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P04578 (ENV_HV1H2) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Envelope glycoprotein gp160
Alternative name(s):
Env polyprotein

Cleaved into the following 2 chains:

  1. Surface protein gp120
    Short name=SU
    Alternative name(s):
    Glycoprotein 120
    Short name=gp120
  2. Transmembrane protein gp41
    Short name=TM
    Alternative name(s):
    Glycoprotein 41
    Short name=gp41
Gene names
Name:env
OrganismHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1) [Reference proteome]
Taxonomic identifier11706 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length856 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The surface protein gp120 (SU) attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. This peculiar 2 stage receptor-interaction strategy allows gp120 to maintain the highly conserved coreceptor-binding site in a cryptic conformation, protected from neutralizing antibodies. Since CD4 also displays a binding site for the disulfide-isomerase P4HB/PDI, a P4HB/PDI-CD4-CXCR4-gp120 complex may form. In that complex, P4HB/PDI could reach and reduce gp120 disulfide bonds, causing major conformational changes in gp120. TXN, another PDI family member could also be involved in disulfide rearrangements in Env during fusion. These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide. Ref.19

Surface protein gp120 (SU) may target the virus to gut-associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7 (alpha-4/beta-7 integrins), a complex that mediates T-cell migration to the GALT. Interaction between gp120 and ITGA4/ITGB7 would allow the virus to enter GALT early in the infection, infecting and killing most of GALT's resting CD4+ T-cells. This T-cell depletion is believed to be the major insult to the host immune system leading to AIDS By similarity. Ref.19

The surface protein gp120 is a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they take up antigen, process it, and present it to T-cells following migration to lymphoid organs. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. Virion capture also seems to lead to MHC-II-restricted viral antigen presentation, and probably to the activation of HIV-specific CD4+ cells. Ref.19

The transmembrane protein gp41 (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. Ref.19

The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface By similarity. Ref.19

The gp120-gp41 heterodimer seems to contribute to T-cell depletion during HIV-1 infection. The envelope glycoproteins expressed on the surface of infected cells induce apoptosis through an interaction with uninfected cells expressing the receptor (CD4) and the coreceptors CXCR4 or CCR5. This type of bystander killing may be obtained by at least three distinct mechanisms. First, the interaction between the 2 cells can induce cellular fusion followed by nuclear fusion within the syncytium. Syncytia are condemned to die from apoptosis. Second, the 2 interacting cells may not fuse entirely and simply exchange plasma membrane lipids, after a sort of hemifusion process, followed by rapid death. Third, it is possible that virus-infected cells, on the point of undergoing apoptosis, fuse with CD4-expressing cells, in which case apoptosis is rapidly transmitted from one cell to the other and thus occurs in a sort of contagious fashion. Ref.19

The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves. Ref.19

Subunit structure

The mature envelope protein (Env) consists of a homotrimer of non-covalently associated gp120-gp41 heterodimers. The resulting complex protrudes from the virus surface as a spike. There seems to be as few as 10 spikes on the average virion. Surface protein gp120 interacts with human CD4, CCR5 and CXCR4, to form a P4HB/PDI-CD4-CXCR4-gp120 complex. Gp120 also interacts with the C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts with human ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction results in rapid activation of integrin ITGAL/LFA-1, which facilitate efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-associated heparan sulfate; this interaction increases virus infectivity on permissive cells and may be involved in infection of CD4- cells. Ref.5 Ref.8 Ref.18

Subcellular location

Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Host cell membrane; Single-pass type I membrane protein. Host endosome membrane; Single-pass type I membrane protein Potential. Note: It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag.

Surface protein gp120: Virion membrane; Peripheral membrane protein. Host cell membrane; Peripheral membrane protein. Host endosome membrane; Single-pass type I membrane protein Potential. Note: The surface protein is not anchored to the viral envelope, but associates with the extravirion surface through its binding to TM. It is probably concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag.

Domain

The YXXL motif is involved in determining the exact site of viral release at the surface of infected mononuclear cells and promotes endocytosis. YXXL and di-leucine endocytosis motifs interact directly or indirectly with the clathrin adapter complexes, opperate independently, and their activities are not additive. Ref.6

The 17 amino acids long immunosuppressive region is present in many retroviral envelope proteins. Synthetic peptides derived from this relatively conserved sequence inhibit immune function in vitro and in vivo By similarity. Ref.6

The CD4-binding region is targeted by the antibody b12. Ref.6

The membrane proximal external region (MPER) present in gp41 is a tryptophan-rich region recognized by the antibodies 2F5, Z13, and 4E10. MPER seems to play a role in fusion. Ref.6

Some of the most genetically diverse regions of the viral genome are present in Env. They are called variable regions 1 through 5 (V1 through V5). Coreceptor usage of gp120 is determined mainly by the primary structure of the third variable region (V3) in the outer domain of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and macrophage tropism), is used to trigger the fusion potential of the Env complex, and hence which cells the virus can infect. Binding to CCR5 involves a region adjacent in addition to V3. Ref.6

Post-translational modification

Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as a inactive precursor that is heavily N-glycosylated and processed likely by host cell furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9 disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to CD4 receptor By similarity.

Palmitoylation of the transmembrane protein and of Env polyprotein (prior to its proteolytic cleavage) is essential for their association with host cell membrane lipid rafts. Palmitoylation is therefore required for envelope trafficking to classical lipid rafts, but not for viral replication By similarity. Ref.4

Miscellaneous

Inhibitors targeting HIV-1 viral envelope proteins are used as antiretroviral drugs. Attachment of virions to the cell surface via non-specific interactions and CD4 binding can be blocked by inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs, PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-induced conformational changes. Env interactions with the coreceptor molecules can be targeted by CCR5 antagonists including SCH-D, maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4 antagonist AMD 070. Fusion of viral and cellular membranes can be inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249). Resistance to inhibitors associated with mutations in Env are observed. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance.

HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).

Ontologies

Keywords
   Biological processApoptosis
Clathrin-mediated endocytosis of virus by host
Fusion of virus membrane with host endosomal membrane
Fusion of virus membrane with host membrane
Host-virus interaction
Viral attachment to host cell
Viral immunoevasion
Viral penetration into host cytoplasm
Virus endocytosis by host
Virus entry into host cell
   Cellular componentHost cell membrane
Host endosome
Host membrane
Membrane
Viral envelope protein
Virion
   DiseaseAIDS
   DomainCoiled coil
Signal
Transmembrane
Transmembrane helix
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

clathrin-mediated endocytosis of virus by host cell

Inferred from electronic annotation. Source: UniProtKB-KW

entry into host cell

Traceable author statement. Source: Reactome

evasion or tolerance by virus of host immune response

Inferred from electronic annotation. Source: UniProtKB-KW

fusion of virus membrane with host endosome membrane

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

viral life cycle

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

viral protein processing

Traceable author statement. Source: Reactome

virion assembly

Traceable author statement. Source: Reactome

virion attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

viral envelope

Inferred from electronic annotation. Source: UniProtKB-KW

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionstructural molecule activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KCNH3Q9ULD83EBI-6163496,EBI-8079227From a different organism.
tatP046084EBI-6163496,EBI-6164389

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 By similarity
Chain33 – 856824Envelope glycoprotein gp160
PRO_0000239240
Chain33 – 511479Surface protein gp120 By similarity
PRO_0000038427
Chain512 – 856345Transmembrane protein gp41 By similarity
PRO_0000038428

Regions

Topological domain33 – 684652Extracellular Potential
Transmembrane685 – 70521Helical; Potential
Topological domain706 – 856151Cytoplasmic Potential
Region131 – 15626V1
Region157 – 19640V2
Region296 – 33035V3
Region364 – 37411CD4-binding loop
Region385 – 41834V4
Region461 – 47111V5
Region512 – 53221Fusion peptide Potential
Region576 – 59217Immunosuppression
Region662 – 68322MPER; binding to GalCer
Coiled coil633 – 66735 Potential
Motif712 – 7154YXXL motif; contains endocytosis signal
Motif855 – 8562Di-leucine internalization motif

Sites

Site511 – 5122Cleavage; by host furin By similarity

Amino acid modifications

Lipidation7641S-palmitoyl cysteine; by host Ref.4
Lipidation8371S-palmitoyl cysteine; by host Ref.4
Glycosylation881N-linked (GlcNAc...); by host Potential
Glycosylation1361N-linked (GlcNAc...); by host Potential
Glycosylation1411N-linked (GlcNAc...); by host Potential
Glycosylation1561N-linked (GlcNAc...); by host Potential
Glycosylation1601N-linked (GlcNAc...); by host Potential
Glycosylation1861N-linked (GlcNAc...); by host Potential
Glycosylation1971N-linked (GlcNAc...); by host Potential
Glycosylation2301N-linked (GlcNAc...); by host Potential
Glycosylation2341N-linked (GlcNAc...); by host Potential
Glycosylation2411N-linked (GlcNAc...); by host Potential
Glycosylation2621N-linked (GlcNAc...); by host Potential
Glycosylation2761N-linked (GlcNAc...); by host Potential
Glycosylation2891N-linked (GlcNAc...); by host Potential
Glycosylation2951N-linked (GlcNAc...); by host Potential
Glycosylation3011N-linked (GlcNAc...); by host Potential
Glycosylation3321N-linked (GlcNAc...); by host Potential
Glycosylation3391N-linked (GlcNAc...); by host Potential
Glycosylation3561N-linked (GlcNAc...); by host Potential
Glycosylation3861N-linked (GlcNAc...); by host Potential
Glycosylation3921N-linked (GlcNAc...); by host Potential
Glycosylation3971N-linked (GlcNAc...); by host Potential
Glycosylation4061N-linked (GlcNAc...); by host Potential
Glycosylation4481N-linked (GlcNAc...); by host Potential
Glycosylation4631N-linked (GlcNAc...); by host Potential
Glycosylation6111N-linked (GlcNAc...); by host Potential
Glycosylation6161N-linked (GlcNAc...); by host Potential
Glycosylation6241N-linked (GlcNAc...); by host Potential
Glycosylation6371N-linked (GlcNAc...); by host Potential
Glycosylation6741N-linked (GlcNAc...); by host Potential
Disulfide bond54 ↔ 74 By similarity
Disulfide bond119 ↔ 205 By similarity
Disulfide bond126 ↔ 196 By similarity
Disulfide bond131 ↔ 157 By similarity
Disulfide bond218 ↔ 247 By similarity
Disulfide bond228 ↔ 239 By similarity
Disulfide bond296 ↔ 331 By similarity
Disulfide bond378 ↔ 445 By similarity
Disulfide bond385 ↔ 418 By similarity
Disulfide bond598 ↔ 604 By similarity

Experimental info

Mutagenesis7641C → S: Complete loss of palmitoylation, decreased association with host cell membrane lipid rafts, decreased incorporation onto virions and severe reduction of infectivity; when associated with S-837. Ref.4
Mutagenesis8371C → S: Complete loss of palmitoylation, decreased association with host cell membrane lipid rafts, decreased incorporation onto virions and severe reduction of infectivity; when associated with S-764. Ref.4

Secondary structure

.................................................................................. 856
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P04578 [UniParc].

Last modified July 15, 1999. Version 2.
Checksum: 6FAB16AF85107FE0

FASTA85697,213
        10         20         30         40         50         60 
MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT TLFCASDAKA 

        70         80         90        100        110        120 
YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV 

       130        140        150        160        170        180 
KLTPLCVSLK CTDLKNDTNT NSSSGRMIME KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD 

       190        200        210        220        230        240 
IIPIDNDTTS YKLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT 

       250        260        270        280        290        300 
NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLNT SVEINCTRPN 

       310        320        330        340        350        360 
NNTRKRIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR EQFGNNKTII 

       370        380        390        400        410        420 
FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW STEGSNNTEG SDTITLPCRI 

       430        440        450        460        470        480 
KQIINMWQKV GKAMYAPPIS GQIRCSSNIT GLLLTRDGGN SNNESEIFRP GGGDMRDNWR 

       490        500        510        520        530        540 
SELYKYKVVK IEPLGVAPTK AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ 

       550        560        570        580        590        600 
ARQLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG 

       610        620        630        640        650        660 
KLICTTAVPW NASWSNKSLE QIWNHTTWME WDREINNYTS LIHSLIEESQ NQQEKNEQEL 

       670        680        690        700        710        720 
LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA VLSIVNRVRQ GYSPLSFQTH 

       730        740        750        760        770        780 
LPTPRGPDRP EGIEEEGGER DRDRSIRLVN GSLALIWDDL RSLCLFSYHR LRDLLLIVTR 

       790        800        810        820        830        840 
IVELLGRRGW EALKYWWNLL QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGACRAI 

       850 
RHIPRRIRQG LERILL 

« Hide

References

[1]"Complete nucleotide sequences of functional clones of the AIDS virus."
Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F.
AIDS Res. Hum. Retroviruses 3:57-69(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F.
Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"The immunosuppressive peptide of HIV-1: functional domains and immune response in AIDS patients."
Denner J., Norley S., Kurth R.
AIDS 8:1063-1072(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: IMMUNOSUPPRESSIVE REGION.
[4]"The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated."
Yang C., Spies C.P., Compans R.W.
Proc. Natl. Acad. Sci. U.S.A. 92:9871-9875(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION, MUTAGENESIS OF CYS-764 AND CYS-837.
[5]"Human immunodeficiency virus type 1 infection of SK-N-MC cells: domains of gp120 involved in entry into a CD4-negative, galactosyl ceramide/3' sulfo-galactosyl ceramide-positive cell line."
Harouse J.M., Collman R.G., Gonzalez-Scarano F.
J. Virol. 69:7383-7390(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF SURFACE PROTEIN GP120 WITH GALACTOSYL CERAMIDE AND SULFO-GALACTOSYL CERAMIDE.
[6]"Polarized human immunodeficiency virus budding in lymphocytes involves a tyrosine-based signal and favors cell-to-cell viral transmission."
Deschambeault J., Lalonde J.P., Cervantes-Acosta G., Lodge R., Cohen E.A., Lemay G.
J. Virol. 73:5010-5017(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN YXXL MOTIF.
[7]"Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a pathogen receptor with broad specificity."
Geijtenbeek T.B., van Kooyk Y.
APMIS 111:698-714(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR."
Lin G., Simmons G., Poehlmann S., Baribaud F., Ni H., Leslie G.J., Haggarty B.S., Bates P., Weissman D., Hoxie J.A., Doms R.W.
J. Virol. 77:1337-1346(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF SURFACE PROTEIN GP120 WITH HOST CD209/DC-SIGN AND CLEC4M/DC-SIGNR.
[9]"Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1."
Yang X., Kurteva S., Ren X., Lee S., Sodroski J.
J. Virol. 79:12132-12147(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STOICHIOMETRY OF ENVELOPE GLYCOPROTEIN.
[10]"The HIV Env-mediated fusion reaction."
Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S., Puri A., Durell S., Blumenthal R.
Biochim. Biophys. Acta 1614:36-50(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Mechanisms of apoptosis induction by the HIV-1 envelope."
Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R., Piacentini M., Kroemer G.
Cell Death Differ. 12:916-923(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[12]"V3: HIV's switch-hitter."
Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.
AIDS Res. Hum. Retroviruses 21:171-189(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[13]"Emerging drug targets for antiretroviral therapy."
Reeves J.D., Piefer A.J.
Drugs 65:1747-1766(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"HIV and the chemokine system: 10 years later."
Lusso P.
EMBO J. 25:447-456(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"Structural definition of a conserved neutralization epitope on HIV-1 gp120."
Zhou T., Xu L., Dey B., Hessell A.J., Van Ryk D., Xiang S.H., Yang X., Zhang M.Y., Zwick M.B., Arthos J., Burton D.R., Dimitrov D.S., Sodroski J., Wyatt R., Nabel G.J., Kwong P.D.
Nature 445:732-737(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CD4-BINDING REGION.
[16]"A conserved dileucine motif mediates clathrin and AP-2-dependent endocytosis of the HIV-1 envelope protein."
Byland R., Vance P.J., Hoxie J.A., Marsh M.
Mol. Biol. Cell 18:414-425(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DI-LEUCINE INTERNALIZATION MOTIF.
[17]"The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design."
Montero M., van Houten N.E., Wang X., Scott J.K.
Microbiol. Mol. Biol. Rev. 72:54-84(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: MEMBRANE-PROXIMAL EXTERNAL REGION.
[18]"The HIV-1 envelope glycoprotein gp120 features four heparan sulfate binding domains, including the co-receptor binding site."
Crublet E., Andrieu J.P., Vives R.R., Lortat-Jacob H.
J. Biol. Chem. 283:15193-15200(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF SURFACE PROTEIN GP120 WITH HEPARAN SULFATE.
Strain: HXBC2.
[19]"HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes."
Miyauchi K., Kim Y., Latinovic O., Morozov V., Melikyan G.B.
Cell 137:433-444(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[20]"Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody."
Kwong P.D., Wyatt R., Robinson J., Sweet R.W., Sodroski J., Hendrickson W.A.
Nature 393:648-659(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 83-492 IN COMPLEX WITH HUMAN CD4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K03455 Genomic RNA. Translation: AAB50262.1.
AF038399 Genomic DNA. Translation: AAB99976.1.
AF033819 Genomic RNA. Translation: AAC82596.1.
RefSeqNP_057856.1. NC_001802.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AIKX-ray2.00C628-661[»]
N546-581[»]
1DF4X-ray1.45A546-655[»]
1DF5X-ray2.70A546-655[»]
1DLBX-ray2.00A546-655[»]
1G9MX-ray2.20G83-492[»]
1GC1X-ray2.50G83-492[»]
1GZLX-ray1.80A/B565-581[»]
C/D630-639[»]
1K33X-ray1.75A546-655[»]
1K34X-ray1.88A546-655[»]
1MZINMR-A659-671[»]
1OPNmodel-G156-492[»]
1OPTmodel-G156-492[»]
1OPWmodel-G156-492[»]
1RZJX-ray2.20G195-492[»]
2CMRX-ray2.00A543-662[»]
2ME1NMR-A657-683[»]
2NY7X-ray2.30G83-492[»]
2PV6NMR-A662-683[»]
2XRAX-ray2.30A543-662[»]
3DNLelectron microscopy20.00A/D/G90-124[»]
B/E/H198-396[»]
C/F/I410-492[»]
3DNNelectron microscopy20.00A/D/G90-124[»]
B/E/H198-396[»]
C/F/I410-492[»]
3DNOelectron microscopy20.00A/D/G90-124[»]
B/E/H198-396[»]
C/F/I410-492[»]
3IDXX-ray2.50G83-492[»]
3IDYX-ray3.20A/G83-492[»]
3TYGX-ray3.25A254-401[»]
3VIEX-ray1.80A/C/E546-581[»]
4JPJX-ray2.50A/B/C/D254-477[»]
4JPKX-ray2.40A254-477[»]
ProteinModelPortalP04578.
SMRP04578. Positions 83-127, 195-492, 512-665.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-58525N.
IntActP04578. 152 interactions.
MINTMINT-7968605.

Chemistry

BindingDBP04578.
ChEMBLCHEMBL3520.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID155971.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
REACT_6900. Immune System.

Family and domain databases

Gene3D2.170.40.20. 2 hits.
InterProIPR000777. HIV1_GP160.
IPR000328. Retroviral_envelope_protein.
[Graphical view]
PfamPF00516. GP120. 1 hit.
PF00517. GP41. 1 hit.
[Graphical view]
SUPFAMSSF56502. SSF56502. 3 hits.
ProtoNetSearch...

Other

EvolutionaryTraceP04578.

Entry information

Entry nameENV_HV1H2
AccessionPrimary (citable) accession number: P04578
Secondary accession number(s): O09779
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: July 15, 1999
Last modified: April 16, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references