Solution structure of the PTB domain of KIAA1075 protein from humanSolution structure of the PTB domain of KIAA1075 protein from human
Structural highlights
2dkq is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
TENS2_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
↑Hafizi S, Ibraimi F, Dahlback B. C1-TEN is a negative regulator of the Akt/PKB signal transduction pathway and inhibits cell survival, proliferation, and migration. FASEB J. 2005 Jun;19(8):971-3. Epub 2005 Apr 7. PMID:15817639 doi:http://dx.doi.org/10.1096/fj.04-2532fje
↑Clark K, Howe JD, Pullar CE, Green JA, Artym VV, Yamada KM, Critchley DR. Tensin 2 modulates cell contractility in 3D collagen gels through the RhoGAP DLC1. J Cell Biochem. 2010 Mar 1;109(4):808-17. PMID:20069572 doi:10.1002/jcb.22460
↑Koh A, Lee MN, Yang YR, Jeong H, Ghim J, Noh J, Kim J, Ryu D, Park S, Song P, Koo SH, Leslie NR, Berggren PO, Choi JH, Suh PG, Ryu SH. C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy. Mol Cell Biol. 2013 Apr;33(8):1608-20. PMID:23401856 doi:10.1128/MCB.01447-12
↑Shih YP, Sun P, Wang A, Lo SH. Tensin1 positively regulates RhoA activity through its interaction with DLC1. Biochim Biophys Acta. 2015 Dec;1853(12):3258-65. PMID:26427649 doi:10.1016/j.bbamcr.2015.09.028
↑Lee J, Koh A, Jeong H, Kim E, Ha TS, Saleem MA, Ryu SH. C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation. Sci Rep. 2017 Sep 27;7(1):12346. PMID:28955049 doi:10.1038/s41598-017-12382-8
↑Kim E, Kim DH, Singaram I, Jeong H, Koh A, Lee J, Cho W, Ryu SH. Cellular phosphatase activity of C1-Ten/Tensin2 is controlled by Phosphatidylinositol-3,4,5-triphosphate binding through the C1-Ten/Tensin2 SH2 domain. Cell Signal. 2018 Nov;51:130-138. PMID:30092354 doi:10.1016/j.cellsig.2018.07.009
