FLNA

For the armed group in northern Mali, see National Liberation Front of Azawad.

FLNA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2AAV, 2BP3, 2BRQ, 2J3S, 2JF1, 2K3T, 2K7P, 2MTP, 2W0P, 2WFN, 3CNK, 3HOC, 3HOP, 3HOR, 3ISW, 3RGH, 4M9P, 4P3W
Identifiers
Aliases	FLNA , ABP-280, ABPX, CSBS, CVD1, FLN, FLN-A, FLN1, FMD, MNS, NHBP, OPD, OPD1, OPD2, XLVD, XMVD, filamin A, FGS2
External IDs	OMIM: 300017; MGI: 95556; HomoloGene: 1119; GeneCards: FLNA; OMA:FLNA - orthologs
Gene location (Human) Chr. X chromosome (human) [1] Band Xq28 Start 154,348,524 bp [1] End 154,374,634 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X A7.3|X 37.89 cM Start 73,267,067 bp [2] End 73,293,426 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right coronary artery popliteal artery tibial arteries ascending aorta Descending thoracic aorta body of uterus saphenous vein gastric mucosa left coronary artery muscle layer of sigmoid colon Top expressed in tunica media of zone of aorta granulocyte ascending aorta uterus cervix umbilical cord external carotid artery aortic valve internal carotid artery tail of embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity protein-containing complex binding transcription factor binding mu-type opioid receptor binding signal transducer activity actin filament binding small GTPase binding kinase binding actin binding SMAD binding Fc-gamma receptor I complex binding G protein-coupled receptor binding GTPase binding RNA binding potassium channel regulator activity transmembrane transporter binding cadherin binding protein binding Cellular component cytoplasm membrane focal adhesion cortical cytoskeleton plasma membrane Myb complex dendritic shaft extracellular region soma cell cortex nucleolus actin filament actin cytoskeleton perinuclear region of cytoplasm extracellular exosome cytoskeleton nucleus apical dendrite filamentous actin extracellular matrix cell-cell junction cytosol Z discdkac Biological process actin cytoskeleton reorganization negative regulation of transcription by RNA polymerase I negative regulation of protein catabolic process establishment of protein localization protein stabilization platelet degranulation mRNA transcription by RNA polymerase II negative regulation of apoptotic process receptor clustering negative regulation of DNA-binding transcription factor activity cytoplasmic sequestering of protein platelet activation mitotic spindle assembly positive regulation of substrate adhesion-dependent cell spreading protein localization to cell surface cell projection organization adenylate cyclase-inhibiting dopamine receptor signaling pathway actin crosslink formation positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of integrin-mediated signaling pathway platelet aggregation cell junction assembly regulation of cell migration wound healing, spreading of cells semaphorin-plexin signaling pathway formation of radial glial scaffolds cerebral cortex development cilium assembly protein localization to plasma membrane positive regulation of potassium ion transmembrane transport regulation of membrane repolarization during atrial cardiac muscle cell action potential regulation of membrane repolarization during cardiac muscle cell action potential positive regulation of neural precursor cell proliferation positive regulation of neuron migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2316 192176 Ensembl ENSG00000196924 ENSMUSG00000031328 UniProt P21333 Q8BTM8 RefSeq (mRNA) NM_001110556 NM_001456 NM_001290421 NM_010227 RefSeq (protein) NP_001104026 NP_001447 NP_001277350 NP_034357 NP_001390993 Location (UCSC) Chr X: 154.35 – 154.37 Mb Chr X: 73.27 – 73.29 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene. ^{[5] [6]}

Structure

The structure of Filamin A, alpha includes an actin binding N terminal domain, 24 internal repeats and 2 hinge regions. ^{[7] [8]}

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. ^[9] At least 31 disease-causing mutations in this gene have been discovered. ^[10]

DNA repair

Interaction of FLNA with the BRCA1 protein is required for efficient regulation of early stages of DNA repair processes. ^[11] FLNA is implicated in the control of the DNA repair process of homologous recombination and non-homologous end joining. ^[11]

Interactions

Filamin has been shown to interact with:

• BRCA2, ^[12]
• CD29 ^{[13] [14]}
• CASR, ^{[15] [16]}
• FBLIM1, ^[17]
• FILIP1, ^[18]
• FLNB, ^[19]
• NPHP1, ^[20]
• RALA, ^[21]
• SH2B3, ^[22]
• TRIO, ^[23] and
• VHL. ^{[24] [25]}

References

1. GRCh38: Ensembl release 89: ENSG00000196924 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031328 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Gorlin JB, Henske E, Warren ST, Kunst CB, D'Urso M, Palmieri G, et al. (October 1993). "Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28". Genomics. 17 (2): 496–498. doi:10.1006/geno.1993.1354. PMID   8406501.
6. Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, et al. (March 2003). "Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans". Nature Genetics. 33 (4): 487–491. doi: 10.1038/ng1119 . PMID   12612583.
7. Gräber P, Witt HT (February 1976). "Relations between the electrical potential, pH gradient, proton flux and phosphorylation in the photosynthetic membrane". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 423 (2): 141–163. doi:10.1016/0005-2728(76)90174-2. PMID   2316.
8. "P21333 (FLNA_HUMAN): Filamin-A". UniProt.
9. "Entrez Gene: FLNA filamin A, alpha (actin binding protein 280)".
10. Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC   6901466 . PMID   31819097.
11. Velkova A, Carvalho MA, Johnson JO, Tavtigian SV, Monteiro AN (April 2010). "Identification of Filamin A as a BRCA1-interacting protein required for efficient DNA repair". Cell Cycle. 9 (7). Georgetown, Tex.: 1421–1433. doi:10.4161/cc.9.7.11256. PMC   3040726 . PMID   20305393.
12. Yuan Y, Shen Z (December 2001). "Interaction with BRCA2 suggests a role for filamin-1 (hsFLNa) in DNA damage response". Journal of Biological Chemistry. 276 (51): 48318–48324. doi: 10.1074/jbc.M102557200 . PMID   11602572.
13. van der Flier A, Kuikman I, Kramer D, Geerts D, Kreft M, Takafuta T, et al. (January 2002). "Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits". The Journal of Cell Biology. 156 (2): 361–376. doi:10.1083/jcb.200103037. PMC   2199218 . PMID   11807098.
14. Loo DT, Kanner SB, Aruffo A (September 1998). "Filamin binds to the cytoplasmic domain of the beta1-integrin. Identification of amino acids responsible for this interaction". Journal of Biological Chemistry. 273 (36): 23304–23312. doi: 10.1074/jbc.273.36.23304 . PMID   9722563.
15. Hjälm G, MacLeod RJ, Kifor O, Chattopadhyay N, Brown EM (September 2001). "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 of Biological Chemistry. 276 (37): 34880–34887. doi: 10.1074/jbc.M100784200 . PMID   11390380.
16. Awata H, Huang C, Handlogten ME, Miller RT (September 2001). "Interaction of the calcium-sensing receptor and filamin, a potential scaffolding protein". Journal of Biological Chemistry. 276 (37): 34871–34879. doi: 10.1074/jbc.M100775200 . PMID   11390379.
17. Tu Y, Wu S, Shi X, Chen K, Wu C (April 2003). "Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation". Cell. 113 (1): 37–47. doi: 10.1016/s0092-8674(03)00163-6 . PMID   12679033.
18. Nagano T, Yoneda T, Hatanaka Y, Kubota C, Murakami F, Sato M (July 2002). "Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone". Nature Cell Biology. 4 (7): 495–501. doi:10.1038/ncb808. PMID   12055638. S2CID   4795393.
19. Sheen VL, Feng Y, Graham D, Takafuta T, Shapiro SS, Walsh CA (November 2002). "Filamin A and Filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact". Human Molecular Genetics. 11 (23): 2845–2854. doi: 10.1093/hmg/11.23.2845 . PMID   12393796.
20. Donaldson JC, Dise RS, Ritchie MD, Hanks SK (August 2002). "Nephrocystin-conserved domains involved in targeting to epithelial cell-cell junctions, interaction with filamins, and establishing cell polarity". Journal of Biological Chemistry. 277 (32): 29028–29035. doi: 10.1074/jbc.M111697200 . PMID   12006559.
21. Ohta Y, Suzuki N, Nakamura S, Hartwig JH, Stossel TP (March 1999). "The small GTPase RalA targets filamin to induce filopodia". Proceedings of the National Academy of Sciences of the United States of America. 96 (5): 2122–2128. Bibcode:1999PNAS...96.2122O. doi: 10.1073/pnas.96.5.2122 . PMC   26747 . PMID   10051605.
22. He X, Li Y, Schembri-King J, Jakes S, Hayashi J (August 2000). "Identification of actin binding protein, ABP-280, as a binding partner of human Lnk adaptor protein". Molecular Immunology. 37 (10): 603–612. doi:10.1016/s0161-5890(00)00070-5. PMID   11163396.
23. Bellanger JM, Astier C, Sardet C, Ohta Y, Stossel TP, Debant A (December 2000). "The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin". Nature Cell Biology. 2 (12): 888–892. doi:10.1038/35046533. PMID   11146652. S2CID   10182923.
24. Tsuchiya H, Iseda T, Hino O (July 1996). "Identification of a novel protein (VBP-1) binding to the von Hippel-Lindau (VHL) tumor suppressor gene product". Cancer Research. 56 (13): 2881–2885. PMID   8674032.
25. Zhou MI, Wang H, Ross JJ, Kuzmin I, Xu C, Cohen HT (October 2002). "The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1". Journal of Biological Chemistry. 277 (42): 39887–39898. doi: 10.1074/jbc.M205040200 . PMID   12169691.

Further reading

• Light S, Sagit R, Ithychanda SS, Qin J, Elofsson A (Sep 2012). "The evolution of filamin — a protein domain repeat perspective". Journal of Structural Biology. 179 (3): 289–298. doi:10.1016/j.jsb.2012.02.010. PMC   3728663 . PMID   22414427.
• Stossel TP, Condeelis J, Cooley L, Hartwig JH, Noegel A, Schleicher M, et al. (Feb 2001). "Filamins as integrators of cell mechanics and signalling". Nature Reviews. Molecular Cell Biology. 2 (2): 138–145. doi:10.1038/35052082. PMID   11252955. S2CID   5203942.
• van der Flier A, Sonnenberg A (Apr 2001). "Structural and functional aspects of filamins". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1538 (2–3): 99–117. doi: 10.1016/S0167-4889(01)00072-6 . PMID   11336782.
• Robertson S (October 2019). "X-Linked Otopalatodigital Spectrum Disorders". In Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, Robertson S (eds.). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle. PMID   20301567. NBK1393.
• Chen MH, Walsh CA (September 2021). "FLNA Deficiency". In Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, Chen MH, Walsh CA (eds.). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle. PMID   20301392. NBK1213.