ENV_HV2NZ
ID ENV_HV2NZ Reviewed; 856 AA.
AC P05883;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 123.
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 NIH-Z) (HIV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11719;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3261862; DOI=10.1073/pnas.85.16.5941;
RA Zagury J.F., Franchini G., Reitz M.S. Jr., Collalti E., Starcich B.R.,
RA Hall L., Fargnoli K.A., Jagodzinski L.L., Guo H.-G., Laure F., Arya S.K.,
RA Josephs S.F., Zagury D., Wong-Staal F., Gallo R.C.;
RT "Genetic variability between isolates of human immunodeficiency virus (HIV)
RT type 2 is comparable to the variability among HIV type 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:5941-5945(1988).
RN [2]
RP INTERACTION OF SURFACE PROTEIN GP120 WITH HOST CD209/DC-SIGN AND
RP CLEC4M/DC-SIGNR.
RC STRAIN=Isolate vcp;
RX PubMed=12502850; DOI=10.1128/jvi.77.2.1337-1346.2003;
RA Lin G., Simmons G., Poehlmann S., Baribaud F., Ni H., Leslie G.J.,
RA Haggarty B.S., Bates P., Weissman D., Hoxie J.A., Doms R.W.;
RT "Differential N-linked glycosylation of human immunodeficiency virus and
RT Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and
RT DC-SIGNR.";
RL J. Virol. 77:1337-1346(2003).
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 -!- CAUTION: The cleavage site does not match the consensus used by furin.
CC {ECO:0000305}.
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DR EMBL; J03654; AAB00761.1; -; Genomic_DNA.
DR SMR; P05883; -.
DR PRIDE; P05883; -.
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 1: Evidence at protein level;
KW AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Coiled coil; 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..22
FT /evidence="ECO:0000255"
FT CHAIN 23..856
FT /note="Envelope glycoprotein gp160"
FT /id="PRO_0000239502"
FT CHAIN 23..502
FT /note="Surface protein gp120"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038447"
FT CHAIN 503..856
FT /note="Transmembrane protein gp41"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038448"
FT TOPO_DOM 23..670
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 671..691
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 692..856
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 113..153
FT /note="V1"
FT REGION 154..195
FT /note="V2"
FT REGION 295..328
FT /note="V3"
FT REGION 389..412
FT /note="V4"
FT REGION 455..460
FT /note="V5"
FT REGION 503..523
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT REGION 566..582
FT /note="Immunosuppression"
FT /evidence="ECO:0000250"
FT REGION 648..669
FT /note="MPER; binding to GalCer"
FT /evidence="ECO:0000250"
FT COILED 615..636
FT /evidence="ECO:0000255"
FT MOTIF 698..701
FT /note="YXXV motif; contains endocytosis signal"
FT /evidence="ECO:0000250"
FT MOTIF 855..856
FT /note="Di-leucine internalization motif"
FT /evidence="ECO:0000250"
FT SITE ?502..?503
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000255"
FT LIPID 764
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 79
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 133
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 182
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
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 390
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 457
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 611
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 DISULFID 44..57
FT /evidence="ECO:0000250"
FT DISULFID 101..204
FT /evidence="ECO:0000250"
FT DISULFID 108..195
FT /evidence="ECO:0000250"
FT DISULFID 113..154
FT /evidence="ECO:0000250"
FT DISULFID 217..247
FT /evidence="ECO:0000250"
FT DISULFID 227..239
FT /evidence="ECO:0000250"
FT DISULFID 295..329
FT /evidence="ECO:0000250"
FT DISULFID 382..439
FT /evidence="ECO:0000250"
FT DISULFID 389..412
FT /evidence="ECO:0000250"
SQ SEQUENCE 856 AA; 98666 MW; A938B0A7E2B881D6 CRC64;
MKGSKNQLLI AIVLASAYLI HCKQFVTVFY GIPAWRNASI PLFCATKNRD TWGTIQCLPD
NDDYQEITLN VTEAFDAWNN TVTEQAVEDV WNLFETSIKP CVKLTPLCVA MNCTRNMTTW
TGRTDTQNIT IINDTSHARA DNCTGLKEEE MIDCQFSMTG LERDKRKQYT EAWYSKDVVC
DNNTSSQSKC YMNHCNTSVI TESCDKHYWD AMRFRYCAPP GFALLRCNDT NYSGFAPNCS
KVVAATCTRM METQTSTWFG FNGTRAENRT YIYWHGKDNR TIISLNNFYN LTMHCKRPGN
KTVLPITFMS GFKFHSQPVI NKKPRQAWCW FEGQWKEAMQ EVKETLAKHP RYKGNRSRTE
NIKFKAPGRG SDPEVTYMWT NCRGESLYCN MTWFLNWVEN RTGQKQRNYA PCRIRQIINT
WHRVGKNLYL PPREGELTCN STVTSIIANI DAGDQTNITF SAEAAELYRL ELGDYKLVEI
TPIGFAPTSV KRYSSAHQRH TRGVFVLGFL GFLATAGSAM GAASLTLSAQ SRTLLAGIVQ
QQQQLLDVVK RQQEMLRLTV WGTKNLQARV TAIEKYLKDQ AQLNSWGCAF RQVCHTSVPW
VNDTLTPDWN NMTWQEWEQK VRYLEANISQ SLEQAQIQQE KNMYELQKLN SWDVFTNWLD
FTSWVRYIQY GVYVVVGIVA LRIVIYIVQM LSRLRKGYRP VFSSPPGYIQ QIHIHKDQEQ
PAREETEEDV GSNGGDRSWP WPIAYIHFLI RLLIRLLTGL YNICRDLLSR ISPILQPIFQ
SLQRALTAIR DWLRLKAAYL QYGCEWIQEA FQALARTTRE TLAGAGRDLW RALQRIGRGI
LAVPRRIRQG AELALL
