 630 640 650
YLEDQAQLNA WGCAFRQVCH TTVPWPNASL TPDWNNDTWQ EWERKVDFLE
660 670 680 690 700
ENITALLEEA QIQQEKNMYE LQKLNSWDVF GNWFDLASWI KYIQYGIYVV
710 720 730 740 750
VGVILLRIVI YIVQMLAKLR QGYRPVFSSP PSYFQXTHTQ QDPALPTREG
760 770 780 790 800
KEGDGGEGGG NSSWPWQIEY IHFLIRQLIR LLTWLFSNCR TLLSRAYQIL
810 820 830 840 850
QPILQRLSAT LRRIREVLRT ELTYLQYGWS YFHEAVQAGW RSATETLAGA
860 870 880
WGDLWETLRR GGRWILAIPR RIRQGLELTL L
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M19499 Genomic RNA No translation available. |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M19499 Genomic RNA No translation available. |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2BF1 | X-ray | 4.00 | A | 66-505 | [»] | |
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Chemistry databases
DrugBanki | DB04473, alpha-L-fucose DB03740, N-acetyl-alpha-D-glucosamine |
Miscellaneous databases
EvolutionaryTracei | P05884 |
Family and domain databases
CDDi | cd09909, HIV-1-like_HR1-HR2, 1 hit |
Gene3Di | 2.170.40.20, 2 hits |
InterProi | View protein in InterPro IPR036377, Gp120_core_sf IPR000328, GP41-like IPR000777, HIV1_Gp120 |
Pfami | View protein in Pfam PF00516, GP120, 1 hit PF00517, GP41, 1 hit |
SUPFAMi | SSF56502, SSF56502, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ENV_SIVMK | |
Accessioni | P05884Primary (citable) accession number: P05884 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1988 |
Last sequence update: | November 1, 1988 | |
Last modified: | June 2, 2021 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references