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:
  • periventricular nodular heterotopia type 1
  • periventricular nodular heterotopia type 4
  • otopalatodigital syndrome type 1
  • otopalatodigital syndrome type 2
  • frontometaphyseal dysplasia
  • Melnick-Needles syndrome
  • cerebrofrontofacial syndrome
  • X-linked congenital idiopathic intestinal pseudoobstruction

More general terms

• filamin (actin-binding protein)

Database

• UniProt: http://www.uniprot.org/uniprot/P21333.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2316
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2316
• OMIM: https://mirror.omim.org/entry/300017
• OMIM: https://mirror.omim.org/entry/300048
• OMIM: https://mirror.omim.org/entry/300049
• OMIM: https://mirror.omim.org/entry/300537
• OMIM: https://mirror.omim.org/entry/304120
• OMIM: https://mirror.omim.org/entry/305620
• OMIM: https://mirror.omim.org/entry/309350
• OMIM: https://mirror.omim.org/entry/311300
• OMIM: https://mirror.omim.org/entry/608578