ENV_SIVTN
ID ENV_SIVTN Reviewed; 871 AA.
AC Q8AIH5;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 97.
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;
OS Simian immunodeficiency virus (isolate TAN1) (SIV-cpz) (Chimpanzee
OS immunodeficiency virus).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=388910;
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=12525658; DOI=10.1128/jvi.77.3.2233-2242.2003;
RA Santiago M.L., Bibollet-Ruche F., Bailes E., Kamenya S., Muller M.N.,
RA Lukasik M., Pusey A.E., Collins D.A., Wrangham R.W., Goodall J., Shaw G.M.,
RA Sharp P.M., Hahn B.H.;
RT "Amplification of a complete simian immunodeficiency virus genome from
RT fecal RNA of a wild chimpanzee.";
RL J. Virol. 77:2233-2242(2003).
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 -!- 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 -!- 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}.
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DR EMBL; AF447763; AAO13966.1; -; Genomic_RNA.
DR SMR; Q8AIH5; -.
DR Proteomes; UP000007222; 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; 2.
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..21
FT /evidence="ECO:0000255"
FT CHAIN 22..871
FT /note="Envelope glycoprotein gp160"
FT /id="PRO_0000249354"
FT CHAIN 31..502
FT /note="Surface protein gp120"
FT /evidence="ECO:0000250"
FT /id="PRO_0000249355"
FT CHAIN 503..871
FT /note="Transmembrane protein gp41"
FT /evidence="ECO:0000250"
FT /id="PRO_0000249356"
FT TOPO_DOM 22..684
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 685..705
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 706..871
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 120..153
FT /note="V1"
FT /evidence="ECO:0000250"
FT REGION 154..193
FT /note="V2"
FT /evidence="ECO:0000250"
FT REGION 292..325
FT /note="V3"
FT /evidence="ECO:0000250"
FT REGION 383..408
FT /note="V4"
FT /evidence="ECO:0000250"
FT REGION 451..458
FT /note="V5"
FT /evidence="ECO:0000250"
FT REGION 502..522
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT REGION 567..583
FT /note="Immunosuppression"
FT /evidence="ECO:0000250"
FT REGION 663..684
FT /note="MPER; binding to GalCer"
FT /evidence="ECO:0000250"
FT COILED 645..668
FT /evidence="ECO:0000255"
FT MOTIF 713..716
FT /note="YXXL motif; contains endocytosis signal"
FT /evidence="ECO:0000250"
FT SITE 502..503
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 142
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 157
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 285
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 398
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 438
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 613
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 626
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 638
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 43..63
FT /evidence="ECO:0000250"
FT DISULFID 108..202
FT /evidence="ECO:0000250"
FT DISULFID 115..193
FT /evidence="ECO:0000250"
FT DISULFID 120..154
FT /evidence="ECO:0000250"
FT DISULFID 215..244
FT /evidence="ECO:0000250"
FT DISULFID 225..236
FT /evidence="ECO:0000250"
FT DISULFID 292..326
FT /evidence="ECO:0000250"
FT DISULFID 376..435
FT /evidence="ECO:0000250"
FT DISULFID 383..408
FT /evidence="ECO:0000250"
SQ SEQUENCE 871 AA; 99210 MW; 265274FD602D459A CRC64;
MKNLIGITLI LIITILGIGF STYYTTVFYG VPVWKEAQPT LFCASDADIT SRDKHNIWAT
HNCVPLDPNP YEVTLANVSI RFNMEENYMV QEMKEDILSL FQQSFKPCVK LTPFCIKMTC
TMTNTTNKTL NSATTTLTPT VNLSSIPNYE VYNCSFNQTT EFRDKKKQIY SLFYREDIVK
EDGNNNSYYL HNCNTSVITQ ECDKSTFEPI PIRYCAPAGF ALLKCRDQNF TGKGQCSNVS
VVHCTHGIYP MIATALHLNG SLEEEETKAY FVNTSVNTPL LVKFNVSINL TCERTGNNTR
GQVQIGPGMT FYNIENVVGD TRKAYCSVNA TTWYRNLDWA MAAINTTMRA RNETVQQTFQ
WQRDGDPEVT SFWFNCQGEF FYCNLTNWTN TWTANRTNNT HGTLVAPCRL RQIVNHWGIV
SKGVYLPPRR GTVKCHSNIT GLIMTAEKDN NNSYTPQFSA VVEDYWKVEL ARYKVVEIQP
LSVAPRPGKR PEIKANHTRS RRDVGIGLLF LGFLSAAGST MGAASIALTA QARGLLSGIV
QQQQNLLQAI EAQQHLLQLS VWGIKQLQAR MLAVEKYIRD QQLLSLWGCA NKLVCHSSVP
WNLTWAEDST KCNHSDAKYY DCIWNNLTWQ EWDRLVENST GTIYSLLEKA QTQQEKNKQE
LLELDKWSSL WDWFDITQWL WYIKIAIIIV AGLVGLRILM FIVNVVKQVR QGYTPLFSQI
PTQAEQDPEQ PGGIAGGGGG RDNIRWTPSP AGFFSIVWED LRNLLIWIYQ TFQNFIWILW
ISLQALKQGI ISLAHSLVIV HRTIIVGVRQ IIEWSSNTYA SLRVLLIQAI DRLANFTGWW
TDLIIEGVVY IARGIRNIPR RIRQGLELAL N
