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Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate MN) (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.UniRule annotation
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.UniRule annotation
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.UniRule annotation

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.UniRule annotation
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).UniRule annotation

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • structural molecule activity Source: InterPro

GO - Biological processi

Keywordsi

Biological processApoptosis, 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 gp160UniRule annotation
Alternative name(s):
Env polyproteinUniRule annotation
Cleaved into the following 2 chains:
Surface protein gp120UniRule annotation
Short name:
SUUniRule annotation
Alternative name(s):
Glycoprotein 120UniRule annotation
Short name:
gp120UniRule annotation
Transmembrane protein gp41UniRule annotation
Short name:
TMUniRule annotation
Alternative name(s):
Glycoprotein 41UniRule annotation
Short name:
gp41UniRule annotation
Gene namesi
Name:envUniRule annotation
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate MN) (HIV-1)
Taxonomic identifieri11696 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007697 Componenti: Genome

Subcellular locationi

Surface protein gp120:
  • Virion membrane UniRule annotation; Peripheral membrane protein UniRule annotation
  • Host cell membrane UniRule annotation; Peripheral membrane protein UniRule annotation
  • Host endosome membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
  • Note: The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag.UniRule annotation
Transmembrane protein gp41:
  • Virion membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
  • Host cell membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
  • Host endosome membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
  • Note: It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag.UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 685ExtracellularUniRule annotationAdd BLAST654
Transmembranei686 – 706HelicalUniRule annotationAdd BLAST21
Topological domaini707 – 856CytoplasmicUniRule annotationAdd BLAST150

GO - Cellular componenti

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31UniRule annotationAdd BLAST31
ChainiPRO_000023948432 – 856Envelope glycoprotein gp160UniRule annotationAdd BLAST825
ChainiPRO_000003840832 – 513Surface protein gp120UniRule annotationAdd BLAST482
ChainiPRO_0000038409514 – 856Transmembrane protein gp41UniRule annotationAdd BLAST343

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi53 ↔ 73UniRule annotation
Glycosylationi87N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi118 ↔ 210UniRule annotation
Disulfide bondi125 ↔ 201UniRule annotation
Glycosylationi129N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi130 ↔ 162UniRule annotation
Glycosylationi135N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi140N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi141N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi146N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi161N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi165N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi191N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi202N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi223 ↔ 252UniRule annotation
Disulfide bondi233 ↔ 244UniRule annotation
Glycosylationi246N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi267N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi281N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi294N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi300N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi301 ↔ 335UniRule annotation
Glycosylationi336N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi343N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi359N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi365N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi381 ↔ 445UniRule annotation
Disulfide bondi388 ↔ 418UniRule annotation
Glycosylationi395N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi401N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi405N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi406N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi413N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi448N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi465N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi599 ↔ 605UniRule annotation
Glycosylationi612N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi617N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi626N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi638N-linked (GlcNAc...) asparagine; by hostUniRule annotation1

Post-translational modificationi

Highly glycosylated by host. The high number of glycan on the protein is reffered to as 'glycan shield' because it contributes to hide protein sequence from adaptive immune system.UniRule annotation
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.UniRule annotation
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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei513 – 514Cleavage; by host furinUniRule annotation2

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 host 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 host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction results in rapid activation of integrin ITGAL/LFA-1, which facilitates 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.UniRule annotation

Binary interactionsi

WithEntry#Exp.IntActNotes
itself6EBI-9255299,EBI-9255299

GO - Molecular functioni

  • identical protein binding Source: IntAct

Structurei

Secondary structure

1856
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi308 – 310Combined sources3
Beta strandi311 – 315Combined sources5
Turni316 – 318Combined sources3
Beta strandi320 – 322Combined sources3
Helixi673 – 675Combined sources3
Helixi676 – 684Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ACYX-ray3.00P306-328[»]
1AI1X-ray2.80P306-328[»]
1F58X-ray2.00P306-328[»]
1GGIX-ray2.80P/Q310-323[»]
1K5MX-ray2.70B314-325[»]
1NAKX-ray2.57P/Q310-323[»]
1NIZNMR-A309-324[»]
1NJ0NMR-A309-324[»]
1Q1JX-ray2.50P/Q310-323[»]
2B0SX-ray2.30P308-323[»]
2QSCX-ray2.80P309-323[»]
3E6HX-ray2.10P314-322[»]
3GO1X-ray1.89P309-322[»]
3MLWX-ray2.70P/Q306-328[»]
3MLXX-ray1.90P/Q306-328[»]
3UJIX-ray1.60P306-328[»]
4M1DX-ray1.80P/Q311-322[»]
4XAWX-ray1.47P672-684[»]
4XBEX-ray1.76P672-684[»]
4XC1X-ray1.63P672-684[»]
4XC3X-ray1.63P672-684[»]
4XCFX-ray1.43P672-684[»]
4XMKX-ray3.18P/Q/R312-322[»]
ProteinModelPortaliP05877.
SMRiP05877.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05877.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni130 – 161V1UniRule annotationAdd BLAST32
Regioni162 – 201V2UniRule annotationAdd BLAST40
Regioni301 – 334V3UniRule annotationAdd BLAST34
Regioni367 – 377CD4-binding loopUniRule annotationAdd BLAST11
Regioni388 – 418V4UniRule annotationAdd BLAST31
Regioni421 – 433Essential for CD4-binding; epitope recognized by the antibody YZ23Add BLAST13
Regioni461 – 473V5Add BLAST13
Regioni463 – 473V5UniRule annotationAdd BLAST11
Regioni514 – 533Fusion peptideUniRule annotationAdd BLAST20
Regioni575 – 593ImmunosuppressionUniRule annotationAdd BLAST19
Regioni663 – 684MPER; binding to GalCerUniRule annotationAdd BLAST22

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili634 – 668UniRule annotationAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi713 – 716YXXL motif; contains endocytosis signalUniRule annotation4
Motifi855 – 856Di-leucine internalization motifUniRule annotation2

Domaini

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.UniRule annotation
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.UniRule annotation
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.UniRule annotation
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.UniRule annotation
The CD4-binding region is targeted by the antibody b12.UniRule annotation

Sequence similaritiesi

Belongs to the HIV-1 env protein family.UniRule annotation

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG09000036.

Family and domain databases

CDDicd09909. HIV-1-like_HR1-HR2. 1 hit.
Gene3Di2.170.40.20. 2 hits.
HAMAPiMF_04083. HIV_ENV. 1 hit.
InterProiView protein in InterPro
IPR036377. Gp120_core_sf.
IPR000328. GP41-like.
IPR000777. HIV1_Gp120.
PfamiView protein in Pfam
PF00516. GP120. 1 hit.
PF00517. GP41. 1 hit.
SUPFAMiSSF56502. SSF56502. 2 hits.

Sequencei

Sequence statusi: Complete.

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

P05877-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVKGIRRNY QHWWGWGTML LGLLMICSAT EKLWVTVYYG VPVWKEATTT
60 70 80 90 100
LFCASDAKAY DTEVHNVWAT QACVPTDPNP QEVELVNVTE NFNMWKNNMV
110 120 130 140 150
EQMHEDIISL WDQSLKPCVK LTPLCVTLNC TDLRNTTNTN NSTANNNSNS
160 170 180 190 200
EGTIKGGEMK NCSFNITTSI RDKMQKEYAL LYKLDIVSID NDSTSYRLIS
210 220 230 240 250
CNTSVITQAC PKISFEPIPI HYCAPAGFAI LKCNDKKFSG KGSCKNVSTV
260 270 280 290 300
QCTHGIRPVV STQLLLNGSL AEEEVVIRSE NFTDNAKTII VHLNESVQIN
310 320 330 340 350
CTRPNYNKRK RIHIGPGRAF YTTKNIIGTI RQAHCNISRA KWNDTLRQIV
360 370 380 390 400
SKLKEQFKNK TIVFNQSSGG DPEIVMHSFN CGGEFFYCNT SPLFNSTWNG
410 420 430 440 450
NNTWNNTTGS NNNITLQCKI KQIINMWQEV GKAMYAPPIE GQIRCSSNIT
460 470 480 490 500
GLLLTRDGGK DTDTNDTEIF RPGGGDMRDN WRSELYKYKV VTIEPLGVAP
510 520 530 540 550
TKAKRRVVQR EKRAAIGALF LGFLGAAGST MGAASVTLTV QARLLLSGIV
560 570 580 590 600
QQQNNLLRAI EAQQHMLQLT VWGIKQLQAR VLAVERYLKD QQLLGFWGCS
610 620 630 640 650
GKLICTTTVP WNASWSNKSL DDIWNNMTWM QWEREIDNYT SLIYSLLEKS
660 670 680 690 700
QTQQEKNEQE LLELDKWASL WNWFDITNWL WYIKIFIMIV GGLVGLRIVF
710 720 730 740 750
AVLSIVNRVR QGYSPLSLQT RPPVPRGPDR PEGIEEEGGE RDRDTSGRLV
760 770 780 790 800
HGFLAIIWVD LRSLFLFSYH HRDLLLIAAR IVELLGRRGW EVLKYWWNLL
810 820 830 840 850
QYWSQELKSS AVSLLNATAI AVAEGTDRVI EVLQRAGRAI LHIPTRIRQG

LERALL
Length:856
Mass (Da):97,140
Last modified:November 1, 1988 - v1
Checksum:iD197D809940BE732
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17449 Genomic RNA. Translation: AAA44857.1.

Similar proteinsi

Entry informationi

Entry nameiENV_HV1MN
AccessioniPrimary (citable) accession number: P05877
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: October 25, 2017
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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