ENV_SIVSP
ID ENV_SIVSP Reviewed; 889 AA.
AC P19503;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Envelope glycoprotein gp160;
DE AltName: Full=Env polyprotein;
DE Contains:
DE RecName: Full=Surface protein gp120;
DE Short=SU;
DE AltName: Full=Glycoprotein 120;
DE Short=gp120;
DE Contains:
DE RecName: Full=Transmembrane protein gp41;
DE Short=TM;
DE AltName: Full=Glycoprotein 32;
DE Short=gp32;
DE Flags: Precursor;
GN Name=env;
OS Simian immunodeficiency virus (isolate PBj14/BCL-3) (SIV-sm) (Simian
OS immunodeficiency virus sooty mangabey monkey).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11738;
OH NCBI_TaxID=9527; Cercopithecidae (Old World monkeys).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1971917; DOI=10.1038/345636a0;
RA Dewhurst S., Embretson J.E., Anderson D.C., Mullins J.I., Fultz P.N.;
RT "Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-
RT PBj14.";
RL Nature 345:636-640(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1503826; DOI=10.1089/aid.1992.8.1179;
RA Dewhurst S., Embretson J.E., Fultz P.N., Mullins J.I.;
RT "Molecular clones from a non-acutely pathogenic derivative of SIVsmmPBj14:
RT characterization and comparison to acutely pathogenic clones.";
RL AIDS Res. Hum. Retroviruses 8:1179-1187(1992).
CC -!- FUNCTION: The surface protein gp120 (SU) attaches the virus to the host
CC lymphoid cell by binding to the primary receptor CD4. This interaction
CC induces a structural rearrangement creating a high affinity binding
CC site for a chemokine coreceptor like CCR5. This peculiar 2 stage
CC receptor-interaction strategy allows gp120 to maintain the highly
CC conserved coreceptor-binding site in a cryptic conformation, protected
CC from neutralizing antibodies. These changes are transmitted to the
CC transmembrane protein gp41 and are thought to activate its fusogenic
CC potential by unmasking its fusion peptide (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: Surface protein gp120 (SU) may target the virus to gut-
CC associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7 (alpha-
CC 4/beta-7 integrins), a complex that mediates T-cell migration to the
CC GALT. Interaction between gp120 and ITGA4/ITGB7 would allow the virus
CC to enter GALT early in the infection, infecting and killing most of
CC GALT's resting CD4+ T-cells. This T-cell depletion is believed to be
CC the major insult to the host immune system leading to AIDS (By
CC similarity). {ECO:0000250}.
CC -!- FUNCTION: The surface protein gp120 is a ligand for CD209/DC-SIGN and
CC CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs),
CC and on endothelial cells of liver sinusoids and lymph node sinuses.
CC These interactions allow capture of viral particles at mucosal surfaces
CC by these cells and subsequent transmission to permissive cells. DCs are
CC professional antigen presenting cells, critical for host immunity by
CC inducing specific immune responses against a broad variety of
CC pathogens. They act as sentinels in various tissues where they take up
CC antigen, process it, and present it to T-cells following migration to
CC lymphoid organs. SIV subverts the migration properties of dendritic
CC cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission
CC to permissive T-cells occurs either in trans (without DCs infection,
CC through viral capture and transmission), or in cis (following DCs
CC productive infection, through the usual CD4-gp120 interaction), thereby
CC inducing a robust infection. In trans infection, bound virions remain
CC infectious over days and it is proposed that they are not degraded, but
CC protected in non-lysosomal acidic organelles within the DCs close to
CC the cell membrane thus contributing to the viral infectious potential
CC during DCs' migration from the periphery to the lymphoid tissues. On
CC arrival at lymphoid tissues, intact virions recycle back to DCs' cell
CC surface allowing virus transmission to CD4+ T-cells. Virion capture
CC also seems to lead to MHC-II-restricted viral antigen presentation, and
CC probably to the activation of SIV-specific CD4+ cells (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: The transmembrane protein gp41 (TM) acts as a class I viral
CC fusion protein. Under the current model, the protein has at least 3
CC conformational states: pre-fusion native state, pre-hairpin
CC intermediate state, and post-fusion hairpin state. During fusion of
CC viral and target intracellular membranes, the coiled coil regions
CC (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC fusion peptide in close proximity to the C-terminal region of the
CC ectodomain. The formation of this structure appears to drive apposition
CC and subsequent fusion of viral and target cell membranes. Complete
CC fusion occurs in host cell endosomes. The virus undergoes clathrin-
CC dependent internalization long before endosomal fusion, thus minimizing
CC the surface exposure of conserved viral epitopes during fusion and
CC reducing the efficacy of inhibitors targeting these epitopes. Membranes
CC fusion leads to delivery of the nucleocapsid into the cytoplasm (By
CC similarity). {ECO:0000250}.
CC -!- FUNCTION: The envelope glycoprotein gp160 precursor down-modulates cell
CC surface CD4 antigen by interacting with it in the endoplasmic reticulum
CC and blocking its transport to the cell surface. {ECO:0000250}.
CC -!- FUNCTION: The gp120-gp41 heterodimer allows rapid transcytosis of the
CC virus through CD4 negative cells such as simple epithelial monolayers
CC of the intestinal, rectal and endocervical epithelial barriers. Both
CC gp120 and gp41 specifically recognize glycosphingolipids galactosyl-
CC ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the
CC lipid rafts structures of epithelial cells. Binding to these
CC alternative receptors allows the rapid transcytosis of the virus
CC through the epithelial cells. This transcytotic vesicle-mediated
CC transport of virions from the apical side to the basolateral side of
CC the epithelial cells does not involve infection of the cells themselves
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC consists of a homotrimer of non-covalently associated gp120-gp41
CC heterodimers. The resulting complex protrudes from the virus surface as
CC a spike. Interacts with host CD4 and CCR5 (By similarity). Gp120 also
CC interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR
CC (collectively referred to as DC-SIGN(R)). {ECO:0000250}.
CC -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC heterodimers. The resulting complex protrudes from the virus surface as
CC a spike. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host
CC cell membrane {ECO:0000250}; Single-pass type I membrane protein
CC {ECO:0000250}. Host endosome membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Note=It is probably concentrated at the
CC site of budding and incorporated into the virions possibly by contacts
CC between the cytoplasmic tail of Env and the N-terminus of Gag.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Host cell
CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Host
CC endosome membrane {ECO:0000305}; Peripheral membrane protein
CC {ECO:0000305}. Note=The surface protein is not anchored to the viral
CC envelope, but associates with the extravirion surface through its
CC binding to TM. It is probably concentrated at the site of budding and
CC incorporated into the virions possibly by contacts between the
CC cytoplasmic tail of Env and the N-terminus of Gag (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC genome are present in Env. They are called variable regions 1 through 5
CC (V1 through V5) (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC many retroviral envelope proteins. Synthetic peptides derived from this
CC relatively conserved sequence inhibit immune function in vitro and in
CC vivo (By similarity). {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC Envelope glycoproteins are synthesized as an inactive precursor that is
CC heavily N-glycosylated and processed likely by host cell furin in the
CC Golgi to yield the mature SU and TM proteins. The cleavage site between
CC SU and TM requires the minimal sequence [KR]-X-[KR]-R (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC (prior to its proteolytic cleavage) is essential for their association
CC with host cell membrane lipid rafts. Palmitoylation is therefore
CC required for envelope trafficking to classical lipid rafts, but not for
CC viral replication (By similarity). {ECO:0000250}.
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DR EMBL; M31325; AAA47757.1; -; Genomic_RNA.
DR PDB; 7LVB; X-ray; 2.25 A; A/B/C/D/E/F/G/H/I/J=185-198.
DR PDBsum; 7LVB; -.
DR SMR; P19503; -.
DR Proteomes; UP000007221; Genome.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0039663; P:membrane fusion involved in viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR Gene3D; 2.170.40.20; -; 2.
DR InterPro; IPR036377; Gp120_core_sf.
DR InterPro; IPR000328; GP41-like.
DR InterPro; IPR000777; HIV1_Gp120.
DR Pfam; PF00516; GP120; 1.
DR Pfam; PF00517; GP41; 1.
DR SUPFAM; SSF56502; SSF56502; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cleavage on pair of basic residues; Coiled coil;
KW Disulfide bond; Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW Viral envelope protein; Viral penetration into host cytoplasm; Virion;
KW Virus entry into host cell.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..889
FT /note="Envelope glycoprotein gp160"
FT /id="PRO_0000085306"
FT CHAIN 23..535
FT /note="Surface protein gp120"
FT /evidence="ECO:0000250"
FT /id="PRO_0000239517"
FT CHAIN 536..889
FT /note="Transmembrane protein gp41"
FT /evidence="ECO:0000250"
FT /id="PRO_0000239518"
FT TOPO_DOM 23..704
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 705..725
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 726..889
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 113..174
FT /note="V1"
FT REGION 120..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..217
FT /note="V2"
FT REGION 317..349
FT /note="V3"
FT REGION 408..442
FT /note="V4"
FT REGION 485..492
FT /note="V5"
FT REGION 536..556
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT REGION 599..615
FT /note="Immunosuppression"
FT /evidence="ECO:0000250"
FT REGION 681..702
FT /note="MPER; binding to GalCer"
FT /evidence="ECO:0000250"
FT COILED 648..675
FT /evidence="ECO:0000255"
FT MOTIF 731..734
FT /note="YXXV motif; contains endocytosis signal"
FT /evidence="ECO:0000250"
FT MOTIF 888..889
FT /note="Di-leucine internalization motif"
FT /evidence="ECO:0000250"
FT SITE 535..536
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000255"
FT LIPID 797
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 486
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 489
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 635
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 644
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 660
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 44..57
FT /evidence="ECO:0000250"
FT DISULFID 101..226
FT /evidence="ECO:0000250"
FT DISULFID 108..217
FT /evidence="ECO:0000250"
FT DISULFID 113..175
FT /evidence="ECO:0000250"
FT DISULFID 239..269
FT /evidence="ECO:0000250"
FT DISULFID 249..261
FT /evidence="ECO:0000250"
FT DISULFID 317..350
FT /evidence="ECO:0000250"
FT DISULFID 401..469
FT /evidence="ECO:0000250"
FT DISULFID 408..442
FT /evidence="ECO:0000250"
SQ SEQUENCE 889 AA; 102054 MW; 1438BD23B900D0AA CRC64;
MGCLGNQLLI ALLLLSASGI YCVQYVTVFY GIPAWRNATV PLFCATKNRD TWGTTQCLPD
NGDYSELAIN VTEAFDAWDN TVTEQAIEDV WNLFETSIKP CVKLTPLCIT MRCNKSETDR
WGLTGTPAPT TTQTTTTQAS TTPTSPITAK VVNDSDPCIK INNCTGLEQE PMVSCKFNMT
GLKRDKKREY NETWYSRDLV CEQNSNETDS KCYMNHCNTS VIQESCDKHY WDAIRFRYCA
PPGYALLRCN DSNYSGFAPN CTKVVVSSCT RMMETQTSTW FGFNGTRAEN RTYIYWHGRS
NRTIISLNKY YNLTMRCRRP GNKTVLPVTI MSGLVFHSQP INERPKQAWC WFGGEWKKAI
QEVKETLVKH PRYTGTNKTE QIKLTAPGGG DPEVTFMWTN CRGEFLYCKM NWFLNWVENI
QNGSRWTSQN QKERQRRNYV PCHIRQIINT WHKVGKNVYL PPREGDLTCN STVTSLIAEI
DWINGNETNI TMSAEVAELY RLELGDYKLV EITPIAFAPT SVKRYTTTGA SRNKRGVFVL
GFLGFLATAG SAMSAASVTL SAQSRTLLAG IVQQQQQLLD VVKRQQELLR LTVWGAKNLQ
TRVTAIEKYL KDQAQLNSWG CAFRQVCHTT VPRPNDTLTP NWNNMTWQEW EKQVNFLEAN
ITQSLEEAQI QQEKNTYELQ KLNSWDIFGN WFDLTSWIKY IQYGVLIVLG VIGLRIVIYV
VQMLARLRQG YRPVFSSPPA YVQQIPIQTG QELPTKEGEE GDGGGRGGNR SWPWQIEYIH
FLIRQLIRLL TWLFSSCRDW LLRNCQTLQP VLQSLSRTLQ RAREVIRVQI AYLQYGWRYL
QEAAQAWWKF VRETLASAWR DLWETLGRVG RGILAIPRRI RQGLELTLL
