FLNA

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

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.^[7] At least 31 disease-causing mutations in this gene have been discovered.^[8]

The protein structure includes an actin binding N terminal domain, 24 internal repeats and 2 hinge regions.^[9][10]

Filamin has been shown to interact with:

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

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).

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.^[25] 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.^[26]

The edited adenosine is located in the 22 immunogloulin^{[check spelling]} like repeat of the protein. This region is an integrin β binding domain^[27] and a RAC1 binding domain.^[20] The amino acid change is likely to effect the electrostatic potential of the binding domains.^[25] 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.^[28] 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.^[25]

The change in electrostatic potential is likely to effect the binding of FLNA to the many proteins it interacts with.^[29]

Interaction of FLNA with the BRCA1 protein is required for efficient regulation of early stages of DNA repair processes.^[30] FLNA is implicated in the control of the DNA repair process of homologous recombination and non-homologous end joining.^[30]