ENV_SIVGB
ID ENV_SIVGB Reviewed; 821 AA.
AC P22380;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 25-MAY-2022, entry version 114.
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;
GN Name=env;
OS Simian immunodeficiency virus (isolate GB1) (SIV-mnd) (Simian
OS immunodeficiency virus mandrill).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11732;
OH NCBI_TaxID=9527; Cercopithecidae (Old World monkeys).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2797181; DOI=10.1038/341539a0;
RA Tsujimoto H., Hasegawa A., Maki N., Fukasawa M., Miura T., Speidel S.,
RA Cooper R.W., Moriyama E.N., Gojobori T., Hayami M.;
RT "Sequence of a novel simian immunodeficiency virus from a wild-caught
RT African mandrill.";
RL Nature 341:539-541(1989).
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 -!- 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 mandrill isolate.
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DR EMBL; M27470; AAB49574.1; -; Genomic_RNA.
DR SMR; P22380; -.
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 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; 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 CHAIN 1..821
FT /note="Envelope glycoprotein gp160"
FT /id="PRO_0000085304"
FT CHAIN 1..569
FT /note="Surface protein gp120"
FT /evidence="ECO:0000250"
FT /id="PRO_0000239509"
FT CHAIN 570..821
FT /note="Transmembrane protein gp41"
FT /evidence="ECO:0000250"
FT /id="PRO_0000239510"
FT TOPO_DOM 1..737
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 738..758
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 759..821
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 139..186
FT /note="V1"
FT REGION 187..223
FT /note="V2"
FT REGION 328..361
FT /note="V3"
FT REGION 446..469
FT /note="V4"
FT REGION 515..526
FT /note="V5"
FT REGION 570..590
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT REGION 715..736
FT /note="MPER; binding to GalCer"
FT /evidence="ECO:0000250"
FT REGION 780..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 607..627
FT /evidence="ECO:0000255"
FT MOTIF 765..768
FT /note="YXXV motif; contains endocytosis signal"
FT /evidence="ECO:0000250"
FT SITE 569..570
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000255"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 394
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 447
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 516
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 669
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 675
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 694
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 67..80
FT /evidence="ECO:0000250"
FT DISULFID 127..232
FT /evidence="ECO:0000250"
FT DISULFID 134..223
FT /evidence="ECO:0000250"
FT DISULFID 139..187
FT /evidence="ECO:0000250"
FT DISULFID 244..272
FT /evidence="ECO:0000250"
FT DISULFID 439..499
FT /evidence="ECO:0000250"
FT DISULFID 446..469
FT /evidence="ECO:0000250"
SQ SEQUENCE 821 AA; 94410 MW; E353367C25CCD095 CRC64;
MSTGNVYQEL IRRYLVVVKK LYEGKYEVSR SFSYTMFSLL VGIIGKQYVT VFYGVPVWKE
AKTHLICATD NSSLWVTTNC IPSLPDYDEV EIPDIKENFT GLIRENQIVY QAWHAMGSML
DTILKPCVKI NPYCVKMQCQ ETENVSATTA KPITTPTTTS TVASSTEIYL DVDKNNTEEK
VERNHVCRYN ITGLCRDSKE EIVTNFRGDD VKCENNTCYM NHCNESVNTE DCQKGLLIRC
ILGCVPPGYV MLRYNEKLNN NKLCSNISAV QCTQHLVATV SSFFGFNGTM HKEGELIPID
DKYRGPEEFH QRKFVYKVPG KYGLKIECHR KGNRSVVSTP SATGLLFYHG LEPGKNLKKG
MCTFKGRWGL ALWSLAKELN KLNDSIKVNQ TCKNFTSTGE ENKQNTDKQK EFAKCIKTLK
IDNYTTSGDR AAEMMMMTCQ GEMFFCNVTR IMRAWNDPNE KKWYPYASCQ IRQIVDDWMQ
VGRKIYLPPT SGFNNHIRCT HRVTEMYFEM QKIDSNETKM QIKFLPPSET SNQFVAYGAH
YKLVKIMPIG IAPTDVKRHT LPEHHKEKRG AVILGILGLL SLAGSAMGSV SVALTVQSQS
LVTGIVEQQK QLLKLIEQQS ELLKLTIWGV KNLQTRLTSL ENYIKDQALL SQWGCSWAQV
CHTSVEWTNT SITPNWTSET WKEWETRTDY LQQNITEMLK QAYDREQRNT YELQKLGDLT
SWASWFDFTW WVQYLKWGVF LVLGIIGLRI LLALWNTISR FRQGYRPVFS QDCQQNLYRK
RPDNGEEESN SLELGEHNSE NLKEESLNRS LIEDLTSFAR E
