ENV_SIVVG
ID ENV_SIVVG Reviewed; 877 AA.
AC P27977;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 25-MAY-2022, entry version 115.
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 agm.vervet (isolate AGM3) (SIV-agm.ver)
OS (Simian immunodeficiency virus African green monkey vervet).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11730;
OH NCBI_TaxID=9527; Cercopithecidae (Old World monkeys).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2158689; DOI=10.1016/0042-6822(90)90246-n;
RA Baier M., Garber C., Mueller C., Cichutek K., Kurth R.;
RT "Complete nucleotide sequence of a simian immunodeficiency virus from
RT African green monkeys: a novel type of intragroup divergence.";
RL Virology 176:216-221(1990).
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 YXXL motif is involved in determining the exact site of
CC viral release at the surface of infected mononuclear cells and promotes
CC endocytosis. {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 -!- MISCELLANEOUS: This is an African green monkey isolate.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M30931; AAA91919.1; -; Genomic_RNA.
DR PIR; C46356; C46356.
DR SMR; P27977; -.
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; -; 1.
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 3: Inferred from homology;
KW Apoptosis; Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW Membrane; Signal; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus entry into host cell.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..877
FT /note="Envelope glycoprotein gp160"
FT /id="PRO_0000239506"
FT CHAIN 20..543
FT /note="Surface protein gp120"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038458"
FT CHAIN 544..877
FT /note="Transmembrane protein gp41"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038459"
FT TOPO_DOM 20..707
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 708..728
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 729..877
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 114..173
FT /note="V1"
FT REGION 174..215
FT /note="V2"
FT REGION 317..349
FT /note="V3"
FT REGION 409..451
FT /note="V4"
FT REGION 494..501
FT /note="V5"
FT REGION 544..564
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT REGION 607..623
FT /note="Immunosuppression"
FT /evidence="ECO:0000250"
FT REGION 689..710
FT /note="MPER; binding to GalCer"
FT /evidence="ECO:0000250"
FT REGION 751..779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 668..692
FT /evidence="ECO:0000255"
FT MOTIF 739..742
FT /note="YXXL motif; contains endocytosis signal"
FT /evidence="ECO:0000250"
FT SITE 543..544
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000255"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
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 379
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 652
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 668
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 102..224
FT /evidence="ECO:0000250"
FT DISULFID 109..215
FT /evidence="ECO:0000250"
FT DISULFID 114..174
FT /evidence="ECO:0000250"
FT DISULFID 237..267
FT /evidence="ECO:0000250"
FT DISULFID 247..259
FT /evidence="ECO:0000250"
FT DISULFID 317..350
FT /evidence="ECO:0000250"
FT DISULFID 402..478
FT /evidence="ECO:0000250"
FT DISULFID 409..451
FT /evidence="ECO:0000250"
SQ SEQUENCE 877 AA; 99521 MW; 957451704D0B7653 CRC64;
MKLTLLIGIL LIGIGVVLNT RQQWVTVFYG VPVWKNSSVQ AFCMTPTTRL WATTNSIPDD
HDYTEVPLNI TEPFEAWADR NPLVAQAGSN IHLLFEQTLK PCVKLSPLCI KMSCVELNSS
EPTTTPKSTT ASTTNITAST TTLPCVQNKT STVLESCNET IIEKELNEEP ASNCTFAMAG
YVRDQKKKYS VVWNDAEIMC KKGNNSNREC YMIHCNDSVI KEACDKTYWD ELRLRYCAPA
GFALLKCNDY DYAGFKTNCS NVSVVHCTNL INTTVTTGLL LNGSYSENRT QIWQKHRVSN
DSVLVLFNKH YNLTVTCKRP GNKTVLPVTI MAGLVFHSQR YNTRLRQAWC HFQGNWRGAW
KEVKNEIVKL PKDRYQGTND TEEIYLQRLF GDPEAANLWF NCQGEFFYCK MDWFLNYLNN
RTVDPDHNPC NGTKGKGKAP GPCAQRTYVA CHIRSVINDW YTLSRKTYAP PREGHLQCTS
TVTGMSVELN YNSKNRTNVT LSPQIETIWA AELGRYKLVE ITPIGFAPTE VRRYTGGHDR
TKRVPFVLGF LGFLGAAGTA MGAAATALTV QSQHLLAGIL QQQKNLLAAV EAQQQMLKLT
IWGVKNLNAR VTALEKYLED QARLNAWGCA WKQVCHTTVP WQWNNRTPDW NNMTWLEWER
QISYLEGNIT TQLEEARAQE EKNLDAYQKL SSWSDFWSWF DFSKWLNILK IGFLDVLGII
GLRLLYTVYS CIARVRQGYS PLSPQIHIHP WKGQPDNAEG PGEGGDKRKN SSEPWQKESG
TAEWKSNWCK RLTNWCSISS IWLYNSCLTL LVHLRSAFQY IQYGLGELKA AAQEAVVALA
RLAQNAGYQI WLACRSAYRA IINSPRRVRQ GLEGILN
