3hqc
From Proteopedia
Crystal structure of Phosphotyrosine-binding domain from the Human Tensin-like C1 domain-containing phosphatase (TENC1)
Structural highlights
FunctionTENS2_HUMAN Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin (PubMed:15817639, PubMed:23401856). Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain (PubMed:30092354). In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy (PubMed:23401856, PubMed:30092354). Negatively regulates PI3K-AKT pathway activation (PubMed:15817639, PubMed:23401856, PubMed:30092354). Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex (PubMed:28955049). Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria (PubMed:28955049). Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix (PubMed:20069572).[UniProtKB:Q8CGB6][1] [2] [3] [4] [5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. References
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Categories: Homo sapiens | Large Structures | Atwell S | Bain K | Burley SK | Dickey M | Do J | Gheyi T | Klemke R | Romero R | Sampathkumar P | Sauder JM | Wasserman S
