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Gene Review

FLNC  -  filamin C, gamma

Homo sapiens

Synonyms: ABP-280, ABP-280-like protein, ABP-L, ABP280A, ABPA, ...
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Disease relevance of FLNC

  • The finding that FLN2 interacts with the sarcoglycans introduces new implications for the pathogenesis of muscular dystrophy [1].
  • In an extended German pedigree with a novel form of MFM characterized by clinical features of a limb-girdle myopathy and morphological features of MFM, we identified a co-segregating, heterozygous nonsense mutation (8130G-->A; W2710X) in the filamin c gene (FLNC) on chromosome 7q32 [2].
  • To approach this problem in vivo, we used the human melanoma cell, M2, which lacks actin-binding protein-280 (ABP-280) and forms membrane blebs, which are not seen in wild-type or ABP-transfected cells [3].
  • These results suggest that KY is an intrinsic part of the protein networks underlying the molecular mechanism of several limb-girdle muscular dystrophies, particularly those where interactions between filamin C and disease causing proteins have been shown [4].
  • The rearrangements are due to insertion of a deleted Moloney murine leukemia virus (Mo-MLV) provirus in the 5' region of the c-myb gene and thus are similar to rearrangements in the ABPL tumors (G. L. C. Shen-Ong, M. Potter, J. F. Mushinski, S. Lavu, and E. P. Reddy, Science 226:1077-1080, 1984) [5].

High impact information on FLNC

  • The ABPL tumors were examined for the expression of other oncogenes that may be associated with their transformed state, in the absence of transforming virus [6].
  • Furthermore, alternative splice variants of filamin-B and filamin-C, from which the flexible hinge-1 region is deleted (DeltaH1), were induced during in vitro differentiation of C2C12 mouse myoblasts [7].
  • 1. The mutation is the first found in FLNC and is localized in the dimerization domain of filamin c. Functional studies showed that, in the truncated mutant protein, this domain has a disturbed secondary structure that leads to the inability to dimerize properly [2].
  • Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines [8].
  • To better understand the structure and function of Z lines, we used sarcomeric isoforms of alpha-actinin and gamma-filamin to screen a human skeletal muscle cDNA library for interacting proteins by using the yeast two-hybrid system [8].

Chemical compound and disease context of FLNC

  • The Pichia expressed protein reacted weakly with IgE, but strongly with IgG of ABPA sera compared to E. coli expressed Asp f 2 [9].

Biological context of FLNC


Anatomical context of FLNC

  • Northern and Western blots showed that both, ABP-L/gamma-filamin mRNA and protein, are absent from proliferating cultured human skeletal muscle cells [15].
  • Stimulation of PKC activity in myotubes, prevented gamma-filamin proteolysis by calpain and resulted in an increase in myotube adhesion [16].
  • Calpain 1-gamma filamin interaction in muscle cells: a possible in situ regulation by PKC-alpha [16].
  • Filamin C may be involved in reorganizing the cytoskeleton in response to signalling events and in muscle it may, in addition, fulfill structural functions at the Z-disk [17].
  • On the one hand, filamin C is associated with the Z-disk of the myofibrillar apparatus and binds to myotilin; on the other hand, it interacts with the sarcoglycan complex at the sarcolemma [17].

Associations of FLNC with chemical compounds

  • We also located the binding domains in the C-terminus of gamma-filamin with a cleavage site between serine 2626 and serine 2627 in the hinge 2 region [16].
  • In this study, actin-binding protein 280 (ABP-280), a widely expressed cytoskeleton-associated protein that plays an important role in regulating cell morphology and motility, was found to associate with the third cytoplasmic loop of dopamine D(2) receptors [18].
  • Phosphorylation of actin-binding protein (ABP-280; filamin) by tyrosine kinase p56lck modulates actin filament cross-linking [19].
  • We have cloned and sequenced a 9.4-kilobase cDNA specifying a new 280-kDa protein interacting with the cytoplasmic tail of glycoprotein (Gp) Ibalpha and showing considerable homology to actin-binding protein 280 (ABP-280) and chicken retinal filamin [20].
  • To elucidate the immunoglobulin E (IgE) binding epitopes in the linear sequence of Asp f 2, we synthesized decamer peptides spanning the whole molecule of Asp f 2 on derivatized cellulose membranes and evaluated IgE binding in ABPA patient and control sera [21].

Other interactions of FLNC

  • To improve candidate gene cloning approaches, FLNB was precisely mapped at 3p14 in an interval of 0.81 cM between WI3771 and WI6691 and FLNC at 7q32 in an interval of 2.07 cM between D7S530 and D7S649 [10].
  • This interaction could co-localize heterologously expressed gamma-filamin with GFP-LL5beta in the unidentified vesicles [22].
  • In contrast, ACTA1 and FLNC appear to be stable proteins, indicating that their interaction with USP25m is not related to their turnover rate [23].
  • In all three conditions, the immunoreactivity in the cores for filamin C was considerably stronger than that for desmin [17].
  • A growing family of Arp2/3 complex activators such as the WASP family, type I myosins, and the newly identified activators cortactin and Abplp tightly regulate this activity within the cell [24].

Analytical, diagnostic and therapeutic context of FLNC


  1. Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein. Thompson, T.G., Chan, Y.M., Hack, A.A., Brosius, M., Rajala, M., Lidov, H.G., McNally, E.M., Watkins, S., Kunkel, L.M. J. Cell Biol. (2000) [Pubmed]
  2. A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy. Vorgerd, M., van der Ven, P.F., Bruchertseifer, V., Lowe, T., Kley, R.A., Schroder, R., Lochmuller, H., Himmel, M., Koehler, K., Furst, D.O., Huebner, A. Am. J. Hum. Genet. (2005) [Pubmed]
  3. Microtubule-associated protein 2c reorganizes both microtubules and microfilaments into distinct cytological structures in an actin-binding protein-280-deficient melanoma cell line. Cunningham, C.C., Leclerc, N., Flanagan, L.A., Lu, M., Janmey, P.A., Kosik, K.S. J. Cell Biol. (1997) [Pubmed]
  4. Filamin C interacts with the muscular dystrophy KY protein and is abnormally distributed in mouse KY deficient muscle fibres. Beatham, J., Romero, R., Townsend, S.K., Hacker, T., van der Ven, P.F., Blanco, G. Hum. Mol. Genet. (2004) [Pubmed]
  5. Generation of altered transcripts by retroviral insertion within the c-myb gene in two murine monocytic leukemias. Gonda, T.J., Cory, S., Sobieszczuk, P., Holtzman, D., Adams, J.M. J. Virol. (1987) [Pubmed]
  6. DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasmacytoid lymphosarcomas. Mushinski, J.F., Potter, M., Bauer, S.R., Reddy, E.P. Science (1983) [Pubmed]
  7. 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]
  8. Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines. Takada, F., Vander Woude, D.L., Tong, H.Q., Thompson, T.G., Watkins, S.C., Kunkel, L.M., Beggs, A.H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. Antibody binding of deletion mutants of Asp f 2, the major Aspergillus fumigatus allergen. Tang, B., Banerjee, B., Greenberger, P.A., Fink, J.N., Kelly, K.J., Kurup, V.P. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  10. Genomic structure and fine mapping of the two human filamin gene paralogues FLNB and FLNC and comparative analysis of the filamin gene family. Chakarova, C., Wehnert, M.S., Uhl, K., Sakthivel, S., Vosberg, H.P., van der Ven, P.F., Fürst, D.O. Hum. Genet. (2000) [Pubmed]
  11. 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]
  12. Molecular cloning of human ABPL, an actin-binding protein homologue. Xie, Z., Xu, W., Davie, E.W., Chung, D.W. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  13. Fragments from actin binding protein (ABP-280; filamin) insert into reconstituted lipid layers. Goldmann, W.H., Teodoridis, J.M., Sharma, C.P., Hu, B., Isenberg, G. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  14. Phosphorylation of filamin (ABP-280) regulates the binding to the lipid membrane, integrin, and actin. Goldmann, W.H. Cell Biol. Int. (2001) [Pubmed]
  15. 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]
  16. Calpain 1-gamma filamin interaction in muscle cells: a possible in situ regulation by PKC-alpha. Fabrice, R., Carole, J.N., Anne, M., Dieter, F., Yves, B. Int. J. Biochem. Cell Biol. (2006) [Pubmed]
  17. Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle. Bönnemann, C.G., Thompson, T.G., van der Ven, P.F., Goebel, H.H., Warlo, I., Vollmers, B., Reimann, J., Herms, J., Gautel, M., Takada, F., Beggs, A.H., Fürst, D.O., Kunkel, L.M., Hanefeld, F., Schröder, R. J. Neurol. Sci. (2003) [Pubmed]
  18. Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280). Li, M., Bermak, J.C., Wang, Z.W., Zhou, Q.Y. Mol. Pharmacol. (2000) [Pubmed]
  19. Phosphorylation of actin-binding protein (ABP-280; filamin) by tyrosine kinase p56lck modulates actin filament cross-linking. Pal Sharma, C., Goldmann, W.H. Cell Biol. Int. (2004) [Pubmed]
  20. 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]
  21. Conformational and linear B-cell epitopes of Asp f 2, a major allergen of Aspergillus fumigatus, bind differently to immunoglobulin E antibody in the sera of allergic bronchopulmonary aspergillosis patients. Banerjee, B., Greenberger, P.A., Fink, J.N., Kurup, V.P. Infect. Immun. (1999) [Pubmed]
  22. LL5beta is a phosphatidylinositol (3,4,5)-trisphosphate sensor that can bind the cytoskeletal adaptor, gamma-filamin. Paranavitane, V., Coadwell, W.J., Eguinoa, A., Hawkins, P.T., Stephens, L. J. Biol. Chem. (2003) [Pubmed]
  23. The ubiquitin-specific protease USP25 interacts with three sarcomeric proteins. Bosch-Comas, A., Lindsten, K., Gonzàlez-Duarte, R., Masucci, M.G., Marfany, G. Cell. Mol. Life Sci. (2006) [Pubmed]
  24. The Arp2/3 complex: a central regulator of the actin cytoskeleton. May, R.C. Cell. Mol. Life Sci. (2001) [Pubmed]
  25. 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]
  26. Mechanical unfolding of single filamin A (ABP-280) molecules detected by atomic force microscopy. Furuike, S., Ito, T., Yamazaki, M. FEBS Lett. (2001) [Pubmed]
  27. Cloning, expression, purification, crystallization and preliminary crystallographic analysis of gamma-filamin repeat 23. Sjekloća, L., Sjöblom, B., Polentarutti, M., Djinović Carugo, K. Acta Crystallogr. D Biol. Crystallogr. (2004) [Pubmed]
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