FLNA

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

Function

Actin-binding protein, or

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

Interactions

Filamin has been shown to

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

Type

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).

Site

The one editing site of FLNA pre-mRNA is located within amino acid 2341 of the final protein. The

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]

Function

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

DNA repair

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]

References