Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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filamin A(FLNA) filamin A(FLNA) Related Genes Homo sapiens
CHROMOSOME X,
CYTOBAND Xq28,
ENSEMBL_GENE_ID ENSG00000196924,
GENERIF_SUMMARY Cell death and mechanoprotection by filamin a in connective tissues after challenge by applied tensile forces, Two new pedigrees of bilateral periventricular nodular heterotopia are reported with a mutation of FLN1 and a deletion in its C-terminus causing a distal protein truncation., FLNa may be essential for Pak1-induced cytoskeletal reorganization, there is a mechanically coupled transcriptional circuit from p38 that induces filamin-A expression [filamin A], an important role for filamin in the endocytic sorting and recycling of the internalized CTR, PH domain of ROCK binds to the carboxy-terminal region of filamin-A containing the last 24th repeat. ROCK co-localized with filamin-A at the protrusive cell membranes of HeLa cells., filamin A has a role in signaling pathways that mediate organogenesis in multiple systems during embryonic development, FLNa interfered with androgen receptor (AR) interdomain interactions and competed with the coactivator transcriptional intermediary factor 2 to specifically down-regulate AR function., Filamin A was identified as a direct binding partner of protein kinase Calpha; two binding sites were identified on filamin A; a Ca2+ and phospholipid-dependent association of the regulatory domain of protein kinase C with these sites was revealed., Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway., Filamin A binding to PSMA reduces the internalization rate of PSMA and its N-acelylated-alpha linked-acidic dipeptidase activity., shear-dependent VWF-induced platelet activation affects filamin A binding to GpIb-IX-V, and filamin A binding to the cytoplasmic tail of GpIbalpha regulates proaggregatory tyrosine kinase signaling., filamin-A was found to have no effect on Kir2.1 channel behavior but, rather, increased the number of functional channels resident within the membrane, filamin-A has a role in the recovery from G2 arrest and subsequent mitotic cell death after DNA damage, A woman with complex partial seizures and periventricular nodular heterotopia (PNH) had an amino acid exchange, a transition of guanine to adenine at the first position of intron 13 (IVS13 + 1 G -> A) causing a splice site mutation (2022 + 1 G -> A), Dual phenotype of periventricular nodular heterotopia and frontometaphyseal dysplasia in one patient is caused by two functionally different, aberrant filamin A proteins, Data provide substantial evidence that ribosomal S6 kinase (RSK) phosphorylates filamin A, and suggest a novel role for RSK in the regulation of the actin cytoskeleton., Filamin-A interacts with c-mip/Tc-mip in a new T-cell signaling pathway., FLNA has diverse roles in embryonic, fetal and postnatal development [review], Periventricular nodular heterotopia caused by FLN1 mutations in men has a wide clinical spectrum and is caused by different genetic mechanisms, including somatic mosaicism., FLN1 mutations may have a role in periventricular heterotopia, Interaction with filamin A increases cellular CaR by preventing CaR degradation, thereby facilitating CaR signaling., 3 filamin A mutations were identified in periventricular heterotopia/Ehlers-Danlos patients, D3R, filamin A, and beta-arrestin form a signaling complex that is destabilized by agonist- or expression-mediated increases in GRK2/3 activity, G12, Rho, filamin-A, and the actin cytoskeleton are required for amino acid-stimulated Ca2+ oscillations produced by the Ca2+-sensing receptor, familial Ehlers-Danlos syndrome and periventricular nodular heterotopia is associated with an amino acid substition sssisns FLNA., calmodulin and calcium regulate the binding of filamin A to actin filaments, A purified C-terminal region of filamin is a suitable substrate for calcineurin in vitro and in vivo, beta-arrestins and FLNA cooperate to regulate ERK activation and actin cytoskeleton reorganization., Mutations in FLNA result in frontometaphyseal dysplasia and phenotypic diversity., A novel role is revealed for filamin A in the T cell receptor/CD28 signaling pathway leading to transcription factor activation and interleukin-2 production via the inducible interaction with protein kinase C theta., This suggests that the titin Z2-Zis1 domain can link filamins and alpha-actinin together in the periphery of the Z-line/dense bodies in a fashion that is conserved in smooth and striated muscles., Data indicate that filamin A binding to CD28 is required to induce the T-cell cytoskeletal rearrangements leading to recruitment of lipid microdomains and signalling mediators into the immunological synapse., filamin A is the first gene known to cause isolated nonsyndromic valvular heart disease., In cells, filamin A tethered plasma membrane CFTR to the underlying actin network. This interaction stabilized CFTR at the cell surface and regulated the plasma membrane dynamics and confinement of the channel., Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement., expression of FLNa regulates constitutive activation of the Ras/ERK pathway partly through a Ras-GRF1 mechanism to modulate the production of MMP-9., Our results suggest a role for cyclin B1/Cdk1 in FLNa-dependent actin remodelling., FlnA restored Casodex anticaner sensitivity in C4-2 prostatic cancer cells by decreasing Akt phosphorylation., A novel mutation, 629G>T, in FLNA that had arisen de novo in the mother lead to Otopalatodigital syndrome type 2., Essential for both the efficient signaling and sequestration of dopamine D3 receptor., Filamin-A as an adaptor protein that links HIV-1 receptors to the actin cytoskeleton remodelling machinery, which may facilitate virus infection., analysis of filamin a IgFLN domains suggests that auto-inhibition by adjacent IgFLN domains may be a general mechanism controlling filamin-ligand interactions., in the absence of filamin A, chronic treatment with morphine, methadone or levorphanol leads to up-regulation of mu opioid receptor, A library of FLNa fragments was generated to examine their F-actin binding to define the structural properties of FLNa that enable its various functions., Review explores the pathogenesis of persistent periventricular nodular heterotopia with respect to filamin-A (FLNa) mutations with mouse models. [review], Filamin A plays a pivotal role in FcgammaRI surface expression via retention of FcgammaRI from a default lysosomal pathway., mutant FLA lacking the actin binding domain is capable of restoring almost as well as full length FLA the down-regulation of the human mu opioid receptor. Some functions of FLA do not act via the actin cytoskeleton., novel mutation, c.987G-->C mutation in exon 6 of the Filamin A (FLNA) gene in the genomic DNA in bilateral periventricular nodular heterotopia, Characterize a novel cell surface protein ECSM2 that regulates endothelial chemotaxis and tube formation, and interacts with filamin A., These data indicate that caveolin-1 specifies filamin A as a novel target for Akt-mediated filamin A Ser-2152 phosphorylation thus mediating the effects of caveolin-1 on IGF-I-induced cancer cell migration., Datas suggest that filamin A links sphingosine kinase 1 and sphingosine-1-phosphate receptor 1 to locally influence the dynamics of actin cytoskeletal structures at lamellipodia to promote cell movement., ASB2 may regulate hematopoietic cell differentiation by modulating cell spreading and actin remodeling through targeting of filamins A and B for degradation., analysis of the migfilin-filamin interaction and competition with integrin beta 7 tails, role of filamin cleavage and protein tyrosine phosphorylation in shear-stress-induced platelet microparticle formation and of its suppression by the monoclonal antibody (mAb) Ib-23 directed against GPIbalpha, Our report also helps define the critical region with exclusion of FLNA in the X-linked mental retardation phenotype., This study reports the structure of FLNa domain 24 (FLNa24), compare the structure with FLNc24, and discuss how dimerization is formed in FLNa24., The interaction between FilGAP and FlnA plays a role in protecting cells against force-induced apoptosis., Wnt5A activates calpain-1, leading to the cleavage of filamin A, which results in a remodeling of the cytoskeleton and an increase in melanoma cell motility, Filamin A modulates kinase activation and intracellular trafficking of epidermal growth factor receptors in human melanoma cells., FLNA genes in cell cycle control and lipid metabolism with dynamically regulated binding sites for sterol regulatory element-binding protein 1 and RNA polymerase II in HepG2 cells, Mutational analysis informed by structure can generate reagents for probing specific cellular interactions of filamin A (FLNa). Disease-related FLNa mutations have demonstrable effects on FLNa function, These findings support a role for FLNa-beta1 integrin as a mechanosensitive complex that bidirectionally senses the tension of the matrix and, in turn, regulates cellular contractility and response to this matrix tension., Study performed all-atom discrete molecular dynamics (DMD) simulations to study thermally and force-induced unfolding of filamin A; DMD allows observation of force-induced unfolding of filamin A Ig domains under physiological forces., High plasma filamin A is associated with high-grade astrocytoma and metastatic breast cancer., propose that binding of pro-PrP to FLNa perturbs FLNa function, thus contributing to the aggressiveness of pancreatic ductal adenocarcinoma, Mechanical force applied to filamin can expose cryptic integrin binding sites., Data suggest that filamin A association with caveolin-1 promotes caveolae-mediated transport by regulating vesicle internalization, clustering, and trafficking., These data provide the first biochemical evidence for a gain-of-function mechanism for the otopalatodigital syndrome due to filamin A mutations., Filamin A associates with vimentin and protein kinase C-epsilon, thereby enabling vimentin phosphorylation, which is important for beta1 integrin activation and cell spreading on collagen., Loss of filamin-A is associated with decreased recombinational DNA double strand break repair in melanoma and breast cancer., spectrum of mutations, including novel point and missense, associated with bilateral periventricular nodular heterotopia, crystal structure of actin-binding domain of filamin A was solved at 3.2 A resolution., We believe the results of this study implicate filamin-A as a tunable mechanosensor, where its sensitivity can be modulated by the degree of phosphorylation., Filamin A is a scaffold protein whose function is to link MKK4 and MKK7 together and promote JNK1 activation., the binding of filamin A to vimentin and protein kinase C epsilon is an essential regulatory step for the trafficking and activation of beta1 integrins and cell spreading on collagen, clinical manifestations and results of FLNA exon 22 mutation screening in two boys with the perinatally lethal form of Melnick-Needles syndrome and their affected mothers, Data report the identification of the actin-binding protein Filamin A (FLNA) as BRCA1 partner and demonstrate that FLNA is required for efficient regulation of early stages of DNA repair processes., Cystic fibrosis transmembrane conductance regulator interacts with multiple immunoglobulin domains of filamin A, analysis of the interaction between cystic fibrosis transmembrane conductance regulator and immunoglobulin-like repeats of filamin, High FLNA is associated with tumor cell migration., data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration, TOD is caused by this single recurrent mutation in the FLNA gene., Pro-prion binds filamin A, facilitating its interaction with integrin beta1, and contributes to melanomagenesis., The cardiological phenotype typically consists of aortic or mitral regurgitation, coarctation of the aorta or other left-sided cardiac malformations., FLNa as an important protein for controlling the internalization and spatial localization of the CCR2B receptor, FLNA p.V528M is neither associated with bilateral periventricular nodular heterotopia nor with thrombocytopenia and giant platelets, and represents a functional polymorphism., In transgenic mice with presenilin mutation Met146Leu, the hippocampus of the left hemisphere displays more pronounced upregulation of filamin than that of the right hemisphere., FLNa down-regulation enhanced calpain activity through the mitogen-activated protein kinase-extracellular signal-regulated kinase cascade and stimulated the cleavage of FA proteins., Although our findings do not suggest that the expression of FLNA alone plays an independent prognostic role, the angiogenesis pathway mediated by FLNA appears to be responsible for controlling the growth of lung tumors., Studies indicate that interactions of filamin A with intermediate filaments and protein kinase C enable tight regulation of beta1 integrin function and consequently early events in cell adhesion and migration on extracellular matrix proteins., These outcomes suggest that the GPIbalpha-filamin A interaction not only regulates the architecture of the membrane skeleton, but also maintains the mechanical stability of the plasma membrane under conditions of high shear., Filamin A mutations have been identified as the cause of the most common genetic heart valvular disorder, familiar cardiac valvular dystrophy. (Review), Filamin A provides a platform for the assembly of the cyclin B1-cdk1- cdc25C complex resulting in cdk1 activation and mitotic progression., The extra nuclear AR/FlnA/integrin beta 1 complex is the key by which androgen activates signaling leading to cell migration. Assembly of this ternary complex may control organ development and prostate cancer metastasis., The presence of these clinical findings in a mutation-confirmed case of OPD2 supports the notion that corneal clouding, bifid tongue, and DWM are part of the constellation of abnormalities caused by mutations in FLNA., filamin is mechanically stretched by integrin or migfilin via a multisite binding mechanism for regulating cytoskeleton and integrin-mediated cell adhesion, Adapter protein SH2B1beta binds filamin A to regulate prolactin-dependent cytoskeletal reorganization and cell motility, Maintaining endothelial barrier function is dependent upon active R-Ras and association between R-Ras and FLNa., filamin A is involved in the distinct step of the Gag trafficking pathway., Review, regulates actin-linked caveolae dynamics following loss of cell adhesion, study reports on two brothers with X-linked cardiac valvular dystrophy and a hemizygous FLNA mutation and review previously described cases from the literature, crystal structure of FlnA-Ig10 determined at 2.44 A resolution provides insight into the perturbations caused by these mutations, Hepatitis C virus nonstructural (NS) 3 and NS5A proteins were associated with filamin A, while core protein partially with filamin A and vimentin., Consistent with structural predictions, strain increases beta-integrin binding to FLNA, whereas it causes FilGAP to dissociate from FLNA, providing a direct and specific molecular basis for cellular mechanotransduction, mutations in FLNA may represent an unrecognized cause of macrothrombocytopenia with an altered platelet production and a modified platelet-vessel wall interaction, data highlight the critical role of FLNA in radial glia organization and function for neurogenesis and migration and also provide insight into the molecular pathogenesis of human periventricular nodular heterotopia, these data demonstrate that coordinated expression of GPIbalpha and filamin is required for efficient trafficking of either protein to the cell surface, and for production of normal-sized platelets., Nephrin ligation resulted in abnormal morphology of actin tails in human podocytes when Ship2, Filamin or Lamellipodin were individually knocked down., These results demonstrate that FLNA is prone to pathogenic rearrangements, findings reveal an additional role for FLNA as a regulator of rRNA gene expression and have important implications for our understanding of the role of FLNA in human disease, FLNa is involved in podosome stability and their organization as rosettes and three-dimensional podosomes in macrophages., Novel FLNA mutations leading to bilateral periventricular nodular heterotopia in three unrelated patients, low-resolution structure of nine C-terminal domains of filamin A (peptide fragments as recombinant proteins); results suggest compact, but flexible, three-branched structure; studies include dimerization and binding of ligands (peptide fragments), present a study of a mother-daughter pair who share bilateral widespread gray matter heterotopia caused by a novel mutation in FLNA and the same pattern of X-chromosome inactivation but who exhibit divergent reading and cognitive profiles, Here we show that BRCA2 is a component of the midbody that is recruited through an interaction with filamin A actin-binding protein., study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein, CCR2B receptor in Rab5-positive vesicles moves along filamin A-positive fibers., EGF regulates alpha5beta1 integrin activation state in cancer cell lines through the p90RSK-dependent phosphorylation of filamin A., Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A., Our findings emphasize that congenital short bowel syndrome can be the presenting symptom in male patients with mutations in FLNA., The combined interactions of calponin homology domains and the IgFLNa10 repeat provide the binding strength of the whole FLNa molecule to actin filaments., FLNA mutation heterogeneity correlates with different platelet functional impacts and points to opposite regulatory roles of FLNA in spreading and flow adhesion under shear., filamin reduces ENaC channel function through direct interaction on the cell surface, PAK1 phosphorylates serine (Ser) 2152 of the actin-binding protein filamin A to a greater extent when PAK1 is tyrosyl phosphorylated by JAK2., These results suggest that a novel RACK1-FlnA interaction is an important regulator of CFTR surface localization., This FLNA mutation, the most distal reported so far, causes in females classical XL-PNH, but in males an unusual, multi-organ phenotype, providing a unique insight into the FLNA-associated phenotypes., Phosphorylation of serine 323 of ASB2 alpha by Erk kinases is critical for ASB2alpha-mediated degradation of FLNA., data therefore reveal ubiquitin acceptor sites in FLNa and establish that ASB2alpha-mediated effects on cell spreading are due to loss of filamins., Grb7 protein interacts with Filamin-a, an actin-crosslinking component of the cell cytoskeleton., filamin A generates a scaffold for organizing a signaling complex that promotes E-cadherin-mediated cell-cell adhesion and keratinocyte differentiation, FlnA mutations alter the balance between RhoA and Rac1 GTPases activities in favor of RhoA., FLNA may play important roles as a negative regulator to nasopharyngeal cancer CNE2 cell by promoting degradation of MMP-9., FLNA expression decreased in gastric cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, and poor overall survival, TGFBR1 and TGFBR2 mutations do not play a major role in isolated myxomatous valve dystrophy. Screening for FLNA mutations is recommended in familial myxomatous valvular dystrophy, particularly if X-linked inheritance is suspected., FLNA may play important roles as a negative regulator to prostate cancer PC-3 cell by promoting the degradation of MMP-9., a major function of FLNa in modulating ion channel abundance and membrane trafficking in neurons, thereby shaping their biophysical properties and function., Crystal Structures of FLNa Domains 3-5 and FLNc Domains 4-5 Show a Novel Domain-Domain Organization., Proline isomerization toggles domain 20 between two conformations; a stable cis conformation with slow unfolding, and a less stable, uninhibited conformation promoted by the trans form., FLNA is involved in SST2 stabilization and signaling in tumoral somatotrophs, playing both a structural and functional role., FLNA expression was decreased in renal cell carcinoma tissue compared to normal kidney. FLNA may play important roles as a a tumor suppressor in RCC by promoting degradation of MMP-9., Enhanced tumorigenesis occurs through increase in EGF-induced EGFR activation in FLNa-expressing melanoma cells., Reviewed findings indicate that FLNA can be considered as a novel target in anti-cancer therapy., Altered FLNA expression increases dendritic complexity and contributes to pathologic dendritic patterning in tuberous sclerosis., Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities., this study proposes that FLNA interaction with ICL3(intracellular loop) is central for endocytosis and signaling of WT and WHIM-like CXCR4 receptors., FLNa is phosphorylated by Cdk1/cyclin B1 in mitosis, The androgen-triggered AR/filamin A complex controls, through Rac 1, the decision of cells to halt cell cycle and migration., Autoinhibited filamin is refractory to phosphorylation by PKA on a known Ser(2152) site despite its consensus motif being exposed and the corresponding isolated peptide being readily phosphorylated., These observations imply that other interactions apart from those mediated by the canonical repeat 24 dimerisation interface contribute to FLNA homodimerization and that mutations affecting this region of the protein can have broad phenotypic effects., FLNa showed low expression in colorectal adenocarcinoma, high correlation with the incidence and development of colorectal cancer, and was considered an indicator of prognosis., Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles Syndrome caused by a single FLNA mutation with combined gain-of-function and loss-of-function effects, FLNA analysis was performed by DHPLC followed by Sanger sequencing [Robertson et al., 2006]. Both sisters were heterozygous for a novel mutation, c.6611C>T in exon 41, that predicts the substitution p.Pro2204Leu within filamin repeat 20, FLNA anchors PC2 to the actin cytoskeleton through complex PC2-FLNA-actin to reduce degradation and increase stability, and possibly regulate PC2 function in a Ca-dependent manner., Missense substitutions in FLNA were identified in four unrelated craniosynostosis patients., Frontometaphyseal dysplasia and keloid formation without normally present in this condition FLNA mutations have been described in six unrelated children patients., Our results support FLNA as a new downstream effector of mTORC2 controlling GBM cell motility., The data suggest a molecular mechanism for direct G protein-coupled receptors -cytoskeleton coupling via filamin A., Extracellular sphingosine-1-phosphate activates NF-kappaB only in melanoma cells that lack FLNA., FLNA functions as a positive cellular transducer linking actin polymerization to MKL1-SRF activity, counteracting the known repressive complex of MKL1 and monomeric G-actin., The function of different integrins is subjected to differential regulation by FLNa., Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona-fide interaction., studies suggest that Vpu hijacks the FLNa function in the modulation of tetherin to neutralize the antiviral factor tetherin.,
OFFICIAL_GENE_SYMBOL FLNA,
OMIM_DISEASE Congenital short bowel syndrome, Intestinal pseudoobstruction, neuronal, Heterotopia, periventricular, Terminal osseous dysplasia, FG syndrome 2, Heterotopia, periventricular, ED variant, Otopalatodigital syndrome, type II, Frontometaphyseal dysplasia, Melnick-Needles syndrome, Otopalatodigital syndrome, type I, Cardiac valvular dysplasia, X-linked,
SP_COMMENT disease:Defects in FLNA are associated with cerebrofrontofacial syndrome [MIM:608578]. This syndrome consists of a phenotype of male PVNH, with relatively normal development, no epilepsy or other neurological abnormality, severe constipation, and facial dysmorphism and without a discernible skeletal phenotype., disease:Defects in FLNA are the cause of frontometaphyseal dysplasia (FMD) [MIM:305620]. FMD is a congenital bone disease characterized by supraorbital hyperostosis, deafness and digital anomalies., disease:Defects in FLNA are the cause of Melnick-Needles syndrome (MNS) [MIM:309350]. MNS is a severe congenital bone disorder characterized by typical facies (exophthalmos, full cheeks, micrognathia and malalignment of teeth), flaring of the metaphyses of long bones, s-like curvature of bones of legs, irregular constrictions in the ribs, and sclerosis of base of skull., disease:Defects in FLNA are the cause of otopalatodigital syndrome type 1 (OPD1) [MIM:311300]. OPD1 is an X-linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias known as oto-palato-digital syndrome spectrum disorders that also include OPD2, Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. FLNA is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. Males with OPD1 have cleft palate, malformations of the ossicles causing deafness and milder bone and limb defects than those associated with OPD2. Obligate female carriers of mutations causing both OPD1 and OPD2 have variable (often milder) expression of a similar phenotypic spectrum., disease:Defects in FLNA are the cause of otopalatodigital syndrome type 2 (OPD2) [MIM:304120]; also known as cranioorodigital syndrome. OPD2 is a congenital bone disorder that is characterized by abnormally modeled, bowed bones, small or absent first digits and, more variably, cleft palate, posterior fossa brain anomalies, omphalocele and cardiac defects., disease:Defects in FLNA are the cause of periventricular nodular heterotopia type 1 (PVNH1) [MIM:300049]; also called nodular heterotopia, bilateral periventricular (NHBP or BPNH). PVNH is a developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH1 is an X-linked dominant form. Heterozygous females have normal intelligence but suffer from seizures and various manifestations outside the central nervous system, especially related to the vascular system. Hemizygous affected males die in the prenatal or perinatal period., disease:Defects in FLNA are the cause of periventricular nodular heterotopia type 4 (PVNH4) [MIM:300537]; also known as periventricular heterotopia Ehlers-Danlos variant. PVNH4 is characterized by nodular brain heterotopia, joint hypermobility and development of aortic dilatation in early adulthood., disease:Defects in FLNA are the cause of X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX) [MIM:300048]. CIIPX is characterized by a severe abnormality of gastrointestinal motility due to primary qualitative defects of enteric ganglia and nerve fibers. Affected individuals manifest recurrent signs of intestinal obstruction in the absence of any mechanical lesion., domain:Comprised of a NH2-terminal actin-binding domain, 24 internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation., function:Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR (By similarity). Phosphorylation extent changes in response to cell activation., PTM:The N-terminus is blocked., similarity:Belongs to the filamin family., similarity:Contains 1 actin-binding domain., similarity:Contains 2 CH (calponin-homology) domains., similarity:Contains 24 filamin repeats., subunit:Interacts with PDLIM2 (By similarity). Homodimer. Interacts with FCGR1A, FLNB, FURIN, HSPB7, INPPL1, KCND2, MYOT, MYOZ1, ARHGAP24, PSEN1, PSEN2 and ECSCR. Interacts also with various other binding partners in addition to filamentous actin., tissue specificity:Ubiquitous.,