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Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate YU-2) (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 YU-2) (HIV-1)
Taxonomic identifieri362651 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007419 Componenti: Genome

Subcellular locationi

Transmembrane protein gp41 :
Surface protein gp120 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 671ExtracellularSequence analysisAdd BLAST640
Transmembranei672 – 692HelicalSequence analysisAdd BLAST21
Topological domaini693 – 843CytoplasmicSequence 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

Keywords - Diseasei

AIDS

Chemistry databases

ChEMBLiCHEMBL6180.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31By similarityAdd BLAST31
ChainiPRO_000023946932 – 843Envelope glycoprotein gp160Add BLAST812
ChainiPRO_000003837732 – 498Surface protein gp120By similarityAdd BLAST467
ChainiPRO_0000038378499 – 843Transmembrane protein gp41By similarityAdd BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi53 ↔ 73By similarity
Glycosylationi87N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi118 ↔ 201By similarity
Disulfide bondi125 ↔ 192By similarity
Glycosylationi129N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi130 ↔ 155By similarity
Glycosylationi135N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi138N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi154N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi158N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi184N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi193N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi214 ↔ 243By similarity
Disulfide bondi224 ↔ 235By similarity
Glycosylationi230N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi237N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi258N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi272N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi285N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi291N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi292 ↔ 326By similarity
Glycosylationi297N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi327N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi351N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi373 ↔ 432By similarity
Disulfide bondi380 ↔ 405By similarity
Glycosylationi381N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi389N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi395N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi400N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi435N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi450N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi598N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi603N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi612N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi624N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi751S-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 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)DescriptionActionsGraphical viewLength
Sitei498 – 499Cleavage; by host furinBy similarity2

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 similarity

Protein-protein interaction databases

DIPiDIP-48439N.

Chemistry databases

BindingDBiP35961.

Structurei

Secondary structure

1843
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi52 – 55Combined sources4
Beta strandi59 – 61Combined sources3
Helixi64 – 72Combined sources9
Beta strandi73 – 75Combined sources3
Beta strandi82 – 84Combined sources3
Beta strandi90 – 93Combined sources4
Helixi94 – 96Combined sources3
Helixi98 – 114Combined sources17
Beta strandi118 – 122Combined sources5
Beta strandi127 – 129Combined sources3
Beta strandi195 – 198Combined sources4
Beta strandi200 – 202Combined sources3
Beta strandi211 – 214Combined sources4
Beta strandi219 – 224Combined sources6
Beta strandi231 – 243Combined sources13
Beta strandi252 – 258Combined sources7
Beta strandi263 – 265Combined sources3
Beta strandi267 – 269Combined sources3
Beta strandi270 – 272Combined sources3
Beta strandi280 – 294Combined sources15
Beta strandi298 – 300Combined sources3
Turni306 – 308Combined sources3
Beta strandi323 – 329Combined sources7
Helixi330 – 348Combined sources19
Beta strandi350 – 352Combined sources3
Beta strandi353 – 356Combined sources4
Beta strandi359 – 361Combined sources3
Helixi364 – 367Combined sources4
Beta strandi369 – 373Combined sources5
Beta strandi376 – 380Combined sources5
Helixi383 – 385Combined sources3
Helixi388 – 390Combined sources3
Helixi392 – 394Combined sources3
Turni396 – 398Combined sources3
Beta strandi400 – 412Combined sources13
Beta strandi414 – 421Combined sources8
Beta strandi426 – 429Combined sources4
Beta strandi430 – 443Combined sources14
Beta strandi446 – 449Combined sources4
Beta strandi452 – 457Combined sources6
Helixi462 – 470Combined sources9
Beta strandi473 – 477Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G9NX-ray2.90G82-126[»]
G191-293[»]
G325-479[»]
1RZKX-ray2.90G82-479[»]
1YYLX-ray2.75G/P82-126[»]
G/P194-296[»]
G/P325-483[»]
1YYMX-ray2.20G/P82-126[»]
G/P191-296[»]
G/P325-483[»]
2I5YX-ray2.20G/P82-126[»]
G/P191-293[»]
G/P325-479[»]
2I60X-ray2.40G/P82-126[»]
G/P191-293[»]
G/P325-479[»]
2NY7X-ray2.30G158-479[»]
2QADX-ray3.30A/E88-120[»]
A/E195-479[»]
3HI1X-ray2.90G/J89-122[»]
G/J195-479[»]
3TGQX-ray3.40A/B/C/D43-479[»]
4DVRX-ray2.50G82-122[»]
G195-301[»]
G324-484[»]
4JO3X-ray2.60P/Q313-327[»]
4JZWX-ray1.78A/G43-479[»]
4JZZX-ray1.49A43-479[»]
4K0AX-ray2.13A43-479[»]
4KA2X-ray1.79A43-479[»]
4LAJX-ray2.14A/B/F/J43-479[»]
4R4FX-ray3.51A43-479[»]
4RQSX-ray4.49G82-126[»]
G191-293[»]
G325-479[»]
4RWYX-ray2.13A43-479[»]
5A7Xelectron microscopy17.00A/E/I82-479[»]
5A8Helectron microscopy23.00A/G/M82-479[»]
ProteinModelPortaliP35961.
SMRiP35961.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35961.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni130 – 154V1Add BLAST25
Regioni155 – 192V2Add BLAST38
Regioni292 – 325V3Add BLAST34
Regioni359 – 369CD4-binding loopBy similarityAdd BLAST11
Regioni380 – 405V4Add BLAST26
Regioni448 – 458V5Add BLAST11
Regioni499 – 519Fusion peptideSequence analysisAdd BLAST21
Regioni525 – 541ImmunosuppressionBy similarityAdd BLAST17
Regioni649 – 670MPER; binding to GalCerBy similarityAdd BLAST22
Regioni649 – 654Involved in GalCer bindingBy similarity6

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili632 – 652Sequence analysisAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi699 – 702YXXL motif; contains endocytosis signalBy similarity4
Motifi842 – 843Di-leucine internalization motifBy similarity2

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

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.

P35961-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRATEIRKNY QHLWKGGTLL LGMLMICSAA EQLWVTVYYG VPVWKEATTT
60 70 80 90 100
LFCASDAKAY DTEVHNVWAT HACVPTDPNP QEVKLENVTE NFNMWKNNMV
110 120 130 140 150
EQMHEDIISL WDQSLKPCVK LTPLCVTLNC TDLRNATNTT SSSWETMEKG
160 170 180 190 200
EIKNCSFNIT TSIRDKVQKE YALFYNLDVV PIDNASYRLI SCNTSVITQA
210 220 230 240 250
CPKVSFEPIP IHYCAPAGFA ILKCNDKKFN GTGPCTNVST VQCTHGIRPV
260 270 280 290 300
VSTQLLLNGS LAEEEIVIRS ENFTNNAKTI IVQLNESVVI NCTRPNNNTR
310 320 330 340 350
KSINIGPGRA LYTTGEIIGD IRQAHCNLSK TQWENTLEQI AIKLKEQFGN
360 370 380 390 400
NKTIIFNPSS GGDPEIVTHS FNCGGEFFYC NSTQLFTWND TRKLNNTGRN
410 420 430 440 450
ITLPCRIKQI INMWQEVGKA MYAPPIRGQI RCSSNITGLL LTRDGGKDTN
460 470 480 490 500
GTEIFRPGGG DMRDNWRSEL YKYKVVKIEP LGVAPTKAKR RVVQREKRAV
510 520 530 540 550
GLGALFLGFL GAAGSTMGAA SITLTVQARQ LLSGIVQQQN NLLRAIEAQQ
560 570 580 590 600
HLLQLTVWGI KQLQARVLAV ERYLRDQQLL GIWGCSGKLI CTTTVPWNTS
610 620 630 640 650
WSNKSLNEIW DNMTWMKWER EIDNYTHIIY SLIEQSQNQQ EKNEQELLAL
660 670 680 690 700
DKWASLWNWF DITKWLWYIK IFIMIVGGLI GLRIVFVVLS IVNRVRQGYS
710 720 730 740 750
PLSFQTHLPA QRGPDRPDGI EEEGGERDRD RSGPLVDGFL AIIWVDLRSL
760 770 780 790 800
CLFSYHRLRD LLLIVTRIVE LLGRRGWGVL KYWWNLLQYW IQELKNSAVS
810 820 830 840
LLNATAIAVA EGTDRVIEIL QRAFRAVLHI PVRIRQGLER ALL
Length:843
Mass (Da):95,648
Last modified:June 1, 1994 - v1
Checksum:iC69DFD971C918B71
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M93258 Genomic RNA. No translation available.
PIRiH44001.

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
M93258 Genomic RNA. No translation available.
PIRiH44001.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G9NX-ray2.90G82-126[»]
G191-293[»]
G325-479[»]
1RZKX-ray2.90G82-479[»]
1YYLX-ray2.75G/P82-126[»]
G/P194-296[»]
G/P325-483[»]
1YYMX-ray2.20G/P82-126[»]
G/P191-296[»]
G/P325-483[»]
2I5YX-ray2.20G/P82-126[»]
G/P191-293[»]
G/P325-479[»]
2I60X-ray2.40G/P82-126[»]
G/P191-293[»]
G/P325-479[»]
2NY7X-ray2.30G158-479[»]
2QADX-ray3.30A/E88-120[»]
A/E195-479[»]
3HI1X-ray2.90G/J89-122[»]
G/J195-479[»]
3TGQX-ray3.40A/B/C/D43-479[»]
4DVRX-ray2.50G82-122[»]
G195-301[»]
G324-484[»]
4JO3X-ray2.60P/Q313-327[»]
4JZWX-ray1.78A/G43-479[»]
4JZZX-ray1.49A43-479[»]
4K0AX-ray2.13A43-479[»]
4KA2X-ray1.79A43-479[»]
4LAJX-ray2.14A/B/F/J43-479[»]
4R4FX-ray3.51A43-479[»]
4RQSX-ray4.49G82-126[»]
G191-293[»]
G325-479[»]
4RWYX-ray2.13A43-479[»]
5A7Xelectron microscopy17.00A/E/I82-479[»]
5A8Helectron microscopy23.00A/G/M82-479[»]
ProteinModelPortaliP35961.
SMRiP35961.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-48439N.

Chemistry databases

BindingDBiP35961.
ChEMBLiCHEMBL6180.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

ReactomeiR-HSA-5621480. Dectin-2 family.

Miscellaneous databases

EvolutionaryTraceiP35961.

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_HV1Y2
AccessioniPrimary (citable) accession number: P35961
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 30, 2016
This is version 139 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

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.