ENV_SIVMK
ID ENV_SIVMK Reviewed; 881 AA.
AC P05884;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 25-MAY-2022, entry version 132.
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 K6W) (SIV-mac) (Simian
OS immunodeficiency virus rhesus monkey).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11735;
OH NCBI_TaxID=9527; Cercopithecidae (Old World monkeys).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3497350; DOI=10.1038/328539a0;
RA Franchini G., Gallo R.C., Guo H.-G., Gurgo C., Callatti E., Fargnoli K.,
RA Hall L., Wong-Staal F., Reitz M.S. Jr.;
RT "Sequence of simian immunodeficiency virus and its relationship to the
RT human immunodeficiency viruses.";
RL Nature 328:539-543(1987).
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}.
CC -!- MISCELLANEOUS: This is a macaque isolate.
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DR EMBL; M19499; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR PDB; 2BF1; X-ray; 4.00 A; A=66-505.
DR PDBsum; 2BF1; -.
DR DrugBank; DB04473; alpha-L-fucose.
DR DrugBank; DB03740; N-acetyl-alpha-D-glucosamine.
DR EvolutionaryTrace; P05884; -.
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; Signal; Transmembrane;
KW Transmembrane helix; 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..881
FT /note="Envelope glycoprotein gp160"
FT /id="PRO_0000239513"
FT CHAIN 20..527
FT /note="Surface protein gp120"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038468"
FT CHAIN 528..881
FT /note="Transmembrane protein gp41"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038469"
FT TOPO_DOM 20..696
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 697..717
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 718..881
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 113..169
FT /note="V1"
FT REGION 170..213
FT /note="V2"
FT REGION 313..345
FT /note="V3"
FT REGION 404..434
FT /note="V4"
FT REGION 477..484
FT /note="V5"
FT REGION 528..548
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT REGION 591..607
FT /note="Immunosuppression"
FT /evidence="ECO:0000250"
FT REGION 673..694
FT /note="MPER; binding to GalCer"
FT /evidence="ECO:0000250"
FT REGION 732..761
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 636..668
FT /evidence="ECO:0000255"
FT MOTIF 723..726
FT /note="YXXV motif; contains endocytosis signal"
FT /evidence="ECO:0000250"
FT MOTIF 880..881
FT /note="Di-leucine internalization motif"
FT /evidence="ECO:0000250"
FT SITE 527..528
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000255"
FT SITE 736
FT /note="In-frame UAG termination codon"
FT LIPID 789
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 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 186
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
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 214
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 286
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 308
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 373
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 462
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 627
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 636
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 DISULFID 44..57
FT /evidence="ECO:0000250"
FT DISULFID 101..222
FT /evidence="ECO:0000250"
FT DISULFID 108..213
FT /evidence="ECO:0000250"
FT DISULFID 113..170
FT /evidence="ECO:0000250"
FT DISULFID 235..265
FT /evidence="ECO:0000250"
FT DISULFID 245..257
FT /evidence="ECO:0000250"
FT DISULFID 313..346
FT /evidence="ECO:0000250"
FT DISULFID 397..461
FT /evidence="ECO:0000250"
FT DISULFID 404..434
FT /evidence="ECO:0000250"
SQ SEQUENCE 881 AA; 101186 MW; 9052B543777DD979 CRC64;
MGCLGNQLLI AILLLSVYGI YCTQYVTVFY GVPAWRNATI PLFCATKNRD TWGTTQCLPD
NGDYSELALN VTESFDAWEN TVTEQAIEDV WQLFETSIKP CVKLSPLCIT MRCNKSETDR
WGLTKSSTTI TTAAPTSAPV SEKIDMVNET SSCIAQNNCT GLEQEQMISC KFTMTGLKRD
KTKEYNETWY STDLVCEQGN STDNESRCYM NHCNTSVIQE SCDKHYWDTI RFRYCAPPGY
ALLRCNDTNY SGFMPKCSKV VVSSCTRMME TQTSTWFGFN GTRAENRTYI YWHGRDNRTI
ISLNKYYNLT MKCRRPGNKT VLPVTIMSGL VFHSQPLTDR PKQAWCWFGG KWKDAIKEVK
QTIVKHPRYT GTNNTDKINL TAPGGGDPEV TFMWTNCRGE FLYCKMNWFL NWVEDRDVTT
QRPKERHRRN YVPCHIRQII NTWHKVGKNV YLPPREGDLT CNSTVTSLIA NIDWTDGNQT
SITMSAEVAE LYRLELGDYK LVEITPIGLA PTDVKRYTTG GTSRNKRGVF VLGFLGFLAT
AGSAMGAASF RLTAQSRTLL AGIVQQQQQL LGVVKRQQEL LRLTVWGTKN LQTRVTAIEK
YLEDQAQLNA WGCAFRQVCH TTVPWPNASL TPDWNNDTWQ EWERKVDFLE ENITALLEEA
QIQQEKNMYE LQKLNSWDVF GNWFDLASWI KYIQYGIYVV VGVILLRIVI YIVQMLAKLR
QGYRPVFSSP PSYFQXTHTQ QDPALPTREG KEGDGGEGGG NSSWPWQIEY IHFLIRQLIR
LLTWLFSNCR TLLSRAYQIL QPILQRLSAT LRRIREVLRT ELTYLQYGWS YFHEAVQAGW
RSATETLAGA WGDLWETLRR GGRWILAIPR RIRQGLELTL L
