Legends: 1, N-linked (GlcNAc...); by host. {ECO:0000255}; 2, SIGNAL {ECO:0000255}; 3, CHAIN Transmembrane protein gp41. {ECO:0000250}; 4, TRANSMEM Helical. {ECO:0000255}; 5, TOPO_DOM Cytoplasmic. {ECO:0000255}; 6, REGION V1; 7, REGION V2; 8, REGION V3; 9, REGION V4; 10, REGION V5; 11, REGION Fusion peptide. {ECO:0000255}; 12, REGION Immunosuppression. {ECO:0000250}; 13, REGION MPER; binding to GalCer. {ECO:0000250}; 14, COILED {ECO:0000255}; 15, MOTIF YXXL motif; contains endocytosis signal. {ECO:0000250}; 16, SITE Cleavage; by host furin. {ECO:0000255}.
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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 30-NOV-2016, entry version 100.
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; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae;
OC Lentivirus; Primate lentivirus group.
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
CC host lymphoid cell by binding to the primary receptor CD4. This
CC interaction induces a structural rearrangement creating a high
CC affinity binding site for a chemokine coreceptor like CCR5. This
CC peculiar 2 stage receptor-interaction strategy allows gp120 to
CC maintain the highly conserved coreceptor-binding site in a cryptic
CC conformation, protected from neutralizing antibodies. These
CC changes are transmitted to the transmembrane protein gp41 and are
CC thought to activate its fusogenic potential by unmasking its
CC fusion peptide (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Surface protein gp120 (SU) may target the virus to gut-
CC associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7
CC (alpha-4/beta-7 integrins), a complex that mediates T-cell
CC migration to the GALT. Interaction between gp120 and ITGA4/ITGB7
CC would allow the virus to enter GALT early in the infection,
CC infecting and killing most of GALT's resting CD4+ T-cells. This T-
CC cell depletion is believed to be the major insult to the host
CC immune system leading to AIDS (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The surface protein gp120 is a ligand for CD209/DC-SIGN
CC and CLEC4M/DC-SIGNR, which are respectively found on dendritic
CC cells (DCs), and on endothelial cells of liver sinusoids and lymph
CC node sinuses. These interactions allow capture of viral particles
CC at mucosal surfaces by these cells and subsequent transmission to
CC permissive cells. DCs are professional antigen presenting cells,
CC critical for host immunity by inducing specific immune responses
CC against a broad variety of pathogens. They act as sentinels in
CC various tissues where they take up antigen, process it, and
CC present it to T-cells following migration to lymphoid organs. SIV
CC subverts the migration properties of dendritic cells to gain
CC access to CD4+ T-cells in lymph nodes. Virus transmission to
CC 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),
CC thereby inducing a robust infection. In trans infection, bound
CC virions remain infectious over days and it is proposed that they
CC are not degraded, but protected in non-lysosomal acidic organelles
CC within the DCs close to the cell membrane thus contributing to the
CC viral infectious potential during DCs' migration from the
CC periphery to the lymphoid tissues. On arrival at lymphoid tissues,
CC intact virions recycle back to DCs' cell surface allowing virus
CC transmission to CD4+ T-cells. Virion capture also seems to lead to
CC MHC-II-restricted viral antigen presentation, and probably to the
CC activation of SIV-specific CD4+ cells (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: The transmembrane protein gp41 (TM) acts as a class I
CC viral fusion protein. Under the current model, the protein has at
CC least 3 conformational states: pre-fusion native state, pre-
CC hairpin intermediate state, and post-fusion hairpin state. During
CC fusion of viral and target intracellular membranes, the coiled
CC coil regions (heptad repeats) assume a trimer-of-hairpins
CC structure, positioning the fusion peptide in close proximity to
CC the C-terminal region of the ectodomain. The formation of this
CC structure appears to drive apposition and subsequent fusion of
CC viral and target cell membranes. Complete fusion occurs in host
CC cell endosomes. The virus undergoes clathrin-dependent
CC internalization long before endosomal fusion, thus minimizing the
CC surface exposure of conserved viral epitopes during fusion and
CC reducing the efficacy of inhibitors targeting these epitopes.
CC Membranes fusion leads to delivery of the nucleocapsid into the
CC cytoplasm (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The envelope glyprotein gp160 precursor down-modulates
CC cell surface CD4 antigen by interacting with it in the endoplasmic
CC reticulum and blocking its transport to the cell surface.
CC {ECO:0000250}.
CC -!- FUNCTION: The gp120-gp41 heterodimer allows rapid transcytosis of
CC the virus through CD4 negative cells such as simple epithelial
CC monolayers of the intestinal, rectal and endocervical epithelial
CC barriers. Both gp120 and gp41 specifically recognize
CC glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-
CC galactosyl-ceramide (GalS) present in the lipid rafts structures
CC of epithelial cells. Binding to these alternative receptors allows
CC the rapid transcytosis of the virus through the epithelial cells.
CC This transcytotic vesicle-mediated transport of virions from the
CC apical side to the basolateral side of the epithelial cells does
CC not involve infection of the cells themselves (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: The mature envelope protein (Env) consists of a
CC homotrimer of non-covalently associated gp120-gp41 heterodimers.
CC The resulting complex protrudes from the virus surface as a spike.
CC Surface protein gp120 interacts with host CD4 and CCR5 (By
CC similarity). Gp120 also interacts with the C-type lectins
CC CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-
CC SIGN(R)) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Transmembrane protein gp41: Virion membrane
CC {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
CC Host cell membrane {ECO:0000250}; Single-pass type I membrane
CC protein {ECO:0000250}. Host endosome membrane {ECO:0000305};
CC Single-pass type I membrane protein {ECO:0000305}. Note=It is
CC probably concentrated at the site of budding and incorporated into
CC the virions possibly by contacts between the cytoplasmic tail of
CC Env and the N-terminus of Gag. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Surface protein gp120: Virion membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Host
CC cell membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}. Host endosome membrane {ECO:0000305}; Peripheral
CC membrane protein {ECO:0000305}. Note=The surface protein is not
CC anchored to the viral envelope, but associates with the
CC extravirion surface through its binding to TM. It is probably
CC concentrated at the site of budding and incorporated into the
CC virions possibly by contacts between the cytoplasmic tail of Env
CC and the N-terminus of Gag (By similarity). {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
CC through 5 (V1 through V5) (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The YXXL motif is involved in determining the exact site
CC of viral release at the surface of infected mononuclear cells and
CC promotes endocytosis. {ECO:0000250}.
CC -!- DOMAIN: The 17 amino acids long immunosuppressive region is
CC present in many retroviral envelope proteins. Synthetic peptides
CC derived from this relatively conserved sequence inhibit immune
CC function in vitro and in vivo (By similarity). {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC Envelope glycoproteins are synthesized as a inactive precursor
CC that is heavily N-glycosylated and processed likely by host cell
CC furin in the Golgi to yield the mature SU and TM proteins. The
CC cleavage site between SU and TM requires the minimal sequence
CC [KR]-X-[KR]-R (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: This is an African green monkey isolate.
DR EMBL; M30931; AAA91919.1; -; Genomic_RNA.
DR PIR; C46356; C46356.
DR ProteinModelPortal; 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: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; -; 3.
DR InterPro; IPR000328; GP41-like.
DR InterPro; IPR000777; HIV1_GP160.
DR Pfam; PF00516; GP120; 1.
DR Pfam; PF00517; GP41; 1.
DR SUPFAM; SSF56502; SSF56502; 3.
PE 3: Inferred from homology;
KW Apoptosis; Cleavage on pair of basic residues; Coiled coil;
KW Disulfide bond; Fusion of virus membrane with host membrane;
KW Glycoprotein; Host cell membrane; Host endosome; Host membrane;
KW Host-virus interaction; Membrane; Signal; Transmembrane;
KW 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 19 {ECO:0000255}.
FT CHAIN 20 877 Envelope glycoprotein gp160.
FT /FTId=PRO_0000239506.
FT CHAIN 20 543 Surface protein gp120. {ECO:0000250}.
FT /FTId=PRO_0000038458.
FT CHAIN 544 877 Transmembrane protein gp41.
FT {ECO:0000250}.
FT /FTId=PRO_0000038459.
FT TOPO_DOM 20 707 Extracellular. {ECO:0000255}.
FT TRANSMEM 708 728 Helical. {ECO:0000255}.
FT TOPO_DOM 729 877 Cytoplasmic. {ECO:0000255}.
FT REGION 114 173 V1.
FT REGION 174 215 V2.
FT REGION 317 349 V3.
FT REGION 409 451 V4.
FT REGION 494 501 V5.
FT REGION 544 564 Fusion peptide. {ECO:0000255}.
FT REGION 607 623 Immunosuppression. {ECO:0000250}.
FT REGION 689 710 MPER; binding to GalCer. {ECO:0000250}.
FT COILED 668 692 {ECO:0000255}.
FT MOTIF 739 742 YXXL motif; contains endocytosis signal.
FT {ECO:0000250}.
FT SITE 543 544 Cleavage; by host furin. {ECO:0000255}.
FT CARBOHYD 36 36 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 69 69 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 118 118 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 135 135 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 148 148 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 158 158 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 173 173 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 204 204 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 216 216 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 258 258 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 261 261 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 272 272 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 282 282 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 288 288 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 300 300 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 312 312 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 322 322 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 379 379 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 420 420 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 431 431 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 495 495 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 498 498 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 652 652 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 668 668 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT DISULFID 102 224 {ECO:0000250}.
FT DISULFID 109 215 {ECO:0000250}.
FT DISULFID 114 174 {ECO:0000250}.
FT DISULFID 237 267 {ECO:0000250}.
FT DISULFID 247 259 {ECO:0000250}.
FT DISULFID 317 350 {ECO:0000250}.
FT DISULFID 402 478 {ECO:0000250}.
FT DISULFID 409 451 {ECO:0000250}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 561 731 ipfam:GP41 [T]
FT MYHIT 23 543 ipfam:GP120 [T]
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
//
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