请输入您要查询的百科知识：

　

词条 FLNA
释义

  1. Function

  2. Structure

  3. Interactions

  4. RNA editing

      Type    Site    Structure    Function  

  5. References

  6. Further reading

  7. External links

{{For|the armed group in northern Mali|National Liberation Front of Azawad}}{{Infobox_gene}}Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene.[1][2]

Function

Actin-binding protein, or filamin, is a 280-kD protein that crosslinks actin filaments into orthogonal networks in cortical cytoplasm and participates in the anchoring of membrane proteins for the actin cytoskeleton. Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the FLNA gene, is a widely expressed filamin that regulates the reorganization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes, and secondary messengers.[supplied by OMIM][3]

Structure

The protein structure includes an actin binding N terminal domain, 24 internal repeats and 2 hinge regions.[4][5]

Interactions

Filamin has been shown to interact with:

{{div col|colwidth=20em}}
  • BRCA2,[6]
  • CD29[7][8]
  • CASR,[9][10]
  • FBLIM1,[11]
  • FILIP1,[12]
  • FLNB,[13]
  • NPHP1,[14]
  • RALA,[15]
  • SH2B3,[16]
  • TRIO,[17] and
  • VHL.[18][19]
{{Div col end}}

RNA editing

The edited residue was previously recorded as a single nucleotide polymorphism(SNP) in dbSNP.

Type

A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine.Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR 1 and ADAR 2 being the only enzymatically active members.ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in a region complementary to the region of the editing site. This complementary region is usually found in a neighbouring intron but can also be located in an exonic sequence. The region that base pairs with the editing region is known as an Editing Complentary Sequence (ECS).

Site

The one editing site of FLNA pre-mRNA is located within amino acid 2341 of the final protein. The Glutamine (Q) codon is altered due to a site specific deamination of an adenosine at the editing site to an Arginine (R) codon. The editing region is predicted to form a double stranded region of 32 base pairs in length with a complementary sequence about 200 nucleotides downstream of the editing site. This ECS is found in an intronic sequence.[20] Editing at the Q/R site is likely to involve both ADAR1 and ADAR2.Mice ADAR2 knockouts show a decrease in editing at the Q/R site.ADAR1 double knockouts have no effect on editing.[21]

Structure

The edited adenosine is located in the 22 immunogloulin like repeat of the protein. This region is an integrin β binding domain[22] and a RAC1 binding domain.[15] The amino acid change is likely to effect the electrostatic potential of the binding domains.[20] FLNA editing site is 2 nucleotides from a splice site like the R/G site of GluR-2. Both transcripts have 7/8 identical nucleotides around their editing sites. Since it is widely thought that editing at the GLUR-2 Q/R site influences splicing, the sequence and editing site similarity could mean that editing at the FLNA site could also regulate splicing. In vitro experiments of gluR-2 have shown that presence of ADAR2 results in inhibition of splicing.[23] Analysis of EST data for FLNA show that there is a link between editing of the last exon codon and retention of the following intron.[20]

Function

The change in electrostatic potential is likely to effect the binding of FLNA to the many proteins it interacts with.[24]{{clear}}

References

1. ^{{cite journal | vauthors = Gorlin JB, Henske E, Warren ST, Kunst CB, D'Urso M, Palmieri G, Hartwig JH, Bruns G, Kwiatkowski DJ | title = Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28 | journal = Genomics | volume = 17 | issue = 2 | pages = 496–8 | date = October 1993 | pmid = 8406501 | pmc = | doi = 10.1006/geno.1993.1354 }}
2. ^{{cite journal | vauthors = Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, Kenwrick SJ, Kim CA, Morava E, Newbury-Ecob R, Orstavik KH, Quarrell OW, Schwartz CE, Shears DJ, Suri M, Kendrick-Jones J, Wilkie AO | title = Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans | journal = Nat Genet | volume = 33 | issue = 4 | pages = 487–91 | date = March 2003 | pmid = 12612583 | pmc = | doi = 10.1038/ng1119 }}
3. ^{{cite web | title = Entrez Gene: FLNA filamin A, alpha (actin binding protein 280)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2316| accessdate = }}
4. ^{{cite journal | vauthors = Gräber P, Witt HT | title = Relations between the electrical potential, pH gradient, proton flux and phosphorylation in the photosynthetic membrane | journal = Biochimica et Biophysica Acta | volume = 423 | issue = 2 | pages = 141–63 | date = February 1976 | pmid = 2316 }}
5. ^{{cite web | title = P21333 (FLNA_HUMAN): Filamin-A | url = https://www.uniprot.org/uniprot/P21333#section_comments | work = UniProt }}
6. ^{{cite journal | vauthors = Yuan Y, Shen Z | title = Interaction with BRCA2 suggests a role for filamin-1 (hsFLNa) in DNA damage response | journal = J. Biol. Chem. | volume = 276 | issue = 51 | pages = 48318–24 | date = December 2001 | pmid = 11602572 | doi = 10.1074/jbc.M102557200 }}
7. ^{{cite journal | vauthors = van der Flier A, Kuikman I, Kramer D, Geerts D, Kreft M, Takafuta T, Shapiro SS, Sonnenberg A | title = Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits | journal = J. Cell Biol. | volume = 156 | issue = 2 | pages = 361–76 | date = January 2002 | pmid = 11807098 | pmc = 2199218 | doi = 10.1083/jcb.200103037 }}
8. ^{{cite journal | vauthors = Loo DT, Kanner SB, Aruffo A | title = Filamin binds to the cytoplasmic domain of the beta1-integrin. Identification of amino acids responsible for this interaction | journal = J. Biol. Chem. | volume = 273 | issue = 36 | pages = 23304–12 | date = September 1998 | pmid = 9722563 | doi = 10.1074/jbc.273.36.23304 }}
9. ^{{cite journal | vauthors = Hjälm G, MacLeod RJ, Kifor O, Chattopadhyay N, Brown EM | title = Filamin-A binds to the carboxyl-terminal tail of the calcium-sensing receptor, an interaction that participates in CaR-mediated activation of mitogen-activated protein kinase | journal = J. Biol. Chem. | volume = 276 | issue = 37 | pages = 34880–7 | date = September 2001 | pmid = 11390380 | doi = 10.1074/jbc.M100784200 }}
10. ^{{cite journal | vauthors = Awata H, Huang C, Handlogten ME, Miller RT | title = Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein | journal = J. Biol. Chem. | volume = 276 | issue = 37 | pages = 34871–9 | date = September 2001 | pmid = 11390379 | doi = 10.1074/jbc.M100775200 }}
11. ^{{cite journal | vauthors = Tu Y, Wu S, Shi X, Chen K, Wu C | title = Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation | journal = Cell | volume = 113 | issue = 1 | pages = 37–47 | date = April 2003 | pmid = 12679033 | doi = 10.1016/s0092-8674(03)00163-6 }}
12. ^{{cite journal | vauthors = Nagano T, Yoneda T, Hatanaka Y, Kubota C, Murakami F, Sato M | title = Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone | journal = Nat. Cell Biol. | volume = 4 | issue = 7 | pages = 495–501 | date = July 2002 | pmid = 12055638 | doi = 10.1038/ncb808 }}
13. ^{{cite journal | vauthors = Sheen VL, Feng Y, Graham D, Takafuta T, Shapiro SS, Walsh CA | title = Filamin A and Filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact | journal = Hum. Mol. Genet. | volume = 11 | issue = 23 | pages = 2845–54 | date = November 2002 | pmid = 12393796 | doi = 10.1093/hmg/11.23.2845 }}
14. ^{{cite journal | vauthors = Donaldson JC, Dise RS, Ritchie MD, Hanks SK | title = Nephrocystin-conserved domains involved in targeting to epithelial cell-cell junctions, interaction with filamins, and establishing cell polarity | journal = J. Biol. Chem. | volume = 277 | issue = 32 | pages = 29028–35 | date = August 2002 | pmid = 12006559 | doi = 10.1074/jbc.M111697200 }}
15. ^1 {{cite journal | vauthors = Ohta Y, Suzuki N, Nakamura S, Hartwig JH, Stossel TP | title = The small GTPase RalA targets filamin to induce filopodia | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 5 | pages = 2122–8 | date = March 1999 | pmid = 10051605 | pmc = 26747 | doi = 10.1073/pnas.96.5.2122 | bibcode = 1999PNAS...96.2122O }}
16. ^{{cite journal | vauthors = He X, Li Y, Schembri-King J, Jakes S, Hayashi J | title = Identification of actin binding protein, ABP-280, as a binding partner of human Lnk adaptor protein | journal = Mol. Immunol. | volume = 37 | issue = 10 | pages = 603–12 | date = August 2000 | pmid = 11163396 | doi = 10.1016/s0161-5890(00)00070-5 }}
17. ^{{cite journal | vauthors = Bellanger JM, Astier C, Sardet C, Ohta Y, Stossel TP, Debant A | title = The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin | journal = Nat. Cell Biol. | volume = 2 | issue = 12 | pages = 888–92 | date = December 2000 | pmid = 11146652 | doi = 10.1038/35046533 }}
18. ^{{cite journal | vauthors = Tsuchiya H, Iseda T, Hino O | title = Identification of a novel protein (VBP-1) binding to the von Hippel-Lindau (VHL) tumor suppressor gene product | journal = Cancer Res. | volume = 56 | issue = 13 | pages = 2881–5 | date = July 1996 | pmid = 8674032 | doi = }}
19. ^{{cite journal | vauthors = Zhou MI, Wang H, Ross JJ, Kuzmin I, Xu C, Cohen HT | title = The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1 | journal = J. Biol. Chem. | volume = 277 | issue = 42 | pages = 39887–98 | date = October 2002 | pmid = 12169691 | doi = 10.1074/jbc.M205040200 }}
20. ^1 2 {{cite journal | vauthors = Levanon EY, Hallegger M, Kinar Y, Shemesh R, Djinovic-Carugo K, Rechavi G, Jantsch MF, Eisenberg E | title = Evolutionarily conserved human targets of adenosine to inosine RNA editing | journal = Nucleic Acids Res. | volume = 33 | issue = 4 | pages = 1162–8 | year = 2005 | pmid = 15731336 | pmc = 549564 | doi = 10.1093/nar/gki239 }}
21. ^{{cite journal | vauthors = Riedmann EM, Schopoff S, Hartner JC, Jantsch MF | title = Specificity of ADAR-mediated RNA editing in newly identified targets | journal = RNA | volume = 14 | issue = 6 | pages = 1110–8 | date = June 2008 | pmid = 18430892 | pmc = 2390793 | doi = 10.1261/rna.923308 }}
22. ^{{cite journal | vauthors = Travis MA, van der Flier A, Kammerer RA, Mould AP, Sonnenberg A, Humphries MJ | title = Interaction of filamin A with the integrin beta 7 cytoplasmic domain: role of alternative splicing and phosphorylation | journal = FEBS Lett. | volume = 569 | issue = 1–3 | pages = 185–90 | date = July 2004 | pmid = 15225631 | doi = 10.1016/j.febslet.2004.04.099 }}
23. ^{{cite journal | vauthors = Bratt E, Ohman M | title = Coordination of editing and splicing of glutamate receptor pre-mRNA | journal = RNA | volume = 9 | issue = 3 | pages = 309–18 | date = March 2003 | pmid = 12592005 | pmc = 1370398 | doi = 10.1261/rna.2750803 }}
24. ^{{cite journal | vauthors = Popowicz GM, Müller R, Noegel AA, Schleicher M, Huber R, Holak TA | title = Molecular structure of the rod domain of dictyostelium filamin | journal = J. Mol. Biol. | volume = 342 | issue = 5 | pages = 1637–46 | date = October 2004 | pmid = 15364587 | doi = 10.1016/j.jmb.2004.08.017 }}

Further reading

{{refbegin|32em}}
  • {{cite journal | vauthors = Light S, Sagit R, Ithychanda SS, Qin J, Elofsson A | title = The evolution of filamin - a protein domain repeat perspective | journal = Journal of Structural Biology | volume = 179 | issue = 3 | pages = 289–98 | date = Sep 2012 | pmid = 22414427 | doi = 10.1016/j.jsb.2012.02.010 | pmc = 3728663 }}
  • {{cite journal | vauthors = Stossel TP, Condeelis J, Cooley L, Hartwig JH, Noegel A, Schleicher M, Shapiro SS | title = Filamins as integrators of cell mechanics and signalling | journal = Nat. Rev. Mol. Cell Biol. | volume = 2 | issue = 2 | pages = 138–45 | year = 2001 | pmid = 11252955 | doi = 10.1038/35052082 }}
  • {{cite journal | vauthors = van der Flier A, Sonnenberg A | title = Structural and functional aspects of filamins | journal = Biochim. Biophys. Acta | volume = 1538 | issue = 2–3 | pages = 99–117 | year = 2001 | pmid = 11336782 | doi = 10.1016/S0167-4889(01)00072-6 }}
{{refend}}

External links

  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=opd GeneReview/NCBI/NIH/UW entry on Otopalatodigital Spectrum Disorders]
  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=x-pvh GeneReviews/NIH/NCBI/UW entry on X-Linked Periventricular Heterotopia or Bilateral Periventricular Nodular Heterotopia]
{{PDB Gallery|geneid=2316}}{{Cytoskeletal proteins}}Filamin
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/9/20 13:48:53