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Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate LW123) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.By similarity
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.By similarity
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.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell

Enzyme and pathway databases

ReactomeiR-HSA-5621480. Dectin-2 family.

Names & Taxonomyi

Protein namesi
Recommended name:
Envelope glycoprotein gp160
Alternative name(s):
Env polyprotein
Cleaved into the following 2 chains:
Surface protein gp120
Short name:
SU
Alternative name(s):
Glycoprotein 120
Short name:
gp120
Alternative name(s):
Glycoprotein 41
Short name:
gp41
Gene namesi
Name:env
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate LW123) (HIV-1)
Taxonomic identifieri82834 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

Transmembrane protein gp41 :
Surface protein gp120 :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 684652ExtracellularSequence analysisAdd
BLAST
Transmembranei685 – 70521HelicalSequence analysisAdd
BLAST
Topological domaini706 – 856151CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host endosome, Host membrane, Membrane, Viral envelope protein, Virion

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232By similarityAdd
BLAST
Chaini33 – 856824Envelope glycoprotein gp160PRO_0000239467Add
BLAST
Chaini33 – 511479Surface protein gp120By similarityPRO_0000038373Add
BLAST
Chaini512 – 856345Transmembrane protein gp41By similarityPRO_0000038374Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi54 ↔ 74By similarity
Glycosylationi88 – 881N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi119 ↔ 205By similarity
Disulfide bondi126 ↔ 196By similarity
Disulfide bondi131 ↔ 157By similarity
Glycosylationi136 – 1361N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi141 – 1411N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi156 – 1561N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi160 – 1601N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi186 – 1861N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi197 – 1971N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi218 ↔ 247By similarity
Disulfide bondi228 ↔ 239By similarity
Glycosylationi230 – 2301N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi234 – 2341N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi241 – 2411N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi262 – 2621N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi276 – 2761N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi289 – 2891N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi295 – 2951N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi296 ↔ 331By similarity
Glycosylationi301 – 3011N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi332 – 3321N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi339 – 3391N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi356 – 3561N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi378 ↔ 445By similarity
Disulfide bondi385 ↔ 418By similarity
Glycosylationi386 – 3861N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi392 – 3921N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi397 – 3971N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi406 – 4061N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi448 – 4481N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi463 – 4631N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi611 – 6111N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi616 – 6161N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi624 – 6241N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi637 – 6371N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi674 – 6741N-linked (GlcNAc...); by hostSequence analysis
Lipidationi764 – 7641S-palmitoyl cysteine; by hostBy similarity
Lipidationi837 – 8371S-palmitoyl cysteine; by hostBy similarity

Post-translational modificationi

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.By similarity
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.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei511 – 5122Cleavage; by host furinBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

PTM databases

UniCarbKBiQ70626.

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 human 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 human ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction results in rapid activation of integrin ITGAL/LFA-1, which facilitate 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.By similarity

Structurei

Secondary structure

1
856
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi535 – 5406Combined sources
Helixi548 – 58033Combined sources
Helixi633 – 68250Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IF3model-A/B/C540-665[»]
2X7RX-ray2.00A/D/N528-581[»]
B/C/E629-683[»]
2Z2TX-ray2.10A/B/C546-581[»]
3AHAX-ray1.70A/C/E548-581[»]
B/D/F628-660[»]
3CP1X-ray2.00A536-663[»]
3CYOX-ray2.10A536-663[»]
3GWOX-ray1.65A/B630-683[»]
3H00X-ray2.20A/B/C/D636-674[»]
3H01X-ray1.70A/B630-683[»]
4I48X-ray2.80C192-200[»]
ProteinModelPortaliQ70626.
SMRiQ70626. Positions 83-127, 195-492, 512-665.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ70626.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni131 – 15626V1Add
BLAST
Regioni157 – 19640V2Add
BLAST
Regioni296 – 33035V3Add
BLAST
Regioni364 – 37411CD4-binding loopBy similarityAdd
BLAST
Regioni385 – 41834V4Add
BLAST
Regioni461 – 47111V5Add
BLAST
Regioni512 – 53221Fusion peptideSequence analysisAdd
BLAST
Regioni576 – 59217ImmunosuppressionBy similarityAdd
BLAST
Regioni662 – 68322MPER; binding to GalCerBy similarityAdd
BLAST
Regioni662 – 6676Involved in GalCer bindingBy similarity

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili633 – 66735Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi855 – 8562Di-leucine internalization motifBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi460 – 4634Poly-Asn

Domaini

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.By similarity
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
The CD4-binding region is targeted by the antibody b12.By similarity
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.By similarity
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.By similarity

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di2.170.40.20. 2 hits.
InterProiIPR000328. GP41-like.
IPR000777. HIV1_GP160.
[Graphical view]
PfamiPF00516. GP120. 1 hit.
PF00517. GP41. 1 hit.
[Graphical view]
SUPFAMiSSF56502. SSF56502. 3 hits.

Sequencei

Sequence statusi: Complete.

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

Q70626-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVKEKYQHL RRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT
60 70 80 90 100
TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM
110 120 130 140 150
VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLKNDTNT NSSSGGMIME
160 170 180 190 200
KGEIKNCSFN ISTSIRGKVQ KEYAFFYKHD IIPIDNDTTS YTLTSCNTSV
210 220 230 240 250
ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT NVSTVQCTHG
260 270 280 290 300
IKPVVSTQLL LNGSLAEEEV VIRSANLTDN VKTIIVQLNQ SVEINCTRPN
310 320 330 340 350
NNTRKRIRIQ RGPGRTFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR
360 370 380 390 400
EQYGNNKTII FKQSSGGDLE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW
410 420 430 440 450
STEGSNNTEG SDTITLPCRI KQIINMWQEV GKAMYAPPIS GQIRCSSNIT
460 470 480 490 500
GLLLTRDGGN NNNGSEIFRP 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 QIWNHTTWME WDREINNYTS LIHSLIEESQ
660 670 680 690 700
NQQEKNEQEL LELDKWASLW NWFNITNWLW YIKIFIMIVG GLVGLRIVFA
710 720 730 740 750
VLSIVNRVRQ GHSPLSFQTH LPTPGGPDRP EGIEEEGGER DRDRSIRLVN
760 770 780 790 800
GSLALIWDDL RSLCLFSYHR LRDLLLIVTR IVELLGRRGW EALKYWWNLL
810 820 830 840 850
QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGACRAI RHIPRRIRQG

LERILL
Length:856
Mass (Da):96,938
Last modified:November 1, 1996 - v1
Checksum:i0C241332CF7E6687
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12055 Genomic RNA. Translation: AAA76690.1.

Cross-referencesi

Web resourcesi

hivdb

HIV drug resistance database

BioAfrica: HIV bioinformatics in Africa
HIV drug resistance mutations

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12055 Genomic RNA. Translation: AAA76690.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IF3model-A/B/C540-665[»]
2X7RX-ray2.00A/D/N528-581[»]
B/C/E629-683[»]
2Z2TX-ray2.10A/B/C546-581[»]
3AHAX-ray1.70A/C/E548-581[»]
B/D/F628-660[»]
3CP1X-ray2.00A536-663[»]
3CYOX-ray2.10A536-663[»]
3GWOX-ray1.65A/B630-683[»]
3H00X-ray2.20A/B/C/D636-674[»]
3H01X-ray1.70A/B630-683[»]
4I48X-ray2.80C192-200[»]
ProteinModelPortaliQ70626.
SMRiQ70626. Positions 83-127, 195-492, 512-665.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

UniCarbKBiQ70626.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

ReactomeiR-HSA-5621480. Dectin-2 family.

Miscellaneous databases

EvolutionaryTraceiQ70626.

Family and domain databases

Gene3Di2.170.40.20. 2 hits.
InterProiIPR000328. GP41-like.
IPR000777. HIV1_GP160.
[Graphical view]
PfamiPF00516. GP120. 1 hit.
PF00517. GP41. 1 hit.
[Graphical view]
SUPFAMiSSF56502. SSF56502. 3 hits.
ProtoNetiSearch...

Publicationsi

  1. "Viral variability and serum antibody response in a laboratory worker infected with HIV type 1 (HTLV type IIIB)."
    Reitz M.S. Jr., Hall L., Robert-Guroff M., Lautenberger J.A., Hahn B.M., Shaw G.M., Kong L.I., Weiss S.H., Waters D., Gallo R.C., Blattner W.
    AIDS Res. Hum. Retroviruses 10:1143-1155(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a pathogen receptor with broad specificity."
    Geijtenbeek T.B., van Kooyk Y.
    APMIS 111:698-714(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  3. Cited for: REVIEW.
  4. Cited for: REVIEW.
  5. Cited for: REVIEW.
  6. "Emerging drug targets for antiretroviral therapy."
    Reeves J.D., Piefer A.J.
    Drugs 65:1747-1766(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  7. "HIV and the chemokine system: 10 years later."
    Lusso P.
    EMBO J. 25:447-456(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiENV_HV1LW
AccessioniPrimary (citable) accession number: Q70626
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: July 6, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

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.
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).

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.