Filamin-A

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 FLNB 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 (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons.

Classification

Family (Pfam)

PF00307 CH, PF00630 Filamin

InterPro

Actinin_actin-bd_CS, CH_dom, CH_dom_sf, Filamin, Filamin/ABP280_repeat-like, Filamin/ABP280_rpt, Ig-like_fold, Ig_E-set

Functional cluster

Small GTPases (Ras/Rab) & related

Experimental structures · PDB · 26

• 2AAV NMR
• 2BP3 X-ray 2.32A
• 2BRQ X-ray 2.10A
• 2J3S X-ray 2.50A
• 2JF1 X-ray 2.20A
• 2K3T NMR
• 2K7P NMR
• 2K7Q NMR
• 2MTP NMR
• 2W0P X-ray 1.90A
• 2WFN X-ray 3.20A
• 3CNK X-ray 1.65A
• … and 14 more

A predicted model is available from AlphaFold.

Gene Ontology · 74

• GO:0015629 actin cytoskeleton
• GO:0005884 actin filament
• GO:0097440 apical dendrite
• GO:0005911 cell-cell junction
• GO:0030863 cortical cytoskeleton
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0043198 dendritic shaft
• GO:0070062 extracellular exosome
• GO:0005576 extracellular region
• GO:0005925 focal adhesion
• GO:0098978 glutamatergic synapse
• GO:0030426 growth cone
• GO:0016020 membrane
• GO:0031523 Myb complex
• GO:0005730 nucleolus
• GO:0005634 nucleus
• GO:0043204 perikaryon
• GO:0048471 perinuclear region of cytoplasm
• GO:0005886 plasma membrane
• GO:0002102 podosome
• GO:0098794 postsynapse
• GO:0030018 Z disc
• GO:0051015 actin filament binding
• GO:0045296 cadherin binding
• GO:0140297 DNA-binding transcription factor binding
• GO:0034988 Fc-gamma receptor I complex binding
• GO:0001664 G protein-coupled receptor binding
• GO:0051020 GTPase binding
• GO:0019900 kinase binding
• GO:0015459 potassium channel regulator activity
• GO:0042803 protein homodimerization activity
• GO:0140311 protein sequestering activity
• GO:0003723 RNA binding
• GO:0046332 SMAD binding
• GO:0031267 small GTPase binding
• GO:0044325 transmembrane transporter binding
• GO:0051764 actin crosslink formation
• GO:0030036 actin cytoskeleton organization
• GO:0007195 adenylate cyclase-inhibiting dopamine receptor signaling pathway
• GO:0007597 blood coagulation, intrinsic pathway
• GO:0021987 cerebral cortex development
• GO:0060271 cilium assembly
• GO:0045184 establishment of protein localization
• GO:0097368 establishment of Sertoli cell barrier
• GO:0021943 formation of radial glial scaffolds
• GO:0035855 megakaryocyte development
• GO:0090307 mitotic spindle assembly
• GO:0042789 mRNA transcription by RNA polymerase II
• GO:0043066 negative regulation of apoptotic process
• GO:0042177 negative regulation of protein catabolic process
• GO:0016479 negative regulation of transcription by RNA polymerase I
• GO:0070527 platelet aggregation
• GO:0032233 positive regulation of actin filament bundle assembly
• GO:0043123 positive regulation of canonical NF-kappaB signal transduction
• GO:2001046 positive regulation of integrin-mediated signaling pathway
• GO:2000179 positive regulation of neural precursor cell proliferation
• GO:2001224 positive regulation of neuron migration
• GO:0010572 positive regulation of platelet activation
• GO:1901381 positive regulation of potassium ion transmembrane transport
• GO:0042307 positive regulation of protein import into nucleus
• GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
• GO:1902396 protein localization to bicellular tight junction
• GO:0034394 protein localization to cell surface
• GO:0072659 protein localization to plasma membrane
• GO:0050821 protein stabilization
• GO:0043113 receptor clustering
• GO:0030334 regulation of cell migration
• GO:1905000 regulation of membrane repolarization during atrial cardiac muscle cell action potential
• GO:1905031 regulation of membrane repolarization during cardiac muscle cell action potential
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0071526 semaphorin-plexin signaling pathway
• GO:0090042 tubulin deacetylation
• GO:0044319 wound healing, spreading of cells

Disease associations

• intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked MONDO:0010232
• heterotopia, periventricular, X-linked dominant MONDO:0010233
• terminal osseous dysplasia-pigmentary defects syndrome MONDO:0010279
• FG syndrome 2 MONDO:0010297
• otopalatodigital syndrome type 2 MONDO:0010571
• frontometaphyseal dysplasia 1 MONDO:0024550
• Melnick-Needles syndrome MONDO:0010650
• otopalatodigital syndrome type 1 MONDO:0010704
• cardiac valvular dysplasia, X-linked MONDO:0010753

Drugs targeting this protein · 1

• SIMUFILAM positive modulator

Related proteins · sequence + function similarity

• Filamin-A 0.99
• Filamin-C 0.97
• Filamin-C 0.96
• Filamin-B 0.96
• Filamin-C 0.96
• Filamin-B 0.96
• Filamin-A 0.92
• Gelation factor 0.74
• Filamin-B 0.69
• Immunoglobulin superfamily member 22 0.56
• Myosin-binding protein C, fast-type 0.55
• Muscle M-line assembly protein unc-89 0.55

Co-cited proteins · studied together in the literature

• Filamin-B 8 shared papers
• Endothelial cell-specific chemotaxis regulator 1 shared papers
• Filamin-C 6 shared papers
• Rho GTPase-activating protein 24 1 shared papers
• Mis18-binding protein 1 1 shared papers
• Filamin-A 5 shared papers
• Leucine zipper protein 1 1 shared papers
• Ankyrin repeat and SOCS box protein 2 1 shared papers
• Filamin-B 3 shared papers
• TATA box-binding protein-associated factor RNA polymerase I subunit B 1 shared papers
• High affinity immunoglobulin gamma Fc receptor I 1 shared papers
• Melanoma-associated antigen 9 1 shared papers

Literature · 81 cited papers

• Identification of Filamin A Mechanobinding Partner II: Fimbacin Is a Novel Actin Cross-Linking and Filamin A Binding Protein. Biochemistry · 2019
• De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay. PLoS Genet. · 2018
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum. J. Hum. Genet. · 2016
• Endothelial RSPO3 controls vascular stability and pruning through non-canonical WNT/Ca(2+)/NFAT signaling. Dev. Cell · 2016
• G Protein-Coupled Receptors Directly Bind Filamin A with High Affinity and Promote Filamin Phosphorylation. Biochemistry · 2015
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
• System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
• A mechanism of global shape-dependent recognition and phosphorylation of filamin by protein kinase A. J. Biol. Chem. · 2015
• Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling. Nat. Commun. · 2014
• Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
• … and 69 more in the literature graph