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==SH3 domain of human Lck tyrosine kinase==
==SH3 domain of human Lck tyrosine kinase==
<StructureSection load='1h92' size='340' side='right'caption='[[1h92]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''>
<StructureSection load='1h92' size='340' side='right'caption='[[1h92]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1h92]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H92 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1h92]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H92 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fbz|1fbz]], [[1lcj|1lcj]], [[1lck|1lck]], [[1qpc|1qpc]], [[1qpd|1qpd]], [[1qpe|1qpe]], [[1qpj|1qpj]], [[3lck|3lck]]</div></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1h92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h92 OCA], [https://pdbe.org/1h92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h92 RCSB], [https://www.ebi.ac.uk/pdbsum/1h92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h92 ProSAT]</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=1h92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h92 OCA], [https://pdbe.org/1h92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h92 RCSB], [https://www.ebi.ac.uk/pdbsum/1h92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h92 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.  
[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref>
[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Biesinger, B]]
[[Category: Biesinger B]]
[[Category: Friedrich, U]]
[[Category: Friedrich U]]
[[Category: Hoffmann, S]]
[[Category: Hoffmann S]]
[[Category: Roesch, P]]
[[Category: Roesch P]]
[[Category: Schweimer, K]]
[[Category: Schweimer K]]
[[Category: Sticht, H]]
[[Category: Sticht H]]
[[Category: Lck]]
[[Category: Sh3 domain]]
[[Category: Signal transduction]]
[[Category: Transferase]]
[[Category: Tyrosine kinase]]

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