PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 9314527-6 1997 In this model, Nef interacts on one side with CD4 through a dileucine-based motif present on CD4 cytoplasmic tail and on the other side with components of clathrin-coated surface domain (i.e., adaptins). dileucine 60-69 S100 calcium binding protein B Homo sapiens 15-18 10814565-2 2000 However, the role of the dileucine-based sorting motif within Nef in these interactions has been incompletely characterized. dileucine 25-34 S100 calcium binding protein B Homo sapiens 62-65 10814565-8 2000 These data suggest that the dileucine motif, required for optimal viral replication, functions through interactions with a variety of AP complexes, including AP-3, potentially by recruiting adaptor complexes to subcellular locations specified by additional determinants in the Nef protein. dileucine 28-37 S100 calcium binding protein B Homo sapiens 277-280 9736718-3 1998 By using a competition assay that functionally discriminates between dileucine-based and tyrosine-based sorting signals, we have categorized the motif through which Nef interacts with the sorting machinery as dileucine-based. dileucine 69-78 S100 calcium binding protein B Homo sapiens 165-168 9736718-3 1998 By using a competition assay that functionally discriminates between dileucine-based and tyrosine-based sorting signals, we have categorized the motif through which Nef interacts with the sorting machinery as dileucine-based. dileucine 209-218 S100 calcium binding protein B Homo sapiens 165-168 9736718-6 1998 The leucine residues in this motif were required for the interaction of full-length Nef with the dileucine-based sorting pathway and were required for Nef-mediated down-regulation of CD4. dileucine 97-106 S100 calcium binding protein B Homo sapiens 84-87 9736718-6 1998 The leucine residues in this motif were required for the interaction of full-length Nef with the dileucine-based sorting pathway and were required for Nef-mediated down-regulation of CD4. dileucine 97-106 S100 calcium binding protein B Homo sapiens 151-154 9736718-8 1998 These data indicate that a dileucine-based sorting signal in Nef is utilized to address the cellular sorting machinery. dileucine 27-36 S100 calcium binding protein B Homo sapiens 61-64 11000208-5 2000 A dileucine motif in Nef, which is essential for CD4 downregulation and is involved in the recruitment of adapter protein complexes by Nef, was required to increase surface levels of both cytokines. dileucine 2-11 S100 calcium binding protein B Homo sapiens 21-24 11000208-5 2000 A dileucine motif in Nef, which is essential for CD4 downregulation and is involved in the recruitment of adapter protein complexes by Nef, was required to increase surface levels of both cytokines. dileucine 2-11 S100 calcium binding protein B Homo sapiens 135-138 10366557-5 1999 The data also suggest that protein interactions mediated by the acidic domain, rather than by the dileucine motif, may contribute to this function of Nef. dileucine 98-107 S100 calcium binding protein B Homo sapiens 150-153 9811606-6 1998 This motif acts as an internalization signal in the context of a CD8-Nef chimera or in a fusion of the interleukin-2 receptor alpha with an 11-amino-acid region from Nef containing the dileucine motif. dileucine 185-194 S100 calcium binding protein B Homo sapiens 69-72 9811611-7 1998 The dileucine-motif-containing segment of Nef bound directly and specifically to the beta-adaptin subunit of the clathrin adaptor complexes AP-1 and AP-2, which are responsible for recruiting sorted proteins into coated pits. dileucine 4-13 S100 calcium binding protein B Homo sapiens 42-45 9811611-8 1998 Unlike wild-type Nef, a mutant form of Nef that lacked the dileucine motif did not localize to clathrin-coated pits and did not downregulate CD4 expression, although it could downregulate MHC class I surface expression. dileucine 59-68 S100 calcium binding protein B Homo sapiens 39-42 34358561-5 2021 We demonstrate that the HIV-1 accessory protein Nef upregulates cell surface levels of the checkpoint receptor Tim-3 and that this is dependent on Nef"s dileucine motif LL164/165. dileucine 153-162 S100 calcium binding protein B Homo sapiens 48-51 34358561-5 2021 We demonstrate that the HIV-1 accessory protein Nef upregulates cell surface levels of the checkpoint receptor Tim-3 and that this is dependent on Nef"s dileucine motif LL164/165. dileucine 153-162 S100 calcium binding protein B Homo sapiens 147-150 34358561-6 2021 Furthermore, we used a bimolecular fluorescence complementation assay to demonstrate that Nef and Tim-3 form a complex within cells that is abrogated upon mutation of the Nef dileucine motif. dileucine 175-184 S100 calcium binding protein B Homo sapiens 90-93 34358561-6 2021 Furthermore, we used a bimolecular fluorescence complementation assay to demonstrate that Nef and Tim-3 form a complex within cells that is abrogated upon mutation of the Nef dileucine motif. dileucine 175-184 S100 calcium binding protein B Homo sapiens 171-174 34358561-7 2021 We also provide evidence that Nef moderately promotes Tim-3 shedding from the cell surface in a dileucine motif-dependent manner. dileucine 96-105 S100 calcium binding protein B Homo sapiens 30-33 30053425-3 2018 The 4.3 A structure of a mutant Nef-induced dimer of AP-1 showed how the closed trimer is regulated by the dileucine loop of Nef. dileucine 107-116 S100 calcium binding protein B Homo sapiens 32-35 34037423-0 2021 An amino acid polymorphism within the HIV-1 Nef dileucine motif functionally uncouples cell surface CD4 and SERINC5 downregulation. dileucine 48-57 S100 calcium binding protein B Homo sapiens 44-47 34037423-2 2021 To counter SERINC5, the HIV-1 accessory protein Nef triggers SERINC5 internalization by engaging the Adaptor Protein 2 (AP-2) complex using the [D/E]xxxL[L/I]167 Nef dileucine motif. dileucine 166-175 S100 calcium binding protein B Homo sapiens 48-51 34037423-2 2021 To counter SERINC5, the HIV-1 accessory protein Nef triggers SERINC5 internalization by engaging the Adaptor Protein 2 (AP-2) complex using the [D/E]xxxL[L/I]167 Nef dileucine motif. dileucine 166-175 S100 calcium binding protein B Homo sapiens 162-165 34037423-3 2021 Nef also engages AP-2 via its dileucine motif to downregulate the CD4 receptor. dileucine 30-39 S100 calcium binding protein B Homo sapiens 0-3 34037423-7 2021 Using a series of Nef chimeras, we mapped the region of 2391 Nef responsible for the functional uncoupling of these two antagonistic pathways to the dileucine motif. dileucine 149-158 S100 calcium binding protein B Homo sapiens 18-21 34037423-7 2021 Using a series of Nef chimeras, we mapped the region of 2391 Nef responsible for the functional uncoupling of these two antagonistic pathways to the dileucine motif. dileucine 149-158 S100 calcium binding protein B Homo sapiens 61-64 34037423-8 2021 Modifications of the first and second "x" positions of the 2410 Nef dileucine motif to asparagine and aspartic acid residues respectively (ND164), impaired cell surface SERINC5 downregulation, which resulted in reduced infectious virus yield in the presence of SERINC5. dileucine 68-77 S100 calcium binding protein B Homo sapiens 64-67 30053425-3 2018 The 4.3 A structure of a mutant Nef-induced dimer of AP-1 showed how the closed trimer is regulated by the dileucine loop of Nef. dileucine 107-116 S100 calcium binding protein B Homo sapiens 125-128 21477083-6 2011 The endocytic dileucine-based sorting motif is exposed at the tip of the acidic loop, giving the myristoylated Nef protein a distinctly dipolar character. dileucine 14-23 S100 calcium binding protein B Homo sapiens 111-114 23151229-3 2013 We investigated how Nef can mediate constitutive receptor endocytosis through the interaction of the dileucine motif in its C-terminal flexible loop (C-loop) with AP2, whereas AP2 binding of the transmembrane receptors usually results in an equilibrated (recycled) endocytosis. dileucine 101-110 S100 calcium binding protein B Homo sapiens 20-23 23151229-4 2013 Our results indicated that in addition to the dileucine motif, there is a second motif in the Nef C-loop involved in the Nef-AP2 interaction. dileucine 46-55 S100 calcium binding protein B Homo sapiens 94-97 23151229-4 2013 Our results indicated that in addition to the dileucine motif, there is a second motif in the Nef C-loop involved in the Nef-AP2 interaction. dileucine 46-55 S100 calcium binding protein B Homo sapiens 121-124 23151229-8 2013 Our data suggest a new model in the Nef-AP2 interaction in which the hydrophobic region in the Nef C-loop with the dileucine (L164L165) motif and M168L170 motif binds to AP2(sigma2), while the acidic motif E174 and D175 binds to AP2(alpha), which explains how Nef through the flexible loop connects CD4 to AP2 for constitutive CD4 downregulation. dileucine 115-124 S100 calcium binding protein B Homo sapiens 36-39 23151229-8 2013 Our data suggest a new model in the Nef-AP2 interaction in which the hydrophobic region in the Nef C-loop with the dileucine (L164L165) motif and M168L170 motif binds to AP2(sigma2), while the acidic motif E174 and D175 binds to AP2(alpha), which explains how Nef through the flexible loop connects CD4 to AP2 for constitutive CD4 downregulation. dileucine 115-124 S100 calcium binding protein B Homo sapiens 95-98 23151229-8 2013 Our data suggest a new model in the Nef-AP2 interaction in which the hydrophobic region in the Nef C-loop with the dileucine (L164L165) motif and M168L170 motif binds to AP2(sigma2), while the acidic motif E174 and D175 binds to AP2(alpha), which explains how Nef through the flexible loop connects CD4 to AP2 for constitutive CD4 downregulation. dileucine 115-124 S100 calcium binding protein B Homo sapiens 95-98 21543478-6 2011 The interaction with AP-1 required for CD28 and CD8beta differed from the AP-1 interaction required for MHC-I downmodulation in that it was mediated through the dileucine motif within Nef (LL(164,165)AA) and did not require the tyrosine binding pocket of the AP-1 mu subunit. dileucine 161-170 S100 calcium binding protein B Homo sapiens 184-187 19129443-4 2009 In particular, dileucine and diacidic motifs in the C-terminal flexible loop of Nef have been shown to mediate binding to a combination of the alpha and sigma2 subunits of AP-2. dileucine 15-24 S100 calcium binding protein B Homo sapiens 80-83 18596106-7 2008 Immunoprecipitation experiments revealed that the Ii chain can interact with Nef in a dileucine-dependent manner. dileucine 86-95 S100 calcium binding protein B Homo sapiens 77-80 15956605-5 2005 Moreover, our results clearly indicate that the dileucine motif of the CD4 cytoplasmic domain, critical for the Nef-induced CD4 down-regulation, is not implicated in the Nef/CD4 complex formation in the cellular context. dileucine 48-57 S100 calcium binding protein B Homo sapiens 112-115 18073204-4 2008 Also present in Nef is a dileucine motif, which does not normally affect MHC-I trafficking and is not needed to recruit AP-1 to the Nef-MHC-I-complex. dileucine 25-34 S100 calcium binding protein B Homo sapiens 16-19 18073204-5 2008 However, evidence is presented here that this dileucine motif can be activated by fusing Nef to the HLA-A2 tail in cis. dileucine 46-55 S100 calcium binding protein B Homo sapiens 89-92 18032517-2 2008 CD4 downregulation depends on a conserved (D/E)XXXL(L/I)-type dileucine motif in the C-terminal, flexible loop of Nef, which mediates binding to the clathrin adaptor complexes AP-1, AP-2, and AP-3. dileucine 62-71 S100 calcium binding protein B Homo sapiens 114-117 18032517-5 2008 We also show that a dileucine motif from tyrosinase, both in its native context and in the context of Nef, can bind to AP-2 independently of a diacidic motif. dileucine 20-29 S100 calcium binding protein B Homo sapiens 102-105 18032517-6 2008 These results thus identify a novel type of AP-2 interaction determinant, support the notion that AP-2 is the key clathrin adaptor for the downregulation of CD4 by Nef, and reveal a previously unrecognized diversity among dileucine sorting signals. dileucine 222-231 S100 calcium binding protein B Homo sapiens 164-167 17267500-9 2007 This interaction requires a dileucine motif in Nef that is also essential for downregulation of CD4. dileucine 28-37 S100 calcium binding protein B Homo sapiens 47-50 16116206-4 2005 However, the mechanistic connection between the C-terminal dileucine motif of Nef and the component(s) of the clathrin-coated pits has not been pinpointed. dileucine 59-68 S100 calcium binding protein B Homo sapiens 78-81 16116206-10 2005 The results demonstrate that, like the tyrosine sorting motif-dependent endocytosis (for which the transferrin receptor and the epidermal growth factor receptor are the two prototypes), dileucine sorting motif-dependent endocytosis of Nef and CD4 are also AP-2 dependent. dileucine 186-195 S100 calcium binding protein B Homo sapiens 235-238 18524831-6 2008 The AP-binding dileucine motif in Nef, ENTSLL(165), was necessary and sufficient for the upregulation of Ii. dileucine 15-24 S100 calcium binding protein B Homo sapiens 34-37 18524831-8 2008 Experiments using Nef variants in which the native dileucine-based sorting motif was replaced with similar motifs from cellular transmembrane proteins allowed modulation of AP-binding specificity. dileucine 51-60 S100 calcium binding protein B Homo sapiens 18-21