FLNA

{{For|the armed group in northern Mali|National Liberation Front of Azawad}}

Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene.{{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 = 496–498 | date = October 1993 | pmid = 8406501 | doi = 10.1006/geno.1993.1354 }}{{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 = Nature Genetics | volume = 33 | issue = 4 | pages = 487–491 | date = March 2003 | pmid = 12612583 | doi = 10.1038/ng1119 | doi-access = free }}

Structure

The structure of Filamin A, alpha includes an actin binding N terminal domain, 24 internal repeats and 2 hinge regions.{{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 = 141–163 | date = February 1976 | pmid = 2316 | doi = 10.1016/0005-2728(76)90174-2 }}{{cite web | title = P21333 (FLNA_HUMAN): Filamin-A | url = https://www.uniprot.org/uniprot/P21333#section_comments | work = UniProt }}

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.{{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 }} At least 31 disease-causing mutations in this gene have been discovered.{{cite journal | vauthors = Šimčíková D, Heneberg P | title = Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 18577 | date = December 2019 | pmid = 31819097 | pmc = 6901466 | doi = 10.1038/s41598-019-54976-4 | bibcode = 2019NatSR...918577S }}

= DNA repair =

Interaction of FLNA with the BRCA1 protein is required for efficient regulation of early stages of DNA repair processes.{{cite journal | vauthors = Velkova A, Carvalho MA, Johnson JO, Tavtigian SV, Monteiro AN | title = Identification of Filamin A as a BRCA1-interacting protein required for efficient DNA repair | journal = Cell Cycle | location = Georgetown, Tex. | volume = 9 | issue = 7 | pages = 1421–1433 | date = April 2010 | pmid = 20305393 | pmc = 3040726 | doi = 10.4161/cc.9.7.11256 }} FLNA is implicated in the control of the DNA repair process of homologous recombination and non-homologous end joining.

Interactions

Filamin has been shown to interact with:

BRCA2,{{cite journal | vauthors = Yuan Y, Shen Z | title = Interaction with BRCA2 suggests a role for filamin-1 (hsFLNa) in DNA damage response | journal = Journal of Biological Chemistry | volume = 276 | issue = 51 | pages = 48318–48324 | date = December 2001 | pmid = 11602572 | doi = 10.1074/jbc.M102557200 | doi-access = free }}
CD29{{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 = The Journal of Cell Biology | volume = 156 | issue = 2 | pages = 361–376 | date = January 2002 | pmid = 11807098 | pmc = 2199218 | doi = 10.1083/jcb.200103037 }}{{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 = Journal of Biological Chemistry | volume = 273 | issue = 36 | pages = 23304–23312 | date = September 1998 | pmid = 9722563 | doi = 10.1074/jbc.273.36.23304 | doi-access = free }}
CASR,{{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 = Journal of Biological Chemistry | volume = 276 | issue = 37 | pages = 34880–34887 | date = September 2001 | pmid = 11390380 | doi = 10.1074/jbc.M100784200 | doi-access = free }}{{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 = Journal of Biological Chemistry | volume = 276 | issue = 37 | pages = 34871–34879 | date = September 2001 | pmid = 11390379 | doi = 10.1074/jbc.M100775200 | doi-access = free }}
FBLIM1,{{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 | doi-access = free }}
FILIP1,{{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 = Nature Cell Biology | volume = 4 | issue = 7 | pages = 495–501 | date = July 2002 | pmid = 12055638 | doi = 10.1038/ncb808 | s2cid = 4795393 }}
FLNB,{{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 = Human Molecular Genetics | volume = 11 | issue = 23 | pages = 2845–2854 | date = November 2002 | pmid = 12393796 | doi = 10.1093/hmg/11.23.2845 | doi-access = free }}
NPHP1,{{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 = Journal of Biological Chemistry | volume = 277 | issue = 32 | pages = 29028–29035 | date = August 2002 | pmid = 12006559 | doi = 10.1074/jbc.M111697200 | doi-access = free }}
RALA,{{cite journal | vauthors = Ohta Y, Suzuki N, Nakamura S, Hartwig JH, Stossel TP | title = The small GTPase RalA targets filamin to induce filopodia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 5 | pages = 2122–2128 | date = March 1999 | pmid = 10051605 | pmc = 26747 | doi = 10.1073/pnas.96.5.2122 | bibcode = 1999PNAS...96.2122O | doi-access = free }}
SH2B3,{{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 = Molecular Immunology | volume = 37 | issue = 10 | pages = 603–612 | date = August 2000 | pmid = 11163396 | doi = 10.1016/s0161-5890(00)00070-5 }}
TRIO,{{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 = Nature Cell Biology | volume = 2 | issue = 12 | pages = 888–892 | date = December 2000 | pmid = 11146652 | doi = 10.1038/35046533 | s2cid = 10182923 }} and
VHL.{{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 Research | volume = 56 | issue = 13 | pages = 2881–2885 | date = July 1996 | pmid = 8674032 }}{{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 = Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39887–39898 | date = October 2002 | pmid = 12169691 | doi = 10.1074/jbc.M205040200 | doi-access = free }}

FLNA

Structure

Function

= DNA repair =

Interactions

References

Further reading