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Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate BRVA) (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 BRVA) (HIV-1)
Taxonomic identifieri11693 [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 domaini31 – 680650ExtracellularSequence analysisAdd
BLAST
Transmembranei681 – 70121HelicalSequence analysisAdd
BLAST
Topological domaini702 – 852151CytoplasmicSequence 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 – 3030By similarityAdd
BLAST
Chaini31 – 852822Envelope glycoprotein gp160PRO_0000239481Add
BLAST
Chaini31 – 507477Surface protein gp120By similarityPRO_0000038402Add
BLAST
Chaini508 – 852345Transmembrane protein gp41By similarityPRO_0000038403Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi49 – 491N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi54 ↔ 74By similarity
Glycosylationi88 – 881N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi119 ↔ 205By similarity
Disulfide bondi126 ↔ 196By similarity
Disulfide bondi131 ↔ 155By similarity
Glycosylationi135 – 1351N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi138 – 1381N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi154 – 1541N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi158 – 1581N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi197 – 1971N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi218 ↔ 247By similarity
Disulfide bondi228 ↔ 239By similarity
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 ↔ 330By similarity
Glycosylationi301 – 3011N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi331 – 3311N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi354 – 3541N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi360 – 3601N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi376 ↔ 439By similarity
Disulfide bondi383 ↔ 412By similarity
Glycosylationi384 – 3841N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi390 – 3901N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi396 – 3961N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi400 – 4001N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi442 – 4421N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi456 – 4561N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi607 – 6071N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi612 – 6121N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi621 – 6211N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi633 – 6331N-linked (GlcNAc...); by hostSequence analysis
Glycosylationi670 – 6701N-linked (GlcNAc...); by hostSequence analysis

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
Sitei507 – 5082Cleavage; by host furinBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

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
852
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni595 – 5973Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IM7NMR-A591-603[»]
1J8NNMR-A591-603[»]
1J8ZNMR-A591-603[»]
1J9VNMR-A591-603[»]
1JAANMR-A591-603[»]
1JARNMR-A591-603[»]
1JC8NMR-A591-603[»]
1JCPNMR-A591-603[»]
ProteinModelPortaliP12488.
SMRiP12488. Positions 90-127, 195-488, 508-586, 624-657.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12488.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni131 – 15424V1Add
BLAST
Regioni155 – 19642V2Add
BLAST
Regioni296 – 32934V3Add
BLAST
Regioni362 – 37211CD4-binding loopBy similarityAdd
BLAST
Regioni383 – 41230V4Add
BLAST
Regioni454 – 46714V5Add
BLAST
Regioni508 – 52821Fusion peptideSequence analysisAdd
BLAST
Regioni572 – 58817ImmunosuppressionBy similarityAdd
BLAST
Regioni658 – 67922MPER; binding to GalCerBy similarityAdd
BLAST
Regioni658 – 6636Involved in GalCer bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi708 – 7114YXXL motif; contains endocytosis signalBy similarity

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

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. 2 hits.

Sequencei

Sequence statusi: Complete.

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

P12488-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVKGIKKNY QHLWRWGGMM LLGILMICSA TDKLWVTVYY GVPVWKEANT
60 70 80 90 100
TLFCASDAKA YDTEIHNVWA THACVPTDPN PQELVMGNVT ENFNMWKNDM
110 120 130 140 150
VEQMHEDIIS LWDQSLKPCV KLTPLCVTLN CHDFNATNAT SNSGKMMEGG
160 170 180 190 200
EMKNCSFNIT TSIRDKMQKE YALFYKLDIV PIDNDKTNTR YRLISCNTSV
210 220 230 240 250
ITQACPKVTF EPIPIHYCAP AGFAILKCNN KKFNGTGPCT NVSTVQCTHG
260 270 280 290 300
IRPVVSTQLL LNGSLAEEEV VIRSENFTNN VKTIIVQLNE SVEINCTRPN
310 320 330 340 350
NNTRKRITMG PGRVYYTTGQ IIGDIRRAHC NLSRSKWENT LKQIVTKLRV
360 370 380 390 400
QFKNKTIVFN RSSGGDPEIV MHSFNCGGEF FFCNTTQLFN STWYRNTTGN
410 420 430 440 450
ITEGNSPITL PCRIKQIINM WQEVGKAMYA PPIRGQIKCS SNITGLLLTR
460 470 480 490 500
DGGNNNETTD TEIFRPGGGN MRDNWRSELY KYKVVKIEPL GVAPTKAKRR
510 520 530 540 550
VVQREKRAVG LGALFLGFLG AAGSTMGAAS LTLTVQARLL LSGIVQQQNN
560 570 580 590 600
LLMAIEAQQH MLELTVWGIK QLQARVLAVE RYLKDQQLLG IWGCSGKLIC
610 620 630 640 650
TTAVPWNASW SNKSLSDIWD NMTWMEWERE IDNYTNLIYS LIEDSQIQQE
660 670 680 690 700
KNEKELLELD KWASLWNWFN ITNWLWYIKI FIMIVGGLIG LRIVFAVLSI
710 720 730 740 750
VNRVRQGYSP LSFQTRLPGR RGPDRPEGIE EEGGERDRDR SSPLVDGFLA
760 770 780 790 800
LFWVDLRSLF LFSYHRLRDL LLIVTRIVEL LGRRGWEVLK YWWNLLQYWS
810 820 830 840 850
QELKNSAVSL LNATAIAVGE RTDRAIEVVQ RAFRAILHIP RRIRQGLERA

LQ
Length:852
Mass (Da):97,203
Last modified:October 1, 1989 - v1
Checksum:i2BB866345DEC915F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M21098 Genomic RNA. Translation: AAA44221.1.
PIRiA31667. VCLJBR.

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
M21098 Genomic RNA. Translation: AAA44221.1.
PIRiA31667. VCLJBR.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IM7NMR-A591-603[»]
1J8NNMR-A591-603[»]
1J8ZNMR-A591-603[»]
1J9VNMR-A591-603[»]
1JAANMR-A591-603[»]
1JARNMR-A591-603[»]
1JC8NMR-A591-603[»]
1JCPNMR-A591-603[»]
ProteinModelPortaliP12488.
SMRiP12488. Positions 90-127, 195-488, 508-586, 624-657.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

ReactomeiR-HSA-5621480. Dectin-2 family.

Miscellaneous databases

EvolutionaryTraceiP12488.

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. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiENV_HV1BN
AccessioniPrimary (citable) accession number: P12488
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: September 7, 2016
This is version 124 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.
This virus is cytopathically active and was harvested from the brain tissue of a neurological AIDS patient.
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.