Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (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 gp41.2 Publications
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.2 Publications
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.2 Publications

Sites

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

GO - Molecular functioni

GO - Biological processi

  • actin filament reorganization Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • clathrin-mediated endocytosis of virus by host cell Source: UniProtKB
  • entry into host cell Source: Reactome
  • evasion or tolerance by virus of host immune response Source: UniProtKB-KW
  • fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
  • fusion of virus membrane with host plasma membrane Source: UniProtKB
  • innate immune response Source: Reactome
  • positive regulation of establishment of T cell polarity Source: UniProtKB
  • positive regulation of plasma membrane raft polarization Source: UniProtKB
  • positive regulation of receptor clustering Source: UniProtKB
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
  • viral life cycle Source: Reactome
  • viral process Source: Reactome
  • viral protein processing Source: UniProtKB
  • virion assembly Source: Reactome
  • virion attachment to host cell Source: UniProtKB
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

ReactomeiREACT_115574. Alpha-defensins.
REACT_163660. Synthesis and processing of ENV and VPU.
REACT_355442. Dectin-2 family.
REACT_6359. Budding and maturation of HIV virion.
REACT_6818. Assembly Of The HIV Virion.
REACT_6903. Binding and entry of HIV virion.

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 HXB2) (HIV-1)
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000002241 Componenti: Genome

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

  • host cell endosome membrane Source: UniProtKB-SubCell
  • host cell plasma membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • viral envelope Source: UniProtKB-KW
  • virion Source: UniProtKB
  • virion membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi764 – 7641C → S: Complete loss of palmitoylation, decreased association with host cell membrane lipid rafts, decreased incorporation onto virions and severe reduction of infectivity; when associated with S-837. 1 Publication
Mutagenesisi837 – 8371C → S: Complete loss of palmitoylation, decreased association with host cell membrane lipid rafts, decreased incorporation onto virions and severe reduction of infectivity; when associated with S-764. 1 Publication

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232By similarityAdd
BLAST
Chaini33 – 856824Envelope glycoprotein gp160PRO_0000239240Add
BLAST
Chaini33 – 511479Surface protein gp120By similarityPRO_0000038427Add
BLAST
Chaini512 – 856345Transmembrane protein gp41By similarityPRO_0000038428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi54 ↔ 74By similarity
Glycosylationi88 – 881N-linked (GlcNAc...); by host1 Publication
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 host3 Publications
Disulfide bondi218 ↔ 247By similarity
Disulfide bondi228 ↔ 239By similarity
Glycosylationi230 – 2301N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi234 – 2341N-linked (GlcNAc...); by host2 Publications
Glycosylationi241 – 2411N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi262 – 2621N-linked (GlcNAc...); by host4 Publications
Glycosylationi276 – 2761N-linked (GlcNAc...); by host3 Publications
Glycosylationi289 – 2891N-linked (GlcNAc...); by host3 Publications
Glycosylationi295 – 2951N-linked (GlcNAc...); by host3 Publications
Disulfide bondi296 ↔ 331By similarity
Glycosylationi301 – 3011N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi332 – 3321N-linked (GlcNAc...); by host2 Publications
Glycosylationi339 – 3391N-linked (GlcNAc...); by host2 Publications
Glycosylationi356 – 3561N-linked (GlcNAc...); by hostCombined sources2 Publications
Disulfide bondi378 ↔ 445By similarity
Disulfide bondi385 ↔ 418By similarity
Glycosylationi386 – 3861N-linked (GlcNAc...); by host2 Publications
Glycosylationi392 – 3921N-linked (GlcNAc...); by host3 Publications
Glycosylationi397 – 3971N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi406 – 4061N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi448 – 4481N-linked (GlcNAc...); by host3 Publications
Glycosylationi463 – 4631N-linked (GlcNAc...); by host2 Publications
Disulfide bondi598 ↔ 604By similarity
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 host1 Publication
Lipidationi837 – 8371S-palmitoyl cysteine; by host1 Publication

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 (PubMed:2450679). About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor (PubMed:12218052).2 Publications
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.1 Publication

Keywords - PTMi

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

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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD63P089624EBI-6179711,EBI-762053From a different organism.
KCNH3Q9ULD83EBI-6163496,EBI-8079227From a different organism.
tatP046084EBI-6163496,EBI-6164389

Protein-protein interaction databases

BioGridi1205544. 153 interactions.
DIPiDIP-58525N.
IntActiP04578. 153 interactions.
MINTiMINT-7968605.

Structurei

Secondary structure

1
856
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi84 – 9310Combined sources
Turni95 – 984Combined sources
Helixi99 – 11315Combined sources
Beta strandi119 – 1235Combined sources
Beta strandi128 – 1303Combined sources
Beta strandi199 – 2013Combined sources
Beta strandi210 – 2123Combined sources
Beta strandi223 – 2286Combined sources
Beta strandi235 – 24713Combined sources
Beta strandi251 – 2544Combined sources
Beta strandi256 – 2583Combined sources
Beta strandi260 – 2623Combined sources
Beta strandi267 – 2693Combined sources
Beta strandi271 – 2733Combined sources
Beta strandi277 – 2793Combined sources
Beta strandi280 – 2823Combined sources
Beta strandi284 – 29714Combined sources
Turni298 – 3003Combined sources
Beta strandi330 – 3345Combined sources
Helixi335 – 35218Combined sources
Beta strandi359 – 3613Combined sources
Helixi369 – 3724Combined sources
Beta strandi374 – 3785Combined sources
Beta strandi381 – 3855Combined sources
Helixi388 – 3903Combined sources
Beta strandi393 – 3953Combined sources
Beta strandi413 – 4175Combined sources
Beta strandi420 – 4256Combined sources
Beta strandi427 – 4304Combined sources
Beta strandi432 – 4343Combined sources
Turni440 – 4423Combined sources
Beta strandi444 – 45613Combined sources
Beta strandi466 – 4705Combined sources
Helixi475 – 4839Combined sources
Beta strandi486 – 4905Combined sources
Helixi549 – 57729Combined sources
Helixi590 – 60415Combined sources
Helixi629 – 65022Combined sources
Helixi663 – 6675Combined sources
Helixi675 – 6784Combined sources
Helixi679 – 6813Combined sources
Helixi683 – 6886Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AIKX-ray2.00C628-661[»]
N546-581[»]
1DF4X-ray1.45A546-579[»]
A628-655[»]
1DF5X-ray2.70A546-579[»]
A628-655[»]
1DLBX-ray2.00A546-579[»]
A628-655[»]
1G9MX-ray2.20G83-127[»]
G195-297[»]
G330-492[»]
1GC1X-ray2.50G83-127[»]
G195-297[»]
G330-396[»]
G410-492[»]
1GZLX-ray1.80A/B565-581[»]
C/D628-639[»]
1K33X-ray1.75A546-579[»]
A628-655[»]
1K34X-ray1.88A546-579[»]
A628-655[»]
1MZINMR-A659-671[»]
1OPNmodel-G156-492[»]
1OPTmodel-G156-492[»]
1OPWmodel-G156-492[»]
1RZJX-ray2.20G195-492[»]
2CMRX-ray2.00A543-662[»]
2ME1NMR-A657-683[»]
2MG1NMR-A683-704[»]
2NY7X-ray2.30G83-492[»]
2PV6NMR-A662-683[»]
2XRAX-ray2.30A543-662[»]
3D0VX-ray2.05C660-670[»]
3DNLelectron microscopy20.00A/D/G90-124[»]
B/E/H198-297[»]
B/E/H330-396[»]
C/F/I410-492[»]
3DNNelectron microscopy20.00A/D/G90-124[»]
B/E/H198-297[»]
B/E/H330-396[»]
C/F/I410-492[»]
3DNOelectron microscopy20.00A/D/G90-124[»]
B/E/H198-297[»]
B/E/H330-396[»]
C/F/I410-492[»]
3IDXX-ray2.50G83-492[»]
3IDYX-ray3.20A/G83-492[»]
3TYGX-ray3.25A254-297[»]
A330-401[»]
3VIEX-ray1.80A/C/E546-581[»]
4JPJX-ray2.50A/B/C/D254-399[»]
4JPKX-ray2.40A254-399[»]
ProteinModelPortaliP04578.
SMRiP04578. Positions 83-127, 195-492, 512-665.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04578.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni131 – 15626V1Add
BLAST
Regioni157 – 19640V2Add
BLAST
Regioni296 – 33035V3Add
BLAST
Regioni364 – 37411CD4-binding loopAdd
BLAST
Regioni385 – 41834V4Add
BLAST
Regioni461 – 47111V5Add
BLAST
Regioni512 – 53221Fusion peptideSequence AnalysisAdd
BLAST
Regioni574 – 59219Immunosuppression1 PublicationAdd
BLAST
Regioni662 – 68322MPER; binding to GalCerAdd
BLAST

Coiled coil

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

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi712 – 7154YXXL motif; contains endocytosis signal
Motifi855 – 8562Di-leucine internalization motif

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.1 Publication
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.1 Publication
The CD4-binding region is targeted by the antibody b12.1 Publication
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.1 Publication
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 V3.1 Publication

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

KOiK19287.

Family and domain databases

Gene3Di2.170.40.20. 2 hits.
InterProiIPR000777. HIV1_GP160.
IPR000328. Retroviral_envelope_protein.
[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.

P04578-1 [UniParc]FASTAAdd to basket

« Hide

        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 YKLTSCNTSV
210 220 230 240 250
ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT NVSTVQCTHG
260 270 280 290 300
IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLNT SVEINCTRPN
310 320 330 340 350
NNTRKRIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR
360 370 380 390 400
EQFGNNKTII FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW
410 420 430 440 450
STEGSNNTEG SDTITLPCRI KQIINMWQKV 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 QIWNHTTWME WDREINNYTS LIHSLIEESQ
660 670 680 690 700
NQQEKNEQEL LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA
710 720 730 740 750
VLSIVNRVRQ GYSPLSFQTH LPTPRGPDRP 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):97,213
Last modified:July 15, 1999 - v2
Checksum:i6FAB16AF85107FE0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03455 Genomic RNA. Translation: AAB50262.1.
AF038399 Genomic DNA. Translation: AAB99976.1.
AF033819 Genomic RNA. Translation: AAC82596.1.
RefSeqiNP_057856.1. NC_001802.1.

Genome annotation databases

GeneIDi155971.
KEGGivg:155971.

Cross-referencesi

Web resourcesi

BioAfrica HIV proteomics resource

Env entry

BioAfrica HIV proteomics resource

gp120 entry

BioAfrica HIV proteomics resource

gp41 entry

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
K03455 Genomic RNA. Translation: AAB50262.1.
AF038399 Genomic DNA. Translation: AAB99976.1.
AF033819 Genomic RNA. Translation: AAC82596.1.
RefSeqiNP_057856.1. NC_001802.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AIKX-ray2.00C628-661[»]
N546-581[»]
1DF4X-ray1.45A546-579[»]
A628-655[»]
1DF5X-ray2.70A546-579[»]
A628-655[»]
1DLBX-ray2.00A546-579[»]
A628-655[»]
1G9MX-ray2.20G83-127[»]
G195-297[»]
G330-492[»]
1GC1X-ray2.50G83-127[»]
G195-297[»]
G330-396[»]
G410-492[»]
1GZLX-ray1.80A/B565-581[»]
C/D628-639[»]
1K33X-ray1.75A546-579[»]
A628-655[»]
1K34X-ray1.88A546-579[»]
A628-655[»]
1MZINMR-A659-671[»]
1OPNmodel-G156-492[»]
1OPTmodel-G156-492[»]
1OPWmodel-G156-492[»]
1RZJX-ray2.20G195-492[»]
2CMRX-ray2.00A543-662[»]
2ME1NMR-A657-683[»]
2MG1NMR-A683-704[»]
2NY7X-ray2.30G83-492[»]
2PV6NMR-A662-683[»]
2XRAX-ray2.30A543-662[»]
3D0VX-ray2.05C660-670[»]
3DNLelectron microscopy20.00A/D/G90-124[»]
B/E/H198-297[»]
B/E/H330-396[»]
C/F/I410-492[»]
3DNNelectron microscopy20.00A/D/G90-124[»]
B/E/H198-297[»]
B/E/H330-396[»]
C/F/I410-492[»]
3DNOelectron microscopy20.00A/D/G90-124[»]
B/E/H198-297[»]
B/E/H330-396[»]
C/F/I410-492[»]
3IDXX-ray2.50G83-492[»]
3IDYX-ray3.20A/G83-492[»]
3TYGX-ray3.25A254-297[»]
A330-401[»]
3VIEX-ray1.80A/C/E546-581[»]
4JPJX-ray2.50A/B/C/D254-399[»]
4JPKX-ray2.40A254-399[»]
ProteinModelPortaliP04578.
SMRiP04578. Positions 83-127, 195-492, 512-665.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1205544. 153 interactions.
DIPiDIP-58525N.
IntActiP04578. 153 interactions.
MINTiMINT-7968605.

Chemistry

BindingDBiP04578.
ChEMBLiCHEMBL3520.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi155971.
KEGGivg:155971.

Phylogenomic databases

KOiK19287.

Enzyme and pathway databases

ReactomeiREACT_115574. Alpha-defensins.
REACT_163660. Synthesis and processing of ENV and VPU.
REACT_355442. Dectin-2 family.
REACT_6359. Budding and maturation of HIV virion.
REACT_6818. Assembly Of The HIV Virion.
REACT_6903. Binding and entry of HIV virion.

Miscellaneous databases

EvolutionaryTraceiP04578.
PROiP04578.

Family and domain databases

Gene3Di2.170.40.20. 2 hits.
InterProiIPR000777. HIV1_GP160.
IPR000328. Retroviral_envelope_protein.
[Graphical view]
PfamiPF00516. GP120. 1 hit.
PF00517. GP41. 1 hit.
[Graphical view]
SUPFAMiSSF56502. SSF56502. 3 hits.
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F.
    Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  3. "Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus."
    McCune J.M., Rabin L.B., Feinberg M.B., Lieberman M., Kosek J.C., Reyes G.R., Weissman I.L.
    Cell 53:55-67(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ENVELOPE GLYCOPROTEIN GP160).
  4. "Changes in the transmembrane region of the human immunodeficiency virus type 1 gp41 envelope glycoprotein affect membrane fusion."
    Helseth E., Olshevsky U., Gabuzda D., Ardman B., Haseltine W., Sodroski J.
    J. Virol. 64:6314-6318(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (TRANSMEMBRANE PROTEIN GP41).
  5. "Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160."
    Hallenberger S., Bosch V., Angliker H., Shaw E., Klenk H.D., Garten W.
    Nature 360:358-361(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ENVELOPE GLYCOPROTEIN GP160).
  6. "The immunosuppressive peptide of HIV-1: functional domains and immune response in AIDS patients."
    Denner J., Norley S., Kurth R.
    AIDS 8:1063-1072(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: IMMUNOSUPPRESSIVE REGION.
  7. "The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated."
    Yang C., Spies C.P., Compans R.W.
    Proc. Natl. Acad. Sci. U.S.A. 92:9871-9875(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION, MUTAGENESIS OF CYS-764 AND CYS-837.
  8. "Human immunodeficiency virus type 1 infection of SK-N-MC cells: domains of gp120 involved in entry into a CD4-negative, galactosyl ceramide/3' sulfo-galactosyl ceramide-positive cell line."
    Harouse J.M., Collman R.G., Gonzalez-Scarano F.
    J. Virol. 69:7383-7390(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF SURFACE PROTEIN GP120 WITH GALACTOSYL CERAMIDE AND SULFO-GALACTOSYL CERAMIDE.
  9. "Polarized human immunodeficiency virus budding in lymphocytes involves a tyrosine-based signal and favors cell-to-cell viral transmission."
    Deschambeault J., Lalonde J.P., Cervantes-Acosta G., Lodge R., Cohen E.A., Lemay G.
    J. Virol. 73:5010-5017(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN YXXL MOTIF.
  10. "A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection."
    Bashirova A.A., Geijtenbeek T.B.H., van Duijnhoven G.C.F., van Vliet S.J., Eilering J.B.G., Martin M.P., Wu L., Martin T.D., Viebig N., Knolle P.A., Kewalramani V.N., van Kooyk Y., Carrington M.
    J. Exp. Med. 193:671-678(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (SURFACE PROTEIN GP120).
  11. "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.
  12. "Protein-disulfide isomerase-mediated reduction of two disulfide bonds of HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion."
    Barbouche R., Miquelis R., Jones I.M., Fenouillet E.
    J. Biol. Chem. 278:3131-3136(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BOND.
  13. "Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR."
    Lin G., Simmons G., Poehlmann S., Baribaud F., Ni H., Leslie G.J., Haggarty B.S., Bates P., Weissman D., Hoxie J.A., Doms R.W.
    J. Virol. 77:1337-1346(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF SURFACE PROTEIN GP120 WITH HOST CD209/DC-SIGN AND CLEC4M/DC-SIGNR.
  14. "Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1."
    Yang X., Kurteva S., Ren X., Lee S., Sodroski J.
    J. Virol. 79:12132-12147(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: STOICHIOMETRY (ENVELOPE GLYCOPROTEIN GP160).
  15. Cited for: REVIEW.
  16. Cited for: REVIEW.
  17. Cited for: REVIEW.
  18. "Emerging drug targets for antiretroviral therapy."
    Reeves J.D., Piefer A.J.
    Drugs 65:1747-1766(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  19. "HIV and the chemokine system: 10 years later."
    Lusso P.
    EMBO J. 25:447-456(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  20. "A conserved dileucine motif mediates clathrin and AP-2-dependent endocytosis of the HIV-1 envelope protein."
    Byland R., Vance P.J., Hoxie J.A., Marsh M.
    Mol. Biol. Cell 18:414-425(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DI-LEUCINE INTERNALIZATION MOTIF.
  21. "The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design."
    Montero M., van Houten N.E., Wang X., Scott J.K.
    Microbiol. Mol. Biol. Rev. 72:54-84(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: MEMBRANE-PROXIMAL EXTERNAL REGION.
  22. "The HIV-1 envelope glycoprotein gp120 features four heparan sulfate binding domains, including the co-receptor binding site."
    Crublet E., Andrieu J.P., Vives R.R., Lortat-Jacob H.
    J. Biol. Chem. 283:15193-15200(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION OF SURFACE PROTEIN GP120 WITH HEPARAN SULFATE.
    Strain: HXBC2.
  23. "HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes."
    Miyauchi K., Kim Y., Latinovic O., Morozov V., Melikyan G.B.
    Cell 137:433-444(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  24. "Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1."
    Denner J., Eschricht M., Lauck M., Semaan M., Schlaermann P., Ryu H., Akyuez L.
    PLoS ONE 8:E55199-E55199(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: IMMUNOSUPPRESSIVE REGION.
  25. "Core structure of gp41 from the HIV envelope glycoprotein."
    Chan D.C., Fass D., Berger J.M., Kim P.S.
    Cell 89:263-273(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 628-661 AND 546-581.
  26. "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody."
    Kwong P.D., Wyatt R., Robinson J., Sweet R.W., Sodroski J., Hendrickson W.A.
    Nature 393:648-659(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 83-127; 195-297; 330-396 AND 410-492, GLYCOSYLATION AT ASN-197; ASN-262; ASN-276; ASN-289; ASN-295; ASN-332; ASN-339; ASN-386; ASN-392 AND ASN-448.
  27. "Helical interactions in the HIV-1 gp41 core reveal structural basis for the inhibitory activity of gp41 peptides."
    Shu W., Liu J., Ji H., Radigen L., Jiang S., Lu M.
    Biochemistry 39:1634-1642(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 546-579 AND 628-655.
  28. "Interactions between HIV-1 gp41 core and detergents and their implications for membrane fusion."
    Shu W., Ji H., Lu M.
    J. Biol. Chem. 275:1839-1845(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 546-579 AND 628-655.
  29. "Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted and primary isolates."
    Kwong P.D., Wyatt R., Majeed S., Robinson J., Sweet R.W., Sodroski J., Hendrickson W.A.
    Structure 8:1329-1339(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 83-127; 195-297 AND 330-492, GLYCOSYLATION AT ASN-197; ASN-234; ASN-262; ASN-276; ASN-289; ASN-295; ASN-339; ASN-386; ASN-392; ASN-448 AND ASN-463.
  30. "Interhelical interactions in the gp41 core: implications for activation of HIV-1 membrane fusion."
    Wang S., York J., Shu W., Stoller M.O., Nunberg J.H., Lu M.
    Biochemistry 41:7283-7292(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 546-579 AND 628-655.
  31. Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 565-581.
  32. "Structural analysis of the epitope of the anti-HIV antibody 2F5 sheds light into its mechanism of neutralization and HIV fusion."
    Barbato G., Bianchi E., Ingallinella P., Hurni W.H., Miller M.D., Ciliberto G., Cortese R., Bazzo R., Shiver J.W., Pessi A.
    J. Mol. Biol. 330:1101-1115(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 659-671.
  33. "Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120."
    Huang C.C., Venturi M., Majeed S., Moore M.J., Phogat S., Zhang M.Y., Dimitrov D.S., Hendrickson W.A., Robinson J., Sodroski J., Wyatt R., Choe H., Farzan M., Kwong P.D.
    Proc. Natl. Acad. Sci. U.S.A. 101:2706-2711(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 195-492, GLYCOSYLATION AT ASN-197; ASN-234; ASN-262; ASN-276; ASN-289; ASN-295; ASN-392; ASN-448 AND ASN-463.
  34. Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 83-492, GLYCOSYLATION AT ASN-356.
  35. "HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane."
    Sun Z.Y., Oh K.J., Kim M., Yu J., Brusic V., Song L., Qiao Z., Wang J.H., Wagner G., Reinherz E.L.
    Immunity 28:52-63(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 662-683.
  36. "Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anion-binding site."
    Julien J.P., Bryson S., Nieva J.L., Pai E.F.
    J. Mol. Biol. 384:377-392(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 660-670.
  37. "Molecular architecture of native HIV-1 gp120 trimers."
    Liu J., Bartesaghi A., Borgnia M.J., Sapiro G., Subramaniam S.
    Nature 455:109-113(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY ELECTRON MICROSCOPY (20.00 ANGSTROMS) OF 90-124; 198-297; 330-396 AND 410-492.
  38. Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 83-492, GLYCOSYLATION AT ASN-88 AND ASN-356.
  39. "Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41."
    Sabin C., Corti D., Buzon V., Seaman M.S., Lutje Hulsik D., Hinz A., Vanzetta F., Agatic G., Silacci C., Mainetti L., Scarlatti G., Sallusto F., Weiss R., Lanzavecchia A., Weissenhorn W.
    PLoS Pathog. 6:E1001195-E1001195(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 543-582; 590-639; 625-662 AND 654-688.
  40. Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 254-297; 330-401; 412-419 AND 445-477, GLYCOSYLATION AT ASN-332.
  41. "Broad antiviral activity and crystal structure of HIV-1 fusion inhibitor sifuvirtide."
    Yao X., Chong H., Zhang C., Waltersperger S., Wang M., Cui S., He Y.
    J. Biol. Chem. 287:6788-6796(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 546-581.
  42. Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 254-399, GLYCOSYLATION AT ASN-262.
  43. "Disruption of helix-capping residues 671 and 674 reveals a role in HIV-1 entry for a specialized hinge segment of the membrane proximal external region of gp41."
    Sun Z.Y., Cheng Y., Kim M., Song L., Choi J., Kudahl U.J., Brusic V., Chowdhury B., Yu L., Seaman M.S., Bellot G., Shih W.M., Wagner G., Reinherz E.L.
    J. Mol. Biol. 426:1095-1108(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 657-683.

Entry informationi

Entry nameiENV_HV1H2
AccessioniPrimary (citable) accession number: P04578
Secondary accession number(s): O09779
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: July 15, 1999
Last modified: July 22, 2015
This is version 139 of the entry and version 2 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, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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 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.