#ID(s) interactor A ID(s) interactor B Alt. ID(s) interactor A Alt. ID(s) interactor B Alias(es) interactor A Alias(es) interactor B Interaction detection method(s) Publication 1st author(s) Publication Identifier(s) Taxid interactor A Taxid interactor B Interaction type(s) Source database(s) Interaction identifier(s) Confidence value(s) Expansion method(s) Biological role(s) interactor A Biological role(s) interactor B Experimental role(s) interactor A Experimental role(s) interactor B Type(s) interactor A Type(s) interactor B Xref(s) interactor A Xref(s) interactor B Interaction Xref(s) Annotation(s) interactor A Annotation(s) interactor B Interaction annotation(s) Host organism(s) Interaction parameter(s) Creation date Update date Checksum(s) interactor A Checksum(s) interactor B Interaction Checksum(s) Negative Feature(s) interactor A Feature(s) interactor B Stoichiometry(s) interactor A Stoichiometry(s) interactor B Identification method participant A Identification method participant B uniprotkb:P03407 uniprotkb:P01730 intact:EBI-7355020|intact:MINT-1206762 intact:EBI-353826|uniprotkb:Q4ZGK2|uniprotkb:Q5U066|uniprotkb:Q9UDE5|uniprotkb:B2R737|uniprotkb:D3DUS5|ensembl:ENSP00000011653 psi-mi:nef_hv1a2(display_long)|uniprotkb:nef(gene name)|psi-mi:nef(display_short)|uniprotkb:Negative factor(gene name synonym)|uniprotkb:3'ORF(gene name synonym) psi-mi:cd4_human(display_long)|uniprotkb:CD4(gene name)|psi-mi:CD4(display_short)|uniprotkb:T-cell surface antigen T4/Leu-3(gene name synonym) psi-mi:"MI:0017"(classical fluorescence spectroscopy) Preusser et al. (2001) pubmed:11264384|doi:10.1128/jvi.75.8.3960-3964.2001|imex:IM-24797 taxid:11685(hv1a2)|taxid:11685("Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)") taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0465"(DIP) intact:EBI-15490466|imex:IM-24797-1|dip:DIP-199728E - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) go:"GO:0005525"(GTP binding)|go:"GO:0005576"(extracellular region)|go:"GO:0007171"(activation of transmembrane receptor protein tyrosine kinase activity)|go:"GO:0016020"(membrane)|go:"GO:0017124"(SH3 domain binding)|go:"GO:0020002"(host cell plasma membrane)|go:"GO:0039504"(suppression by virus of host adaptive immune response)|go:"GO:0039505"(suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II)|go:"GO:0039521"(suppression by virus of host autophagy)|go:"GO:0044178"(host cell Golgi membrane)|go:"GO:0046776"(suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I)|interpro:IPR001558(HIV negative factor Nef)|interpro:IPR027480|interpro:IPR027481|rcsb pdb:3RBB|rcsb pdb:3REA|rcsb pdb:3REB|rcsb pdb:4ORZ|rcsb pdb:4U1K|rcsb pdb:4U1L|rcsb pdb:4U1M|rcsb pdb:4U1N|rcsb pdb:4U5W|rcsb pdb:5XOV|rcsb pdb:6B72|rcsb pdb:7D7S|dip:DIP-29212N refseq:NP_000607.1|rcsb pdb:1CDI|rcsb pdb:1CDJ|rcsb pdb:1CDU|rcsb pdb:1CDY|rcsb pdb:1G9M|rcsb pdb:1G9N|rcsb pdb:1GC1|rcsb pdb:1JL4|rcsb pdb:1OPN|rcsb pdb:1OPT|rcsb pdb:1OPW|rcsb pdb:1Q68|rcsb pdb:1RZJ|rcsb pdb:1RZK|rcsb pdb:1WBR|rcsb pdb:1WIO|rcsb pdb:1WIP|rcsb pdb:1WIQ|rcsb pdb:2B4C|rcsb pdb:1CDH|rcsb pdb:2JKR|rcsb pdb:2JKT|reactome:R-HSA-202430|reactome:R-HSA-202433|reactome:R-HSA-202427|reactome:R-HSA-389948|reactome:R-HSA-449836|reactome:R-HSA-8856825|reactome:R-HSA-8856828|ensembl:ENST00000011653(transcript)|go:"GO:0045657"(positive regulation of monocyte differentiation)|go:"GO:0045860"(positive regulation of protein kinase activity)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0046598"(positive regulation of viral entry into host cell)|go:"GO:0050731"(positive regulation of peptidyl-tyrosine phosphorylation)|go:"GO:0050829"(defense response to Gram-negative bacterium)|go:"GO:0050850"(positive regulation of calcium-mediated signaling)|go:"GO:0050863"(regulation of T cell activation)|go:"GO:0050870"(positive regulation of T cell activation)|go:"GO:0051924"(regulation of calcium ion transport)|go:"GO:0070374"(positive regulation of ERK1 and ERK2 cascade)|go:"GO:0097011"(cellular response to granulocyte macrophage colony-stimulating factor stimulus)|go:"GO:1990782"(protein tyrosine kinase binding)|interpro:IPR000973(T-cell surface antigen CD4)|interpro:IPR003598(Immunoglobulin subtype 2)|interpro:IPR003599(Immunoglobulin subtype)|interpro:IPR007110(Immunoglobulin-like)|interpro:IPR008424(Immunoglobulin C2-set)|interpro:IPR013106(Immunoglobulin V-set)|interpro:IPR013151(Immunoglobulin)|interpro:IPR013783(Immunoglobulin-like fold)|interpro:IPR015274(CD4, extracellular)|interpro:IPR021963|interpro:IPR036179|mint:P01730|go:"GO:0001618"(virus receptor activity)|go:"GO:0001934"(positive regulation of protein phosphorylation)|go:"GO:0002250"(adaptive immune response)|go:"GO:0004888"(transmembrane signaling receptor activity)|go:"GO:0005201"(extracellular matrix structural constituent)|go:"GO:0005769"(early endosome)|go:"GO:0005788"(endoplasmic reticulum lumen)|go:"GO:0005789"(endoplasmic reticulum membrane)|go:"GO:0005886"(plasma membrane)|go:"GO:0005887"(integral component of plasma membrane)|go:"GO:0006948"(induction by virus of host cell-cell fusion)|go:"GO:0006955"(immune response)|go:"GO:0007155"(cell adhesion)|go:"GO:0007165"(signal transduction)|go:"GO:0007166"(cell surface receptor signaling pathway)|go:"GO:0007167"(enzyme linked receptor protein signaling pathway)|go:"GO:0007169"(transmembrane receptor protein tyrosine kinase signaling pathway)|go:"GO:0008270"(zinc ion binding)|go:"GO:0009897"(external side of plasma membrane)|go:"GO:0015026"(coreceptor activity)|go:"GO:0019899"(enzyme binding)|go:"GO:0019901"(protein kinase binding)|go:"GO:0023026"(MHC class II protein complex binding)|go:"GO:0030217"(T cell differentiation)|go:"GO:0030225"(macrophage differentiation)|go:"GO:0030669"(clathrin-coated endocytic vesicle membrane)|go:"GO:0032507"(maintenance of protein location in cell)|go:"GO:0032743"(positive regulation of interleukin-2 production)|go:"GO:0033674"(positive regulation of kinase activity)|go:"GO:0035397"(helper T cell enhancement of adaptive immune response)|go:"GO:0035723"(interleukin-15-mediated signaling pathway)|go:"GO:0038023"(signaling receptor activity)|go:"GO:0042011"(interleukin-16 binding)|go:"GO:0042012"(interleukin-16 receptor activity)|go:"GO:0042101"(T cell receptor complex)|go:"GO:0042110"(T cell activation)|go:"GO:0042289"(MHC class II protein binding)|go:"GO:0042802"(identical protein binding)|go:"GO:0042803"(protein homodimerization activity)|go:"GO:0043123"(positive regulation of I-kappaB kinase/NF-kappaB signaling)|go:"GO:0043410"(positive regulation of MAPK cascade)|go:"GO:0045058"(T cell selection)|go:"GO:0045121"(membrane raft)|rcsb pdb:2KLU|rcsb pdb:2NXY|rcsb pdb:2NXZ|rcsb pdb:2NY0|rcsb pdb:2NY1|rcsb pdb:2NY2|rcsb pdb:2NY3|rcsb pdb:2NY4|rcsb pdb:2NY5|rcsb pdb:2NY6|rcsb pdb:2QAD|rcsb pdb:3B71|rcsb pdb:3CD4|rcsb pdb:3J70|rcsb pdb:3JCB|rcsb pdb:3JCC|rcsb pdb:3JWD|rcsb pdb:3JWO|rcsb pdb:3LQA|rcsb pdb:3O2D|rcsb pdb:3S4S|rcsb pdb:3S5L|rcsb pdb:3T0E|rcsb pdb:4H8W|rcsb pdb:4JM2|rcsb pdb:4P9H|rcsb pdb:4Q6I|rcsb pdb:4R2G|rcsb pdb:4R4H|rcsb pdb:4RQS|rcsb pdb:5A7X|rcsb pdb:5A8H|rcsb pdb:5CAY|rcsb pdb:5THR|rcsb pdb:5U1F|rcsb pdb:5VN3|rcsb pdb:6CM3|rcsb pdb:6EDU|rcsb pdb:6L1Y|rcsb pdb:6MEO|rcsb pdb:6MET|rcsb pdb:6OPN|rcsb pdb:6OPO|rcsb pdb:6OPP|rcsb pdb:6OPQ|rcsb pdb:6QH6|rcsb pdb:6QH7|rcsb pdb:6U0L|rcsb pdb:6U0N|rcsb pdb:6URI|rcsb pdb:6X5B|rcsb pdb:6X5C|reactome:R-HSA-1462054|reactome:R-HSA-167590|reactome:R-HSA-173107|reactome:R-HSA-180534|reactome:R-HSA-202424|ensembl:ENSG00000010610(gene)|dip:DIP-617N psi-mi:"MI:0465"(dip) function:"Down-modulates surface MHC-I molecules. Internalized molecules are sequestred to the trans-Golgi network (TGN). Also decreases cell surface CD4 antigen by interacting with the Src family kinase LCK thereby inducing LCK-CD4 dissociation and by increasing clathrin-dependent endocytosis of this antigen to target it to lysosomal degradation. Peroxisomal acyl-coenzyme A thioester hydrolase 1 (PTE1) seems to be involved in this process. May serve as a direct bridge between CD4 and the cellular endocytic machinery by interacting with beta-COP and adaptins. In consequence, surface MHC-I and CD4 are decreased and infected cells are masked for immune recognition by cytotoxic T lymphocytes. Decreasing the number of viral receptors prevents reinfection by more HIV particles"|function:"Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interacts with the TCR-zeta chain to up-regulate the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules send attacking cytotoxic T-cell into apoptosis"|function:Protects the infected cell from apoptosis in order to keep it alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5. Interacts with p53 and decreases the half-life of the latter, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that induces phosphorylation of Bad|comment:mint|comment:homomint|function:Early protein that seems to play a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Enhances virus infectivity and pathogenicity - full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2017/08/04 2017/08/10 rogid:5t7cTiE8lwJClrc3l7SQN9+TC6M11685 rogid:twRRh+v4xPOIlmeD9jl+Jpqjle09606 rigid:C6L32654hnJio3gN5B+ZSMSWrYc false - sufficient binding region:428-444|mutation disrupting interaction strength:438-439|fluorescein label:n-n - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:P03407 uniprotkb:P01730 intact:EBI-7355020|intact:MINT-1206762 intact:EBI-353826|uniprotkb:Q4ZGK2|uniprotkb:Q5U066|uniprotkb:Q9UDE5|uniprotkb:B2R737|uniprotkb:D3DUS5|ensembl:ENSP00000011653 psi-mi:nef_hv1a2(display_long)|uniprotkb:nef(gene name)|psi-mi:nef(display_short)|uniprotkb:Negative factor(gene name synonym)|uniprotkb:3'ORF(gene name synonym) psi-mi:cd4_human(display_long)|uniprotkb:CD4(gene name)|psi-mi:CD4(display_short)|uniprotkb:T-cell surface antigen T4/Leu-3(gene name synonym) psi-mi:"MI:0077"(nuclear magnetic resonance) Preusser et al. (2001) pubmed:11264384|doi:10.1128/jvi.75.8.3960-3964.2001|imex:IM-24797 taxid:11685(hv1a2)|taxid:11685("Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)") taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0465"(DIP) intact:EBI-15490489|imex:IM-24797-2|dip:DIP-199728E - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) go:"GO:0005525"(GTP binding)|go:"GO:0005576"(extracellular region)|go:"GO:0007171"(activation of transmembrane receptor protein tyrosine kinase activity)|go:"GO:0016020"(membrane)|go:"GO:0017124"(SH3 domain binding)|go:"GO:0020002"(host cell plasma membrane)|go:"GO:0039504"(suppression by virus of host adaptive immune response)|go:"GO:0039505"(suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II)|go:"GO:0039521"(suppression by virus of host autophagy)|go:"GO:0044178"(host cell Golgi membrane)|go:"GO:0046776"(suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I)|interpro:IPR001558(HIV negative factor Nef)|interpro:IPR027480|interpro:IPR027481|rcsb pdb:3RBB|rcsb pdb:3REA|rcsb pdb:3REB|rcsb pdb:4ORZ|rcsb pdb:4U1K|rcsb pdb:4U1L|rcsb pdb:4U1M|rcsb pdb:4U1N|rcsb pdb:4U5W|rcsb pdb:5XOV|rcsb pdb:6B72|rcsb pdb:7D7S|dip:DIP-29212N refseq:NP_000607.1|rcsb pdb:1CDI|rcsb pdb:1CDJ|rcsb pdb:1CDU|rcsb pdb:1CDY|rcsb pdb:1G9M|rcsb pdb:1G9N|rcsb pdb:1GC1|rcsb pdb:1JL4|rcsb pdb:1OPN|rcsb pdb:1OPT|rcsb pdb:1OPW|rcsb pdb:1Q68|rcsb pdb:1RZJ|rcsb pdb:1RZK|rcsb pdb:1WBR|rcsb pdb:1WIO|rcsb pdb:1WIP|rcsb pdb:1WIQ|rcsb pdb:2B4C|rcsb pdb:1CDH|rcsb pdb:2JKR|rcsb pdb:2JKT|reactome:R-HSA-202430|reactome:R-HSA-202433|reactome:R-HSA-202427|reactome:R-HSA-389948|reactome:R-HSA-449836|reactome:R-HSA-8856825|reactome:R-HSA-8856828|ensembl:ENST00000011653(transcript)|go:"GO:0045657"(positive regulation of monocyte differentiation)|go:"GO:0045860"(positive regulation of protein kinase activity)|go:"GO:0045893"(positive regulation of transcription, DNA-templated)|go:"GO:0046598"(positive regulation of viral entry into host cell)|go:"GO:0050731"(positive regulation of peptidyl-tyrosine phosphorylation)|go:"GO:0050829"(defense response to Gram-negative bacterium)|go:"GO:0050850"(positive regulation of calcium-mediated signaling)|go:"GO:0050863"(regulation of T cell activation)|go:"GO:0050870"(positive regulation of T cell activation)|go:"GO:0051924"(regulation of calcium ion transport)|go:"GO:0070374"(positive regulation of ERK1 and ERK2 cascade)|go:"GO:0097011"(cellular response to granulocyte macrophage colony-stimulating factor stimulus)|go:"GO:1990782"(protein tyrosine kinase binding)|interpro:IPR000973(T-cell surface antigen CD4)|interpro:IPR003598(Immunoglobulin subtype 2)|interpro:IPR003599(Immunoglobulin subtype)|interpro:IPR007110(Immunoglobulin-like)|interpro:IPR008424(Immunoglobulin C2-set)|interpro:IPR013106(Immunoglobulin V-set)|interpro:IPR013151(Immunoglobulin)|interpro:IPR013783(Immunoglobulin-like fold)|interpro:IPR015274(CD4, extracellular)|interpro:IPR021963|interpro:IPR036179|mint:P01730|go:"GO:0001618"(virus receptor activity)|go:"GO:0001934"(positive regulation of protein phosphorylation)|go:"GO:0002250"(adaptive immune response)|go:"GO:0004888"(transmembrane signaling receptor activity)|go:"GO:0005201"(extracellular matrix structural constituent)|go:"GO:0005769"(early endosome)|go:"GO:0005788"(endoplasmic reticulum lumen)|go:"GO:0005789"(endoplasmic reticulum membrane)|go:"GO:0005886"(plasma membrane)|go:"GO:0005887"(integral component of plasma membrane)|go:"GO:0006948"(induction by virus of host cell-cell fusion)|go:"GO:0006955"(immune response)|go:"GO:0007155"(cell adhesion)|go:"GO:0007165"(signal transduction)|go:"GO:0007166"(cell surface receptor signaling pathway)|go:"GO:0007167"(enzyme linked receptor protein signaling pathway)|go:"GO:0007169"(transmembrane receptor protein tyrosine kinase signaling pathway)|go:"GO:0008270"(zinc ion binding)|go:"GO:0009897"(external side of plasma membrane)|go:"GO:0015026"(coreceptor activity)|go:"GO:0019899"(enzyme binding)|go:"GO:0019901"(protein kinase binding)|go:"GO:0023026"(MHC class II protein complex binding)|go:"GO:0030217"(T cell differentiation)|go:"GO:0030225"(macrophage differentiation)|go:"GO:0030669"(clathrin-coated endocytic vesicle membrane)|go:"GO:0032507"(maintenance of protein location in cell)|go:"GO:0032743"(positive regulation of interleukin-2 production)|go:"GO:0033674"(positive regulation of kinase activity)|go:"GO:0035397"(helper T cell enhancement of adaptive immune response)|go:"GO:0035723"(interleukin-15-mediated signaling pathway)|go:"GO:0038023"(signaling receptor activity)|go:"GO:0042011"(interleukin-16 binding)|go:"GO:0042012"(interleukin-16 receptor activity)|go:"GO:0042101"(T cell receptor complex)|go:"GO:0042110"(T cell activation)|go:"GO:0042289"(MHC class II protein binding)|go:"GO:0042802"(identical protein binding)|go:"GO:0042803"(protein homodimerization activity)|go:"GO:0043123"(positive regulation of I-kappaB kinase/NF-kappaB signaling)|go:"GO:0043410"(positive regulation of MAPK cascade)|go:"GO:0045058"(T cell selection)|go:"GO:0045121"(membrane raft)|rcsb pdb:2KLU|rcsb pdb:2NXY|rcsb pdb:2NXZ|rcsb pdb:2NY0|rcsb pdb:2NY1|rcsb pdb:2NY2|rcsb pdb:2NY3|rcsb pdb:2NY4|rcsb pdb:2NY5|rcsb pdb:2NY6|rcsb pdb:2QAD|rcsb pdb:3B71|rcsb pdb:3CD4|rcsb pdb:3J70|rcsb pdb:3JCB|rcsb pdb:3JCC|rcsb pdb:3JWD|rcsb pdb:3JWO|rcsb pdb:3LQA|rcsb pdb:3O2D|rcsb pdb:3S4S|rcsb pdb:3S5L|rcsb pdb:3T0E|rcsb pdb:4H8W|rcsb pdb:4JM2|rcsb pdb:4P9H|rcsb pdb:4Q6I|rcsb pdb:4R2G|rcsb pdb:4R4H|rcsb pdb:4RQS|rcsb pdb:5A7X|rcsb pdb:5A8H|rcsb pdb:5CAY|rcsb pdb:5THR|rcsb pdb:5U1F|rcsb pdb:5VN3|rcsb pdb:6CM3|rcsb pdb:6EDU|rcsb pdb:6L1Y|rcsb pdb:6MEO|rcsb pdb:6MET|rcsb pdb:6OPN|rcsb pdb:6OPO|rcsb pdb:6OPP|rcsb pdb:6OPQ|rcsb pdb:6QH6|rcsb pdb:6QH7|rcsb pdb:6U0L|rcsb pdb:6U0N|rcsb pdb:6URI|rcsb pdb:6X5B|rcsb pdb:6X5C|reactome:R-HSA-1462054|reactome:R-HSA-167590|reactome:R-HSA-173107|reactome:R-HSA-180534|reactome:R-HSA-202424|ensembl:ENSG00000010610(gene)|dip:DIP-617N psi-mi:"MI:0465"(dip) function:"Down-modulates surface MHC-I molecules. Internalized molecules are sequestred to the trans-Golgi network (TGN). Also decreases cell surface CD4 antigen by interacting with the Src family kinase LCK thereby inducing LCK-CD4 dissociation and by increasing clathrin-dependent endocytosis of this antigen to target it to lysosomal degradation. Peroxisomal acyl-coenzyme A thioester hydrolase 1 (PTE1) seems to be involved in this process. May serve as a direct bridge between CD4 and the cellular endocytic machinery by interacting with beta-COP and adaptins. In consequence, surface MHC-I and CD4 are decreased and infected cells are masked for immune recognition by cytotoxic T lymphocytes. Decreasing the number of viral receptors prevents reinfection by more HIV particles"|function:"Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interacts with the TCR-zeta chain to up-regulate the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules send attacking cytotoxic T-cell into apoptosis"|function:Protects the infected cell from apoptosis in order to keep it alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5. Interacts with p53 and decreases the half-life of the latter, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that induces phosphorylation of Bad|comment:mint|comment:homomint|function:Early protein that seems to play a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Enhances virus infectivity and pathogenicity - full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2017/08/04 2017/08/10 rogid:5t7cTiE8lwJClrc3l7SQN9+TC6M11685 rogid:twRRh+v4xPOIlmeD9jl+Jpqjle09606 rigid:C6L32654hnJio3gN5B+ZSMSWrYc false - sufficient binding region:403-433 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant)