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Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (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 BRU/LAI) (HIV-1)
Taxonomic identifieri11686 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007692 Componenti: Genome

Subcellular locationi

Transmembrane protein gp41 :
Surface protein gp120 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 689ExtracellularSequence analysisAdd BLAST657
Transmembranei690 – 710HelicalSequence analysisAdd BLAST21
Topological domaini711 – 861CytoplasmicSequence analysisAdd BLAST151

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi184 – 185LD → AA: Partial loss of CD4-independent binding. 1 Publication2
Mutagenesisi769C → F: Almost no effect on virions assembly and infectivity. 1 Publication1

Keywords - Diseasei

AIDS

Chemistry databases

ChEMBLiCHEMBL5826.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32By similarityAdd BLAST32
ChainiPRO_000023947433 – 861Envelope glycoprotein gp160Add BLAST829
ChainiPRO_000003838833 – 516Surface protein gp120Add BLAST484
ChainiPRO_0000038389517 – 861Transmembrane protein gp41Add BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 741 Publication
Glycosylationi88N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi119 ↔ 2101 Publication
Disulfide bondi126 ↔ 2011 Publication
Disulfide bondi131 ↔ 1621 Publication
Glycosylationi136N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi141N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi146N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi161N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi165N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi191N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi202N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi223 ↔ 2521 Publication
Disulfide bondi233 ↔ 2441 Publication
Glycosylationi235N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi239N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi246N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi267N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi281N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi294N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi300N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi301 ↔ 3361 Publication
Glycosylationi306N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi337N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi344N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi361N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi383 ↔ 4501 Publication
Disulfide bondi390 ↔ 4231 Publication
Glycosylationi391N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi397N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi402N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi411N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi453N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi468N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi603 ↔ 6091 Publication
Glycosylationi616N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi621N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi630N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi642N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi679N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi769S-palmitoyl cysteine; by hostBy similarity1
Lipidationi842S-palmitoyl cysteine; by hostBy similarity1

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 similarity2 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei516 – 517Cleavage; by host furin2

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.By similarity4 Publications

Protein-protein interaction databases

IntActiP03377. 1 interactor.

Chemistry databases

BindingDBiP03377.

Structurei

Secondary structure

1861
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi311 – 314Combined sources4
Beta strandi322 – 325Combined sources4
Helixi559 – 594Combined sources36
Helixi633 – 655Combined sources23
Helixi659 – 674Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ENVX-ray2.60A546-593[»]
A633-670[»]
1ERFinfrared-A517-539[»]
1FAVX-ray3.00A546-595[»]
C639-670[»]
1P5Ainfrared-A517-539[»]
1U6UNMR-A310-326[»]
1U6VNMR-A310-326[»]
2ZZOX-ray2.20C633-666[»]
N551-586[»]
3G9RX-ray2.00A/B/C/D/E/F667-689[»]
3MNWX-ray2.20P657-676[»]
3VGXX-ray1.74C558-595[»]
D626-657[»]
3VTPX-ray1.90C555-595[»]
D631-666[»]
ProteinModelPortaliP03377.
SMRiP03377.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03377.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni131 – 161V1Add BLAST31
Regioni162 – 201V2Add BLAST40
Regioni301 – 335V3Add BLAST35
Regioni369 – 379CD4-binding loopBy similarityAdd BLAST11
Regioni390 – 423V4Add BLAST34
Regioni466 – 476V5Add BLAST11
Regioni517 – 537Fusion peptideSequence analysisAdd BLAST21
Regioni581 – 597ImmunosuppressionBy similarityAdd BLAST17
Regioni667 – 688MPER; binding to GalCerBy similarityAdd BLAST22
Regioni667 – 672Involved in GalCer bindingBy similarity6

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili638 – 672Sequence analysisAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi184 – 186Putative binding site to alpha-4/beta-7 integrin3
Motifi717 – 720YXXL motif; contains endocytosis signalBy similarity4
Motifi860 – 861Di-leucine internalization motifBy similarity2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi465 – 468Poly-Asn4

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

Sequence similaritiesi

Belongs to the lentiviruses env family.Curated

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Family and domain databases

CDDicd09909. HIV-1-like_HR1-HR2. 1 hit.
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.

P03377-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVKEKYQHL WRWGWKWGTM LLGILMICSA TEKLWVTVYY GVPVWKEATT
60 70 80 90 100
TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM
110 120 130 140 150
VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLGNATNT NSSNTNSSSG
160 170 180 190 200
EMMMEKGEIK NCSFNISTSI RGKVQKEYAF FYKLDIIPID NDTTSYTLTS
210 220 230 240 250
CNTSVITQAC PKVSFEPIPI HYCAPAGFAI LKCNNKTFNG TGPCTNVSTV
260 270 280 290 300
QCTHGIRPVV STQLLLNGSL AEEEVVIRSA NFTDNAKTII VQLNQSVEIN
310 320 330 340 350
CTRPNNNTRK SIRIQRGPGR AFVTIGKIGN MRQAHCNISR AKWNATLKQI
360 370 380 390 400
ASKLREQFGN NKTIIFKQSS GGDPEIVTHS FNCGGEFFYC NSTQLFNSTW
410 420 430 440 450
FNSTWSTEGS NNTEGSDTIT LPCRIKQFIN MWQEVGKAMY APPISGQIRC
460 470 480 490 500
SSNITGLLLT RDGGNNNNGS EIFRPGGGDM RDNWRSELYK YKVVKIEPLG
510 520 530 540 550
VAPTKAKRRV VQREKRAVGI GALFLGFLGA AGSTMGARSM TLTVQARQLL
560 570 580 590 600
SGIVQQQNNL LRAIEAQQHL LQLTVWGIKQ LQARILAVER YLKDQQLLGI
610 620 630 640 650
WGCSGKLICT TAVPWNASWS NKSLEQIWNN MTWMEWDREI NNYTSLIHSL
660 670 680 690 700
IEESQNQQEK NEQELLELDK WASLWNWFNI TNWLWYIKIF IMIVGGLVGL
710 720 730 740 750
RIVFAVLSIV NRVRQGYSPL SFQTHLPTPR GPDRPEGIEE EGGERDRDRS
760 770 780 790 800
IRLVNGSLAL IWDDLRSLCL FSYHRLRDLL LIVTRIVELL GRRGWEALKY
810 820 830 840 850
WWNLLQYWSQ ELKNSAVSLL NATAIAVAEG TDRVIEVVQG ACRAIRHIPR
860
RIRQGLERIL L
Length:861
Mass (Da):97,488
Last modified:July 21, 1986 - v1
Checksum:i04DE2B4D4E4FD63A
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti135 – 137GNA → KND in strain: Clone pNL4-3. 3
Natural varianti143 – 147Missing in strain: Clone pNL4-3. 5
Natural varianti151 – 153EMM → RMI in strain: Clone pNL4-3. 3
Natural varianti172G → D in strain: Clone pNL4-3. 1
Natural varianti187I → V in strain: Clone pNL4-3. 1
Natural varianti192 – 193Missing in strain: Clone pNL4-3. 2
Natural varianti197 – 199TLT → RLI in strain: Clone pNL4-3. 3
Natural varianti274E → D in strain: Clone pNL4-3. 1
Natural varianti295Q → T in strain: Clone pNL4-3. 1
Natural varianti538R → A in strain: Clone pNL4-3. 1
Natural varianti552G → D in strain: Clone pNL4-3. 1
Natural varianti689I → L in strain: Clone pNL4-3. 1
Natural varianti728T → I in strain: Clone pNL4-3. 1
Natural varianti818S → N in strain: Clone pNL4-3. 1
Natural varianti838 – 842VQGAC → LQAAY in strain: Clone pNL4-3. 5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02013 Genomic RNA. Translation: AAB59751.1.
A04321 Unassigned RNA. Translation: CAA00352.1.
M19921 Genomic RNA. Translation: AAA44992.2.
PIRiA03975. VCLJLV.

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
K02013 Genomic RNA. Translation: AAB59751.1.
A04321 Unassigned RNA. Translation: CAA00352.1.
M19921 Genomic RNA. Translation: AAA44992.2.
PIRiA03975. VCLJLV.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ENVX-ray2.60A546-593[»]
A633-670[»]
1ERFinfrared-A517-539[»]
1FAVX-ray3.00A546-595[»]
C639-670[»]
1P5Ainfrared-A517-539[»]
1U6UNMR-A310-326[»]
1U6VNMR-A310-326[»]
2ZZOX-ray2.20C633-666[»]
N551-586[»]
3G9RX-ray2.00A/B/C/D/E/F667-689[»]
3MNWX-ray2.20P657-676[»]
3VGXX-ray1.74C558-595[»]
D626-657[»]
3VTPX-ray1.90C555-595[»]
D631-666[»]
ProteinModelPortaliP03377.
SMRiP03377.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP03377. 1 interactor.

Chemistry databases

BindingDBiP03377.
ChEMBLiCHEMBL5826.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

ReactomeiR-HSA-5621480. Dectin-2 family.

Miscellaneous databases

EvolutionaryTraceiP03377.

Family and domain databases

CDDicd09909. HIV-1-like_HR1-HR2. 1 hit.
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...

Entry informationi

Entry nameiENV_HV1BR
AccessioniPrimary (citable) accession number: P03377
Secondary accession number(s): Q85582
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 141 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, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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.