UniProtKB - P03375 (ENV_HV1B1)
Envelope glycoprotein gp160
env
Functioni
Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.
UniRule annotationAttaches 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 CXCR4 and/or CCR5. Acts as 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. HIV 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.
UniRule annotationActs 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 and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. 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.
UniRule annotationMiscellaneous
GO - Molecular functioni
- CD4 receptor binding Source: UniProtKB
- protein-containing complex binding Source: UniProtKB
- structural molecule activity Source: UniProtKB-UniRule
GO - Biological processi
- actin filament reorganization Source: UniProtKB-UniRule
- clathrin-dependent endocytosis of virus by host cell Source: UniProtKB
- fusion of virus membrane with host endosome membrane Source: UniProtKB-UniRule
- fusion of virus membrane with host plasma membrane Source: UniProtKB
- mitigation of host immune response by virus Source: UniProtKB-UniRule
- positive regulation of establishment of T cell polarity Source: UniProtKB-UniRule
- positive regulation of plasma membrane raft polarization Source: UniProtKB-UniRule
- positive regulation of receptor clustering Source: UniProtKB-UniRule
- viral protein processing Source: UniProtKB
- virion attachment to host cell Source: UniProtKB
Keywordsi
Enzyme and pathway databases
Reactomei | R-HSA-5621480, Dectin-2 family |
Names & Taxonomyi
Protein namesi | Recommended name: Envelope glycoprotein gp160UniRule annotationAlternative name(s): Env polyproteinUniRule annotation Cleaved into the following 2 chains: Alternative name(s): Glycoprotein 120UniRule annotation Short name: gp120UniRule annotation Alternative name(s): Glycoprotein 41UniRule annotation Short name: gp41UniRule annotation |
Gene namesi | Name:envUniRule annotation |
Organismi | Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1) |
Taxonomic identifieri | 11678 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Pararnavirae › Artverviricota › Revtraviricetes › Ortervirales › Retroviridae › Orthoretrovirinae › Lentivirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Subcellular locationi
- Virion membrane UniRule annotation; Peripheral membrane protein UniRule annotation
- Host cell membrane UniRule annotation; Peripheral membrane protein UniRule annotation
- Host endosome membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation 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.UniRule annotation
- Virion membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
- Host cell membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
- Host endosome membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation 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.UniRule annotation
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 33 – 684 | ExtracellularUniRule annotationAdd BLAST | 652 | |
Transmembranei | 685 – 705 | HelicalUniRule annotationAdd BLAST | 21 | |
Topological domaini | 706 – 856 | CytoplasmicUniRule annotationAdd BLAST | 151 |
Keywords - Cellular componenti
Host cell membrane, Host endosome, Host membrane, Membrane, Viral envelope protein, VirionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 32 | UniRule annotationAdd BLAST | 32 | |
ChainiPRO_0000239239 | 33 – 856 | Envelope glycoprotein gp160UniRule annotationAdd BLAST | 824 | |
ChainiPRO_0000038371 | 33 – 511 | Surface protein gp120UniRule annotationAdd BLAST | 479 | |
ChainiPRO_0000038372 | 512 – 856 | Transmembrane protein gp41UniRule annotationAdd BLAST | 345 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 54 ↔ 74 | UniRule annotation1 Publication | ||
Glycosylationi | 88 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Disulfide bondi | 119 ↔ 205 | UniRule annotation1 Publication | ||
Disulfide bondi | 126 ↔ 196 | UniRule annotation1 Publication | ||
Disulfide bondi | 131 ↔ 157 | UniRule annotation1 Publication | ||
Glycosylationi | 136 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 141 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 156 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 160 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 186 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 197 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Disulfide bondi | 218 ↔ 247 | UniRule annotation1 Publication | ||
Disulfide bondi | 228 ↔ 239 | UniRule annotation1 Publication | ||
Glycosylationi | 230 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 234 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 241 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 262 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 276 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 289 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 295 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Disulfide bondi | 296 ↔ 331 | UniRule annotation1 Publication | ||
Glycosylationi | 301 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 332 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 339 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 356 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Disulfide bondi | 378 ↔ 445 | UniRule annotation1 Publication | ||
Disulfide bondi | 385 ↔ 418 | UniRule annotation1 Publication | ||
Glycosylationi | 386 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 392 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 397 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 406 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 448 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Glycosylationi | 463 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication | 1 | |
Disulfide bondi | 598 ↔ 604 | UniRule annotation | ||
Glycosylationi | 611 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Glycosylationi | 616 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Glycosylationi | 625 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Glycosylationi | 637 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Glycosylationi | 674 | N-linked (GlcNAc...) asparagine; by hostUniRule annotation | 1 | |
Lipidationi | 764 | S-palmitoyl cysteine; by hostUniRule annotation | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 511 – 512 | Cleavage; by host furinUniRule annotation | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, PalmitatePTM databases
iPTMneti | P03375 |
Interactioni
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. There seems to be as few as 10 spikes on the average virion.
Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction results in rapid activation of integrin ITGAL/LFA-1, which facilitates efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-associated heparan sulfate; this interaction increases virus infectivity on permissive cells and may be involved in infection of CD4- cells.
UniRule annotation1 PublicationThe 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. There seems to be as few as 10 spikes on the average virion.
UniRule annotation1 PublicationGO - Molecular functioni
- CD4 receptor binding Source: UniProtKB
Protein-protein interaction databases
MINTi | P03375 |
Structurei
Secondary structure
3D structure databases
BMRBi | P03375 |
SMRi | P03375 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P03375 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 131 – 156 | V1UniRule annotationAdd BLAST | 26 | |
Regioni | 157 – 196 | V2UniRule annotationAdd BLAST | 40 | |
Regioni | 296 – 330 | V3UniRule annotationAdd BLAST | 35 | |
Regioni | 364 – 374 | CD4-binding loopUniRule annotationAdd BLAST | 11 | |
Regioni | 385 – 418 | V4UniRule annotationAdd BLAST | 34 | |
Regioni | 461 – 471 | V5Add BLAST | 11 | |
Regioni | 463 – 471 | V5UniRule annotation | 9 | |
Regioni | 512 – 532 | Fusion peptideUniRule annotationAdd BLAST | 21 | |
Regioni | 574 – 592 | ImmunosuppressionUniRule annotationAdd BLAST | 19 | |
Regioni | 662 – 683 | MPER; binding to GalCerUniRule annotationAdd BLAST | 22 | |
Regioni | 662 – 667 | Involved in GalCer binding | 6 | |
Regioni | 721 – 740 | DisorderedSequence analysisAdd BLAST | 20 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 633 – 667 | UniRule annotationAdd BLAST | 35 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 712 – 715 | YXXL motif; contains endocytosis signalUniRule annotation | 4 | |
Motifi | 855 – 856 | Di-leucine internalization motifUniRule annotation | 2 |
Domaini
Sequence similaritiesi
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 |
HAMAPi | MF_04083, HIV_ENV, 1 hit |
InterProi | View protein in InterPro IPR036377, Gp120_core_sf IPR037527, Gp160 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
MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT
60 70 80 90 100
TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM
110 120 130 140 150
VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLKNDTNT NSSSGRMIME
160 170 180 190 200
KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD IIPIDNDTTS YTLTSCNTSV
210 220 230 240 250
ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT NVSTVQCTHG
260 270 280 290 300
IRPVVSTQLL LNGSLAEEEV VIRSANFTDN AKTIIVQLNQ SVEINCTRPN
310 320 330 340 350
NNTRKSIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIDSKLR
360 370 380 390 400
EQFGNNKTII FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW
410 420 430 440 450
STKGSNNTEG SDTITLPCRI KQIINMWQEV GKAMYAPPIS GQIRCSSNIT
460 470 480 490 500
GLLLTRDGGN SNNESEIFRP GGGDMRDNWR SELYKYKVVK IEPLGVAPTK
510 520 530 540 550
AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ ARQLLSGIVQ
560 570 580 590 600
QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG
610 620 630 640 650
KLICTTAVPW NASWSNKSLE QIWNNMTWME WDREINNYTS LIHSLIEESQ
660 670 680 690 700
NQQEKNEQEL LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA
710 720 730 740 750
VLSVVNRVRQ GYSPLSFQTH LPIPRGPDRP EGIEEEGGER DRDRSIRLVN
760 770 780 790 800
GSLALIWDDL RSLCLFSYHR LRDLLLIVTR IVELLGRRGW EALKYWWNLL
810 820 830 840 850
QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGAYRAI RHIPRRIRQG
LERILL
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 403 | K → E in strain: Isolate PV22. | 1 | |
Natural varianti | 423 | I → F in strain: Isolate PV22. | 1 | |
Natural varianti | 461 | S → N in strain: Isolate PV22. | 1 | |
Natural varianti | 668 | S → N in strain: Isolate PV22. | 1 | |
Natural varianti | 673 | F → L in strain: Isolate PV22. | 1 | |
Natural varianti | 704 | V → I in strain: Isolate PV22. | 1 | |
Natural varianti | 723 | I → T in strain: Isolate PV22. | 1 | |
Natural varianti | 737 | G → D in strain: Isolate PV22. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15654 Genomic RNA Translation: AAA44205.1 K02083 Genomic DNA Translation: AAB59873.1 X01762 Genomic RNA Translation: CAA25903.1 Sequence problems. |
PIRi | A03973, VCLJH3 A03974, VCLJVL |
Similar proteinsi
Cross-referencesi
Web resourcesi
hivdb HIV drug resistance database |
HIV drug resistance mutations |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15654 Genomic RNA Translation: AAA44205.1 K02083 Genomic DNA Translation: AAB59873.1 X01762 Genomic RNA Translation: CAA25903.1 Sequence problems. |
PIRi | A03973, VCLJH3 A03974, VCLJVL |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2ARI | NMR | - | A | 512-541 | [»] | |
3VGY | X-ray | 2.03 | C | 546-588 | [»] | |
3VH7 | X-ray | 2.02 | A/C/E | 546-588 | [»] | |
3VU5 | X-ray | 2.09 | A | 553-590 | [»] | |
3VU6 | X-ray | 2.32 | A | 553-590 | [»] | |
3W19 | X-ray | 1.28 | C | 553-590 | [»] | |
6ME1 | X-ray | 1.97 | E/F | 512-521 | [»] | |
BMRBi | P03375 | |||||
SMRi | P03375 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
MINTi | P03375 |
Chemistry databases
ChEMBLi | CHEMBL5057 |
PTM databases
iPTMneti | P03375 |
Protocols and materials databases
ABCDi | P03375, 2 sequenced antibodies |
Enzyme and pathway databases
Reactomei | R-HSA-5621480, Dectin-2 family |
Miscellaneous databases
EvolutionaryTracei | P03375 |
Family and domain databases
CDDi | cd09909, HIV-1-like_HR1-HR2, 1 hit |
Gene3Di | 2.170.40.20, 2 hits |
HAMAPi | MF_04083, HIV_ENV, 1 hit |
InterProi | View protein in InterPro IPR036377, Gp120_core_sf IPR037527, Gp160 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_HV1B1 | |
Accessioni | P03375Primary (citable) accession number: P03375 Secondary accession number(s): P03376 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | July 21, 1986 | |
Last modified: | May 25, 2022 | |
This is version 172 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-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families