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| ==Solution NMR Structure of PH Domain of Tyrosine-protein kinase Tec from Homo sapiens, Northeast Structural Genomics Consortium (NESG) Target HR3504C== | | ==Solution NMR Structure of PH Domain of Tyrosine-protein kinase Tec from Homo sapiens, Northeast Structural Genomics Consortium (NESG) Target HR3504C== |
- | <StructureSection load='2lul' size='340' side='right'caption='[[2lul]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lul' size='340' side='right'caption='[[2lul]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2lul]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LUL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lul]] 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=2LUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LUL FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PSCTK4, TEC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=2lul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lul OCA], [https://pdbe.org/2lul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lul RCSB], [https://www.ebi.ac.uk/pdbsum/2lul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lul 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=2lul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lul OCA], [https://pdbe.org/2lul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lul RCSB], [https://www.ebi.ac.uk/pdbsum/2lul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lul ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[https://www.uniprot.org/uniprot/TEC_HUMAN TEC_HUMAN]] Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.<ref>PMID:10518561</ref> <ref>PMID:19883687</ref> <ref>PMID:20230531</ref> <ref>PMID:9753425</ref>
| + | [https://www.uniprot.org/uniprot/TEC_HUMAN TEC_HUMAN] Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.<ref>PMID:10518561</ref> <ref>PMID:19883687</ref> <ref>PMID:20230531</ref> <ref>PMID:9753425</ref> |
| | | |
| ==See Also== | | ==See Also== |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Non-specific protein-tyrosine kinase]]
| + | [[Category: Acton TB]] |
- | [[Category: Acton, T B]] | + | [[Category: Everett JK]] |
- | [[Category: Everett, J K]] | + | [[Category: Hamilton K]] |
- | [[Category: Hamilton, K]] | + | [[Category: Huang YJ]] |
- | [[Category: Huang, Y J]] | + | [[Category: Janjua H]] |
- | [[Category: Janjua, H]] | + | [[Category: Kohan E]] |
- | [[Category: Kohan, E]] | + | [[Category: Lee H]] |
- | [[Category: Lee, H]] | + | [[Category: Liu G]] |
- | [[Category: Liu, G]] | + | [[Category: Montelione GT]] |
- | [[Category: Montelione, G T]] | + | [[Category: Pederson K]] |
- | [[Category: Structural genomic]]
| + | [[Category: Shastry R]] |
- | [[Category: Pederson, K]] | + | [[Category: Xiao R]] |
- | [[Category: Shastry, R]] | + | |
- | [[Category: Xiao, R]] | + | |
- | [[Category: Nesg]]
| + | |
- | [[Category: PSI, Protein structure initiative]]
| + | |
- | [[Category: Psi-biology]]
| + | |
- | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TEC_HUMAN Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.[1] [2] [3] [4]
See Also
References
- ↑ Ohya K, Kajigaya S, Kitanaka A, Yoshida K, Miyazato A, Yamashita Y, Yamanaka T, Ikeda U, Shimada K, Ozawa K, Mano H. Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11976-81. PMID:10518561
- ↑ Susaki K, Kitanaka A, Dobashi H, Kubota Y, Kittaka K, Kameda T, Yamaoka G, Mano H, Mihara K, Ishida T. Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte. Immunol Lett. 2010 Jan 4;127(2):135-42. doi: 10.1016/j.imlet.2009.10.009. Epub, 2009 Oct 31. PMID:19883687 doi:http://dx.doi.org/10.1016/j.imlet.2009.10.009
- ↑ Ebert AD, Laussmann M, Wegehingel S, Kaderali L, Erfle H, Reichert J, Lechner J, Beer HD, Pepperkok R, Nickel W. Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic. 2010 Jun;11(6):813-26. doi: 10.1111/j.1600-0854.2010.01059.x. Epub 2010 , Mar 10. PMID:20230531 doi:http://dx.doi.org/10.1111/j.1600-0854.2010.01059.x
- ↑ Mano H, Ohya K, Miyazato A, Yamashita Y, Ogawa W, Inazawa J, Ikeda U, Shimada K, Hatake K, Kasuga M, Ozawa K, Kajigaya S. Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase. Genes Cells. 1998 Jul;3(7):431-41. PMID:9753425
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