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    CD4 CD4 molecule [ Homo sapiens (human) ]

    Gene ID: 920, updated on 6-Jun-2017
    Official Symbol
    CD4provided by HGNC
    Official Full Name
    CD4 moleculeprovided by HGNC
    Primary source
    HGNC:HGNC:1678
    See related
    Ensembl:ENSG00000010610 MIM:186940; Vega:OTTHUMG00000168514
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CD4mut
    Summary
    This gene encodes a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigenes and is also a receptor for the human immunodeficiency virus. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, and granulocytes. It is also expressed in specific regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Aug 2010]
    Orthologs
    Location:
    12p13.31
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 12 NC_000012.12 (6789472..6820810)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (6898638..6929976)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene lymphocyte activating 3 Neighboring gene RNA, 7SL, cytoplasmic 380, pseudogene Neighboring gene G protein-coupled receptor 162 Neighboring gene prolyl 3-hydroxylase 3

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Okt4 epitope deficiency
    MedGen: C3151379 OMIM: 613949 GeneReviews: Not available
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    NHGRI GWAS Catalog

    Description
    Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men.
    NHGRI GWA Catalog

    Replication interactions

    Interaction Pubs
    siRNA knockdown of CD4 decreases CCR5-tropic (ADA) and dual-tropic (89.6) pseudotyped virus (luciferase reporter HIV backbone presumed) infection of MDMs, yet does not affect MLV- and VSV-pseudotyped virus infection, as measured by luciferase activity PubMed
    siRNA knockdown of CD4 decreases HIV production from monocyte-derived macrophages (MDMs) infected with HIV-1 (SX strain) at a low multiplicity of infection (MOI= 0.02) PubMed
    Knockdown of CD4 by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed
    Knockdown of CD4 by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 Env (ADA) mutation N197S confers independence from CD4-mediated HIV-1 entry in to host cells PubMed
    env HIV-1 Env (NL4-3) conformational dynamics and states are stabilized by soluble CD4 [and the coreceptor surrogate antibody 17b] PubMed
    env Enhanced CD4 binding activity of HIV-1 isolate R3A gp120/gp41 contributes to activate plasmacytoid dendritic cells (pDCs) PubMed
    env HIV-1 gp120 interacts with CD4 and CXCR4 to enhance CCR7-dependent human CD4+ T cell migration PubMed
    env HIV-1 gp120 enhances CCL-21-induced CD4+ T cell chemotaxis in a CXCR4- and CD4-dependent manner PubMed
    env HbAHP-25, an analogue of Hb-alpha derived peptide, inhibits CCR5-tropic and CXCR4-tropic HIV-1 strains by blocking the binding of CD4 to HIV-1 gp120 and the subsequent steps leading to entry and/or fusion PubMed
    env Soluble CD4 can bind to HIV-1 gp120 and block HIV-1 infectivity PubMed
    env Anti-CD4 antibodies are capable of neutralizing HIV-1 strains or blocking the binding of HIV-1 envelope glycoprotein gp120 and cell surface receptor CD4 PubMed
    env HIV-1 gp120 with T257S/S375W double mutation is stabilized into the CD4-bound state, with increasing relative fixation between core, full-length monomeric, and full-length trimeric versions of gp120 PubMed
    env HIV-1 envelope glycoprotein gp120 binds to the cell surface receptor CD4 or soluble CD4; the carbohydrates present on gp120 are necessary for CD4 binding during HIV-1 entry PubMed
    env CD4 binding results in a major reorganization of the gp120 trimer, causing an outward rotation and displacement of each gp120 monomer PubMed
    env The CCR5 chemokine receptor is required for the entry of macrophage-tropic HIV-1 into target cells; the HIV-1 gp120-CD4 complex binds CCR5, which inhibits the binding of the natural CCR5 ligands macrophage inflammatory protein (MIP)-1alpha and MIP-1beta PubMed
    env CXCR4, a 45kDa cellular membrane protein, interacts with the cell surface HIV-1 gp120-CD4 complex and acts as a coreceptor to preferentially support T cell line-tropic HIV-1 Env-mediated cell fusion and HIV-1 infection PubMed
    env Monoclonal antibodies (MAbs) to defined peptide epitopes or N-linked glycans in HIV-1 gp120 inhibit the binding of gp120 to CD4 and exhibit neutralizing activities against HIV-1 PubMed
    env Divergent HIV-1 strains differ in their stoichiometry of entry and require between 1 to 7 HIV-1 gp120/gp41 trimers, with most strains depending on 2 to 3 trimers to complete entry through the interaction with CD4 PubMed
    env Two independent mutations in HIV-1 subtype A gp120, G312V (V3 loop) and A204E (C2 region), are identified to gain increased affinity to soluble CD4 compared to the wild-type PubMed
    env Some synthetic peptides as agonists of the HIV-1 envelope glycoprotein gp120 or CD4 receptor block the binding of gp120 and CD4; other peptides do not block the binding between gp120 and CD4 PubMed
    env Using single-molecule fluorescence resonance energy transfer within the context of native gp120 trimers on the surface of HIV-1 virions, indicates a significant conformational change between unliganded and CD4-binding trimers PubMed
    env SMS2, but not SMS1, is involved in enhancement of HIV-1 gp120/gp41-mediated membrane fusion through CD4 receptor and CCR5/CXCR4 coreceptors PubMed
    env CD4 binding to HIV-1 gp120/gp41 trimers results in significant conformational changes in M150 and M161 in gp120 V1/V2 and F316 in gp120 V3, but causes little changes in M104, M95, and the triad of gp41 leucines PubMed
    env CCR5 expression inhibits HIV-1 gp120-induced LIMK1 activation and cofilin phosphorylation in CD4/CXCR4 expressing 293T cells PubMed
    env CCR5 expression inhibits HIV-1 gp120 binding to CD4/CXCR4 complexes in 293T cells PubMed
    env CCR5 expression inhibits HIV-1 gp120-mediated early actin rearrangement in CD4/CXCR4 expressing 293T cells PubMed
    env HIV-1 gp120-enhanced CD4/CXCR4 conformation changes are regulated by CCR5 expression in 293T cells PubMed
    env The net charge of HIV-1 gp120 V3 loop influences the global structure and diversity of the interaction surface of the gp120 outer domain to CD4 binding and epitopes exposure PubMed
    env HIV-1 gp120 interacts with CD4 and alpha5beta3 in peripheral blood monocyte-derived macrophages; neutralizing antibodies against the alpha5beta3 integrin interfere with the coprecipitation of alpha5beta3 with an anti-gp120 antibody PubMed
    env CD4 binding residues T257, E370, S375, N425, G429, and G473 of HIV-1 gp120 are involved in NBD analogues interaction with gp120 PubMed
    env The Cryo-EM structure shows that localization at the gp120-gp41 interface allows the fusion peptide region to be released in response to CD4 and co-receptor-induced conformational changes within gp120 and gp41 that drive membrane fusion PubMed
    env HIV-1 gp120 is incapable of binding a fully oxidized, monomeric 2dCD4 in which both domain 1 and 2 disulfides are intact, but binds to reduced counterparts that are the ostensible products of Trx-mediated isomerization PubMed
    env Deletion of both HIV-1 nef and vpu genes enhance a significant engagement between HIV-1 gp120 and CD4 at the cell surface, suggesting Nef and Vpu prevent the exposure of epitopes recognized by anti-gp120 antibody-dependent cell-mediated cytotoxicity PubMed
    env HIV-1 gp120 is sulfated at positions Y173 and Y177 in the V2 domain by tyrosyl sulfotransferase 2 (TPST2), leading to modulate gp120 epitope exposure and neutralization sensitivity to soluble CD4 PubMed
    env The ability of thioredoxin, a protein disulfide isomerase (PDI), to reduce the disulfide bond in CD4 is enhanced in the presence of HIV-1 gp120 PubMed
    env Small molecules exhibit strong anti-HIV-1 activity by binding specifically to both HIV-1 gp120 and/or cell surface receptors (CD4, CCR5, CXCR4) and prevent gp120/CD4/CCR5 and gp120/CD4/CXCR4 complex formation and cell-cell fusion PubMed
    env The interaction between exposed cyclophilin A (CypA) and cell surface heparans represents the initial step of HIV-1 attachment and is a necessary step for HIV-1 gp120 binding to CD4 PubMed
    env Antibodies to specific epitopes of the CCR5 or CXCR4 chemokine receptors inhibit the entry of M-tropic, T-tropic, or dual-tropic HIV-1 into target cells by blocking the interaction of the receptors with the HIV-1 gp120/CD4 complex PubMed
    env Protein-disulfide isomerase (PDI) cleaves disulfide bonds in recombinant HIV-1 envelope glycoprotein gp120, and gp120 bound to the surface receptor CD4 undergoes a disulfide reduction that is prevented by PDI inhibitors PubMed
    env Binding of recombinant soluble CD4 (sCD4), the purified V1 domain of sCD4, or neutralizing antibodies to the HIV-1 surface glycoprotein gp120 on virions results in rapid dissociation of gp120 from its complex with the transmembrane glycoprotein gp41 PubMed
    env A high affinity interaction between the HIV-1 glycoprotein gp120/gp41 complex and the cellular receptor CD4 is necessary for both virus-cell and cell-cell fusion; the V3 region (amino acids 301-336) of gp120 and gp41 amino terminus are involved in fusion PubMed
    env HIV-1 gp120 induces the dissociation of p56lck from CD4 and the downregulation of CD4 from the cellular surface PubMed
    env The layer 3 residues (amino acids 247-254 and 476-483) of HIV-1 gp120 are located in the beta8 strand and alpha5 helix of the CD4-bound gp120. The five layer 3 mutants T248A, H249A, R476A, N478A, and W479A exhibit decreased CD4-binding activity PubMed
    env Gelsolin overexpression impairs HIV-1 gp120-induced cortical F-actin reorganization and capping and gp120-mediated CD4-CCR5 and CD4-CXCR4 redistribution in permissive lymphocytes PubMed
    env HIV-1 gp120 binds and signals through CD4, which leads to T cell activation with upregulation of the CXCR5, PD-1, Fas, and FasL expression PubMed
    env CD4-mediated endocytosis of HIV-1 gp120 results in MHC-II (HLA-DR) presentation to CD4+ T cells PubMed
    env Immature HIV-1 virions are competent for CD4-induced gp120 conformational changes PubMed
    env HIV-1 gp120-mediated inhibition of IFN-alpha production involves CD4 and BDCA2 in plasmacytoid dendritic cells PubMed
    env CD4 binding shifts the V1/V2 regions of HIV-1 gp120 to unmask the co-receptor binding site, and triggers profound dynamic changes in gp120 spanning from the binding site to the gp41-interactive face of gp120 PubMed
    env Brain-derived HIV-1 Env gp120 proteins efficiently use very low levels of CD4 to enter cells, whereas lymph-node-derived gp120 proteins are dependent on higher levels of CD4 to enter cells PubMed
    env N425K mutation of HIV-1 gp120 impacts CD4 interactions and confers HIV-1 resistance to maraviroc (MVC) PubMed
    env Small molecule BMS-488043 inhibits the interaction of HIV-1 gp120 with CD4 by blocking the rotation of the Trp112 located on the alpha1 helix of gp120 PubMed
    env CD4-linker-DC-SIGN fusion proteins enhance binding affinity to HIV-1 gp140 and gp120 in comparison to sCD4 and sDC-SIGN. These fusion proteins inhibit HIV-1 capture and transfer via DC-SIGN-expressing cells and iMDDCs PubMed
    env HIV-1 induces an elongated phenotype in infected CD4+ T cells. These HIV-infected T cells tether to other lymph node CD4+ cells and form syncytia through gp120/gp41, and migrate to distant tissues to disseminate PubMed
    env The N260Q gp120 mutant has a significantly lower binding to the recombinant soluble CD4 in comparison with wild-type PubMed
    env Human alpha-defensin-5 binds to both HIV-1 gp120 and CD4 and blocks the interaction of CD4 with gp120, which leads to inhibit HIV-1 replication in human primary CD4+ T lymphocytes PubMed
    env Feglymycin, a natural Streptomyces-derived 13mer peptide, inhibits HIV-1 gp120 binding to CD4 PubMed
    env A single Y681H substitution in HIV-1 gp41 increases the gp120-CD4 binding and enhances infectivity in low CD4 expressing cells PubMed
    env Individual gp120-CD4 bonds undergo rapid destabilization and this destabilization is significantly enhanced by the coreceptor CCR5, not by CXCR4 PubMed
    env Association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane PubMed
    env Interaction of the X4-tropic protein HIV-1 gp120 with CD4 augments ezrin and moesin phosphorylation in human permissive T cells, thereby regulating ezrin-moesin activation PubMed
    env HIV-1 gp120 isolated from southern African HIV type 1 subtype C exhibits high-affinity binding to CD4 and the Cys228-Cys239 disulfide bond of gp120 is required for the high-affinity binding to CD4 PubMed
    env Antibodies to LFA-3 block the early stages of HIV-1 infection by cell-free virus following HIV-1 gp120 binding to CD4 PubMed
    env The binding of HIV-1 gp120 to CD4 molecules on T cells interrupts the sequential cascade of intercellular interactions involving antigen/MHC class II-TCR/CD4, CD40L-CD40, and B71-CD28 PubMed
    env Alpha-defensins inhibit the binding of HIV-1 gp120 to CD4 through interaction with the D1 domain of CD4 PubMed
    env The V3 domain of HIV-1 gp120 induces associations between CD4 and CCR5 receptors in cholesterol-rich microenvironments PubMed
    env Binding gp140 to the synthetic CD4-mimicking mini protein leads to an outward domain shift of the three gp120 subunits, which diminishes gp120-gp41 interactions PubMed
    env D279 in the C2 region and N362 in the C3 region of HIV-1 gp120 augment the gp120-CD4 interaction PubMed
    env HIV-1 gp120 drastically reduces the ratio of CD4 dimers/monomers PubMed
    env Maleic anhydride-modified ovalbumin inhibits HIV-1 entry by targeting both gp120 on HIV-1 virions and CD4 receptor on the host cells PubMed
    env Palmitic acid analog 2-bromopalmitate (2-BP) efficiently binds to CD4 leading to the inhibition of gp120-to-CD4 binding PubMed
    env HIV-1 gp120 interacts with CD4 to cause apoptosis in human mesenchymal stem cells PubMed
    env A fusion of the CD4- and CCR5-mimetic peptides, DM1, binds gp120 and neutralizes R5, R5X4, and X4 HIV-1 isolates comparably to CD4 PubMed
    env Griffithsin (GRFT) interaction with gp120 exposes the CD4 binding site by binding the glycan at position 386 PubMed
    env Sphingomyelinase inhibits viral fusion after the engagement of HIV-1 gp120 with CD4 and this inhibition is dependent on CD4 expression levels PubMed
    env Tick salivary protein Salp15 prevents gp120-CD4 interaction at least partially through its direct interaction with the envelope glycoprotein in the C1 domain of gp120 PubMed
    env Competition assays with CD4 and mAbs suggest that SP-A inhibits infectivity by occlusion of the CD4-binding site on gp120 PubMed
    env In resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration PubMed
    env In a CD4-bound state, gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation PubMed
    env Co-expression of CD4 and DC-SIGN in Raji cells promotes internalization and intracellular retention of HIV-1 through interaction with HIV-1 gp120 PubMed
    env Expression of CD4 on Raji B cells strongly inhibits DC-SIGN-mediated HIV-1 transmission to T cells, presumably through interaction with HIV-1 gp120 PubMed
    env CCR5- or CXCR4-tropic HIV-1 induce Indoleamine 2,3-dioxygenase (IDO) in plasmacytoid dendritic cells and this induction is inhibited by the blockade of gp120/CD4 interactions with antibodies to CD4 PubMed
    env Substitution of highly conserved isoleucine with methionine at position 424 in the C4 domain of gp120 confers enhanced neutralization sensitivity to plasma antibodies and increases its interaction with sCD4 but not with CCR5 PubMed
    env HIV-1 infections originating from cell-free virus by CD4/gp120 interactions decrease strongly in the presence of antiretrovirals tenofovir and efavirenz whereas infections involving cell-to-cell spread are markedly less sensitive to the drugs PubMed
    env Bile salt-stimulated lipase (BSSL), a Lewis X (LeX)-containing glycoprotein found in human milk, binds to DC-SIGN and inhibits the interaction of gp120 with CD4 PubMed
    env The disulfide cross-linking interaction between gp120 and PDI is enhanced by CD4 protein PubMed
    env Focal adhesion kinase (FAK), CD4, and HIV-1 gp120 co-localize in T cells. The formation of FAK-CD4 complex is induced by gp120 PubMed
    env Epigallocatechin gallate (EGCG) purified from the green tea catechin inhibits attachment of HIV-1 glycoprotein 120 to the CD4 molecule on T cells PubMed
    env H66N change in gp120 stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved and decreases the probability of CD4-induced inactivation PubMed
    env Two potentially flexible topological layers (layers 1 and 2) in the gp120 inner domain (layer 1-layer 2) interactions strengthen gp120-CD4 binding by reducing the off rate when CD4 makes initial contact with the gp120 outer domain PubMed
    env HIV-1 gp120-induced Ca(2+) fluxing is CD4 dependent and coreceptor specific, and is mediated by the CCR5 and CXCR4 coreceptors PubMed
    env Virions carrying both HIV-1 R5 env and VSV-G can fuse to naive CD4+ T cells because CD4 binding allows viral uptake PubMed
    env Genistein, tyrosine kinase inhibitor, inhibits cell fusion between macrophages and HIV-1 Env expressing cells. Genistein treatment does not change CD4 or CCR5 surface expression and has no effect on gp120-CD4-CCR5 complex formation PubMed
    env Studies by sequential (SAP) and competitive (CAP) antigen panning methodologies show that some antibodies bind better to gp120-CD4 complexes than to gp120 alone PubMed
    env The ability of gp120 to inhibit SDF-1alpha-induced chemotaxis is mediated by the CD4 receptor and Lck signaling PubMed
    env Subtype C gp120 isolates carrying I309L enhance utilization of CD4 but do not affect the ability to use CCR5 PubMed
    env Virological synapse-mediated cell-to-cell HIV-1 transfer is dependent upon gp120/gp41 and CD4 interactions and is more efficient than that of a cell-free mode of uptake, yet the presence of the full CD4 cytoplasmic tail is not essential for the process PubMed
    env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
    env The V1-V3 region of a brain-derived HIV envelope glycoprotein plays a crucial role in determining the virus' low CD4 dependence and increased macrophage tropism, as well as its augmented fusogenicity and reduced sensitivity to the inhibitor BMS-378806 PubMed
    env HIV-1 gp120 hydrogen bond interactions among transmembrane residues Y108, E283, and Y251, are crucial for HIV-1-gp120/sCD4 complex binding and HIV-1 fusion. HIV-1 gp120 binding to CCR5 disrupts these interhelix hydrogen bond interactions PubMed
    env Deletion of the HIV-1 gp120 major variable regions (V1/V2/V3) stabilizes gp120 core proteins into the conformation recognized by CD4 PubMed
    env A synthetic CD4-mimetic peptide conjugating with a heparan sulfate dodecasaccharide binds to gp120 and induces the exposure of the coreceptor binding domain available for interaction with the oligosaccharide PubMed
    env HIV-1 gp120 promotes filamin binding to both CD4 and CXCR4 PubMed
    env CIITA-mediated enhancement of HIV-1 infection is gp120/gp41/CD4-dependent and occurs at the early steps in the infection cycle PubMed
    env Elimination of the CD4 domain 2 disulfide bond (Cys130-Cys159) by mutation enhances HIV-1 gp120/gp41-mediated cell-cell fusion and virus entry PubMed
    env Thioredoxin cleaves the gp120 disulfide bond (Cys296-Cys331) in the V3 domain and the cleavage is enhanced by CD4-expressing cells PubMed
    env The cis expression of DC-SIGN on multiple lymphoid cell lines enables more efficient entry and replication of CXCR4-tropic and CCR5/CXCR4 dual-tropic HIV-1 through its binding to the HIV-1 gp120-CD4-CXCR4 complex PubMed
    env HIV-1 gp120 specifically recognizes the C-terminal heparin-binding domain of fibronectin (Fn) and this binding inhibits the interaction of gp120 with soluble CD4 PubMed
    env Apoptosis of CD4+ lymphocytes induced by HIV-1 gp120 cross-linking to CD4 is inhibited by IL-12 PubMed
    env HIV-1 envelope glycoproteins gp120 and gp160 directly and specifically impair the CD3/TcR-mediated activation of phospholipase C (PLC) via the CD4 molecule in uninfected T cells PubMed
    env Galectin-1, a dimeric beta-galactoside-binding protein, promotes infection with CCR5-tropic, CXCR4-tropic, and CCR5/CXCR4 dual-tropic HIV-1 variants by facilitating attachment of HIV-1 gp120 to CD4 at the cell surface PubMed
    env The binding of HIV-1 gp120 to CD4+-permissive cells increases the level of acetylated alpha-tubulin in a CD4-dependent manner; overexpression of Histone Deacetylase 6 (HDAC6) inhibits the acetylation of alpha-tubulin and prevents HIV-1-cell fusion PubMed
    env Griffithsin isolated from an aqueous extract of the red alga Griffithsia species blocks CD4-dependent HIV-1 gp120 binding to receptor-expressing cells and binds to viral coat glycoproteins (gp120, gp41, and gp160) in a glycosylation-dependent manner PubMed
    env HIV-1 gp120-CD4 interaction is necessary to repress HIV-1 long terminal repeat-dependent luciferase activity; the cytoplasmic domain of CD4 is found to be required for this effect to occur PubMed
    env Binding of HIV-1 gp120 to CD4 molecules in cells results in the association of Lck and Raf-1, which is abolished by preincubation of the virus with soluble CD4 PubMed
    env The fusion of insulin-like growth factor I (IGF I) with stromal cell-derived factor I or alpha1 proteinase inhibitor has the capacity to compete with the binding of HIV-1 gp120 to CD4 receptor PubMed
    env Phorbol myristate acetate (PMA) pretreatment of CD4+ cells prevents subsequent HIV-1 gp120-induced downregulation of CD4 receptor molecules PubMed
    env Expression of the HIV-1 envelope gene in CD4+ T cell lines and binding of HIV-1 gp120 to CD4 is sufficient for the induction of apoptosis PubMed
    env Combinations of CD4-based molecules and antibodies to HIV-1 gp120 and/or gp41 inhibit cell fusion formation mediated by the interaction of CD4 to gp120 PubMed
    env Following incubation with a soluble form of CD4, gp120 of highly purified HIV-1 preparations is cleaved without addition of exogenous proteinase, yielding two proteins of 50 and 70 kDa; this cleavage likely occurs in the gp120 V3 loop PubMed
    env Mutants with amino acid changes in the V1/V2 region (residues 131-196) of the HIV-1 gp120 are able to bind CD4 but are deficient in syncytium formation and/or virus entry PubMed
    env Release of neurotoxins from monocytes through HIV-1 gp120 stimulation involves CD4 receptors; toxin production can be inhibited either by a monoclonal antibody to the CD4-binding region of gp120 or by soluble CD4 receptors PubMed
    env Calcium ions are required for cell fusion mediated by interactions between CD4 and HIV-1 gp120/gp41; EDTA and EGTA block cell fusion in culture media containing calcium ions PubMed
    env The third complementarity-determining region (CDR3; residues 79-96) within domain 1 of the human CD4 molecule plays a critical role in membrane fusion mediated by the interaction of CD4 with HIV-1 gp120 PubMed
    env Binding of HIV-1 gp120 to the CD4 receptor molecule results in co-stimulation of CD3-induced T cell activation PubMed
    env HIV-1 gp120-mediated CD4 engagement is involved in the induction of susceptibility of primary human T lymphocytes to CD95-mediated apoptosis through ezrin phosphorylation and ezrin-to-CD95 association PubMed
    env Human C" beta strand (amino acids 42-47) of CD4, particularly Phe-43, plays a crucial role in HIV-1 coreceptor function as well as in HIV-1 gp120-CD4 binding capacity PubMed
    env The chemokine receptor CCR5 is posttranslationally modified by sulfation of its N-terminal tyrosines; sulfated tyrosines contribute to the binding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells PubMed
    env The inhibition of IL-2R expression and proliferation induced by the interaction of CD4 with HIV-1 envelope glycoprotein gp120 is correlated with the inhibition of expression and activation of Janus kinase JAK3 PubMed
    env Antibodies to specific epitopes of HIV-1 gp120 block the interaction of CCR5 with the gp120/CD4 complex, suggesting that a CD4-mediated conformational change in gp120 is required for subsequent binding to CCR5 PubMed
    env A specific interaction between CD4 and HIV-1 gp120 is required for phosphorylation of CD4, which could involve protein kinase C PubMed
    env Amino acid residues 42-49 and 54-57 in the V1 region of CD4 are involved in the interaction of CD4 with both HIV-1 gp120 and class II major histocompatibility complex molecules PubMed
    env Mutations at four locations (amino acids 29, 59-64, 77-81, and 85) outside the antigen-complementarity-determining region (CDR2)-like sequence of CD4 markedly affect HIV-1 gp120 binding PubMed
    env Removal of the N-linked sugars on HIV-1 gp120 by endoglycosidase H treatment results in deglycosylated proteins that are unable to bind to CD4, suggesting that glycosylation contributes to the ability of gp120 to bind to CD4 PubMed
    env Deletion analysis shows that amino acid regions 82-95, 386-389, 424-432, and 487-499 constitute a part of the HIV-1 gp120 binding region to CD4 PubMed
    env HIV-1 gp120/160 deglycosylated by Endo H and Endo F still binds to CD4, indicating that the carbohydrates of gp120/160 do not play a significant role in the in vitro binding to CD4 PubMed
    env HIV-1 gp120 suppresses T and B cell activation and the expression of cytolytic activities through its interaction with CD4 PubMed
    env HIV-1 gp120 and class II MHC binding sites of CD4 are distinct and can be separated PubMed
    env A single amino-acid change (cysteine 402 or tryptophan 432) in HIV-1 gp120 can abrogate CD4 binding PubMed
    env Apoptosis induced by HIV-1 gp120/CD4 cross-linking in Th1 clones is inhibited by anti-CD95 or anti-CD95L neutralizing monoclonal antibodies, as well as by a specific interleukin-1 beta converting enzyme (ICE) inhibitor PubMed
    env IL-16 induces rapid translocation of PKC from the cytosol to the membrane in CD4+ cells; PKC inhibitors completely block IL-16-induced lymphocyte migration as well as the motile response induced by HIV-1 gp120 and anti-CD4 antibody binding to CD4 PubMed
    env CD4 downregulation by the treatment of macrophages with HIV-1 gp120 is mediated through the induction of endogenous TNF-alpha PubMed
    env A CD4 peptide (amino acids 74-95) inhibits the binding of gp120 to CD4+ human lymphoblastic leukemia (CEM) cells PubMed
    env Through binding to cell surface CD4, both HIV-1 gp120 and gp160 inhibit syncytia formation between HIV-1-infected cells and CD4+ cells PubMed
    env Chimpanzee CD4 molecules bearing the human amino acid at position 87 support syncytium formation, while human CD4 molecules bearing the chimpanzee residue at position 87 do not; HIV-1 gp120 binding to CD4 is not affected by the substitution at position 87 PubMed
    env Expression of a soluble CD4 mutant molecule lacking transmembrane and cytoplasmic domains blocks secretion of HIV-1 gp120 and surface expression of HIV-1 gp120 and gp41 from the endoplasmic reticulum PubMed
    env Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), block the binding of gp120 to CD4, but do not interfere with the binding of CD4 to class II major histocompatibility complex molecules PubMed
    env HIV-1 gp120 with substitution of cysteine's 296, 331, 418 or 445 on fails to bind to CD4 PubMed
    env The N-terminal region of HIV-1 gp120 contains conserved residues (amino acids 56-62 and 108-116) critical for binding to CD4 PubMed
    env Changes in two hydrophobic regions (Thr-257 and Trp-427) and two hydrophilic regions (Asp-368, Glu-370, and Asp-457) of HIV-1 gp120 result in significant reductions in CD4 binding PubMed
    env Expression of the human CD4 receptor in murine T-cells is sufficient for syncytia formation with HIV-1 envelope expressing cells and entry of MLV/HIV pseudotyped retroviral vectors, suggesting that the murine CXCR4 is a functional coreceptor PubMed
    env CD4(+)CD45RO(+) cells display high HIV-1 gp120-binding capacity, whereas CD4(+)CD45RO(-) cells show undetectable HIV-1 gp120 binding PubMed
    env The physiological levels of cell-surface CD4 interfere with HIV-1 replication in T cells by a mechanism that inhibits HIV-1 gp120 envelope incorporation into viral membranes PubMed
    env Syncytial apoptosis mediated by the fusion of cells expressing HIV-1 gp120 with cells expressing the CD4/CXCR4 receptor/coreceptor complex causes phosphorylation of p53 on serine 15 and Bax upregulation PubMed
    env Mutation of two basic amino acids Lys46 and Arg59 in CD4 dramatically disrupts its ability to bind HIV-1 gp120 PubMed
    env CD4-expressing human T cell lines induce significant and rapid conformational changes in gp120-gp41 from T cell-tropic HIV-1 strains, and little conformational changes in gp120-gp41 from macrophage-tropic HIV-1 strains PubMed
    env Binding of HIV-1 gp120 to CD4 receptor induces p56lck activation and zeta-chain (TCR) associated protein kinase 70kDa desensitization independent of TCR tyrosine phosphorylation PubMed
    env Pretreatment of HIV-1 infected cells with TNF alpha augments syncytia formation mediated by the interaction of HIV-1 gp120 with cell surface CD4 molecules PubMed
    env Interaction of HIV-1 gp120 with cell-associated CD4 leads to the induction of IFN alpha; preincubation of cells with anti-CD4 or the presence of soluble CD4 during incubation inhibits IFN alpha induction PubMed
    env Cleavage at position R315 of HIV-1 gp120 by thrombin is enhanced by soluble CD4 binding PubMed
    env Two disulfide bonds linking cysteine residues at positions 378 and 445 and positions 385 and 418 in the carboxyl terminus of HIV-1 gp120 contribute to CD4 binding PubMed
    env Amino acid residues (102-126) and (425-452) of HIV-1 gp120 contribute to the binding site for CD4 and are expected to be juxtaposed in the folded gp120 chain PubMed
    env Crosslinking of HIV-1 gp120 on human CD4+ T cells followed by signaling through the TCR results in activation-induced apoptosis PubMed
    env LFA-1 adhesion molecules are not involved in the early stages of cell membrane fusion mediated by the interaction of gp120 with CD4 PubMed
    env Down modulation of the interaction between HIV-1 gp120 and CD4 by TPA is blocked by protein kinase C (PKC) inhibitors, suggesting PKC may play an important role in HIV-1 infection PubMed
    env 12-O-tetradecanoylphorbol-13-acetate (TPA) down-modulates the expression of CD4, which is essential for syncytia formation through interaction with the HIV-1 envelope protein gp120 PubMed
    env Glycolipids such as galactosylceramides, sulfogalactoceramides, globotriosylceramide, and gangliosides play an important role as HIV-1 fusion cofactors following the interaction of CD4 and HIV-1 gp120 PubMed
    env Gross cystic disease fluid protein-15 (GCDFP-15) binds to CD4, a T-cell co-receptor involved in antigen recognition, thereby inhibiting the ability of the receptor to interact with the HIV-1 envelope protein gp120 PubMed
    env Contact of CD4+ T cells with HIV-1 infected or HIV-1 gp120-expressing cells induces PARP hydrolysis, which leads to the cleavage of 116 kDa PARP into two fragments PubMed
    env CD4-p56Lck interaction is required for HIV-1 gp120-induced nuclear translocation of NF-kappaB in HeLa cells PubMed
    env Adsorption of multivalent gp120-containing HIV-1 virion particles into CD4+ T lymphocytes results in segregation of CD4 and CXCR4 into distinct lipid micro domains PubMed
    env A fusion protein between HIV-1 gp120 hepatitis B surface antigen (HBsAg) is capable of spontaneous assembly into virus-like particles and exhibits high affinity binding to CD4 PubMed
    env Retrocyclin binds to soluble CD4 and HIV-1 gp120, colocalizes with CD4, CXCR4, and CCR5, and inhibits replication of CCR5-tropic and CXCR4-tropic strains of HIV-1 in human cells, presumably through inhibition of gp120-CD4 binding PubMed
    env The level of HIV-1 gp120-mediated syncytium formation and infectivity is enhanced in the presence of neuraminidase (NA) and involves the interaction between gp120, CD4, and chemokine coreceptors PubMed
    env CD26 (dipeptidyl peptidase IV) cleaves the highly conserved V3 loop of HIV-1 gp120 and functions as a cofactor for entry of HIV-1 in CD4+ human cells; coexpression of human CD4 and CD26 in murine NIH 3T3 cells renders them permissive to HIV-1 PubMed
    env Cells expressing a chimeric molecule consisting of the first 177 residues of CD4 attached to residues from the hinge, transmembrane, and cytoplasmic domains of CD8 are susceptible to fusion with cells expressing HIV-1 gp120 PubMed
    env Several polyanionic anti-HIV compounds, including dextran sulfate, pentosan polysulfate, heparin, aurintricarboxylic acid (ATA), suramin, and Evans blue, interact with HIV-1 gp120 to block the binding of gp120 to CD4 PubMed
    env A 287 residue variant of HIV-1 gp120 (ENV59) missing 197 amino acids binds to CD4 with high affinity PubMed
    env Cell-cell contact between T cells expressing HIV-1 gp120/gp41 and other T cells expressing CD4 receptors leads to the rapid accumulation of cyclin B and tyrosine-hyperphosphorylated p34cdc2 (cdk1) kinase, indicative of cell cycle arrest at G2 phase PubMed
    env HIV-1 envelope protein gp120 can specifically inhibit CD4-dependent class II MHC-restricted T cell response to Antigens PubMed
    env 95- and 25-kDa peptides derived from the disulfide bond reduction of HIV-1 gp120 bind to human CD4 PubMed
    env The first two domains (amino acid residues 1-177) of human CD4 bind effectively to HIV-1 gp120, and most residues interacting with gp120 lie within amino acids 21-64; the COOH-terminal half of the molecule is not necessary PubMed
    env Amino acid sequences 397-439 in HIV-1 gp120 are directly involved in the binding of gp120 to the CD4 receptor PubMed
    env Cleavage of HIV-1 gp120 with trypsin at residue 432 destroys CD4 binding PubMed
    env Inhibition of HIV-1 binding to CD4 by suramin is reversed by human albumin, suggesting that only free suramin has antiviral properties PubMed
    env HIV-1 gp120 stimulates monocytes to release TNF-alpha, IL-1 beta, IL-6, and granulocyte-macrophage-CSF, and this effect can be blocked with soluble CD4 PubMed
    env T-tropic HIV-1 gp120s are capable of priming phorbol ester (PMA) induced co-down-modulation of gp120 complexes with tailless CD4 by interacting with CXCR4, whereas M-tropic gp120 are not, even in the presence of CCR5 PubMed
    env CD38 expression blocks lymphocyte susceptibility to HIV-1 infection by inhibiting HIV-1 gp120/CD4-dependent viral binding to target cells PubMed
    env HIV-1 gp120 induces CD4 association with lymphocyte surface molecules CD3, CD11a, CD27, CD45RA, CD45RB, CD45RO, CD49d, CD38, CD26, CD59, CD95 and class I MHC molecules PubMed
    env HIV-1 gp120 induces a specific phospholipase A2 (PLA2) activation in lymphocytes through binding to CD4, but this effect is not sufficient to accomplish virus/cell fusion PubMed
    Envelope surface glycoprotein gp160, precursor env HIV-1 glycoprotein gp160 binds to both cell surface receptor and soluble CD4 and the interaction of gp160 with CD4 results in virus-cell and cell-cell fusion PubMed
    env HIV-1 gp160 molecules exist predominantly as a dimer, but higher forms corresponding to trimers and tetramers are also observed; multiple CD4 molecules bind to the gp160 oligomers PubMed
    env HIV-1 heterotrimeric gp140 of inter- and intra-subtype combinations (subtype A, B, C, D and F) are shown to bind CD4 and a panel of neutralizing monoclonal antibodies with similar affinity to monovalent UG37 gp140 PubMed
    env CD4 interaction with HIV-1 Env is necessary for contact induced cytoplasmic remodeling such as mitochondria polarization in HIV-1 infected T cells PubMed
    env The double alanine mutations at HIV-1 Env positions 671 and 674 result in attenuation of Env-mediated cell-cell fusion and hemifusion, as well as viral infectivity mediated by both CD4-dependent and CD4-independent viruses PubMed
    env CD4-linker-DC-SIGN fusion proteins enhance binding affinity to HIV-1 gp140 and gp120 in comparison to sCD4 and sDC-SIGN. These fusion proteins inhibit HIV-1 capture and transfer via DC-SIGN-expressing cells and iMDDCs PubMed
    env DC-SIGN increases the binding affinity of trimeric gp140 envelope glycoproteins to CD4 on permissive cell surface PubMed
    env HIV-1 Env from subtype P downregulates CD4 cell surface expression PubMed
    env Binding gp140 to the synthetic CD4-mimicking mini protein leads to an outward domain shift of the three gp120 subunits, which diminishes gp120-gp41 interactions PubMed
    env A soluble HIV-1 Env trimeric construct may better expose crucial epitopes such as the CD4 binding site and V3, as well as epitopes in the vicinity of gp41, subsequent to conjugation with the synthetic CD4-mimicking mini protein PubMed
    env Coexpression of HIV-1 gp160 and human CD4 in HeLa cells severely impairs HIV-1 gp120 production due to the formation of intracellular gp160-CD4 complexes; this CD4-mediated inhibition of gp160 processing is alleviated by coexpression of Vpu PubMed
    env Interaction of HIV-1 gp160 with CD4 increases p56lck autophosphorylation and kinase activity PubMed
    env ICAM-1 promotes HIV-1 gp160-mediated syncytium formation, and the ICAM-1 contrareceptor LFA-1 attenuates the syncytium-inhibiting activity of virus-neutralizing monoclonal antibodies and soluble CD4 PubMed
    env HIV-1 gp160 and gp120 specifically recognize the C-terminal heparin-binding domain of fibronectin (Fn) and this binding inhibits the interaction of gp160/gp120 with soluble CD4 PubMed
    env A complete disappearance of surface CD4 preceding single-cell death occurs in cell clones expressing gp160, in which a complex between CD4 and gp160 is formed and then accumulates intracellularly PubMed
    env Newly synthesized CD4 and HIV-1 gp160 form a complex prior to transport from the endoplasmic reticulum (ER) PubMed
    env Dimeric HIV-1 gp160 binds to two CD4 molecules PubMed
    env HIV-1 gp160 alone or CD4/gp160 cross-linking induces tyrosine phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also leads to ras activation PubMed
    env Amino acid residues 257, 368, 370, and 457 of HIV-1 gp160 are critical for both cell surface and intracellular interaction between gp160 and CD4 PubMed
    env Interaction of the anchoring domain of HIV-1 gp160 with the endoplasmic reticulum membrane is responsible for gp160-mediated cell surface downregulation of CD4 PubMed
    Envelope transmembrane glycoprotein gp41 env Enhanced CD4 binding activity of HIV-1 isolate R3A gp120/gp41 contributes to activate plasmacytoid dendritic cells (pDCs) PubMed
    env HIV-1 gp120 and gp41 form a transitional complex with the CD4 receptor and CCR5/CXCR4 coreceptors during virus-cell and cell-cell membrane fusion PubMed
    env Divergent HIV-1 strains differ in their stoichiometry of entry and require between 1 to 7 HIV-1 gp120/gp41 trimers, with most strains depending on 2 to 3 trimers to complete entry through the interaction with CD4 PubMed
    env SMS2, but not SMS1, is involved in enhancement of HIV-1 gp120/gp41-mediated membrane fusion through CD4 receptor and CCR5/CXCR4 coreceptors PubMed
    env Double alanine mutations at positions 671 and 674 of Env in the gp41 MPER region (residues 662-683) attenuate Env-mediated cell-cell fusion and hemifusion, as well as viral infectivity mediated by both CD4-dependent and -independent viruses PubMed
    env CD4 binding to HIV-1 gp120/gp41 trimers results in significant conformational changes in M150 and M161 in gp120 V1/V2 and F316 in gp120 V3, but causes little changes in M104, M95, and the triad of gp41 leucines PubMed
    env Shingopeptides disrupt HIV-1 gp41 fusion protein folding and CD4 receptor diffusion in vitro, suggesting that shingopeptides abolish the interaction of gp41 with CD4 in vivo PubMed
    env A bivalent HIV-1 inactivator 2DLT by linking the D1D2 domain of CD4 to HIV-1 fusion inhibitor T1144 induces the formation of the gp41 prehairpin fusion-intermediate (PFI) and the T1144 domain in 2DLT then binds to the exposed PFI PubMed
    env HIV-1 induces an elongated phenotype in infected CD4+ T cells. These HIV-infected T cells tether to other lymph node CD4+ cells and form syncytia through gp120/gp41, and migrate to distant tissues to disseminate PubMed
    env A single Y681H substitution in HIV-1 gp41 increases the gp120-CD4 binding and enhances infectivity in low CD4 expressing cells PubMed
    env A truncated cytoplasmic domain of 27 amino acids in HIV-1 gp41 can expose highly conserved domains involved in both HIV-1 coreceptor and CD4 binding PubMed
    env Binding gp140 to the synthetic CD4-mimicking mini protein leads to an outward domain shift of the three gp120 subunits, which diminishes gp120-gp41 interactions PubMed
    env A point mutation (V38E) in the gp41 region of HIV-1 abolishes HIV-1-mediated apoptosis by CASP3 and minimizes CD4 loss in humanized mice without altering viral replication PubMed
    env In resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration PubMed
    env The HIV-1 transmembrane glycoprotein gp41 is an amino acceptor and donor substrate for transglutaminase in vitro; soluble CD4 can block the transglutaminase-catalyzed incorporation of the polyamine spermidine into HIV-1 gp41 PubMed
    env Virological synapse-mediated cell-to-cell HIV-1 transfer is dependent upon gp120/gp41 and CD4 interactions and is more efficient than that of a cell-free mode of uptake, yet the presence of the full CD4 cytoplasmic tail is not essential for the process PubMed
    env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
    env CIITA-mediated enhancement of HIV-1 infection is gp120/gp41/CD4-dependent and occurs at the early steps in the infection cycle PubMed
    env Elimination of the CD4 domain 2 disulfide bond (Cys130-Cys159) by mutation enhances HIV-1 gp120/gp41-mediated cell-cell fusion and virus entry PubMed
    Nef nef HIV-1 Nef core domain directly interacts with CD4 and is highly conserved amongst Nef from [the] HIV-1/-2/SIV strains [tested] in 293T cells as shown by FACS-Forster resonance energy transfer (FRET)- and site-directed mutagenesis-based experiments PubMed
    nef HIV-1 Nef downmodulates CD4 in primary HIV-1 infected CD4+ T cells PubMed
    nef HIV-1 (NL4-3) Nef downregulates CD4 via a cullin-RING E3 ubiquitin ligase complex- independent mechanism PubMed
    nef HIV-1 Nef downregulates CD4 molecules from the cell surface of T, B, peripheral blood mononuclear and monocyte/macrophage cell lines as well as non-lymphoid cell lines PubMed
    nef HIV-1 isolate R3A Nef mutants G2, WL58, RR106, LL165, E160NNSLL165, and DD175 fail to induce release of IFN-alpha in pDCs, suggesting that the Nef function responsible for CD4 downregulation is crucial for pDCs stimulation by R3A PubMed
    nef HIV-1 Nef clones from acute controllers display a lesser ability to downregulate CD4 and HLA class I from the cell surface, and a reduced ability to enhance virion infectivity compared to those from acute progressors PubMed
    nef HIV-1 Nef-mediated CD4 degradation requires ALIX and interaction of Nef with ALIX in endosomes containing CD4 in cells PubMed
    nef HIV-1 Nef mutants D108K, R134E, E177K, DD174/175AA do not downregulate CD4 on cell surface of HeLa cells PubMed
    nef Deletion of both HIV-1 nef and vpu genes enhance a significant engagement between HIV-1 gp120 and CD4 at the cell surface, suggesting Nef and Vpu prevent the exposure of epitopes recognized by anti-gp120 antibody-dependent cell-mediated cytotoxicity PubMed
    nef Neffin, a camelid single-domain antibody fragment (termed sdAb19) fused to the SH3 domain of Nef, strongly binds to HIV-1 Nef with a stoichiometric 2:2 ratio and inhibits Nef-mediated downregulation of CD4 in HeLa-CD4 cells PubMed
    nef Interaction of HIV-1 Nef with AP-2 alpha-sigma dimer is required for Nef-mediated CD4 downregulation. The dileucine L164L165 and M168L170 motifs bind to the sigma unit, while the acidic motif E174 and D175 binds to the alpha unit PubMed
    nef HIV-1 Nef clones, isolated from plasma of elite controllers (EC) and chronic progressors (CP), show significantly lower CD4 downregulation activity in EC than that in CP PubMed
    nef HIV-1 Nef clones obtained from chronic patients infected with HIV-1 subtypes A, B, C or D show a functional hierarchy of subtype B > A/D > C for Nef-mediated CD4 downregulation PubMed
    nef Functional ARF1 is required for HIV-1 Nef-dependent endogenous HLA-A2 and CD4 downregulation in HIV-infected primary T cells PubMed
    nef The hydrophobic region (residues 168-173) downstream of the HIV-1 Nef dileucine motif (L164L165) is involved in HIV-1 Nef-mediated CD4 downregulation PubMed
    nef HIV-1 Nef enhances the infectivity of CD4-chemokine receptor-pseudotyped HIV-1 for target cells expressing HIV-1 Env. Virus-producing cells expressing dominant-negative dynamin 2 (K44A) selectively inhibits these receptor-pseudotyped virions PubMed
    nef CD4 and MHC-1 downregulation are highly conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable PubMed
    nef HIV-1 Nef mutants LLAA and delta12-39 significantly impair downregulation of CD4. Nef LLAA mutant fails to interact with the endocytic machinery and Nef delta12-39 mutant lacks the interaction with the Nef-associated kinase complex PubMed
    nef HIV-1 Nef drastically reduces the ratio of CD4 dimers/monomers PubMed
    nef beta-COP as a cellular cofactor is required for HIV-1 Nef-mediated HLA-A2, CD4, and CD8 downregulation PubMed
    nef Single mutation at the ubiquitination residue K144 or at the tyrosine motif Y202F203 in HIV-1 Nef greatly impairs Nef-mediated CD4 downregulation PubMed
    nef TPCK and TLCK alkylation reagents chemically modify HIV-1 Nef at residues Cys55 and Cys206. Cys55 modification reduces the strength of the interaction between Nef and CD4 tail peptide PubMed
    nef HIV-1 Nef expression from unintegrated HIV-1 DNA downregulates the surface levels of CD4, CCR5, and CXCR4 on T-lymphocytes and monocytes PubMed
    nef HIV-1 Nef interacts with CD4 in living cells PubMed
    nef HIV-1 Nef targets CD4 to CD63-containing lysosomes for Nef-induced degradation of CD4, which requires the VPS4-mediated ESCRT machinery PubMed
    nef K295, K297, K298, and R340 basic residues on the AP-2 alpha subunit are required for its binding to HIV-1 Nef. The K297 and R340 residues are required for Nef-induced CD4 downregulation and the cooperative assembly of a Nef-CD4-AP-2 complex PubMed
    nef L37, P78 and E177 residues of HIV-1 Nef are required for its effect on CD4 internalization and recycling but dispensable for Nef-induced retention and degradation of intracellular CD4 PubMed
    nef HIV-1 Nef-Vpr fusion proteins are efficiently incorporated into HIV-1 particles and possess CD4 downregulation activity in target cells PubMed
    nef An intact Nef dimerization interface, including the multiple hydrophobic (I109, L112, Y115, and F121) and electrostatic (R105 and D123) residues, is required for Nef-induced CD4 downregulation in cells PubMed
    nef An intact hydrophobic interface (residues I109, L112, Y115, and F121) is essential for HIV-1 Nef dimerization in cells and is required for Nef-mediated CD4 receptor downregulation PubMed
    nef HIV-1 Vpr increases expression of Nef protein from integrase-defective HIV-1. The Vpr-mediated expression of Nef from IN-minus HIV-1 results in CD4 downregulation PubMed
    nef Expression of p56(lck) in nonlymphoid CD4-expressing cells restores the ability of Nef in order to increase the internalization rate of CD4 PubMed
    nef HIV-1 Nef downregulates CD4 expression on the surface of Jurkat cells and blocks the CD3 signaling pathway; mutations at amino acids 174 and 175 reduce the ability of Nef to downregulate CD4 expression PubMed
    nef The HIV-1 Nef mutant F12-HIVNef, containing three rare amino acid substitutions, G(140)E, V(153)L and E(177)G, represses Nef-induced accelerated rates of CD4 internalization and p62NAK activation PubMed
    nef A dileucine motif in Nef is required for CD4 downregulation and for interaction with clathrin adaptor complexes AP-1 and AP-2, which are responsible for recruiting sorted proteins into clathrin-coated pits PubMed
    nef Deletion of the 19 N-terminal amino acids, including the myristoylation signal from HIV-1 Nef inhibits both MHC-I and CD4 downregulation while preserving most CTL, T-helper and B-cell epitopes PubMed
    nef Different levels of CD4 modulation are induced by different HIV-1 Nef proteins derived from HIV-1 infected adults and children PubMed
    nef The functional ability of HIV-1 Nef to downregulate CD4, but not MHC class I, is associated with Nef-mediated enhancement of HIV-1 pathogenicity in severe combined immunodeficiency (SCID) mice implanted with human fetal thymus and liver PubMed
    nef CD4 downregulation by HIV-1 Nef enhances the efficiency of HIV-1 replication in both activated human primary T lymphocytes and lymphoid tissues; Nef-induced CD4 downregulation correlates with severe depletion of CD4+ T cells in lymphoid tissues PubMed
    nef Expression of HIV-1 Nef in human monocyte-derived dendritic cells using an adenovirus based delivery system decreases CD4 levels, but has no effect on class I MHC PubMed
    nef HIV-1 Nef downregulates CD4 in Jurkat cells in a concentration-dependent manner PubMed
    nef HIV-1 Nef mutants C142A and K158A/E160G exhibit a temperature-dependent ability to downregulate CD4 PubMed
    nef HIV-1 Nef downregulates CD4 rapidly during the early phase of virus infection, whereas HIV-1 Vpu and Env function late in the infection; in primary cells, down-modulation of CD4 has a stronger dependence on Nef function for reducing cell surface CD4 PubMed
    nef High levels of CD4 on the surface of an HIV-1 producing cell block viral infectivity by interfering with incorporation of HIV-1 envelope into the virion; HIV-1 Nef and Vpu inhibit this block by downregulating CD4 from the cell surface PubMed
    nef Mutational analysis of HIV-1 Nef shows that a membrane targeting domain (residues 2-7) and a conserved glutamic acid-rich segment (residues 60-71) are required for CD4 downregulation but not for viral infectivity enhancement PubMed
    nef HIV-1 Nef downregulates cell surface expression of CD4 in CEM Nef+ cells by promoting the accumulation of CD4 in an acidic early endosome PubMed
    nef An isoleucine residue at position 410 and two leucine residues at positions 413 and 414 in CD4 are required for HIV-1 Nef-mediated CD4 downregulation in cells PubMed
    nef Two distinct regions within HIV-1 Nef, amino acid residues 96-144 and 175-186, are required for CD4 downregulation in cells PubMed
    nef The presence of an alpha-helix in CD4, which extends from residues Gln403 to Arg406, promotes the binding of CD4 to HIV-1 Nef PubMed
    nef Yeast two-hybrid assays show that a nearly complete HIV-1 Nef protein is required for binding to the CD4 cytoplasmic domain (residues 394-416), and the dileucine motif in CD4 (residues 413-414) is essential for this direct interaction PubMed
    nef Solution NMR spectroscopy studies show a 13 amino acid peptide (residues 407-419) derived from the CD4 cytoplasmic domain binds directly to HIV-1 Nef in a manner that involves amino acid residues 57-59, 95-97, 106, and 110 in Nef PubMed
    nef CEM cells stably transfected with a replication-defective provirus of HIV-1 that has a rev-splicing mutation and expresses an intact nef gene have markedly reduced cell surface expression of CD4 PubMed
    nef HIV-1 Nef-mediated downregulation of CD4 is induced by an accelerated dissociation of the T-cell tyrosine kinase Lck and CD4, and a decrease in the half-life of CD4 PubMed
    nef A dileucine motif in the cytoplasmic domain of CD4 is involved in the association of CD4 with the tyrosine kinase Lck and the downregulation of CD4 by HIV-1 Nef, however Nef does not induce dissociation of Lck from CD4 in acutely HIV-infected cells PubMed
    nef A dileucine motif in the cytoplasmic tail of CD4 is not required for HIV-1 Nef binding in insect cells, but is essential for Nef-induced CD4 downregulation PubMed
    nef Experiments using both a recombinant HIV-1 Integrase-defective virus and a diketo acid Integrase inhibitor demonstrate that HIV-1 Nef expressed from extra chromosomal DNA (E-DNA) downregulates CD4 surface expression on primary CD4(+) T lymphocytes PubMed
    nef The Nef protein from the primary virus isolate HIV-1 KS2 lacks two glutamic acid residues (EE154-5) and has a decreased ability to downregulate CD4 PubMed
    nef HIV-1 expressing Nef proteins defective in CD4 downregulation activity retain wild-type levels of infectivity in single-round assays, but exhibit delayed replication kinetics and lower titers compared to the wild-type virus in monocyte-derived macrophages PubMed
    nef PMA treatment of T cells expressing HIV-1 Nef, which downregulates CD4, restores cell surface CD4 up to 35%; mutations in the phosphorylation sites of the CD4 cytoplasmic tail (Ser408 and Ser415) abolish this effect of PMA PubMed
    nef HIV-1 Nef-mediated CD4 downregulation is profoundly inhibited by the synergistic effect of Eps15DIII, a dominant negative mutant of Eps involved in endocytosis and RNA interference of AP-2 expression PubMed
    nef Bioluminescence resonance energy transfer (BRET) and co-immunoprecipitation assays have been used to demonstrate the interaction of HIV-1 Nef and CD4 in intact human cells PubMed
    nef HIV-1 group N and group O Nef alleles only weakly downregulate CD4, CD28, and class I and II MHC molecules PubMed
    nef A dileucine motif in the CD4 cytoplasmic domain is required for its downregulation by HIV-1 Nef; cysteine residues in the cytoplasmic domain of CD4 are essential for the binding of Lck but are not required for Nef-induced downregulation PubMed
    nef HIV-1 Nef induces drastic and moderate downregulation of CD4 and MHC-I in resting CD4(+) T lymphocytes, respectively, but markedly upregulates cell surface levels of the MHC-II invariant chain CD74 PubMed
    nef HIV-1 Nef forms a ternary complex with ARF1 and beta-COP in endosomes, which facilitates Nef-induced downregulation and transport of CD4 to acidic late-endosomal compartments PubMed
    nef HIV-1 Nef-induced CD4 degradation is regulated by a highly conserved diacidic-based motif in Nef that acts as a lysosomal targeting signal through the binding of beta-COP in endosomes PubMed
    nef Nef from primary isolates of HIV-1 suppresses surface CD4 expression in human and mouse T cells PubMed
    nef Transduction of the HIV-1 nef gene into murine cells expressing human, chimpanzee, or murine CD4 induces cell surface downregulation of all three molecules; the cytoplasmic domain of CD4 is required for its downregulation by Nef PubMed
    nef In adult HIV-1 Nef transgenic mice, CD4 downregulation is found in CD4- and CD8-double positive thymocytes; co-localization of CD4 with a Golgi-specific marker indicates Nef interferes with CD4 intracellular trafficking PubMed
    nef CD4 is downregulated by nef alleles isolated from peripheral blood leukocytes of HIV-1-infected individuals; Nef proteins with point mutations at positions Gly2, Asp36, Cys122, and Val148 exhibit different levels of CD4 downregulation PubMed
    nef CD4 downregulation by HIV-1 Nef is independent of the level of CD4 mRNA expressed in cells and of the level of CD4 serine phosphorylation PubMed
    nef Overexpression of Nef-associated factor 1, Naf1, increases cell surface CD4 expression; HIV-1 Nef suppresses this activity of Naf1 to downregulate CD4 expression PubMed
    Pr55(Gag) gag The rapid kinetics of HIV-1 Gag transfer corresponds to similar time-dependent increases in CD4+ T cell infection from HIV-1 infected monocyte-derived macrophages PubMed
    gag HIV-1 Gag/p24 co-localizes with CD4 in the intracellular CD4+ compartments in primary T lymphocytes PubMed
    gag HIV-1 Gag-positive uropods form contacts enriched in CD4 PubMed
    Tat tat HIV-1 Tat-induced upregulation of miR-222 results in the post-transcriptional inhibition of CD4 expression PubMed
    tat CD4 and CD1a surface expression are greatly decreased in Tat expression Jurkat cells PubMed
    tat Expression of HRES-1/Rab4 is induced by HIV-1 tat, which in turn down-regulates expression of CD4 and susceptibility to re-infection by HIV-1 PubMed
    tat HIV-1 Tat upregulates mRNA expression and cell surface levels of CD4 antigen in Jurkat cells PubMed
    Vif vif Vif plays an important role in promoting HIV-1 binding to CD4 PubMed
    Vpr vpr HIV-1 Nef-Vpr fusion proteins are efficiently incorporated into HIV-1 particles and possess CD4 downregulation activity in target cells PubMed
    vpr HIV-1 Vpr increases expression of Nef protein from integrase-defective HIV-1. The Vpr-mediated expression of Nef from IN-minus HIV-1 results in CD4 downregulation PubMed
    vpr HIV-1 Vpr downregulates the expression of surface CD4 receptors in Jurkat T cells PubMed
    Vpu vpu HIV-1 Vpu downregulates cell (CEMT4, Primary CD4+ T cells) surface expression of CD4 PubMed
    vpu HIV-1 Vpu downregulates CD4 and is dependent on neddylation (covalent addition of NEDD8 onto a lysine residue on cullin backbone inducing conformational change in the cullin-RING E3 ubiquitin ligase complex rendering enzyme catalytically active) via NAE1 PubMed
    vpu Downregulation of CD4 from the surface of HIV-1 infected cells by HIV-1 Vpu increases viral infectivity PubMed
    vpu HIV-1 Vpu mediates retention of CD4 in the ER. Transmembrane domain interactions are the main determinant of ER retention of CD4 by Vpu PubMed
    vpu Poly-ubiquitination of the CD4 cytosolic tail by SCFbeta-TrCP is required for HIV-1 Vpu-induced CD4 degradation PubMed
    vpu The C-terminal domain of HIV-1 Vpu (amino acids 76-81) interacts with the cytoplasmic domain of CD4 (amino acids 402-425) and causes the rapid degradation of CD4 in the endoplasmic reticulum PubMed
    vpu HIV-1 Vpu mediated degradation of CD4 requires the function of proteasomes and results from the formation of a ternary complex between beta-TrCP, Vpu and CD4 which connects CD4 to the endoplasmic reticulum degradation pathway PubMed
    vpu Deletion of both HIV-1 nef and vpu genes enhance a significant engagement between HIV-1 gp120 and CD4 at the cell surface, suggesting Nef and Vpu prevent the exposure of epitopes recognized by anti-gp120 antibody-dependent cell-mediated cytotoxicity PubMed
    vpu Biotinylation technique in living cells demonstrates HIV-1 Vpu-induced retro-translocation of CD4 travels with oxidized intrachain disulfide bridges and accumulates in the cytosol as reduced and deglycosylated molecules only upon proteasomal inhibition PubMed
    vpu HIV-1 Vpu mutations (A19E, E29K, II43,46SL, R49G/T, SN53,55RH, S53N, E58K) derived from HIV-1 infected patients have defects for both CD4 and tetherin downregulation PubMed
    vpu Individual Vpu proteins isolated from chronically or acutely infected patients differ substantially in their CD4 and tetherin downregulation function at the cell surface PubMed
    vpu HIV-1 Vpu interacts with CD4 in living cells PubMed
    vpu Cell surface CD4 inhibits HIV-1 particle release by interfering with Vpu activity, possibly by disrupting the oligomeric structure of Vpu PubMed
    vpu HIV-1 Vpu regulates the formation of intracellular HIV-1 gp160-CD4 complexes and liberates Golgi-targeted gp160 from CD4-dependent retention in the endoplasmic reticulum PubMed
    vpu Chimeras between the TMD of HIV-1 M Vpu and the cytoplasmic domains of SIVcpzPtt, SIVcpzPts, and SIVgor Vpu proteins are capable of binding to human CD4 PubMed
    vpu A combination of molecular dynamics simulations and docking approaches shows the lowest energy structure of Vpu-CD4, indicating that the residues Leu-419 and Ile-416 in CD4 interact with the alanine rim (Ala-8/11/15/19) of Vpu PubMed
    vpu Magic angle sample spinning NMR analysis confirms the correct insertion of the transmembrane domains from both HIV-1 Vpu and CD4 (residues 372-433) into the lipid bilayers PubMed
    vpu The Val20 and Ser23 residues within the Vpu TMD are critical for Vpu-induced CD4 retention in the ER PubMed
    vpu Mutation of the HIV-1 Vpu Trp22 does not prevent Vpu-CD4 interaction but enhances Vpu oligomerization. The CD4 Gly415 residue within the CD4 TMD is required for both Vpu-CD4 interaction and Vpu-induced CD4 degradation PubMed
    vpu The HIV-1 Vpu Trp22 mutation in the Vpu transmembrane domain fails to induce CD4 degradation by reduced CD4 polyubiquitination. The Trp residue is highly conserved in all HIV-1 Vpu variants, including those of HIV-1 groups M, N, and O PubMed
    vpu NMR analysis indicates that amino acids (residues 39-48 and 64-70) in both helices of the HIV-1 Vpu cytoplasmic region are important for its binding to CD4 PubMed
    vpu Tetherin delGPI mutant directly interacts with HIV-1 Vpu and inhibits Vpu-induced degradation of tetherin and CD4 PubMed
    vpu The putative cholesterol recognition amino acid consensus (CRAC) motif (residues 25-31) of HIV-1 Vpu mediates lipid raft association of Vpu and affects the downregulation of cell surface CD4 PubMed
    vpu HIV-1 Vpu from subtype P can downregulate CD4 from cell surface PubMed
    vpu Downregulation of CD4 and BST2 by HIV-1 Vpu is observed in HIV-1 infected humanized mice PubMed
    vpu SCYL2 inhibits Vpu-induced BST2 and CD4 reduction at the cell surface by suppressing the phosphorylation of Vpu at positions Ser-52 and Ser-56 PubMed
    vpu Co-expression of HIV-1 Vpu with beta-TrCP2 induces degradation of total cellular CD4 content; Vpu-mediated CD4 down-modulation is inhibited by double silencing of beta-TrCP1 and beta-TrCP2 PubMed
    vpu The invariant leucine 63 and the valine 68 within the predicted second alpha-helical domain of the HIV-1 Vpu cytoplasmic tail are required for CD4 down-modulation. L63A and V68A mutants still bind CD4 and retain the ability to interact with beta-TrCP1 PubMed
    vpu Replication-defective Vpu TM mutants (V9D and I19D) and cytoplasmic domain mutants (S56G and E59K) fail to downregulate cell surface CD4, suggesting that viral replication potential and ability to downregulate CD4 by Vpu are correlated PubMed
    vpu HIV-1 Vpu Y35A/L39G mutant has a significant increase in CD4 surface expression compared to wild-type Vpu PubMed
    vpu HIV-1 Vpu proteins from pandemic HIV-1 M strains, but not from nonpandemic HIV-1 N strains, degrade the viral receptor CD4 PubMed
    vpu The VCP-UFD1L-NPL4 complex is required for HIV-1 Vpu-induced CD4 degradation in the ER-associated degradation pathway. The ATPase activity of VCP and ubiquitin binding to UFD1L are important for CD4 degradation by Vpu PubMed
    vpu A simian-human immunodeficiency virus (SHIVtm) with a scrambled amino acid sequence in the transmembrane domain of HIV-1 Vpu fails to downregulate cell surface expression of CD4 PubMed
    vpu Phosphorylation of HIV-1 Vpu on two serine phosphoacceptor sites (amino acids 52 and 56) by casein kinase 2 is required for Vpu-mediated degradation of CD4 in the endoplasmic reticulum PubMed

    Go to the HIV-1, Human Interaction Database

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
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      Alpha-defensins, organism-specific biosystemHumans have 7 alpha defensin genes plus 5 pseudogenes (see HGNC at http://www.genenames.org/genefamilies/DEFA). Alpha-defensins have six cysteines linked 1-6, 2-4, 3-5. The canonical sequence of alph...
    • Antigen processing and presentation, organism-specific biosystem (from KEGG)
      Antigen processing and presentation, organism-specific biosystem
      Antigen processing and presentation
    • Antigen processing and presentation, conserved biosystem (from KEGG)
      Antigen processing and presentation, conserved biosystem
      Antigen processing and presentation
    • Antimicrobial peptides, organism-specific biosystem (from REACTOME)
      Antimicrobial peptides, organism-specific biosystemAntimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum of antimicrobial activity against bacteria, viruses, and fungi (Zasloff M 2002; Radek K & Gallo R 2007). The majo...
    • Arf1 pathway, organism-specific biosystem (from Pathway Interaction Database)
      Arf1 pathway, organism-specific biosystem
      Arf1 pathway
    • Binding and entry of HIV virion, organism-specific biosystem (from REACTOME)
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    • C-MYB transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      C-MYB transcription factor network, organism-specific biosystem
      C-MYB transcription factor network
    • CXCR4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      CXCR4-mediated signaling events, organism-specific biosystem
      CXCR4-mediated signaling events
    • Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
      Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystemRecruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-...
    • Cell adhesion molecules (CAMs), organism-specific biosystem (from KEGG)
      Cell adhesion molecules (CAMs), organism-specific biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Cell adhesion molecules (CAMs), conserved biosystem (from KEGG)
      Cell adhesion molecules (CAMs), conserved biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
      Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
    • Costimulation by the CD28 family, organism-specific biosystem (from REACTOME)
      Costimulation by the CD28 family, organism-specific biosystemOptimal activation of T-lymphocytes requires at least two signals. A primary one is delivered by the T-cell receptor (TCR) complex after antigen recognition and additional costimulatory signals are d...
    • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
      Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
    • Cytokines and Inflammatory Response, organism-specific biosystem (from WikiPathways)
      Cytokines and Inflammatory Response, organism-specific biosystemInflammation is a protective response to infection by the immune system that requires communication between different classes of immune cells to coordinate their actions. Acute inflammation is an imp...
    • Defensins, organism-specific biosystem (from REACTOME)
      Defensins, organism-specific biosystemThe defensins are a family of antimicrobial cationic peptide molecules which in mammals have a characteristic beta-sheet-rich fold and framework of six disulphide-linked cysteines (Selsted & Ouellet...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Downstream TCR signaling, organism-specific biosystem (from REACTOME)
      Downstream TCR signaling, organism-specific biosystemChanges in gene expression are required for the T cell to gain full proliferative competence and to produce effector cytokines. Three transcription factors in particular have been found to play a key...
    • Early Phase of HIV Life Cycle, organism-specific biosystem (from REACTOME)
      Early Phase of HIV Life Cycle, organism-specific biosystemIn the early phase of HIV lifecycle, an active virion binds and enters a target cell mainly by specific interactions of the viral envelope proteins with host cell surface receptors. The virion core...
    • Generation of second messenger molecules, organism-specific biosystem (from REACTOME)
      Generation of second messenger molecules, organism-specific biosystemIn addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have be...
    • HIV Infection, organism-specific biosystem (from REACTOME)
      HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
    • HIV Life Cycle, organism-specific biosystem (from REACTOME)
      HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
    • Hematopoietic cell lineage, organism-specific biosystem (from KEGG)
      Hematopoietic cell lineage, organism-specific biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
    • Hematopoietic cell lineage, conserved biosystem (from KEGG)
      Hematopoietic cell lineage, conserved biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
    • Host Interactions of HIV factors, organism-specific biosystem (from REACTOME)
      Host Interactions of HIV factors, organism-specific biosystemLike all viruses, HIV-1 must co-opt the host cell macromolecular transport and processing machinery. HIV-1 Vpr and Rev proteins play key roles in this co-optation. Efficient HIV-1 replication likewis...
    • IL12 signaling mediated by STAT4, organism-specific biosystem (from Pathway Interaction Database)
      IL12 signaling mediated by STAT4, organism-specific biosystem
      IL12 signaling mediated by STAT4
    • IL12-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL12-mediated signaling events, organism-specific biosystem
      IL12-mediated signaling events
    • IL23-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL23-mediated signaling events, organism-specific biosystem
      IL23-mediated signaling events
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Infectious disease, organism-specific biosystem (from REACTOME)
      Infectious disease, organism-specific biosystem
      Infectious disease
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • Membrane Trafficking, organism-specific biosystem (from REACTOME)
      Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
    • Nef Mediated CD4 Down-regulation, organism-specific biosystem (from REACTOME)
      Nef Mediated CD4 Down-regulation, organism-specific biosystemThe presence of Nef accelerates endocytosis and lysosomal degradation of the transmembrane glycoprotein CD4. CD4 has its own internalization motif, though this motif is normally concealed by CD4 inte...
    • Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters, organism-specific biosystem (from REACTOME)
      Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters, organism-specific biosystemThe maximal virulence of HIV-1 requires Nef, a virally encoded peripheral membrane protein. Nef binds to the adaptor protein (AP) complexes of coated vesicles, inducing an expansion of the endosomal ...
    • Notch-mediated HES/HEY network, organism-specific biosystem (from Pathway Interaction Database)
      Notch-mediated HES/HEY network, organism-specific biosystem
      Notch-mediated HES/HEY network
    • PD-1 signaling, organism-specific biosystem (from REACTOME)
      PD-1 signaling, organism-specific biosystemThe Programmed cell death protein 1 (PD-1) is one of the negative regulators of TCR signaling. PD-1 may exert its effects on cell differentiation and survival directly by inhibiting early activation ...
    • Phosphorylation of CD3 and TCR zeta chains, organism-specific biosystem (from REACTOME)
      Phosphorylation of CD3 and TCR zeta chains, organism-specific biosystemPrior to T cell receptor (TCR) stimulation, CD4/CD8 associated Lck remains seperated from the TCR and is maintained in an inactive state by the action of Csk. Csk phosphorylates the negative regulato...
    • Primary immunodeficiency, organism-specific biosystem (from KEGG)
      Primary immunodeficiency, organism-specific biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
    • Primary immunodeficiency, conserved biosystem (from KEGG)
      Primary immunodeficiency, conserved biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
    • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
      Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
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    • T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystem (from WikiPathways)
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    • T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystem (from WikiPathways)
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    • TCR signaling, organism-specific biosystem (from REACTOME)
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    • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
      TCR signaling in naive CD4+ T cells, organism-specific biosystem
      TCR signaling in naive CD4+ T cells
    • Th1 and Th2 cell differentiation, organism-specific biosystem (from KEGG)
      Th1 and Th2 cell differentiation, organism-specific biosystemImmunity to different classes of microorganisms is orchestrated by separate lineages of effector T helper (TH)-cells, which differentiate from naive CD4+ precursor cells in response to cues provided ...
    • Th1 and Th2 cell differentiation, conserved biosystem (from KEGG)
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    • Th17 cell differentiation, organism-specific biosystem (from KEGG)
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    • Th17 cell differentiation, conserved biosystem (from KEGG)
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    • The role of Nef in HIV-1 replication and disease pathogenesis, organism-specific biosystem (from REACTOME)
      The role of Nef in HIV-1 replication and disease pathogenesis, organism-specific biosystemThe HIV-1 Nef protein is a 27-kDa myristoylated protein that is abundantly produced during the early phase of viral replication cycle. It is highly conserved in all primate lentiviruses, suggesting t...
    • Translocation of ZAP-70 to Immunological synapse, organism-specific biosystem (from REACTOME)
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    • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
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    • Vpu mediated degradation of CD4, organism-specific biosystem (from REACTOME)
      Vpu mediated degradation of CD4, organism-specific biosystemThe HIV-1 Vpu protein promotes the degradation of the CD4 receptor by recruiting an SCF like ubiquitination complex that promotes CD4 degradation. Vpu links beta-TrCP to CD4 at the ER membrane thro...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    MHC class II protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MHC class II protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    MHC class II protein binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    coreceptor activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    extracellular matrix structural constituent NAS
    Non-traceable Author Statement
    more info
    PubMed 
    glycoprotein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    immunoglobulin binding IEA
    Inferred from Electronic Annotation
    more info
     
    interleukin-16 binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    interleukin-16 receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein tyrosine kinase binding IEA
    Inferred from Electronic Annotation
    more info
     
    receptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    transmembrane signaling receptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    virus receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    zinc ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    T cell costimulation TAS
    Traceable Author Statement
    more info
     
    T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    T cell selection IDA
    Inferred from Direct Assay
    more info
    PubMed 
    adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
     
    cell adhesion IEA
    Inferred from Electronic Annotation
    more info
     
    cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    cellular response to granulocyte macrophage colony-stimulating factor stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytokine production IEA
    Inferred from Electronic Annotation
    more info
     
    defense response to Gram-negative bacterium IEA
    Inferred from Electronic Annotation
    more info
     
    entry into host cell TAS
    Traceable Author Statement
    more info
     
    enzyme linked receptor protein signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    fusion of virus membrane with host plasma membrane TAS
    Traceable Author Statement
    more info
     
    helper T cell enhancement of adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
     
    immune response NAS
    Non-traceable Author Statement
    more info
    PubMed 
    induction by virus of host cell-cell fusion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    interleukin-15-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    maintenance of protein location in cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane organization TAS
    Traceable Author Statement
    more info
     
    positive regulation of ERK1 and ERK2 cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of I-kappaB kinase/NF-kappaB signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of MAPK cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of calcium ion transport into cytosol IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of calcium-mediated signaling IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of interleukin-2 biosynthetic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of monocyte differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of peptidyl-tyrosine phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of viral entry into host cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of calcium ion transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of defense response to virus by virus TAS
    Traceable Author Statement
    more info
     
    response to estradiol IEA
    Inferred from Electronic Annotation
    more info
     
    response to vitamin D IEA
    Inferred from Electronic Annotation
    more info
     
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    transmembrane receptor protein tyrosine kinase signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    T cell receptor complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    clathrin-coated vesicle membrane TAS
    Traceable Author Statement
    more info
     
    early endosome TAS
    Traceable Author Statement
    more info
     
    endoplasmic reticulum lumen IEA
    Inferred from Electronic Annotation
    more info
     
    endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral component of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane raft IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    T-cell surface glycoprotein CD4
    Names
    CD4 antigen (p55)
    CD4 receptor
    T-cell surface antigen T4/Leu-3

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_027688.1 RefSeqGene

      Range
      5001..36339
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000616.4NP_000607.1  T-cell surface glycoprotein CD4 isoform 1 precursor

      See identical proteins and their annotated locations for NP_000607.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1) including a signal peptide and a mature peptide.
      Source sequence(s)
      AK316462, BC025782, CA305950, DA384217, U47924
      Consensus CDS
      CCDS8562.1
      UniProtKB/Swiss-Prot
      P01730
      UniProtKB/TrEMBL
      B4DT49
      Related
      ENSP00000011653.4, OTTHUMP00000238897, ENST00000011653.8, OTTHUMT00000399978
      Conserved Domains (6) summary
      cd07690
      Location:28121
      Ig1_CD4; First immunoglobulin (Ig) domain of CD4
      cd07694
      Location:123204
      Ig2_CD4; Second immunoglobulin (Ig) domain of CD4
      smart00410
      Location:27122
      IG_like; Immunoglobulin like
      pfam05790
      Location:317389
      C2-set; Immunoglobulin C2-set domain
      pfam09191
      Location:208316
      CD4-extracel; CD4, extracellular
      pfam12104
      Location:426453
      Tcell_CD4_C; T cell CD4 receptor C terminal region
    2. NM_001195014.2NP_001181943.1  T-cell surface glycoprotein CD4 isoform 2

      See identical proteins and their annotated locations for NP_001181943.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site, lacks two consecutive exons and initiates translation from an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AK300052, AK315898, AK316462, BX378810, CA305950, DA384217, U47924
      UniProtKB/TrEMBL
      B0AZV7, B4DT49
      Conserved Domains (4) summary
      cd12087
      Location:209249
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      pfam05790
      Location:138210
      C2-set; Immunoglobulin C2-set domain
      pfam09191
      Location:29137
      CD4-extracel; CD4, extracellular
      pfam12104
      Location:247274
      Tcell_CD4_C; T cell CD4 receptor C terminal region
    3. NM_001195015.2NP_001181944.1  T-cell surface glycoprotein CD4 isoform 3

      See identical proteins and their annotated locations for NP_001181944.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site, lacks two consecutive exons and initiates translation from a downstream, in-frame start codon, compared to variant 1. Variants 3, 4 and 5 encode isoform 3, which has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AK300052, AK316462, BX378810, CA305950, DA384217
      UniProtKB/TrEMBL
      B4DT49
      Conserved Domains (4) summary
      cd12087
      Location:115155
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      pfam05790
      Location:44116
      C2-set; Immunoglobulin C2-set domain
      pfam12104
      Location:153180
      Tcell_CD4_C; T cell CD4 receptor C terminal region
      cl11960
      Location:143
      Ig; Immunoglobulin domain
    4. NM_001195016.2NP_001181945.1  T-cell surface glycoprotein CD4 isoform 3

      See identical proteins and their annotated locations for NP_001181945.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks two consecutive exons and initiates translation from a downstream, in-frame start codon, compared to variant 1. Variants 3, 4 and 5 encode isoform 3, which has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AK300052, AK316461, AK316462, BX378810, CA305950, DA384217
      UniProtKB/TrEMBL
      B4DT49
      Conserved Domains (4) summary
      cd12087
      Location:115155
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      pfam05790
      Location:44116
      C2-set; Immunoglobulin C2-set domain
      pfam12104
      Location:153180
      Tcell_CD4_C; T cell CD4 receptor C terminal region
      cl11960
      Location:143
      Ig; Immunoglobulin domain
    5. NM_001195017.2NP_001181946.1  T-cell surface glycoprotein CD4 isoform 3

      See identical proteins and their annotated locations for NP_001181946.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site, lacks two consecutive exons and initiates translation from a downstream, in-frame start codon, compared to variant 1. Variants 3, 4 and 5 encode isoform 3, which has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AK300052, AK316462, BX378810, CA305950, DA384217
      UniProtKB/TrEMBL
      B4DT49
      Conserved Domains (4) summary
      cd12087
      Location:115155
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      pfam05790
      Location:44116
      C2-set; Immunoglobulin C2-set domain
      pfam12104
      Location:153180
      Tcell_CD4_C; T cell CD4 receptor C terminal region
      cl11960
      Location:143
      Ig; Immunoglobulin domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p7 Primary Assembly

      Range
      6789472..6820810
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017020228.1XP_016875717.1  T-cell surface glycoprotein CD4 isoform X1

      UniProtKB/TrEMBL
      B4DT49
      Conserved Domains (4) summary
      cd12087
      Location:115155
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      pfam05790
      Location:44116
      C2-set; Immunoglobulin C2-set domain
      pfam12104
      Location:153180
      Tcell_CD4_C; T cell CD4 receptor C terminal region
      cl11960
      Location:143
      Ig; Immunoglobulin domain

    Alternate CHM1_1.1

    Genomic

    1. NC_018923.2 Alternate CHM1_1.1

      Range
      6897616..6928653
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_036545.1: Suppressed sequence

      Description
      NR_036545.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
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