ENV_HV2D1
ID ENV_HV2D1 Reviewed; 851 AA.
AC P17755;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 2.
DT 23-FEB-2022, entry version 125.
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 41;
DE Short=gp41;
DE Flags: Precursor;
GN Name=env;
OS Human immunodeficiency virus type 2 subtype A (isolate D194) (HIV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11713;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2235509; DOI=10.1093/nar/18.20.6142;
RA Kuehnel H., Kreutz R., Ruebsamen-Waigmann H.;
RT "Nucleotide sequence of HIV-2D194, an isolate from a Gambian case of
RT 'neuro-AIDS', which showed excellent growth in macrophages.";
RL Nucleic Acids Res. 18:6142-6142(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-266.
RX PubMed=2467304; DOI=10.1073/pnas.86.7.2383;
RA Kuehnel H., von Briesen H., Dietrich U., Adamski M., Mix D., Biesert L.,
RA Kreutz R., Immelmann A., Henco K., Meichsner C., Andreesen R.,
RA Gelderblom H., Ruebsamen-Waigmann H.;
RT "Molecular cloning of two west African human immunodeficiency virus type 2
RT isolates that replicate well in macrophages: a Gambian isolate, from a
RT patient with neurologic acquired immunodeficiency syndrome, and a highly
RT divergent Ghanian isolate.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2383-2387(1989).
RN [3]
RP REVIEW.
RX PubMed=12029140; DOI=10.1099/0022-1317-83-6-1253;
RA Reeves J.D., Doms R.W.;
RT "Human immunodeficiency virus type 2.";
RL J. Gen. Virol. 83:1253-1265(2002).
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 CXCR4 and/or CCR5. This peculiar 2
CC stage receptor-interaction strategy allows gp120 to maintain the highly
CC conserved coreceptor-binding site in a cryptic conformation, protected
CC from neutralizing antibodies. Since CD4 also displays a binding site
CC for the disulfide-isomerase P4HB/PDI, a P4HB/PDI-CD4-CXCR4-gp120
CC complex may form. In that complex, P4HB/PDI could reach and reduce
CC gp120 disulfide bonds, causing major conformational changes in gp120.
CC TXN, another PDI family member could also be involved in disulfide
CC rearrangements in Env during fusion. These changes are transmitted to
CC the transmembrane protein gp41 and are thought to activate its
CC fusogenic potential by unmasking its fusion peptide (By similarity).
CC {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. HIV 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 HIV-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 and is dynamin-dependent, however
CC some lipid transfer might occur at the plasma membrane. The virus
CC undergoes clathrin-dependent internalization long before endosomal
CC fusion, thus minimizing the surface exposure of conserved viral
CC epitopes during fusion and reducing the efficacy of inhibitors
CC targeting these epitopes. Membranes fusion leads to delivery of the
CC nucleocapsid into the cytoplasm (By 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 seems to contribute to T-cell
CC depletion during HIV-1 infection. The envelope glycoproteins expressed
CC on the surface of infected cells induce apoptosis through an
CC interaction with uninfected cells expressing the receptor (CD4) and the
CC coreceptors CXCR4 or CCR5. This type of bystander killing may be
CC obtained by at least three distinct mechanisms. First, the interaction
CC between the 2 cells can induce cellular fusion followed by nuclear
CC fusion within the syncytium. Syncytia are condemned to die from
CC apoptosis. Second, the 2 interacting cells may not fuse entirely and
CC simply exchange plasma membrane lipids, after a sort of hemifusion
CC process, followed by rapid death. Third, it is possible that virus-
CC infected cells, on the point of undergoing apoptosis, fuse with CD4-
CC expressing cells, in which case apoptosis is rapidly transmitted from
CC one cell to the other and thus occurs in a sort of contagious fashion
CC (By similarity). {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. There seems to be as few as 10 spikes on the average virion.
CC Interacts with human CD4, CCR5 and CXCR4, to form a P4HB/PDI-CD4-CXCR4-
CC gp120 complex. Gp120 also interacts with the C-type lectins CD209/DC-
CC SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R)).
CC Gp120 and gp41 interact with GalCer (By similarity). {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. There seems to be as few as 10 spikes on the average virion.
CC {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). Coreceptor usage of gp120 is determined mainly by the
CC primary structure of the third variable region (V3) in the outer domain
CC of gp120. Binding to CCR5 involves a region adjacent in addition to V3
CC (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: Some HIV-2 isolates have been described that can infect
CC cells independently of CD4, using CXCR4 as primary receptor. These
CC isolates may have an exposed coreceptor binding site.
CC -!- MISCELLANEOUS: This isolate is from a Gambian case of 'neuro-AIDS'.
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DR EMBL; J04542; AAA76847.1; -; Genomic_DNA.
DR EMBL; X52223; CAA36471.1; -; Genomic_DNA.
DR PIR; S12159; S12159.
DR SMR; P17755; -.
DR PRIDE; P17755; -.
DR Proteomes; UP000007422; 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:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039587; P:suppression by virus of host tetherin activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; 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 AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host tetherin by virus; Lipoprotein; Membrane; Palmitate;
KW Signal; Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW Viral envelope protein; Viral immunoevasion;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..851
FT /note="Envelope glycoprotein gp160"
FT /id="PRO_0000239495"
FT CHAIN 25..501
FT /note="Surface protein gp120"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038433"
FT CHAIN 502..851
FT /note="Transmembrane protein gp41"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038434"
FT TOPO_DOM 25..669
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 670..690
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 691..851
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 113..153
FT /note="V1"
FT REGION 154..194
FT /note="V2"
FT REGION 294..327
FT /note="V3"
FT REGION 387..410
FT /note="V4"
FT REGION 453..459
FT /note="V5"
FT REGION 502..522
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT REGION 565..581
FT /note="Immunosuppression"
FT /evidence="ECO:0000250"
FT REGION 647..668
FT /note="MPER; binding to GalCer"
FT /evidence="ECO:0000250"
FT MOTIF 697..700
FT /note="YXXV motif; contains endocytosis signal"
FT /evidence="ECO:0000250"
FT MOTIF 850..851
FT /note="Di-leucine internalization motif"
FT /evidence="ECO:0000250"
FT SITE 501..502
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250"
FT LIPID 763
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 127
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
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 157
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
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 299
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 388
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 401
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 453
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 456
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 601
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 610
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 DISULFID 44..57
FT /evidence="ECO:0000250"
FT DISULFID 101..203
FT /evidence="ECO:0000250"
FT DISULFID 108..194
FT /evidence="ECO:0000250"
FT DISULFID 113..154
FT /evidence="ECO:0000250"
FT DISULFID 216..246
FT /evidence="ECO:0000250"
FT DISULFID 226..238
FT /evidence="ECO:0000250"
FT DISULFID 294..328
FT /evidence="ECO:0000250"
FT DISULFID 380..437
FT /evidence="ECO:0000250"
FT DISULFID 387..410
FT /evidence="ECO:0000250"
SQ SEQUENCE 851 AA; 97179 MW; 3B002FCD0B9FF118 CRC64;
MEPGRNQLLV AILLTSACLI YCKQYVTVFY GIPAWRNASI PLFCATKNRD TWGTIQCLPD
NDDYQEITLN VTEAFDAWDN TVTEQAIEDV WRLFETSIKP CVKLTPLCVA MNCNITSGTT
ATPSPPNITI IDENSTCIGD NNCTGLGKEE VVECEFNMTG LEQDKKRKYN DAWYSRDVVC
DKTNGTGTCY MRHCNTSVIK ESCDKHYWDA MKFRYCAPPG FALLRCNDTN YSGFEPKCSK
VVAASCTRMM ETQTSTWFGF NGTRAENRTY IYWHGKDNRT IISLNKYYNL TMHCKRPGNK
TVVPITLMSG RRFHSRPVYN KKPGQAWCWF QGNWIEAMRE VKQTLAKHPR YGGTNDTGKI
NFTKPGIGSD PEVTYMWTNC RGEFLYCNMT WFLNWVENKT NQTHGNYAPC HIRQIINTWH
KVGTNVYLPP REGELTCNST VTSIIANIDS DGNQTNITFS AEVAELYRLE LGDYKLIEVT
PIPFAPTKEK RYSSAPVRNK RGVFVLGFLG FLATAGSAMG GASLTLSAQS RTLLAGIVQQ
QQQLLDVVKR QQEMLRLTVW GTKNLQARVT AIEKYLKDQA QLNSWGCAFR QVCHTTVPWV
NDSLTPDWNN MTWQEWEKRV HYLEANISQS LEQAQIQQEK NMYELQKLNS WDVFGNWFDL
TSWIKYIQYG VYIVVGIIGL RIAIYIVQLL SRLRKGYRPV FSSPPGYLQQ IHIHTDRGQP
ANEETEEDAG DDSGFGLWPW PLNYIQFLIH LLTRLLTGLY NSCRGLLSKN SPTRRLISQS
LTAIRDWLRL KAAYLQYGCE WIQEAFRAFA RTARETIAGA WRGLCEAAQR IGRGILAVPR
RIRQGAEIAL L
