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UniProtKB - P03375 (ENV_HV1B1)

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Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1)
Status
Reviewed-Annotation score: -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

  • CD4 receptor binding Source: UniProtKB
  • protein-containing complex binding Source: UniProtKB
  • structural molecule activity Source: InterPro
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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 BH10) (HIV-1)
Taxonomic identifieri11678 [NCBI]
Taxonomic lineageiViruses › Ortervirales › Retroviridae › Orthoretrovirinae › Lentivirus ›
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007690 Componenti: Genome
  • UP000107234 Componenti: Genome
  • UP000126245 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 domaini33 – 684ExtracellularUniRule annotationAdd BLAST652
Transmembranei685 – 705HelicalUniRule annotationAdd BLAST21
Topological domaini706 – 856CytoplasmicUniRule annotationAdd BLAST151

GO - Cellular componenti

View the complete GO annotation on QuickGO ...

Keywords - Cellular componenti

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

Pathology & Biotechi

Keywords - Diseasei

AIDS

Chemistry databases

ChEMBLiCHEMBL5057

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32UniRule annotationAdd BLAST32
ChainiPRO_000023923933 – 856Envelope glycoprotein gp160UniRule annotationAdd BLAST824
ChainiPRO_000003837133 – 511Surface protein gp120UniRule annotationAdd BLAST479
ChainiPRO_0000038372512 – 856Transmembrane protein gp41UniRule annotationAdd BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 74UniRule annotation1 Publication
Glycosylationi88N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Disulfide bondi119 ↔ 205UniRule annotation1 Publication
Disulfide bondi126 ↔ 196UniRule annotation1 Publication
Disulfide bondi131 ↔ 157UniRule annotation1 Publication
Glycosylationi136N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi141N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi156N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi160N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi186N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi197N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Disulfide bondi218 ↔ 247UniRule annotation1 Publication
Disulfide bondi228 ↔ 239UniRule annotation1 Publication
Glycosylationi230N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi234N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi241N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi262N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi276N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi289N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi295N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Disulfide bondi296 ↔ 331UniRule annotation1 Publication
Glycosylationi301N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi332N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi339N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi356N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Disulfide bondi378 ↔ 445UniRule annotation1 Publication
Disulfide bondi385 ↔ 418UniRule annotation1 Publication
Glycosylationi386N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi392N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi397N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi406N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi448N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Glycosylationi463N-linked (GlcNAc...) asparagine; by hostUniRule annotation1 Publication1
Disulfide bondi598 ↔ 604UniRule annotation
Glycosylationi611N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi616N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi625N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi637N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi674N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Lipidationi764S-palmitoyl cysteine; 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 annotation3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei511 – 512Cleavage; by host furinUniRule annotation2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PRIDEiP03375

PTM databases

iPTMnetiP03375

Miscellaneous databases

PMAP-CutDBiP03376

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 annotation1 Publication

GO - Molecular functioni

  • CD4 receptor binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

IntActiP03375, 1 interactor
MINTiP03375

Structurei

Secondary structure

1856
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi516 – 530Combined sources15
Turni531 – 533Combined sources3
Beta strandi536 – 538Combined sources3
Helixi554 – 589Combined sources36

3D structure databases

ProteinModelPortaliP03375
SMRiP03375
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03375

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni131 – 156V1UniRule annotationAdd BLAST26
Regioni157 – 196V2UniRule annotationAdd BLAST40
Regioni296 – 330V3UniRule annotationAdd BLAST35
Regioni364 – 374CD4-binding loopUniRule annotationAdd BLAST11
Regioni385 – 418V4UniRule annotationAdd BLAST34
Regioni461 – 471V5Add BLAST11
Regioni463 – 471V5UniRule annotation9
Regioni512 – 532Fusion peptideUniRule annotationAdd BLAST21
Regioni574 – 592ImmunosuppressionUniRule annotationAdd BLAST19
Regioni662 – 683MPER; binding to GalCerUniRule annotationAdd BLAST22
Regioni662 – 667Involved in GalCer binding6

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili633 – 667UniRule annotationAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi712 – 715YXXL 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
IPR037527 Gp160
IPR000328 GP41-like
IPR000777 HIV1_Gp120
PfamiView protein in Pfam
PF00516 GP120, 1 hit
PF00517 GP41, 1 hit
SUPFAMiSSF56502 SSF56502, 3 hits

Sequencei

Sequence statusi: Complete.

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

P03375-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT 
        60         70         80         90        100
TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM 
       110        120        130        140        150
VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLKNDTNT NSSSGRMIME 
       160        170        180        190        200
KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD IIPIDNDTTS YTLTSCNTSV 
       210        220        230        240        250
ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT NVSTVQCTHG 
       260        270        280        290        300
IRPVVSTQLL LNGSLAEEEV VIRSANFTDN AKTIIVQLNQ SVEINCTRPN 
       310        320        330        340        350
NNTRKSIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIDSKLR 
       360        370        380        390        400
EQFGNNKTII FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW 
       410        420        430        440        450
STKGSNNTEG SDTITLPCRI KQIINMWQEV GKAMYAPPIS GQIRCSSNIT 
       460        470        480        490        500
GLLLTRDGGN SNNESEIFRP GGGDMRDNWR SELYKYKVVK IEPLGVAPTK 
       510        520        530        540        550
AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ ARQLLSGIVQ 
       560        570        580        590        600
QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG 
       610        620        630        640        650
KLICTTAVPW NASWSNKSLE QIWNNMTWME WDREINNYTS LIHSLIEESQ 
       660        670        680        690        700
NQQEKNEQEL LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA 
       710        720        730        740        750
VLSVVNRVRQ GYSPLSFQTH LPIPRGPDRP EGIEEEGGER DRDRSIRLVN 
       760        770        780        790        800
GSLALIWDDL RSLCLFSYHR LRDLLLIVTR IVELLGRRGW EALKYWWNLL 
       810        820        830        840        850
QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGAYRAI RHIPRRIRQG 

LERILL
Length:856
Mass (Da):97,225
Last modified:July 21, 1986 - v1
Checksum:i0BFFB1A18931BB27
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti403K → E in strain: Isolate PV22. 1
Natural varianti423I → F in strain: Isolate PV22. 1
Natural varianti461S → N in strain: Isolate PV22. 1
Natural varianti668S → N in strain: Isolate PV22. 1
Natural varianti673F → L in strain: Isolate PV22. 1
Natural varianti704V → I in strain: Isolate PV22. 1
Natural varianti723I → T in strain: Isolate PV22. 1
Natural varianti737G → D in strain: Isolate PV22. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15654 Genomic RNA Translation: AAA44205.1
K02083 Genomic DNA Translation: AAB59873.1
X01762 Genomic RNA Translation: CAA25903.1 Sequence problems.
PIRiA03973 VCLJH3
A03974 VCLJVL

Similar proteinsi

Entry informationi

Entry nameiENV_HV1B1
AccessioniPrimary (citable) accession number: P03375
Secondary accession number(s): P03376
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 18, 2018
This is version 151 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, Direct protein sequencing, Reference proteome

Documents

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

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