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P04578

- ENV_HV1H2

UniProt

P04578 - ENV_HV1H2

Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 129 (01 Oct 2014)
      Sequence version 2 (15 Jul 1999)
      Previous versions | rss
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    Functioni

    The surface protein gp120 (SU) 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. This peculiar 2 stage receptor-interaction strategy allows gp120 to maintain the highly conserved coreceptor-binding site in a cryptic conformation, protected from neutralizing antibodies. Since CD4 also displays a binding site for the disulfide-isomerase P4HB/PDI, a P4HB/PDI-CD4-CXCR4-gp120 complex may form. In that complex, P4HB/PDI could reach and reduce gp120 disulfide bonds, causing major conformational changes in gp120. TXN, another PDI family member could also be involved in disulfide rearrangements in Env during fusion. These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide.1 Publication
    Surface protein gp120 (SU) may target the virus to gut-associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7 (alpha-4/beta-7 integrins), a complex that mediates T-cell migration to the GALT. Interaction between gp120 and ITGA4/ITGB7 would allow the virus to enter GALT early in the infection, infecting and killing most of GALT's resting CD4+ T-cells. This T-cell depletion is believed to be the major insult to the host immune system leading to AIDS By similarity.By similarity
    The surface protein gp120 is 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. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they take up antigen, process it, and present it to T-cells following migration to lymphoid organs. 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. Virion capture also seems to lead to MHC-II-restricted viral antigen presentation, and probably to the activation of HIV-specific CD4+ cells.1 Publication
    The transmembrane protein gp41 (TM) 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.1 Publication
    The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface.By similarity
    The gp120-gp41 heterodimer seems to contribute to T-cell depletion during HIV-1 infection. The envelope glycoproteins expressed on the surface of infected cells induce apoptosis through an interaction with uninfected cells expressing the receptor (CD4) and the coreceptors CXCR4 or CCR5. This type of bystander killing may be obtained by at least three distinct mechanisms. First, the interaction between the 2 cells can induce cellular fusion followed by nuclear fusion within the syncytium. Syncytia are condemned to die from apoptosis. Second, the 2 interacting cells may not fuse entirely and simply exchange plasma membrane lipids, after a sort of hemifusion process, followed by rapid death. Third, it is possible that virus-infected cells, on the point of undergoing apoptosis, fuse with CD4-expressing cells, in which case apoptosis is rapidly transmitted from one cell to the other and thus occurs in a sort of contagious fashion.1 Publication
    The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves.1 Publication

    Sites

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

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. structural molecule activity Source: InterPro

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. clathrin-mediated endocytosis of virus by host cell Source: UniProtKB-KW
    3. entry into host cell Source: Reactome
    4. evasion or tolerance by virus of host immune response Source: UniProtKB-KW
    5. fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
    6. innate immune response Source: Reactome
    7. viral life cycle Source: Reactome
    8. viral process Source: Reactome
    9. viral protein processing Source: Reactome
    10. virion assembly Source: Reactome
    11. virion attachment to host cell Source: UniProtKB-KW

    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_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: Genome

    Subcellular locationi

    Chain Transmembrane protein gp41 : Virion membrane; Single-pass type I membrane protein. Host cell membrane; Single-pass type I membrane protein. Host endosome membrane Curated; Single-pass type I membrane protein Curated
    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.
    Chain Surface protein gp120 : Virion membrane; Peripheral membrane protein. Host cell membrane; Peripheral membrane protein. Host endosome membrane Curated; Single-pass type I membrane protein Curated
    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.

    GO - Cellular componenti

    1. host cell endosome membrane Source: UniProtKB-SubCell
    2. host cell plasma membrane Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW
    4. viral envelope Source: UniProtKB-KW
    5. virion membrane Source: UniProtKB-SubCell

    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 hostSequence Analysis
    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 hostSequence Analysis
    Disulfide bondi218 ↔ 247By similarity
    Disulfide bondi228 ↔ 239By similarity
    Glycosylationi230 – 2301N-linked (GlcNAc...); by hostSequence Analysis
    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 ↔ 331By similarity
    Glycosylationi301 – 3011N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi332 – 3321N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi339 – 3391N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi356 – 3561N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi378 ↔ 445By similarity
    Disulfide bondi385 ↔ 418By similarity
    Glycosylationi386 – 3861N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi392 – 3921N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi397 – 3971N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi406 – 4061N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi448 – 4481N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi463 – 4631N-linked (GlcNAc...); by hostSequence Analysis
    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. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor By similarity.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.By similarity

    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, to form a P4HB/PDI-CD4-CXCR4-gp120 complex. 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.4 Publications

    Binary interactionsi

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

    Protein-protein interaction databases

    DIPiDIP-58525N.
    IntActiP04578. 152 interactions.
    MINTiMINT-7968605.

    Structurei

    Secondary structure

    1
    856
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi84 – 9310
    Turni95 – 984
    Helixi99 – 11315
    Beta strandi119 – 1235
    Beta strandi128 – 1303
    Beta strandi199 – 2013
    Beta strandi210 – 2123
    Beta strandi223 – 2286
    Beta strandi235 – 24713
    Beta strandi251 – 2544
    Beta strandi256 – 2583
    Beta strandi260 – 2623
    Beta strandi267 – 2693
    Beta strandi271 – 2733
    Beta strandi277 – 2793
    Beta strandi284 – 29714
    Turni298 – 3003
    Beta strandi330 – 3345
    Helixi335 – 35218
    Beta strandi359 – 3613
    Helixi369 – 3724
    Beta strandi374 – 3785
    Beta strandi381 – 3855
    Helixi388 – 3903
    Beta strandi393 – 3953
    Beta strandi413 – 4175
    Beta strandi420 – 4256
    Beta strandi427 – 4304
    Beta strandi432 – 4343
    Turni440 – 4423
    Beta strandi444 – 45613
    Beta strandi466 – 4705
    Helixi475 – 4839
    Beta strandi486 – 4905
    Helixi549 – 57729
    Helixi590 – 60415
    Helixi615 – 62511
    Helixi629 – 65022
    Helixi663 – 6675
    Helixi675 – 6784
    Helixi679 – 6813
    Helixi683 – 6886

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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-ray2.20G83-492[»]
    1GC1X-ray2.50G83-492[»]
    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[»]
    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-ray3.25A254-401[»]
    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.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini33 – 684652ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini706 – 856151CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei685 – 70521HelicalSequence AnalysisAdd
    BLAST

    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
    Regioni576 – 59217ImmunosuppressionAdd
    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 By similarity.By similarity
    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

    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

    MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT    50
    TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM 100
    VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLKNDTNT NSSSGRMIME 150
    KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD IIPIDNDTTS YKLTSCNTSV 200
    ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT NVSTVQCTHG 250
    IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLNT SVEINCTRPN 300
    NNTRKRIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR 350
    EQFGNNKTII FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW 400
    STEGSNNTEG SDTITLPCRI KQIINMWQKV GKAMYAPPIS GQIRCSSNIT 450
    GLLLTRDGGN SNNESEIFRP GGGDMRDNWR SELYKYKVVK IEPLGVAPTK 500
    AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ ARQLLSGIVQ 550
    QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG 600
    KLICTTAVPW NASWSNKSLE QIWNHTTWME WDREINNYTS LIHSLIEESQ 650
    NQQEKNEQEL LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA 700
    VLSIVNRVRQ GYSPLSFQTH LPTPRGPDRP EGIEEEGGER DRDRSIRLVN 750
    GSLALIWDDL RSLCLFSYHR LRDLLLIVTR IVELLGRRGW EALKYWWNLL 800
    QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGACRAI RHIPRRIRQG 850
    LERILL 856
    Length:856
    Mass (Da):97,213
    Last modified:July 15, 1999 - v2
    Checksum:i6FAB16AF85107FE0
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.

    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K03455 Genomic RNA. Translation: AAB50262.1 .
    AF038399 Genomic DNA. Translation: AAB99976.1 .
    AF033819 Genomic RNA. Translation: AAC82596.1 .
    RefSeqi NP_057856.1. NC_001802.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AIK X-ray 2.00 C 628-661 [» ]
    N 546-581 [» ]
    1DF4 X-ray 1.45 A 546-579 [» ]
    A 628-655 [» ]
    1DF5 X-ray 2.70 A 546-579 [» ]
    A 628-655 [» ]
    1DLB X-ray 2.00 A 546-579 [» ]
    A 628-655 [» ]
    1G9M X-ray 2.20 G 83-492 [» ]
    1GC1 X-ray 2.50 G 83-492 [» ]
    1GZL X-ray 1.80 A/B 565-581 [» ]
    C/D 628-639 [» ]
    1K33 X-ray 1.75 A 546-579 [» ]
    A 628-655 [» ]
    1K34 X-ray 1.88 A 546-579 [» ]
    A 628-655 [» ]
    1MZI NMR - A 659-671 [» ]
    1OPN model - G 156-492 [» ]
    1OPT model - G 156-492 [» ]
    1OPW model - G 156-492 [» ]
    1RZJ X-ray 2.20 G 195-492 [» ]
    2CMR X-ray 2.00 A 543-662 [» ]
    2ME1 NMR - A 657-683 [» ]
    2NY7 X-ray 2.30 G 83-492 [» ]
    2PV6 NMR - A 662-683 [» ]
    2XRA X-ray 2.30 A 543-662 [» ]
    3D0V X-ray 2.05 C 660-670 [» ]
    3DNL electron microscopy 20.00 A/D/G 90-124 [» ]
    B/E/H 198-297 [» ]
    B/E/H 330-396 [» ]
    C/F/I 410-492 [» ]
    3DNN electron microscopy 20.00 A/D/G 90-124 [» ]
    B/E/H 198-297 [» ]
    B/E/H 330-396 [» ]
    C/F/I 410-492 [» ]
    3DNO electron microscopy 20.00 A/D/G 90-124 [» ]
    B/E/H 198-297 [» ]
    B/E/H 330-396 [» ]
    C/F/I 410-492 [» ]
    3IDX X-ray 2.50 G 83-492 [» ]
    3IDY X-ray 3.20 A/G 83-492 [» ]
    3TYG X-ray 3.25 A 254-401 [» ]
    3VIE X-ray 1.80 A/C/E 546-581 [» ]
    4JPJ X-ray 2.50 A/B/C/D 254-399 [» ]
    4JPK X-ray 2.40 A 254-399 [» ]
    ProteinModelPortali P04578.
    SMRi P04578. Positions 83-127, 195-492, 512-665.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-58525N.
    IntActi P04578. 152 interactions.
    MINTi MINT-7968605.

    Chemistry

    BindingDBi P04578.
    ChEMBLi CHEMBL3520.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 155971.

    Enzyme and pathway databases

    Reactomei REACT_115574. Alpha-defensins.
    REACT_163660. Synthesis and processing of ENV and VPU.
    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

    EvolutionaryTracei P04578.

    Family and domain databases

    Gene3Di 2.170.40.20. 2 hits.
    InterProi IPR000777. HIV1_GP160.
    IPR000328. Retroviral_envelope_protein.
    [Graphical view ]
    Pfami PF00516. GP120. 1 hit.
    PF00517. GP41. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56502. SSF56502. 3 hits.
    ProtoNeti Search...

    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. "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.
    4. "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.
    5. "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.
    6. "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.
    7. "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.
    8. "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.
    9. "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 OF ENVELOPE GLYCOPROTEIN.
    10. Cited for: REVIEW.
    11. Cited for: REVIEW.
    12. Cited for: REVIEW.
    13. "Emerging drug targets for antiretroviral therapy."
      Reeves J.D., Piefer A.J.
      Drugs 65:1747-1766(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    14. "HIV and the chemokine system: 10 years later."
      Lusso P.
      EMBO J. 25:447-456(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    15. Cited for: CD4-BINDING REGION.
    16. "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.
    17. "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.
    18. "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.
    19. "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.
    20. "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 (2.5 ANGSTROMS) OF 83-492 IN COMPLEX WITH HUMAN CD4.

    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: October 1, 2014
    This is version 129 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