5iu2: Difference between revisions

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== Structural highlights ==

<table><tr><td colspan='2'>[[5iu2]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU2 OCA]. For a guided tour on the structure components use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5IU2 FirstGlance].

<table><tr><td colspan='2'>[[5iu2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU2 OCA]. For a guided tour on the structure components use [https://proteopedia.org/fgij/fg.htm?mol=5IU2 FirstGlance].

</td></tr><tr id='ligand'><td class="sblockLbl">[[Ligand|Ligands:]]</td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DA:N-[2-(MORPHOLIN-4-YL)ETHYL]-6-(8-PHENYL-1H-IMIDAZO[4,5-C][1,7]NAPHTHYRIDIN-1-YL)-1,3-BENZOTHIAZOL-2-AMINE'>6DA</scene></td></tr>

<tr id='activity'><td class="sblockLbl">Activity:</td><td class="sblockDat">[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </td></tr>

<tr id='resources'><td class="sblockLbl">Resources:</td><td class="sblockDat">[https://proteopedia.org/fgij/fg.htm?mol=5iu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu2 OCA], [https://pdbe.org/5iu2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iu2 RCSB], [https://www.ebi.ac.uk/pdbsum/5iu2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu2 ProSAT]</td></tr>

<tr id='resources'><td class="sblockLbl">Resources:</td><td class="sblockDat">[~~http~~://proteopedia.org/fgij/fg.htm?mol=5iu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu2 OCA], [~~http~~://pdbe.org/5iu2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5iu2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5iu2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu2 ProSAT]</td></tr>

</table>

== Function ==

[~~[http~~://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN]] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>

[https://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>

== Publication Abstract from PubMed ==

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[[Category: Homo sapiens]]

[[Category: Large Structures]]

~~[[Category: Mitogen-activated protein kinase kinase kinase]]~~

[[Category: Gutmann S]]

[[Category: Gutmann, S]]

[[Category: Hinniger A]]

[[Category: Hinniger, A]]

~~[[Category: Complex]]~~

~~[[Category: Cot]]~~

~~[[Category: Inhibitor]]~~

~~[[Category: Kinase]]~~

~~[[Category: Map3k8]]~~

~~[[Category: Tpl-2]]~~

~~[[Category: Transferase~~]]

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@@ Line 3: / Line 3: @@
 <StructureSection load='5iu2' size='340' side='right'caption='[[5iu2]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5iu2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IU2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5iu2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IU2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IU2 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DA:N-[2-(MORPHOLIN-4-YL)ETHYL]-6-(8-PHENYL-1H-IMIDAZO[4,5-C][1,7]NAPHTHYRIDIN-1-YL)-1,3-BENZOTHIAZOL-2-AMINE'>6DA</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5iu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu2 OCA], [https://pdbe.org/5iu2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iu2 RCSB], [https://www.ebi.ac.uk/pdbsum/5iu2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu2 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5iu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iu2 OCA], [http://pdbe.org/5iu2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iu2 RCSB], [http://www.ebi.ac.uk/pdbsum/5iu2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iu2 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN]] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>
+[https://www.uniprot.org/uniprot/M3K8_HUMAN M3K8_HUMAN] Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.<ref>PMID:11342626</ref> <ref>PMID:12667451</ref> <ref>PMID:15169888</ref> <ref>PMID:16371247</ref> <ref>PMID:1833717</ref> <ref>PMID:19001140</ref> <ref>PMID:19754427</ref> <ref>PMID:19808894</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 24: @@
 [[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Mitogen-activated protein kinase kinase kinase]]
+[[Category: Gutmann S]]
-[[Category: Gutmann, S]]
+[[Category: Hinniger A]]
-[[Category: Hinniger, A]]
-[[Category: Complex]]
-[[Category: Cot]]
-[[Category: Inhibitor]]
-[[Category: Kinase]]
-[[Category: Map3k8]]
-[[Category: Tpl-2]]
-[[Category: Transferase]]