Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene. [5] [6]
Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene. [5] [6]
Actin-binding protein, or filamin, is a 280-kD protein that crosslinks actin filaments into orthogonal networks in cortical cytoplasm and participates in the anchoring of membrane proteins for the actin cytoskeleton. Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the FLNA gene, is a widely expressed filamin that regulates the reorganization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes, and secondary messengers. [7] At least 31 disease-causing mutations in this gene have been discovered. [8]
The protein structure includes an actin binding N terminal domain, 24 internal repeats and 2 hinge regions. [9] [10]
Filamin has been shown to interact with:
The edited residue was previously recorded as a single nucleotide polymorphism(SNP) in dbSNP.
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).
The one editing site of FLNA pre-mRNA is located within amino acid 2341 of the final protein. The Glutamine (Q) codon is altered due to a site specific deamination of an adenosine at the editing site to an Arginine (R) codon. The editing region is predicted to form a double stranded region of 32 base pairs in length with a complementary sequence about 200 nucleotides downstream of the editing site. This ECS is found in an intronic sequence. [25] Editing at the Q/R site is likely to involve both ADAR1 and ADAR2.Mice ADAR2 knockouts show a decrease in editing at the Q/R site.ADAR1 double knockouts have no effect on editing. [26]
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]
The change in electrostatic potential is likely to effect the binding of FLNA to the many proteins it interacts with. [29]
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]
Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.
Glutamate receptor 3 is a protein that in humans is encoded by the GRIA3 gene.
Disintegrin and metalloproteinase domain-containing protein 12 is an enzyme that in humans is encoded by the ADAM12 gene. ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.
Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.
Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.
The double-stranded RNA-specific adenosine deaminase enzyme family are encoded by the ADAR family genes. ADAR stands for adenosine deaminase acting on RNA. This article focuses on the ADAR proteins; This article details the evolutionary history, structure, function, mechanisms and importance of all proteins within this family.
Vasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the VASP gene.
Alpha-actinin-4 is a protein that in humans is encoded by the ACTN4 gene.
Glutamate ionotropic receptor kainate type subunit 2, also known as ionotropic glutamate receptor 6 or GluR6, is a protein that in humans is encoded by the GRIK2 gene.
Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.
Insulin-like growth factor-binding protein 7 is a protein that in humans is encoded by the IGFBP7 gene. The major function of the protein is the regulation of availability of insulin-like growth factors (IGFs) in tissue as well as in modulating IGF binding to its receptors. IGFBP7 binds to IGF with low affinity compared to IGFBPs 1-6. It also stimulates cell adhesion. The protein is implicated in some cancers.
Filamin B, beta (FLNB), also known as Filamin B, beta , is a cytoplasmic protein which in humans is encoded by the FLNB gene.
Beta-adducin is a protein that in humans is encoded by the ADD2 gene.
Glutamate receptor, ionotropic, kainate 1, also known as GRIK1, is a protein that in humans is encoded by the GRIK1 gene.
Cytoplasmic FMR1-interacting protein 2 is a protein that in humans is encoded by the CYFIP2 gene. Cytoplasmic FMR1 interacting protein is a 1253 amino acid long protein and is highly conserved sharing 99% sequence identity to the mouse protein. It is expressed mainly in brain tissues, white blood cells and the kidney.
Glutamate receptor 4 is a protein that in humans is encoded by the GRIA4 gene.
APOBEC1 complementation factor is a protein that in humans is encoded by the A1CF gene.
Far upstream element-binding protein 2 is a protein that in humans is encoded by the KHSRP gene.
Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ITGB1BP1 gene.
Filamin-binding LIM protein 1 is a protein that in humans is encoded by the FBLIM1 gene.
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