Entry sw:ENV_SIVMB

ID   ENV_SIVMB               Reviewed;         880 AA.
AC   Q1A261;
DT   05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   11-JUL-2006, sequence version 1.
DT   30-NOV-2016, entry version 64.
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 MB66) (SIV-cpz) (Chimpanzee
OS   immunodeficiency virus).
OC   Viruses; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae;
OC   Lentivirus; Primate lentivirus group.
OX   NCBI_TaxID=388911;
OH   NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=16728595; DOI=10.1126/science.1126531;
RA   Keele B.F., Van Heuverswyn F., Li Y., Bailes E., Takehisa J.,
RA   Santiago M.L., Bibollet-Ruche F., Chen Y., Wain L.V., Liegeois F.,
RA   Loul S., Ngole E.M., Bienvenue Y., Delaporte E., Brookfield J.F.,
RA   Sharp P.M., Shaw G.M., Peeters M., Hahn B.H.;
RT   "Chimpanzee reservoirs of pandemic and nonpandemic HIV-1.";
RL   Science 313:523-526(2006).
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 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   -!- 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. YXXL and di-leucine endocytosis motifs
CC       interact directly or indirectly with the clathrin adapter
CC       complexes, opperate independently, and their activities are not
CC       additive (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}.
DR   EMBL; DQ373063; ABD19481.1; -; Genomic_RNA.
DR   ProteinModelPortal; Q1A261; -.
DR   Proteomes; UP000009152; 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: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; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_GP160.
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;
KW   Complete proteome; Disulfide bond;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane;
KW   Host-virus interaction; Membrane; Reference proteome; Signal;
KW   Transmembrane; 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     33       {ECO:0000255}.
FT   CHAIN        34    880       Envelope glycoprotein gp160.
FT                                /FTId=PRO_0000249352.
FT   CHAIN        34    527       Surface protein gp120. {ECO:0000250}.
FT                                /FTId=PRO_0000249351.
FT   CHAIN       528    880       Transmembrane protein gp41.
FT                                {ECO:0000250}.
FT                                /FTId=PRO_0000249353.
FT   TOPO_DOM     34    700       Extracellular. {ECO:0000255}.
FT   TRANSMEM    701    721       Helical. {ECO:0000255}.
FT   TOPO_DOM    722    880       Cytoplasmic. {ECO:0000255}.
FT   REGION      134    173       V1. {ECO:0000250}.
FT   REGION      174    220       V2. {ECO:0000250}.
FT   REGION      319    352       V3. {ECO:0000250}.
FT   REGION      410    434       V4. {ECO:0000250}.
FT   REGION      480    487       V5. {ECO:0000250}.
FT   REGION      528    548       Fusion peptide. {ECO:0000255}.
FT   REGION      593    609       Immunosuppression. {ECO:0000250}.
FT   REGION      679    700       MPER; binding to GalCer. {ECO:0000250}.
FT   COILED      660    684       {ECO:0000255}.
FT   MOTIF       729    732       YXXL motif; contains endocytosis signal.
FT                                {ECO:0000250}.
FT   MOTIF       879    880       Di-leucine internalization motif.
FT                                {ECO:0000250}.
FT   SITE        527    528       Cleavage; by host furin. {ECO:0000250}.
FT   CARBOHYD     91     91       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    133    133       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    145    145       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    148    148       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    157    157       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    163    163       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    173    173       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    177    177       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    221    221       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    256    256       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    265    265       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    286    286       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    299    299       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    312    312       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    318    318       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    324    324       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    356    356       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    372    372       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    381    381       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    411    411       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    417    417       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    423    423       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    429    429       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    464    464       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    479    479       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    628    628       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    633    633       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    642    642       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   CARBOHYD    654    654       N-linked (GlcNAc...); by host.
FT                                {ECO:0000255}.
FT   DISULFID     57     77       {ECO:0000250}.
FT   DISULFID    122    229       {ECO:0000250}.
FT   DISULFID    129    220       {ECO:0000250}.
FT   DISULFID    134    174       {ECO:0000250}.
FT   DISULFID    242    271       {ECO:0000250}.
FT   DISULFID    252    263       {ECO:0000250}.
FT   DISULFID    319    353       {ECO:0000250}.
FT   DISULFID    403    461       {ECO:0000250}.
FT   DISULFID    410    434       {ECO:0000250}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT        37    527       ipfam:GP120 [T]
FT   MYHIT       547    737       ipfam:GP41 [T]
SQ   SEQUENCE   880 AA;  99656 MW;  BCCC5BC63574F63D CRC64;
     MKAMETQRNC RTLSLKEIIL CTLVLGIIGI IKCEDNMWVT VYYGVPVWRE ADTTLFCASD
     AKAQNPEVHN VWASQACVST NPNPEEIELT NVTEYFNAWE NNMVEQMHED IVNLWDQSVK
     PCVKLIPLCV TLNCSLFKCI KENGNTTNCT VQISTGNDST ANNITVGTID MYNCSFNATT
     ELRDRKKQVY SLFYRQDLEP LEGNKPPEGD KNALYRLYNC NTTAMTQACS KVSLEPIPIH
     YCAPAGFALL KCNDKNFTGI GQCKNVSTVH CTHGIRPVVS TQFLLNGTLE EKVTVLDRNV
     SNDMDTIIVK LNETVRLNCT RTGNNTIKGI PIGPSQIFYG IETVIGDTRQ AFCQLNKTVW
     TNTFKKVRHA LNETYKGYLG NETITFGPST GGDLEVTNLH LICGGEFFYC NTSILFNTSI
     IFNETKDDNI TIPCRIRQIV RLWQRVGRGI FLPPIRGTIN CISNITGILF AQQKTDRMNK
     SAMFTPVGGE MRNNWRSELY KYKVVRIEPL GVAPTKAKRR TVHREKRAAV GLGALFLGFL
     GAAGSTMGAA SLTLTVQARQ LLSGIVQQQS NLLRAIEAQQ HLLQLSVWGI KQLQARVLAV
     ERYLKDQQLL GLWGCSGKLI CTTSVPWNTT WTNKSYDDIW YNMTWMQWDK EVSNYTDVIY
     NLLEKAQTQQ ENNEKELLEL DKWASLWNWF DITSWLWYIK IFIIIVGGLI GLRIVFALLS
     IVNRVRQGYS PLSFQTLIPA RRDRDRPEEI EEGGGEPDNV RSIRLVSGFL ALAWNDLRDL
     CLFLYHRLRD LLLIVLRTLE LVGQTLLKGL RRGREALIHL RGILQYWGQE LKTSAISLLD
     TTAIAVAEGT DRIIEIAQRF GRGILNIPRR IRQGLERALL
//