Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - P03375 (ENV_HV1B1)

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Envelope glycoprotein gp160

Gene

env

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (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 gp4.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

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).

GO - Molecular functioni

  • CD4 receptor binding Source: UniProtKB
  • protein complex binding Source: UniProtKB
  • structural molecule activity Source: InterPro
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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 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
Transmembrane protein gp41
Short name:
TM
Alternative name(s):
Glycoprotein 41
Short name:
gp41
Gene namesi
Name:env
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1)
Taxonomic identifieri11678 [NCBI]
Taxonomic lineageiViruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group ›
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007690 Componenti: Genome
  • UP000107234 Componenti: Genome
  • UP000126245 Componenti: Genome

Subcellular locationi

Transmembrane protein gp41 :
Surface protein gp120 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 684ExtracellularSequence analysisAdd BLAST652
Transmembranei685 – 705HelicalSequence analysisAdd BLAST21
Topological domaini706 – 856CytoplasmicSequence 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

ChEMBLiCHEMBL5057.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32By similarityAdd BLAST32
ChainiPRO_000023923933 – 856Envelope glycoprotein gp160Add BLAST824
ChainiPRO_000003837133 – 511Surface protein gp120By similarityAdd BLAST479
ChainiPRO_0000038372512 – 856Transmembrane protein gp41By similarityAdd BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 741 Publication
Glycosylationi88N-linked (GlcNAc...) asparagine; by host1 Publication1
Disulfide bondi119 ↔ 2051 Publication
Disulfide bondi126 ↔ 1961 Publication
Disulfide bondi131 ↔ 1571 Publication
Glycosylationi136N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi141N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi156N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi160N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi186N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi197N-linked (GlcNAc...) asparagine; by host1 Publication1
Disulfide bondi218 ↔ 2471 Publication
Disulfide bondi228 ↔ 2391 Publication
Glycosylationi230N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi234N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi241N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi262N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi276N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi289N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi295N-linked (GlcNAc...) asparagine; by host1 Publication1
Disulfide bondi296 ↔ 3311 Publication
Glycosylationi301N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi332N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi339N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi356N-linked (GlcNAc...) asparagine; by host1 Publication1
Disulfide bondi378 ↔ 4451 Publication
Disulfide bondi385 ↔ 4181 Publication
Glycosylationi386N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi392N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi397N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi406N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi448N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi463N-linked (GlcNAc...) asparagine; by host1 Publication1
Glycosylationi611N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi616N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi625N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi637N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi674N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Lipidationi764S-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 similarity3 Publications
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
Sitei511 – 512Cleavage; by host furinBy similarity2

Keywords - PTMi

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

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 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 similarity1 Publication

GO - Molecular functioni

  • CD4 receptor binding Source: UniProtKB
  • protein complex binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

MINTiMINT-1523031.

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ARINMR-A512-541[»]
3VGYX-ray2.03C546-588[»]
3VH7X-ray2.02A/C/E546-588[»]
3VU5X-ray2.09A553-590[»]
3VU6X-ray2.32A553-590[»]
3W19X-ray1.28C553-590[»]
ProteinModelPortaliP03375.
SMRiP03375.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03375.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni131 – 156V1Add BLAST26
Regioni157 – 196V2Add BLAST40
Regioni296 – 330V3Add BLAST35
Regioni364 – 374CD4-binding loopBy similarityAdd BLAST11
Regioni385 – 418V4Add BLAST34
Regioni461 – 471V5Add BLAST11
Regioni512 – 532Fusion peptideSequence analysisAdd BLAST21
Regioni576 – 592ImmunosuppressionBy similarityAdd BLAST17
Regioni662 – 683MPER; binding to GalCerBy similarityAdd BLAST22
Regioni662 – 667Involved in GalCer binding6

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili633 – 667Sequence analysisAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi712 – 715YXXL motif; contains endocytosis signalBy similarity4
Motifi855 – 856Di-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

Phylogenomic databases

OrthoDBiVOG09000036.

Family and domain databases

CDDicd09909. HIV-1-like_HR1-HR2. 1 hit.
InterProiView protein in InterPro
IPR000328. GP41-like.
IPR000777. HIV1_GP160.
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

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.

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: May 10, 2017
This is version 141 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