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Gene Review

FLNB  -  filamin B, beta

Homo sapiens

Synonyms: ABP-278, ABP-280, ABP-280 homolog, AOI, Actin-binding-like protein, ...
 
 
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Disease relevance of FLNB

  • The thyrotropin receptor (TSHR) is the thyroid autoantigen against which stimulating autoantibodies are directed in Graves' hyperthyroidism [1].
  • Earlier reports have claimed that NIS may represent a major thyroid autoantigen that elicits formation of functionally relevant autoantibodies in a significant proportion of patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) [2].
  • Thyroid autoantigen presentation by HLA class II expressing thyroid follicular cells thus only occurs in Graves' disease, suggesting that HLA class II expression on thyroid follicular cells is an essential feature, but by itself not sufficient for the induction of autoimmunity [3].
  • To determine whether this treatment can be applied to older patients, we have analyzed HDM/SCT treatment outcomes for 65 patients (aged 65 years or older) with AL amyloidosis compared with outcomes for 280 younger patients [4].
  • [18F]FDG-PET has an important prognostic role in the pretransplantation evaluation of patients with lymphoma and enlarges the concept of chemosensitivity used to select patients for HDT/SCT [5].
 

Psychiatry related information on FLNB

  • The SCT, as scored for women, seems to be particularly sensitive to differences in responsible caring in relationships, an aspect of personality development often neglected by other tests [6].
  • The data indicate that the concept of TABP has construct validity and that it does not reflect the distinguishing characteristics of personality traits or psychopathology that are measured by standard psychometric inventories [7].
  • OBJECTIVE: To investigate the role of cognitive and social processing in posttraumatic stress symptoms and disorder (PTSD) among mothers of children undergoing bone marrow and hematopoietic stem-cell transplantation (BMT/SCT) [8].
 

High impact information on FLNB

  • We found that filamin B is expressed in human growth plate chondrocytes and in the developing vertebral bodies in the mouse [9].
  • These results indicate that mDia1 may coordinate microtubules and F-actin through its FH2 and FH1 regions, respectively [10].
  • However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa [11].
  • Interestingly, the simultaneous deletion of the H1 region is required for the localization of filamin-B at the tips of actin stress fibers [12].
  • Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits [12].
 

Chemical compound and disease context of FLNB

 

Biological context of FLNB

 

Anatomical context of FLNB

  • A monoclonal antibody recognizing ABP280 and Fh1 binds to blood vessels, astrocytes, neurofibrillary tangles, neuropil threads, and dystrophic neurites in the AD brain [16].
  • A polyclonal antibody to the unique beta-filamin first hinge sequence identifies a strong 280-kDa band in HUVECs but only a weak band in platelets, and stains normal human endothelial cells in culture and in situ [17].
  • Furthermore, filamin-B variants lacking the H1 region induce the formation of thinner myotubes than those in cells containing variants with this region [12].
  • 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 [12].
  • Although TABP mRNA is expressed widely, immunoblot analysis demonstrated the presence of TABP antibodies specifically in the sera of a minority of subjects with autoimmune thyroid disease [20].
 

Associations of FLNB with chemical compounds

  • TABP lacks an actin binding domain but contains two predicted beta-sheet repeats within which is a putative dimerization domain and between which lies a putative glycoprotein binding site containing a consensus site for phosphorylation by Ca(2+)-calmodulin kinase II [20].
  • In a yeast two-hybrid search of a human placental library, using as bait repeats 10-18 of filamin B, we isolated a cDNA coding for a novel 374 amino acid protein containing a proline-rich domain near its N terminus and two LIM domains at its C terminus [21].
  • Blood glucose excursions were larger in the SCT group than in the SCA and IMT group from post-lunch to pre-dinner measurements and from pre- to post-dinner measurements [22].
  • The serum fructosamine value was within normal limits in three patients in the IMT group, in six patients in the SCA group and in none of the patients in the SCT group following the intervention period (p < 0.01) [22].
  • Analysis of truncated ABP proteins revealed that removal of 26 or more residues from the C-terminus eliminates secretion and DHT-binding activity [23].
 

Physical interactions of FLNB

  • Human beta-filamin is a new protein that interacts with the cytoplasmic tail of glycoprotein Ibalpha [17].
  • The resultant substitutions, L171R and S235P, lie within the calponin homology 2 region of the actin binding domain of filamin B and occur at sites that are evolutionarily well conserved [24].
 

Other interactions of FLNB

  • 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 [18].
  • This is the first demonstration of both extensive and local homologies between one thyroid autoantigen (NIS) and microbiological proteins [25].
  • The identification and cloning of TPO (the "thyroid microsomal antigen") provided the critical tool for analyzing B and T cell reactivity to this major thyroid autoantigen [26].
  • Yeast two-hybrid studies with deletion mutants localized the areas of interaction in FBLP-1 to its N-terminal domain and in filamin B to repeats 10-13 [21].
  • The gene encoding thyroglobulin (Tg), which encodes a major thyroid autoantigen, maps to this region, and a recent study has reported the association of several exonic single-nucleotide polymorphisms (SNPs) with disease [27].
 

Analytical, diagnostic and therapeutic context of FLNB

  • We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study [28].
  • Bimodality surveillance incorporates autofluorescence bronchoscopy (AFB) and spiral CT (SCT) scanning in high-risk patients as a primary lung cancer surveillance strategy, based entirely on risk factors [29].
  • Since graft-versus-leukemia (GVL) is the main weapon for disease eradication after reduced intensity conditioning (RIC) allogeneic SCT, the availability of sensitive and specific techniques to monitor changes in tumor load after transplant are especially helpful [30].
  • Following debridement, peak pressures at the callus sites decreased in the NCT group and increased in the SCT group, but there was no statistically significant between-group difference (P = 0.16) [31].
  • We report induction of complete remission in a 37-year-old woman with rapidly progressive stage IV MF with allogeneic stem cell transplantation (Allo SCT) [32].

References

  1. Interleukin-6 stimulates thyrotropin receptor expression in human orbital preadipocyte fibroblasts from patients with Graves' ophthalmopathy. Jyonouchi, S.C., Valyasevi, R.W., Harteneck, D.A., Dutton, C.M., Bahn, R.S. Thyroid (2001) [Pubmed]
  2. Autoimmunity involving the human sodium/iodide symporter: fact or fiction? Heufelder, A.E., Joba, W., Morgenthaler, N.G. Exp. Clin. Endocrinol. Diabetes (2001) [Pubmed]
  3. Pathogenetic relevance of HLA class II expressing thyroid follicular cells in nontoxic Goiter and in Graves' disease. Grubeck-Loebenstein, B., Londei, M., Greenall, C., Pirich, K., Kassal, H., Waldhäusl, W., Feldmann, M. J. Clin. Invest. (1988) [Pubmed]
  4. Successful treatment of AL amyloidosis with high-dose melphalan and autologous stem cell transplantation in patients over age 65. Seldin, D.C., Anderson, J.J., Skinner, M., Malek, K., Wright, D.G., Quillen, K., Finn, K., Oran, B., Sanchorawala, V. Blood (2006) [Pubmed]
  5. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Spaepen, K., Stroobants, S., Dupont, P., Vandenberghe, P., Maertens, J., Bormans, G., Thomas, J., Balzarini, J., De Wolf-Peeters, C., Mortelmans, L., Verhoef, G. Blood (2003) [Pubmed]
  6. Ego development in adult women. White, M.S. Journal of personality. (1985) [Pubmed]
  7. The relationship of type A behavior pattern to coronary heart disease. Rosenman, R.H., Chesney, M.A. Activitas nervosa superior. (1980) [Pubmed]
  8. Predictors of PTSD in mothers of children undergoing bone marrow transplantation: the role of cognitive and social processes. Manne, S., DuHamel, K., Nereo, N., Ostroff, J., Parsons, S., Martini, R., Williams, S., Mee, L., Sexson, S., Wu, L., Difede, J., Redd, W.H. Journal of pediatric psychology. (2002) [Pubmed]
  9. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Krakow, D., Robertson, S.P., King, L.M., Morgan, T., Sebald, E.T., Bertolotto, C., Wachsmann-Hogiu, S., Acuna, D., Shapiro, S.S., Takafuta, T., Aftimos, S., Kim, C.A., Firth, H., Steiner, C.E., Cormier-Daire, V., Superti-Furga, A., Bonafe, L., Graham, J.M., Grix, A., Bacino, C.A., Allanson, J., Bialer, M.G., Lachman, R.S., Rimoin, D.L., Cohn, D.H. Nat. Genet. (2004) [Pubmed]
  10. Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1. Ishizaki, T., Morishima, Y., Okamoto, M., Furuyashiki, T., Kato, T., Narumiya, S. Nat. Cell Biol. (2001) [Pubmed]
  11. Expression of LewisX and sialylated LewisX antigens in human colorectal polyps. Yuan, M., Itzkowitz, S.H., Ferrell, L.D., Fukushi, Y., Palekar, A., Hakomori, S., Kim, Y.S. J. Natl. Cancer Inst. (1987) [Pubmed]
  12. 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]
  13. Hemophagocytosis during fludarabine-based SCT for systemic juvenile idiopathic arthritis. Ferreira, R.A., Vastert, S.J., Abinun, M., Foster, H.E., Modesto, C., Olivé, T., Kuis, W., Wulffraat, N.M. Bone Marrow Transplant. (2006) [Pubmed]
  14. Phenotypic variation among familial hypercholesterolemics heterozygous for either one of two Afrikaner founder LDL receptor mutations. Kotze, M.J., De Villiers, W.J., Steyn, K., Kriek, J.A., Marais, A.D., Langenhoven, E., Herbert, J.S., Graadt Van Roggen, J.F., Van der Westhuyzen, D.R., Coetzee, G.A. Arterioscler. Thromb. (1993) [Pubmed]
  15. Thalidomide induced remission of refractory diffuse large B-Cell Lymphoma post-allogeneic SCT. Tueger, S., Chen, F.E., Ahsan, G., McDonald, V., Andrews, V.E., Madrigal, J.A., Kazmi, M.A. Haematologica (2006) [Pubmed]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. Cloning from the thyroid of a protein related to actin binding protein that is recognized by Graves disease immunoglobulins. Leedman, P.J., Faulkner-Jones, B., Cram, D.S., Harrison, P.J., West, J., O'Brien, E., Simpson, R., Coppel, R.L., Harrison, L.C. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  21. A new member of the LIM protein family binds to filamin B and localizes at stress fibers. Takafuta, T., Saeki, M., Fujimoto, T.T., Fujimura, K., Shapiro, S.S. J. Biol. Chem. (2003) [Pubmed]
  22. Impact of injection sites for soluble insulin on glycaemic control in type 1 (insulin-dependent) diabetic patients treated with a multiple insulin injection regimen. Henriksen, J.E., Djurhuus, M.S., Vaag, A., Thye-Rønn, P., Knudsen, D., Hother-Nielsen, O., Beck-Nielsen, H. Diabetologia (1993) [Pubmed]
  23. Mutagenesis of essential functional residues of rat androgen-binding protein/sex hormone-binding globulin. Joseph, D.R., Lawrence, W. Mol. Endocrinol. (1993) [Pubmed]
  24. Mutations in FLNB cause boomerang dysplasia. Bicknell, L.S., Morgan, T., Bonafé, L., Wessels, M.W., Bialer, M.G., Willems, P.J., Cohn, D.H., Krakow, D., Robertson, S.P. J. Med. Genet. (2005) [Pubmed]
  25. Homologies of the thyroid sodium-iodide symporter with bacterial and viral proteins. Benvenga, S., Alesci, S., Trimarchi, F., Facchiano, A. J. Endocrinol. Invest. (1999) [Pubmed]
  26. Autoimmune response to the thyroid in humans: thyroid peroxidase--the common autoantigenic denominator. McLachlan, S.M., Rapoport, B. Int. Rev. Immunol. (2000) [Pubmed]
  27. The thyroglobulin gene: the third locus for autoimmune thyroid disease or a false dawn? Gough, S. Trends in molecular medicine. (2004) [Pubmed]
  28. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Vey, N., Thomas, X., Picard, C., Kovascovicz, T., Charin, C., Cayuela, J.M., Dombret, H., Dastugue, N., Huguet, F., Bastard, C., Stamatoulas, A., Giollant, M., Tournilhac, O., Macintyre, E., Buzyn, A., Bories, D., Kuentz, M., Dreyfus, F., Delannoy, A., Raynaud, S., Gratecos, N., Bordessoule, D., de Botton, S., Preudhomme, C., Reman, O., Troussard, X., Pigneux, A., Bilhou, C., Vernant, J.P., Boucheix, C., Gabert, J. Leukemia (2006) [Pubmed]
  29. Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment. Loewen, G., Natarajan, N., Tan, D., Nava, E., Klippenstein, D., Mahoney, M., Cummings, M., Reid, M. Thorax (2007) [Pubmed]
  30. Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation. Pérez-Simón, J.A., Caballero, D., Diez-Campelo, M., Lopez-Pérez, R., Mateos, G., Cañizo, C., Vazquez, L., Vidriales, B., Mateos, M.V., Gonzalez, M., San Miguel, J.F. Leukemia (2002) [Pubmed]
  31. Debridement of plantar callosities in rheumatoid arthritis: a randomized controlled trial. Davys, H.J., Turner, D.E., Helliwell, P.S., Conaghan, P.G., Emery, P., Woodburn, J. Rheumatology (Oxford, England) (2005) [Pubmed]
  32. Induction of complete remission of advanced stage mycosis fungoides by allogeneic hematopoietic stem cell transplantation. Masood, N., Russell, K.J., Olerud, J.E., Sabath, D.E., Sale, G.E., Doney, K.C., Flowers, M.E., Fefer, A., Thompson, J.A. J. Am. Acad. Dermatol. (2002) [Pubmed]
 
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