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Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus 1
Status
Unreviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Envelope glycoprotein gp160: 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 annotation
Surface protein gp120: 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 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 annotation
Transmembrane protein gp41: 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 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 annotation

Miscellaneous

HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).UniRule annotation
Inhibitors targeting HIV-1 viral envelope proteins are used as antiretroviral drugs. Attachment of virions to the cell surface via non-specific interactions and CD4 binding can be blocked by inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs, PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-induced conformational changes. Env interactions with the coreceptor molecules can be targeted by CCR5 antagonists including SCH-D, maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4 antagonist AMD 070. Fusion of viral and cellular membranes can be inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249). Resistance to inhibitors associated with mutations in Env are observed. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance.UniRule annotation

Caution

Lacks conserved residue(s) required for the propagation of feature annotation.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei148MannoseCombined sources1
Binding sitei398Mannose; via carbonyl oxygenCombined sources1

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • structural molecule activity Source: UniProtKB-UniRule

GO - Biological processi

Keywordsi

Biological processApoptosisUniRule annotationSAAS annotation, Clathrin-mediated endocytosis of virus by hostUniRule annotation, Fusion of virus membrane with host endosomal membraneUniRule annotation, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cellUniRule annotationSAAS annotation, Viral immunoevasionUniRule annotation, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell

Names & Taxonomyi

Protein namesi
Recommended name:
Envelope glycoprotein gp160UniRule annotation
Alternative name(s):
Env polyproteinUniRule annotation
Cleaved into the following 2 chains:
Transmembrane protein gp41UniRule annotation
Short name:
TMUniRule annotation
Alternative name(s):
Glycoprotein 41UniRule annotation
Short name:
gp41UniRule annotation
Surface protein gp120UniRule annotation
Short name:
SUUniRule annotation
Alternative name(s):
Glycoprotein 120UniRule annotation
Short name:
gp120UniRule annotation
Gene namesi
Name:envUniRule annotationImported
OrganismiHuman immunodeficiency virus 1Imported
Taxonomic identifieri11676 [NCBI]
Taxonomic lineageiVirusesOrterviralesRetroviridaeOrthoretrovirinaeLentivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000124534 Componenti: Genome

Subcellular locationi

  • Host cell membrane SAAS annotation; Peripheral membrane protein SAAS annotation
  • Host cell membrane SAAS annotation; Single-pass type I membrane protein SAAS annotation
  • Host endosome membrane SAAS annotation; Single-pass type I membrane protein SAAS annotation
  • Virion membrane SAAS annotation; Single-pass type I membrane protein SAAS annotation
  • 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 keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei12 – 30HelicalUniRule annotationAdd BLAST19
Transmembranei503 – 526HelicalUniRule annotationAdd BLAST24
Transmembranei669 – 690HelicalUniRule annotationAdd BLAST22
Topological domaini697 – 847CytoplasmicUniRule annotationAdd BLAST151

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membraneUniRule annotationSAAS annotation, Host endosomeUniRule annotationSAAS annotation, Host membrane, Membrane, Viral envelope proteinUniRule annotationSAAS annotationImported, Virion

PTM / Processingi

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi53 ↔ 73UniRule annotationCombined sources
Glycosylationi87N-linked (GlcNAc...) asparagineCombined sources1
Disulfide bondi118 ↔ 202Combined sources
Disulfide bondi125 ↔ 193Combined sources
Disulfide bondi130 ↔ 154Combined sources
Glycosylationi134N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi153N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi157N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi184N-linked (GlcNAc...) asparagineCombined sources1
Disulfide bondi215 ↔ 244UniRule annotationCombined sources
Disulfide bondi225 ↔ 236UniRule annotationCombined sources
Glycosylationi238N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi259N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi273N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi292N-linked (GlcNAc...) asparagineCombined sources1
Disulfide bondi293 ↔ 327Combined sources
Glycosylationi298N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi328N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi335N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi351N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi357N-linked (GlcNAc...) asparagineCombined sources1
Disulfide bondi373 ↔ 436Combined sources
Disulfide bondi380 ↔ 409Combined sources
Glycosylationi381N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi387N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi392N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi439N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi454N-linked (GlcNAc...) asparagineCombined sources1
Disulfide bondi589 ↔ 595UniRule annotation
Glycosylationi602N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi607N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi616N-linked (GlcNAc...) asparagineCombined sources1
Glycosylationi628N-linked (GlcNAc...) asparagineCombined sources1
Lipidationi755S-palmitoyl cysteine; by hostUniRule annotation1

Post-translational modificationi

Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system.UniRule annotation
Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication.UniRule annotation
Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as a 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. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei502 – 503Cleavage; by host furinUniRule annotation2

Keywords - PTMi

Cleavage on pair of basic residuesUniRule annotation, Disulfide bondUniRule annotationSAAS annotation, GlycoproteinUniRule annotation, Lipoprotein, PalmitateUniRule annotation

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. Surface protein gp120 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 annotation

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

DIPiDIP-59960N
IntActiQ75760, 3 interactors
MINTiQ75760

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TJGX-ray2.00P653-659[»]
2B4CX-ray3.30G81-483[»]
2F5BX-ray2.00P653-659[»]
4JM2X-ray3.10E88-483[»]
5FYKX-ray3.11B503-655[»]
G30-497[»]
ProteinModelPortaliQ75760
SMRiQ75760
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ75760

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 141GP120InterPro annotationAdd BLAST109
Domaini146 – 502GP120InterPro annotationAdd BLAST357
Domaini521 – 711GP41InterPro annotationAdd BLAST191

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni154 – 193V2UniRule annotationAdd BLAST40
Regioni359 – 369CD4-binding loopUniRule annotationAdd BLAST11
Regioni452 – 462V5UniRule annotationAdd BLAST11
Regioni503 – 523Fusion peptideUniRule annotationAdd BLAST21
Regioni565 – 583ImmunosuppressionUniRule annotationAdd BLAST19
Regioni653 – 674MPER; binding to GalCerUniRule annotationAdd BLAST22

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili624 – 658UniRule annotationAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi703 – 706YXXL motif; contains endocytosis signalUniRule annotation4
Motifi846 – 847Di-leucine internalization motifUniRule annotation2

Domaini

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). Coreceptor usage of gp120 is determined mainly by the primary structure of the third variable region (V3) in the outer domain of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and macrophage tropism), is used to trigger the fusion potential of the Env complex, and hence which cells the virus can infect. Binding to CCR5 involves a region adjacent in addition to V3.UniRule annotation
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.UniRule annotation
The CD4-binding region is targeted by the antibody b12.UniRule annotation
The YXXL motif is involved in determining the exact site of viral release at the surface of infected mononuclear cells and promotes endocytosis. YXXL and di-leucine endocytosis motifs interact directly or indirectly with the clathrin adapter complexes, opperate independently, and their activities are not additive.UniRule annotation
The membrane proximal external region (MPER) present in gp41 is a tryptophan-rich region recognized by the antibodies 2F5, Z13, and 4E10. MPER seems to play a role in fusion.UniRule annotation

Sequence similaritiesi

Belongs to the HIV-1 env protein family.UniRule annotation

Keywords - Domaini

Coiled coilUniRule annotation, SignalUniRule annotation, Transmembrane, Transmembrane helixUniRule annotationSAAS annotation

Family and domain databases

CDDicd09909 HIV-1-like_HR1-HR2, 1 hit
Gene3Di2.170.40.20, 2 hits
HAMAPiMF_04083 HIV_ENV, 1 hit
InterProiView protein in InterPro
IPR036377 Gp120_core_sf
IPR037527 Gp160
IPR000328 GP41-like
IPR000777 HIV1_Gp120
PfamiView protein in Pfam
PF00516 GP120, 2 hits
PF00517 GP41, 1 hit
SUPFAMiSSF56502 SSF56502, 2 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q75760-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVKGIRKSY QYLWKGGTLL LGILMICSAV EKLWVTVYYG VPVWKEATTT
60 70 80 90 100
LFCASDAKAY DTEVHNVWAT HACVPTDPNP QEVVLENVTE HFNMWKNNMV
110 120 130 140 150
EQMQEDIISL WDQSLKPCVK LTPLCVTLNC KDVNATNTTN DSEGTMERGE
160 170 180 190 200
IKNCSFNITT SIRDEVQKEY ALFYKLDVVP IDNNNTSYRL ISCDTSVITQ
210 220 230 240 250
ACPKISFEPI PIHYCAPAGF AILKCNDKTF NGKGPCKNVS TVQCTHGIRP
260 270 280 290 300
VVSTQLLLNG SLAEEEVVIR SDNFTNNAKT IIVQLKESVE INCTRPNNNT
310 320 330 340 350
RKSIHIGPGR AFYTTGEIIG DIRQAHCNIS RAKWNDTLKQ IVIKLREQFE
360 370 380 390 400
NKTIVFNHSS GGDPEIVMHS FNCGGEFFYC NSTQLFNSTW NNNTEGSNNT
410 420 430 440 450
EGNTITLPCR IKQIINMWQE VGKAMYAPPI RGQIRCSSNI TGLLLTRDGG
460 470 480 490 500
INENGTEIFR PGGGDMRDNW RSELYKYKVV KIEPLGVAPT KAKRRVVQRE
510 520 530 540 550
KRAVGIGAVF LGFLGAAGST MGAASMTLTV QARLLLSGIV QQQNNLLRAI
560 570 580 590 600
EAQQRMLQLT VWGIKQLQAR VLAVERYLGD QQLLGIWGCS GKLICTTAVP
610 620 630 640 650
WNASWSNKSL DRIWNNMTWM EWEREIDNYT SEIYTLIEES QNQQEKNEQE
660 670 680 690 700
LLELDKWASL WNWFDITKWL WYIKIFIMIV GGLVGLRLVF TVLSIVNRVR
710 720 730 740 750
QGYSPLSFQT LLPAPRGPDR PEGIEEEGGE RDRDRSGRLV NGFLALIWVD
760 770 780 790 800
LRSLCLFSYH RLRDLLLTVT RIVELLGRRG WEVLKYWWNL LQYWSQELKN
810 820 830 840
SAVSLLNATA IAVAEGTDRI IEALQRTYRA ILHIPTRIRQ GLERALL
Length:847
Mass (Da):96,160
Last modified:November 1, 1996 - v1
Checksum:i022D5F24E04FB29F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63632 Genomic DNA Translation: AAB05604.1
PIRiS13289
T09448

Similar proteinsi

Entry informationi

Entry nameiQ75760_9HIV1
AccessioniPrimary (citable) accession number: Q75760
Entry historyiIntegrated into UniProtKB/TrEMBL: November 1, 1996
Last sequence update: November 1, 1996
Last modified: June 20, 2018
This is version 144 of the entry and version 1 of the sequence. See complete history.
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Miscellaneousi

Keywords - Technical termi

3D-structureCombined sources, Complete proteomeImported

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