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UniProtKB - P05884 (ENV_SIVMK)

Protein

Envelope glycoprotein gp160

Gene

env

Organism
Simian immunodeficiency virus (isolate K6W) (SIV-mac) (Simian immunodeficiency virus rhesus monkey)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 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. These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide (By similarity).By similarity
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. SIV 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 SIV-specific CD4+ cells (By similarity).By similarity
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. 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).By similarity
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 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 (By similarity).By similarity

Miscellaneous

This is a macaque isolate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei736In-frame UAG termination codon1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processApoptosis, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Virus entry into host cell

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 32
Short name:
gp32
Gene namesi
Name:env
OrganismiSimian immunodeficiency virus (isolate K6W) (SIV-mac) (Simian immunodeficiency virus rhesus monkey)
Taxonomic identifieri11735 [NCBI]
Taxonomic lineageiViruses › Ortervirales › Retroviridae › Orthoretrovirinae › Lentivirus ›
Virus hostiCercopithecidae (Old World monkeys) [TaxID: 9527]

Subcellular locationi

Transmembrane protein gp41 :
Surface protein gp120 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 696ExtracellularSequence analysisAdd BLAST677
Transmembranei697 – 717HelicalSequence analysisAdd BLAST21
Topological domaini718 – 881CytoplasmicSequence analysisAdd BLAST164

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

Chemistry databases

DrugBankiDB04473 Alpha-L-Fucose
DB03740 N-acetyl-alpha-D-glucosamine

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000023951320 – 881Envelope glycoprotein gp160Add BLAST862
ChainiPRO_000003846820 – 527Surface protein gp120By similarityAdd BLAST508
ChainiPRO_0000038469528 – 881Transmembrane protein gp41By similarityAdd BLAST354

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi37N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi44 ↔ 57By similarity
Glycosylationi70N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi101 ↔ 222By similarity
Disulfide bondi108 ↔ 213By similarity
Disulfide bondi113 ↔ 170By similarity
Glycosylationi114N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi148N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi158N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi186N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi200N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi204N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi214N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi235 ↔ 265By similarity
Disulfide bondi245 ↔ 257By similarity
Glycosylationi246N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi249N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi280N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi286N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi297N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi308N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi313 ↔ 346By similarity
Glycosylationi318N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi373N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi379N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi397 ↔ 461By similarity
Disulfide bondi404 ↔ 434By similarity
Glycosylationi462N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi478N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi627N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi636N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Glycosylationi652N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Lipidationi789S-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 (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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei527 – 528Cleavage; by host furinSequence analysis2

Keywords - PTMi

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

Proteomic databases

PRIDEiP05884

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. Surface protein gp120 interacts with host CD4 and CCR5 (By similarity). Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R)) (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliP05884
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05884

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni113 – 169V1Add BLAST57
Regioni170 – 213V2Add BLAST44
Regioni313 – 345V3Add BLAST33
Regioni404 – 434V4Add BLAST31
Regioni477 – 484V58
Regioni528 – 548Fusion peptideSequence analysisAdd BLAST21
Regioni591 – 607ImmunosuppressionBy similarityAdd BLAST17
Regioni673 – 694MPER; binding to GalCerBy similarityAdd BLAST22

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili636 – 668Sequence analysisAdd BLAST33

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi723 – 726YXXV motif; contains endocytosis signalBy similarity4
Motifi880 – 881Di-leucine internalization motifBy similarity2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi565 – 569Poly-Gln5

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) (By similarity).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).By similarity

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Family and domain databases

CDDicd09909 HIV-1-like_HR1-HR2, 1 hit
Gene3Di2.170.40.20, 2 hits
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, 1 hit

Sequencei

Sequence statusi: Complete.

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

P05884-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGCLGNQLLI AILLLSVYGI YCTQYVTVFY GVPAWRNATI PLFCATKNRD 
        60         70         80         90        100
TWGTTQCLPD NGDYSELALN VTESFDAWEN TVTEQAIEDV WQLFETSIKP 
       110        120        130        140        150
CVKLSPLCIT MRCNKSETDR WGLTKSSTTI TTAAPTSAPV SEKIDMVNET 
       160        170        180        190        200
SSCIAQNNCT GLEQEQMISC KFTMTGLKRD KTKEYNETWY STDLVCEQGN 
       210        220        230        240        250
STDNESRCYM NHCNTSVIQE SCDKHYWDTI RFRYCAPPGY ALLRCNDTNY 
       260        270        280        290        300
SGFMPKCSKV VVSSCTRMME TQTSTWFGFN GTRAENRTYI YWHGRDNRTI 
       310        320        330        340        350
ISLNKYYNLT MKCRRPGNKT VLPVTIMSGL VFHSQPLTDR PKQAWCWFGG 
       360        370        380        390        400
KWKDAIKEVK QTIVKHPRYT GTNNTDKINL TAPGGGDPEV TFMWTNCRGE 
       410        420        430        440        450
FLYCKMNWFL NWVEDRDVTT QRPKERHRRN YVPCHIRQII NTWHKVGKNV 
       460        470        480        490        500
YLPPREGDLT CNSTVTSLIA NIDWTDGNQT SITMSAEVAE LYRLELGDYK 
       510        520        530        540        550
LVEITPIGLA PTDVKRYTTG GTSRNKRGVF VLGFLGFLAT AGSAMGAASF 
       560        570        580        590        600
RLTAQSRTLL AGIVQQQQQL LGVVKRQQEL LRLTVWGTKN LQTRVTAIEK 
       610        620        630        640        650
YLEDQAQLNA WGCAFRQVCH TTVPWPNASL TPDWNNDTWQ EWERKVDFLE 
       660        670        680        690        700
ENITALLEEA QIQQEKNMYE LQKLNSWDVF GNWFDLASWI KYIQYGIYVV 
       710        720        730        740        750
VGVILLRIVI YIVQMLAKLR QGYRPVFSSP PSYFQXTHTQ QDPALPTREG 
       760        770        780        790        800
KEGDGGEGGG NSSWPWQIEY IHFLIRQLIR LLTWLFSNCR TLLSRAYQIL 
       810        820        830        840        850
QPILQRLSAT LRRIREVLRT ELTYLQYGWS YFHEAVQAGW RSATETLAGA 
       860        870        880 
WGDLWETLRR GGRWILAIPR RIRQGLELTL L
Length:881
Mass (Da):101,186
Last modified:November 1, 1988 - v1
Checksum:i9052B543777DD979
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19499 Genomic RNA No translation available.

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19499 Genomic RNA No translation available.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BF1X-ray4.00A66-505[»]
ProteinModelPortaliP05884
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

DrugBankiDB04473 Alpha-L-Fucose
DB03740 N-acetyl-alpha-D-glucosamine

Proteomic databases

PRIDEiP05884

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP05884

Family and domain databases

CDDicd09909 HIV-1-like_HR1-HR2, 1 hit
Gene3Di2.170.40.20, 2 hits
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, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiENV_SIVMK
AccessioniPrimary (citable) accession number: P05884
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: November 7, 2018
This is version 123 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

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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