Human filamin A is a 280 kDa protein involved in actin-filament cross-linking. It is structurally divided into an actin-binding headpiece (ABD) and a rod domain containing 24 immunoglobulin-like (Ig) repeats. A fragment of human filamin A (Ig repeats 14-16) was cloned and expressed in Escherichia coli and the purified protein was crystallized in 1.6 M ammonium sulfate, 2% PEG 1000 and 100 mM HEPES pH 7.5. The crystals diffracted to 1.95 A and belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 50.63, b = 52.10, c = 98.46 A, alpha = beta = gamma = 90 degrees.
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Filamin A C-terminal fragment modulates Orai1 expression by inhibition of protein degradation.
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Department of Physiology (Cellular Physiology Research Group),Institute of Molecular Pathology Biomarkers (IMPB), University of Extremadura, 10003-Caceres, Spain.
Filamin A (FLNA) is an actin-binding protein that has been reported to interact with STIM1 modulating the activation of Orai1 channels. Cleaving of FLNA by calpain leads to a C-terminal fragment that is involved in a variety of functional and pathological events, including pro-oncogenic activity in different types of cancer. Here we show that full-length FLNA is downregulated in samples from colon cancer patients as well as in the adenocarcinoma cell line HT-29.
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Eur J Clin Invest
December 2024
Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Introduction: The filamins are cytoskeletal binding proteins that dynamically crosslink actin into orthogonal networks or bundle it into stress fibres. The domain structure of filamin proteins is very well characterised, with an N-terminal actin-binding region, followed by 24 immunoglobulin-like repeat units. The repeat domains are separated into distinct segments by two regions of low-complexity known as hinge-1 and hinge-2.
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Cells
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Sabri Ülker Center for Metabolic Research, Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Human cancers express altered levels of actin-binding cytoskeletal filamin A (FLNA) protein. FLNA in mammals consists of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules interrupted by two hinge regions between repeats 15-16 and 23-24. Cleavage of these hinge regions produces a naturally occurring C-terminal 90 kDa fragment of FLNA (FLNA) that physically interacts with multiple proteins with diverse functions.
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Pathogenic FLNA variants affecting the hinge region of filamin A are associated with male survival.
Am J Med Genet A
October 2024
Department of Women's and Children's Health, Dunedin School of Medicine, Otago University, Dunedin, New Zealand.
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