Filamin-A; alpha-filamin; Filamin-1; endothelial actin-binding protein; actin-binding protein 280; ABP-280; non-muscle filamin (FLNA, FLN, FLN1)

Function: - regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes & second messengers - promotes orthogonal branching of actin filaments - links actin filaments to membrane glycoproteins - anchors various transmembrane proteins to the actin cytoskeleton & serves as a scaffold for a wide range of cytoplasmic signaling proteins - role in neuroblast migration from the ventricular zone into the cortical plate - tethers cell surface-localized furin, modulates its rate of internalization & directsits intracellular trafficking (putative) - phosphorylated upon DNA damage, probably by ATM or ATR - phosphorylation changes in response to cell activation - interacts with PDLIM2 (putative) - interacts with FCGR1A, FLNB, FURIN, HSPB7, INPPL1, KCND2, MYOT, MYOZ1, ARHGAP24, PSEN1, PSEN2 & ECSCR - interacts with various other binding partners in addition to filamentous actin - interacts with CD65, prevents CD64 degradation - binding of IgG to CD64 (high affinity Fc receptor) of myeloid cells releases filamin-A from CD64 Structure: - homodimer - the N-terminus is blocked - comprised of a NH2-terminal actin-binding domain, 24 internally homologous repeats & two hinge regions - repeat 24 & the 2nd hinge domain are important for dimer formation - belongs to the filamin family - contains 1 actin-binding domain - contains 2 CH (calponin-homology) domains - contains 24 filamin repeats Compartment: - cytoplasm, cell cortex. cytoplasm, cytoskeleton Alternative splicing: named isoforms=2 Expression: ubiquitous Pathology: - defects in FLNA are the cause of: a) periventricular nodular heterotopia type 1 b) periventricular nodular heterotopia type 4 c) otopalatodigital syndrome type 1 d) otopalatodigital syndrome type 2 e) frontometaphyseal dysplasia f) Melnick-Needles syndrome g) cerebrofrontofacial syndrome h) X-linked congenital idiopathic intestinal pseudoobstruction

Properties

CONFIGURATION: dimer SIZE: entity length = 2647 aa MW = 281 kD COMPARTMENT: cytoplasm MOTIF: actin-binding site SITE: 2-274 FOR-BINDING-OF: F-actin acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl calponin homology domain NAME: calponin homology domain SITE: 43-149 calponin homology domain NAME: calponin homology domain SITE: 166-266 Filamin {276-374} MOTIF: Tyr phosphorylation site {Y373} Filamin {376-474} Filamin {475-570} Filamin {571-663} Filamin {667-763} Filamin {764-866} Filamin {867-965} Filamin {966-1061} MOTIF: Tyr phosphorylation site {Y1047} Filamin {1062-1154} MOTIF: Ser phosphorylation site {S1081} Ser phosphorylation site {S1084} Thr phosphorylation site {T1089} Filamin {1155-1249} Filamin {1250-1349} MOTIF: Thr phosphorylation site {T1286} Ser phosphorylation site {S1338} Filamin {1350-1442} Filamin {1443-1539} MOTIF: Ser phosphorylation site {S1459} furin interaction {1490-1607} MOTIF: Ser phosphorylation site {S1533} Filamin {1540-1636} MOTIF: Tyr phosphorylation site {Y1604} Ser phosphorylation site {S1630} Filamin {1649-1740} Hinge 1 {1741-1778} MOTIF: peptide motif {1761-1762} Filamin {1779-1860} Filamin {1861-1950} Filamin {1951-2039} Filamin {2042-2131} MOTIF: Ser phosphorylation site {S2053} Filamin {2132-2230} MOTIF: Ser phosphorylation site {S2152} Ser phosphorylation site {S2158} Filamin {2233-2325} MOTIF: Ser phosphorylation site {S2284} Filamin {2327-2420} MOTIF: Ser phosphorylation site {S2327} Tyr phosphorylation site {Y2388} Ser phosphorylation site {S2414} Filamin {2424-2516} MOTIF: Ser phosphorylation site {S2510} self-association {2517-2647} MOTIF: Hinge 2 {2517-2551} Filamin {2552-2646}

Database Correlations

OMIM correlations MORBIDMAP 300017 UniProt P21333 PFAM correlations Entrez Gene 2316 Kegg hsa:2316