User:Johno4302/FLNA RNA EDITING

FLNA (Filamin A) is a 2647 amino acid protein that is widely expressed in many tissues.It crosslinks actin filaments and limks the membrane proteins with the actin cytoskeleton.The protein interacts with a wide variety of proteins.Mutations in this gene are implicated in several conditions such as  periventricular nodular heterotopias ,frontometaphyseal dysplasia and Melnick-Needles syndrome among others.

Editing site
The RNA editing site was originally identified by comparative genomics and expressed sequence analysis.The editing site was previously recorded as a SNP in the dbSNP as rs3179473. the editing site is found at amino acid posistion 2341 in humans (and also in mice).The editing region forms a 32 base pair lomng duplex structure with an intronic sequence 200 base pairs upstream.the editing site occurs in the 22nd immunoglobulin like domain of the protein.This region is known to be important in integrin beta binding and also for binding to small gtpase RAC1 (involved in cytoskeleton reorganisation).

Editing regulation
Editing occurs in a wide variety of tissues.Some indications that editing occurs due to both ADAR1 and ADAR2 editing enzymes.In mice knockouts, the absence of ADAR2 causes a slight decrease in editing while in the absense of ADAR1 has no detectable effect.Lack of both results in a lack of editing. Editing levels can vary between human tumour and normal cells.This has been demonstrated brain and oral cavbity normal and cancerous tissues.In one experiment normal brain tissue editing levels were 21.5% and in malignant tissue were 8.5%.Also in oral cavity tissue, editing levels were 9.13% and 4.4% in malignant tissue.

Protein structure changes
Rna editing at the editing site causes an amino acid change

Protein Function changes
Biological consequences of editing are unknown.However the editing site occurs in repeat 22 of the protein.This region is known to bing to various other proteins such as GLU-R7,Androgen-R, BRCA-2 ,integrin among others.(POPOWICZ et al).Editing of this site may affect the binding of these proteins. The edited residue also occurs near an exon/intron boundary indicating may regulate splicing.