2mk2

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==Solution NMR structure of N-terminal domain (SH2 domain) of human Inositol polyphosphate phosphatase-like protein 1 (INPPL1) (fragment 20-117), Northeast Structural Genomics Consortium Target HR9134A==
==Solution NMR structure of N-terminal domain (SH2 domain) of human Inositol polyphosphate phosphatase-like protein 1 (INPPL1) (fragment 20-117), Northeast Structural Genomics Consortium Target HR9134A==
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<StructureSection load='2mk2' size='340' side='right' caption='[[2mk2]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2mk2' size='340' side='right'caption='[[2mk2]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2mk2]] 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=2MK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MK2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2mk2]] 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=2MK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MK2 FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">INPPL1, SHIP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">INPPL1, SHIP2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-3,4,5-trisphosphate_5-phosphatase Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.86 3.1.3.86] </span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphatidylinositol-3,4,5-trisphosphate_5-phosphatase Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.86 3.1.3.86] </span></td></tr>
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<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=2mk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mk2 OCA], [http://pdbe.org/2mk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mk2 RCSB], [http://www.ebi.ac.uk/pdbsum/2mk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mk2 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mk2 OCA], [https://pdbe.org/2mk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mk2 RCSB], [https://www.ebi.ac.uk/pdbsum/2mk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mk2 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/SHIP2_HUMAN SHIP2_HUMAN]] Defects in INPPL1 may be a cause of susceptibility to type 2 diabetes mellitus non-insulin dependent (NIDDM) [MIM:[http://omim.org/entry/125853 125853]].<ref>PMID:12086927</ref> <ref>PMID:15687335</ref> Note=Genetic variations in INPPL1 may be a cause of susceptibility to metabolic syndrome. Metabolic syndrome is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia is absent.
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[[https://www.uniprot.org/uniprot/SHIP2_HUMAN SHIP2_HUMAN]] Defects in INPPL1 may be a cause of susceptibility to type 2 diabetes mellitus non-insulin dependent (NIDDM) [MIM:[https://omim.org/entry/125853 125853]].<ref>PMID:12086927</ref> <ref>PMID:15687335</ref> Note=Genetic variations in INPPL1 may be a cause of susceptibility to metabolic syndrome. Metabolic syndrome is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia is absent.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/SHIP2_HUMAN SHIP2_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. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling. Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.<ref>PMID:9660833</ref> <ref>PMID:11349134</ref> <ref>PMID:11739414</ref> <ref>PMID:12235291</ref> <ref>PMID:12676785</ref> <ref>PMID:12690104</ref> <ref>PMID:15668240</ref> <ref>PMID:17135240</ref>
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[[https://www.uniprot.org/uniprot/SHIP2_HUMAN SHIP2_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. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling. Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6.<ref>PMID:9660833</ref> <ref>PMID:11349134</ref> <ref>PMID:11739414</ref> <ref>PMID:12235291</ref> <ref>PMID:12676785</ref> <ref>PMID:12690104</ref> <ref>PMID:15668240</ref> <ref>PMID:17135240</ref>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Human]]
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[[Category: Large Structures]]
[[Category: Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase]]
[[Category: Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase]]
[[Category: Everett, J K]]
[[Category: Everett, J K]]

Revision as of 15:16, 2 June 2021

Solution NMR structure of N-terminal domain (SH2 domain) of human Inositol polyphosphate phosphatase-like protein 1 (INPPL1) (fragment 20-117), Northeast Structural Genomics Consortium Target HR9134A

PDB ID 2mk2

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