FLNA
Encyclopedia
Filamin-A is a protein
that in humans is encoded by the FLNA gene
.
binding N terminal domain ,24 internal repeats and 2 hinge regions.
with FILIP1
, RALA
, FBLIM1
, FLNB
, Calcium-sensing receptor
, TRIO
, SH2B3
, NPHP1
, BRCA2
, CD29
and Von Hippel-Lindau tumor suppressor
.
.
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).
(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. 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.
binding domain. The amino acid change is likely to effect the electrostatic potential of the binding domains. 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. 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.ing occurs at a site.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the FLNA gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
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 protein that regulates reorganization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes, and second messengers.[supplied by OMIM]Structure
The protein structure includes an actinActin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
binding N terminal domain ,24 internal repeats and 2 hinge regions.
Interactions
Filamin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with FILIP1
FILIP1
Filamin-A-interacting protein 1 is a protein that in humans is encoded by the FILIP1 gene.-Further reading:...
, RALA
RALA
Ras-related protein Ral-A is a protein that in humans is encoded by the RALA gene.-Interactions:RALA has been shown to interact with Filamin, Phospholipase D1 and RALBP1.-Further reading:...
, FBLIM1
FBLIM1
Filamin-binding LIM protein 1 is a protein that in humans is encoded by the FBLIM1 gene.-Interactions:FBLIM1 has been shown to interact with Filamin, PLEKHC1 and FLNB.-Further reading:...
, FLNB
FLNB
Filamin B, beta , also known as FLNB, is a human cytoplasmic protein. It regulates intracellular communication and signalling by cross-linking the protein actin to allow direct communication between the cell membrane and cytoskeletal network, to control and guide proper skeletal...
, Calcium-sensing receptor
Calcium-sensing receptor
The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...
, TRIO
TRIO (gene)
Triple functional domain protein is a protein that in humans is encoded by the TRIO gene.-Interactions:TRIO has been shown to interact with Filamin and RHOA.-Further reading:...
, SH2B3
SH2B3
SH2B adapter protein 3 is a protein that in humans is encoded by the SH2B3 gene.-Further reading:...
, NPHP1
NPHP1
Nephrocystin-1 is a protein that in humans is encoded by the NPHP1 gene.-Interactions:NPHP1 has been shown to interact with BCAR1, PTK2B, Filamin and INVS.-Further reading:...
, BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....
, CD29
CD29
Integrin beta-1 is a protein that in humans is encoded by the ITGB1 gene. CD29 is an integrin unit associated with very late antigen receptors. It is known to conjoin with alpha-3 subunit to create α3β1 complex that reacts to such molecules as netrin-1 and reelin.Integrins are heterodimeric...
and Von Hippel-Lindau tumor suppressor
Von Hippel-Lindau tumor suppressor
The Von Hippel–Lindau tumor suppressor also known as pVHL is a protein that in humans is encoded by the VHL gene. Mutations of the VHL gene are associated with Von Hippel–Lindau disease....
.
RNA editing
The edited residue was previously recorded as a single nucleotide polymorphism(SNP) in dbSNPDbSNP
The Single Nucleotide Polymorphism Database is a free public archive for genetic variation within and across different species developed and hosted by the National Center for Biotechnology Information in collaboration with the National Human Genome Research Institute...
.
Type
A to I RNA editingRNA editing
The term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup. To date, such changes have been observed in tRNA, rRNA, mRNA and microRNA molecules of eukaryotes but not prokaryotes...
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
Guanosine
Guanosine is a purine nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate , cyclic guanosine monophosphate , guanosine diphosphate , and guanosine triphosphate...
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
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
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 GlutamineGlutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
(Q) codon is altered due to a site specific deamination of an adenosine at the editing site to an Arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
(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. 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.
Structure
The edited adenosine is located in the 22 immunogloulin like repeat of the protein. This region is an integrin β binding domain and a RAC1RAC1
Ras-related C3 botulinum toxin substrate 1 also known as Rac1 is a protein that in humans is encoded by the RAC1 gene. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.- Function :Rac1 is...
binding domain. The amino acid change is likely to effect the electrostatic potential of the binding domains. 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. 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.ing occurs at a site.
Function
The change in electrostatic potential is likely to effect the binding of FLNA to the many proteins it interacts with.External links
- GeneReview/NCBI/NIH/UW entry on Otopalatodigital Spectrum Disorders
- GeneReviews/NIH/NCBI/UW entry on X-Linked Periventricular Heterotopia or Bilateral Periventricular Nodular Heterotopia