FLNC (gene)

Filamin C, gamma

PDB rendering based on 1v05.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols FLNC ; ABP-280; ABP280A; ABPA; ABPL; FLN2; MFM5; MPD4
External IDs OMIM: 102565 MGI: 95557 HomoloGene: 37481 GeneCards: FLNC Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 2318 68794
Ensembl ENSG00000128591 ENSMUSG00000068699
UniProt Q14315 Q8VHX6
RefSeq (mRNA) NM_001127487 NM_001081185
RefSeq (protein) NP_001120959 NP_001074654
Location (UCSC) Chr 7:
128.83 – 128.86 Mb		 Chr 6:
29.43 – 29.46 Mb
PubMed search

Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a protein that in humans is encoded by the FLNC gene.[1][2][3] Filamin-C is mainly expressed in cardiac and skeletal muscles, and functions at Z-discs and in subsarcolemmal regions.

Structure

Filamin-C is a 290.8 kDa protein composed of 2725 amino acids.[4][5] Filamin-C, like the ubiquitously-expressed isoform Filamin-A, have an N-terminal filamentous actin-binding domain, followed by a lengthy C-terminal self-association domain containing a series of immunoglobulin-like domains, and a membrane glycoprotein-binding domain.[6] Filamin-C interacts with γ-sarcoglycan and δ-sarcoglycan at the sarcolemma;[7][7][8][8] myotilin and FATZ/calsarcin/myozenin at Z-lines,[9][10][11][12] as well as LL5β.[13] Filamin-C has also been shown to interact with INPPL1,[14] KCND2,[15] and MAP2K4.[16]

Function

The family of Filamin proteins crosslink actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin cytoskeleton. However, the precise function of the Filamin-C isoform is still under investigation. As Filamin-C is localized mainly to striated muscle, its functions are likely specific to the specialized sarcomeric cytoskeleton present in muscle. As Filamin-C is found at both subsarcolemmal regions and at Z-lines, one plausible function of Filamin-C would be to act as a mode of communication between the membrane and the sarcomere. In skeletal muscle, Filamin-C is found at sites of core formation in skeletal myopathies,[17] and alterations in subcellular localization of Filamin-C have been exhibited in limb-girdle muscular dystrophy and Duchenne muscular dystrophy.[18]

Clinical significance

Mutations in Filamin C have been associated with human hypertrophic cardiomyopathy and a higher incidence of sudden cardiac death.[19] Expression of mutant protein in rat cardiac cells demonstrated that mutant Filamin C forms aggregates, which may provide a mechanistic link to the observed cardiac dysfunction.[19] Deficiency of this protein has been associated with muscle weakness.[20]

References

  1. ↑ Maestrini E, Patrosso C, Mancini M, Rivella S, Rocchi M, Repetto M, Villa A, Frattini A, Zoppè M, Vezzoni P (Jun 1993). "Mapping of two genes encoding isoforms of the actin binding protein ABP-280, a dystrophin like protein, to Xq28 and to chromosome 7". Human Molecular Genetics 2 (6): 761–6. doi:10.1093/hmg/2.6.761. PMID 7689010.
  2. ↑ Gariboldi M, Maestrini E, Canzian F, Manenti G, De Gregorio L, Rivella S, Chatterjee A, Herman GE, Archidiacono N, Antonacci R (May 1994). "Comparative mapping of the actin-binding protein 280 genes in human and mouse". Genomics 21 (2): 428–30. doi:10.1006/geno.1994.1288. PMID 8088838.
  3. ↑ "Entrez Gene: FLNC filamin C, gamma (actin binding protein 280)".
  4. ↑ http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q14315. Missing or empty |title= (help)
  5. ↑ Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  6. ↑ van der Flier A, Sonnenberg A (2001). "Structural and functional aspects of filamins". Biochim. Biophys. Acta 1538 (2-3): 99–117. doi:10.1016/s0167-4889(01)00072-6. PMID 11336782.
  7. 1 2 Guyon JR, Kudryashova E, Potts A, Dalkilic I, Brosius MA, Thompson TG, Beckmann JS, Kunkel LM, Spencer MJ (Oct 2003). "Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans". Muscle & Nerve 28 (4): 472–83. doi:10.1002/mus.10465. PMID 14506720.
  8. 1 2 Thompson TG, Chan YM, Hack AA, Brosius M, Rajala M, Lidov HG, McNally EM, Watkins S, Kunkel LM (Jan 2000). "Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein". The Journal of Cell Biology 148 (1): 115–126. doi:10.1083/jcb.148.1.115. PMC 3207142. PMID 10629222.
  9. ↑ van der Ven PF, Wiesner S, Salmikangas P, Auerbach D, Himmel M, Kempa S, Hayess K, Pacholsky D, Taivainen A, Schröder R, Carpén O, Fürst DO (2000). "Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin". J. Cell Biol. 151 (2): 235–48. doi:10.1083/jcb.151.2.235. PMC 2192634. PMID 11038172.
  10. ↑ Takada F, Vander Woude DL, Tong HQ, Thompson TG, Watkins SC, Kunkel LM, Beggs AH (Feb 2001). "Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines". Proceedings of the National Academy of Sciences of the United States of America 98 (4): 1595–600. doi:10.1073/pnas.041609698. PMC 29302. PMID 11171996.
  11. ↑ Frey N, Olson EN (Apr 2002). "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins". The Journal of Biological Chemistry 277 (16): 13998–4004. doi:10.1074/jbc.M200712200. PMID 11842093.
  12. ↑ Faulkner G, Pallavicini A, Comelli A, Salamon M, Bortoletto G, Ievolella C, Trevisan S, Kojic' S, Dalla Vecchia F, Laveder P, Valle G, Lanfranchi G (Dec 2000). "FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle". The Journal of Biological Chemistry 275 (52): 41234–42. doi:10.1074/jbc.M007493200. PMID 10984498.
  13. ↑ Paranavitane V, Coadwell WJ, Eguinoa A, Hawkins PT, Stephens L (Jan 2003). "LL5beta is a phosphatidylinositol (3,4,5)-trisphosphate sensor that can bind the cytoskeletal adaptor, gamma-filamin". The Journal of Biological Chemistry 278 (2): 1328–35. doi:10.1074/jbc.M208352200. PMID 12376540.
  14. ↑ Dyson JM, O'Malley CJ, Becanovic J, Munday AD, Berndt MC, Coghill ID, Nandurkar HH, Ooms LM, Mitchell CA (Dec 2001). "The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2, binds filamin and regulates submembraneous actin". The Journal of Cell Biology 155 (6): 1065–79. doi:10.1083/jcb.200104005. PMC 2150887. PMID 11739414.
  15. ↑ Petrecca K, Miller DM, Shrier A (Dec 2000). "Localization and enhanced current density of the Kv4.2 potassium channel by interaction with the actin-binding protein filamin". The Journal of Neuroscience 20 (23): 8736–44. PMID 11102480.
  16. ↑ Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel TP, Kyriakis JM, Avruch J (Jan 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". The Journal of Biological Chemistry 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID 9006895.
  17. ↑ 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 (2003). "Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle". Journal of the neurological sciences 206 (1): 71–8. doi:10.1016/s0022-510x(02)00341-6. PMID 12480088.
  18. ↑ Thompson, T. G.; Chan, Y. M.; Hack, A. A.; Brosius, M; Rajala, M; Lidov, H. G.; McNally, E. M.; Watkins, S; Kunkel, L. M. (2000). "Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein". The Journal of Cell Biology 148 (1): 115–26. doi:10.1083/jcb.148.1.115. PMC 3207142. PMID 10629222.
  19. 1 2 Valdes-Mas R, Gutierrez-Fernandez A, Gomez J, Coto E, Astudillo A, Puente DA, Reguero JR, Alvarez V, Moris C, Leon D, Martin M, Puente XS, Lopez-Otin C (2014). "Mutations in filamin C cause a new form of familial hypertrophic cardiomyopathy". Nature Communications 5: 5326. doi:10.1038/ncomms6326. PMID 25351925.
  20. ↑ Guergueltcheva V, Peeters K, Baets J, Ceuterick-de Groote C, Martin JJ, Suls A, De Vriendt E, Mihaylova V, Chamova T, Almeida-Souza L, Ydens E, Tzekov C, Hadjidekov G, Gospodinova M, Storm K, Reyniers E, Bichev S, van der Ven PF, Fürst DO, Mitev V, Lochmüller H, Timmerman V, Tournev I, De Jonghe P, Jordanova A (Dec 2011). "Distal myopathy with upper limb predominance caused by filamin C haploinsufficiency". Neurology 77 (24): 2105–14. doi:10.1212/WNL.0b013e31823dc51e. PMID 22131542.

Further reading

External links

  1. ↑
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