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Gene Review

FLNA  -  filamin A, alpha

Homo sapiens

Synonyms: ABP-280, ABPX, Actin-binding protein 280, Alpha-filamin, CSBS, ...
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Disease relevance of FLNA


Psychiatry related information on FLNA


High impact information on FLNA


Chemical compound and disease context of FLNA


Biological context of FLNA


Anatomical context of FLNA

  • ABP-280 recruitment to TF adhesion contacts is associated with reorganization of actin filaments, but cytoskeletal adaptor molecules typically found in integrin-mediated focal contacts are not associated with TF [3].
  • However, although ABP-280 directs the rate of furin internalization, the efficiency of sorting of the endoprotease from the cell surface to early endosomes is independent of expression of ABP-280 [21].
  • In addition, ABP-280 is also required for the correct localization of late endosomes (dextran bead uptake) and lysosomes (LAMP-1 staining), demonstrating a pleiotropic role for this actin binding protein in the organization of cellular compartments and directing protein traffic [21].
  • A monoclonal antibody recognizing ABP280 and Fh1 binds to blood vessels, astrocytes, neurofibrillary tangles, neuropil threads, and dystrophic neurites in the AD brain [22].
  • Overexpression of PS1 appears to modify the distribution of ABP280 and Fh1 proteins in cultured cells [22].

Associations of FLNA with chemical compounds


Physical interactions of FLNA

  • Leucine-rich repeat region of decorin binds to filamin-A [28].
  • Cell surface PS1 formed complexes in vivo with actin-binding protein filamin (ABP-280), which is known to form bridges between cell surface receptors and cytoskeleton and mediate cell adhesion and cell motility [29].
  • Here we show that Trio GEFD1 interacts through its PH domain with the actin-filament-crosslinking protein filamin, and localizes with endogenous filamin in HeLa cells [30].
  • Coimmunoprecipitation experiments and in vitro binding assays demonstrated that FLNa binds constitutively to IR and that neither insulin nor depolymerization of actin by cytochalasin D affected this interaction [31].
  • In a two-hybrid screening, we found that the actin-binding protein filamin interacted with the C-terminal tail of the CTR [32].

Enzymatic interactions of FLNA

  • Filamin was directly cleaved by granzyme B when target cells were exposed to granzyme B and the lytic protein perforin, but it was also cleaved in a caspase-dependent manner following the ligation of Fas receptors [33].

Co-localisations of FLNA

  • Although full-length FLNa was predominantly cytoplasmic, a C-terminal 100-kDa fragment of FLNa colocalized with AR to the nucleus [34].

Regulatory relationships of FLNA


Other interactions of FLNA

  • We have characterized a negative regulatory domain in the AR hinge region, which interacted with filamin A (FLNa), an actin-binding cytoskeletal protein [34].
  • Interaction with BRCA2 suggests a role for filamin-1 (hsFLNa) in DNA damage response [38].
  • Two principal forms of the actin binding protein, filamin, are expressed in mammalian cells: nonmuscle and muscle isotypes (FLN-1 and FLN-2) [39].
  • We report that the LRR region of decorin interacts with the cytoskeletal protein, filamin-A (ABP-280), a peripheral cytoplasmic protein [28].
  • Two-hybrid screening identified actin-binding protein 280 (ABP-280) as ligand for the TF cytoplasmic domain [3].

Analytical, diagnostic and therapeutic context of FLNA


  1. A new osteochondrodysplasia with severe osteopenia, preaxial polydactyly, clefting and dysmorphic features resembling filamin-related disorders. Colombani, M., Laurent, N., Le Merrer, M., Delezoide, A.L., Thauvin-Robinet, C., Huet, F., Sagot, P., Couvreur, S., Rousseau, T., Robertson, S.P., Faivre, L. Prenat. Diagn. (2006) [Pubmed]
  2. Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin. van der Ven, P.F., Wiesner, S., Salmikangas, P., Auerbach, D., Himmel, M., Kempa, S., Hayess, K., Pacholsky, D., Taivainen, A., Schröder, R., Carpén, O., Fürst, D.O. J. Cell Biol. (2000) [Pubmed]
  3. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. Ott, I., Fischer, E.G., Miyagi, Y., Mueller, B.M., Ruf, W. J. Cell Biol. (1998) [Pubmed]
  4. The small GTPase RalA targets filamin to induce filopodia. Ohta, Y., Suzuki, N., Nakamura, S., Hartwig, J.H., Stossel, T.P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Bilateral periventricular heterotopias in an X-linked dominant transmission in a family with two affected males. Gérard-Blanluet, M., Sheen, V., Machinis, K., Neal, J., Apse, K., Danan, C., Sinico, M., Brugières, P., Mage, K., Ratsimbazafy, L., Elbez, A., Janaud, J.C., Amselem, S., Walsh, C., Encha-Razavi, F. Am. J. Med. Genet. A (2006) [Pubmed]
  6. Verbal learning and memory in schizotypal personality disorder. Bergman, A.J., Harvey, P.D., Roitman, S.L., Mohs, R.C., Marder, D., Silverman, J.M., Siever, L.J. Schizophrenia bulletin. (1998) [Pubmed]
  7. The prevalence of cyclothymia in borderline personality disorder. Levitt, A.J., Joffe, R.T., Ennis, J., MacDonald, C., Kutcher, S.P. The Journal of clinical psychiatry. (1990) [Pubmed]
  8. Multivariate modelling and the Defence Mechanism Test: a comparative study of defensive structures in borderline, other personality disorders and schizophrenic disorder. Sundbom, E., Kullgren, G. Acta psychiatrica Scandinavica. (1992) [Pubmed]
  9. Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Tu, Y., Wu, S., Shi, X., Chen, K., Wu, C. Cell (2003) [Pubmed]
  10. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Robertson, S.P., Twigg, S.R., Sutherland-Smith, A.J., Biancalana, V., Gorlin, R.J., Horn, D., Kenwrick, S.J., Kim, C.A., Morava, E., Newbury-Ecob, R., Orstavik, K.H., Quarrell, O.W., Schwartz, C.E., Shears, D.J., Suri, M., Kendrick-Jones, J., Wilkie, A.O. Nat. Genet. (2003) [Pubmed]
  11. Emerin deletion reveals a common X-chromosome inversion mediated by inverted repeats. Small, K., Iber, J., Warren, S.T. Nat. Genet. (1997) [Pubmed]
  12. Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280). Li, M., Li, C., Weingarten, P., Bunzow, J.R., Grandy, D.K., Zhou, Q.Y. Biochem. Pharmacol. (2002) [Pubmed]
  13. Etiological heterogeneity of familial periventricular heterotopia and hydrocephalus. Sheen, V.L., Basel-Vanagaite, L., Goodman, J.R., Scheffer, I.E., Bodell, A., Ganesh, V.S., Ravenscroft, R., Hill, R.S., Cherry, T.J., Shugart, Y.Y., Barkovich, J., Straussberg, R., Walsh, C.A. Brain Dev. (2004) [Pubmed]
  14. Acute vascular responses to isometric handgrip exercise and effects of training in persons medicated for hypertension. McGowan, C.L., Levy, A.S., Millar, P.J., Guzman, J.C., Morillo, C.A., McCartney, N., Macdonald, M.J. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  15. A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats. Ghoshal, K., Li, X., Datta, J., Bai, S., Pogribny, I., Pogribny, M., Huang, Y., Young, D., Jacob, S.T. J. Nutr. (2006) [Pubmed]
  16. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. Kutay, H., Bai, S., Datta, J., Motiwala, T., Pogribny, I., Frankel, W., Jacob, S.T., Ghoshal, K. J. Cell. Biochem. (2006) [Pubmed]
  17. A dual phenotype of periventricular nodular heterotopia and frontometaphyseal dysplasia in one patient caused by a single FLNA mutation leading to two functionally different aberrant transcripts. Zenker, M., Rauch, A., Winterpacht, A., Tagariello, A., Kraus, C., Rupprecht, T., Sticht, H., Reis, A. Am. J. Hum. Genet. (2004) [Pubmed]
  18. Phenotypic overlap in Melnick-Needles, serpentine fibula-polycystic kidney and Hajdu-Cheney syndromes: a clinical and molecular study in three patients. Albano, L.M., Bertola, D.R., Barba, M.F., Valente, M., Robertson, S.P., Kim, C.A. Clin. Dysmorphol. (2007) [Pubmed]
  19. Filamin A mutations cause periventricular heterotopia with Ehlers-Danlos syndrome. Sheen, V.L., Jansen, A., Chen, M.H., Parrini, E., Morgan, T., Ravenscroft, R., Ganesh, V., Underwood, T., Wiley, J., Leventer, R., Vaid, R.R., Ruiz, D.E., Hutchins, G.M., Menasha, J., Willner, J., Geng, Y., Gripp, K.W., Nicholson, L., Berry-Kravis, E., Bodell, A., Apse, K., Hill, R.S., Dubeau, F., Andermann, F., Barkovich, J., Andermann, E., Shugart, Y.Y., Thomas, P., Viri, M., Veggiotti, P., Robertson, S., Guerrini, R., Walsh, C.A. Neurology (2005) [Pubmed]
  20. Autosomal recessive form of periventricular heterotopia. Sheen, V.L., Topçu, M., Berkovic, S., Yalnizoglu, D., Blatt, I., Bodell, A., Hill, R.S., Ganesh, V.S., Cherry, T.J., Shugart, Y.Y., Walsh, C.A. Neurology (2003) [Pubmed]
  21. Cytoskeletal protein ABP-280 directs the intracellular trafficking of furin and modulates proprotein processing in the endocytic pathway. Liu, G., Thomas, L., Warren, R.A., Enns, C.A., Cunningham, C.C., Hartwig, J.H., Thomas, G. J. Cell Biol. (1997) [Pubmed]
  22. Interaction of presenilins with the filamin family of actin-binding proteins. Zhang, W., Han, S.W., McKeel, D.W., Goate, A., Wu, J.Y. J. Neurosci. (1998) [Pubmed]
  23. Filamin A binding to the cytoplasmic tail of glycoprotein Ibalpha regulates von Willebrand factor-induced platelet activation. Feng, S., Reséndiz, J.C., Lu, X., Kroll, M.H. Blood (2003) [Pubmed]
  24. Human beta-filamin is a new protein that interacts with the cytoplasmic tail of glycoprotein Ibalpha. Takafuta, T., Wu, G., Murphy, G.F., Shapiro, S.S. J. Biol. Chem. (1998) [Pubmed]
  25. H2O2-induced filamin redistribution in endothelial cells is modulated by the cyclic AMP-dependent protein kinase pathway. Hastie, L.E., Patton, W.F., Hechtman, H.B., Shepro, D. J. Cell. Physiol. (1997) [Pubmed]
  26. Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Gargiulo, A., Auricchio, R., Barone, M.V., Cotugno, G., Reardon, W., Milla, P.J., Ballabio, A., Ciccodicola, A., Auricchio, A. Am. J. Hum. Genet. (2007) [Pubmed]
  27. Structure of three tandem filamin domains reveals auto-inhibition of ligand binding. Lad, Y., Kiema, T., Jiang, P., Pentikäinen, O.T., Coles, C.H., Campbell, I.D., Calderwood, D.A., Ylänne, J. EMBO J. (2007) [Pubmed]
  28. Leucine-rich repeat region of decorin binds to filamin-A. Yoshida, K., Suzuki, Y., Honda, E., Amemiya, K., Nakatani, T., Ebina, M., Narumi, K., Satoh, K., Munakata, H. Biochimie (2002) [Pubmed]
  29. Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix. Schwarzman, A.L., Singh, N., Tsiper, M., Gregori, L., Dranovsky, A., Vitek, M.P., Glabe, C.G., St George-Hyslop, P.H., Goldgaber, D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  30. The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin. Bellanger, J.M., Astier, C., Sardet, C., Ohta, Y., Stossel, T.P., Debant, A. Nat. Cell Biol. (2000) [Pubmed]
  31. Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway. He, H.J., Kole, S., Kwon, Y.K., Crow, M.T., Bernier, M. J. Biol. Chem. (2003) [Pubmed]
  32. Binding of filamin to the C-terminal tail of the calcitonin receptor controls recycling. Seck, T., Baron, R., Horne, W.C. J. Biol. Chem. (2003) [Pubmed]
  33. Filamin (280-kDa actin-binding protein) is a caspase substrate and is also cleaved directly by the cytotoxic T lymphocyte protease granzyme B during apoptosis. Browne, K.A., Johnstone, R.W., Jans, D.A., Trapani, J.A. J. Biol. Chem. (2000) [Pubmed]
  34. Filamin-A fragment localizes to the nucleus to regulate androgen receptor and coactivator functions. Loy, C.J., Sim, K.S., Yong, E.L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  35. Overlapping expression of ARFGEF2 and Filamin A in the neuroependymal lining of the lateral ventricles: insights into the cause of periventricular heterotopia. Lu, J., Tiao, G., Folkerth, R., Hecht, J., Walsh, C., Sheen, V. J. Comp. Neurol. (2006) [Pubmed]
  36. MEKK4 Signaling Regulates Filamin Expression and Neuronal Migration. Sarkisian, M.R., Bartley, C.M., Chi, H., Nakamura, F., Hashimoto-Torii, K., Torii, M., Flavell, R.A., Rakic, P. Neuron (2006) [Pubmed]
  37. FOXC1 transcriptional regulatory activity is impaired by PBX1 in a filamin A-mediated manner. Berry, F.B., O'Neill, M.A., Coca-Prados, M., Walter, M.A. Mol. Cell. Biol. (2005) [Pubmed]
  38. Interaction with BRCA2 suggests a role for filamin-1 (hsFLNa) in DNA damage response. Yuan, Y., Shen, Z. J. Biol. Chem. (2001) [Pubmed]
  39. Expression and subcellular distribution of filamin isotypes in endothelial cells and pericytes. Shojaee, N., Patton, W.F., Chung-Welch, N., Su, Q., Hechtman, H.B., Shepro, D. Electrophoresis (1998) [Pubmed]
  40. Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits. van der Flier, A., Kuikman, I., Kramer, D., Geerts, D., Kreft, M., Takafuta, T., Shapiro, S.S., Sonnenberg, A. J. Cell Biol. (2002) [Pubmed]
  41. Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28. Gorlin, J.B., Henske, E., Warren, S.T., Kunst, C.B., D'Urso, M., Palmieri, G., Hartwig, J.H., Bruns, G., Kwiatkowski, D.J. Genomics (1993) [Pubmed]
  42. Characterization of muscle filamin isoforms suggests a possible role of gamma-filamin/ABP-L in sarcomeric Z-disc formation. van der Ven, P.F., Obermann, W.M., Lemke, B., Gautel, M., Weber, K., Fürst, D.O. Cell Motil. Cytoskeleton (2000) [Pubmed]
  43. Identification of filamin as a novel ligand for caveolin-1: evidence for the organization of caveolin-1-associated membrane domains by the actin cytoskeleton. Stahlhut, M., van Deurs, B. Mol. Biol. Cell (2000) [Pubmed]
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