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| | ==Solution structure of the human SHIP SH2 domain== | | ==Solution structure of the human SHIP SH2 domain== |
| - | <StructureSection load='2ysx' size='340' side='right' caption='[[2ysx]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2ysx' size='340' side='right'caption='[[2ysx]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ysx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YSX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ysx]] 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=2YSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YSX FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SHIP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ysx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ysx OCA], [http://pdbe.org/2ysx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ysx RCSB], [http://www.ebi.ac.uk/pdbsum/2ysx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ysx ProSAT], [http://www.topsan.org/Proteins/RSGI/2ysx TOPSAN]</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=2ysx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ysx OCA], [https://pdbe.org/2ysx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ysx RCSB], [https://www.ebi.ac.uk/pdbsum/2ysx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ysx ProSAT], [https://www.topsan.org/Proteins/RSGI/2ysx TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SHIP1_HUMAN SHIP1_HUMAN]] Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.<ref>PMID:12421919</ref> <ref>PMID:16682172</ref> | + | [https://www.uniprot.org/uniprot/SHIP1_HUMAN SHIP1_HUMAN] Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.<ref>PMID:12421919</ref> <ref>PMID:16682172</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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Harada, T]] | + | [[Category: Large Structures]] |
| - | [[Category: Kasai, T]] | + | [[Category: Harada T]] |
| - | [[Category: Kigawa, T]] | + | [[Category: Kasai T]] |
| - | [[Category: Koshiba, S]] | + | [[Category: Kigawa T]] |
| - | [[Category: Structural genomic]] | + | [[Category: Koshiba S]] |
| - | [[Category: Watanabe, S]] | + | [[Category: Watanabe S]] |
| - | [[Category: Yokoyama, S]] | + | [[Category: Yokoyama S]] |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Phosphotyrosine binding domain]]
| + | |
| - | [[Category: Protein tyrosine kinase]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| - | [[Category: Sh2 domain]]
| + | |
| - | [[Category: Signal transduction]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
SHIP1_HUMAN Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Freeburn RW, Wright KL, Burgess SJ, Astoul E, Cantrell DA, Ward SG. Evidence that SHIP-1 contributes to phosphatidylinositol 3,4,5-trisphosphate metabolism in T lymphocytes and can regulate novel phosphoinositide 3-kinase effectors. J Immunol. 2002 Nov 15;169(10):5441-50. PMID:12421919
- ↑ Vaillancourt M, Levasseur S, Tremblay ML, Marois L, Rollet-Labelle E, Naccache PH. The Src homology 2-containing inositol 5-phosphatase 1 (SHIP1) is involved in CD32a signaling in human neutrophils. Cell Signal. 2006 Nov;18(11):2022-32. Epub 2006 Apr 3. PMID:16682172 doi:http://dx.doi.org/S0898-6568(06)00078-7
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