Filamin-A (FLNA)
The protein contains 2647 amino acids for an estimated molecular weight of 280739 Da.
Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). (updated: Nov. 13, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
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Biological Process
Actin crosslink formation
Actin cytoskeleton reorganization
Adenylate cyclase-inhibiting dopamine receptor signaling pathway
Angiogenesis
Blood coagulation
Blood vessel remodeling
Cell junction assembly
Cell-cell junction organization
Cerebral cortex development
Cilium assembly
Cilium assembly
Cytoplasmic sequestering of protein
Defense response to virus
Early endosome to late endosome transport
Epithelial to mesenchymal transition
Establishment of protein localization
Establishment of Sertoli cell barrier
Formation of radial glial scaffolds
Heart morphogenesis
Mitotic spindle assembly
MRNA transcription by RNA polymerase II
Negative regulation of apoptotic process
Negative regulation of DNA-binding transcription factor activity
Negative regulation of neuron projection development
Negative regulation of protein catabolic process
Negative regulation of transcription by RNA polymerase I
Obsolete positive regulation of transcription factor import into nucleus
Platelet activation
Platelet aggregation
Platelet degranulation
Positive regulation of actin filament bundle assembly
Positive regulation of axon regeneration
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of integrin-mediated signaling pathway
Positive regulation of neural precursor cell proliferation
Positive regulation of neuron migration
Positive regulation of potassium ion transmembrane transport
Positive regulation of protein import into nucleus
Positive regulation of substrate adhesion-dependent cell spreading
Protein localization to bicellular tight junction
Protein localization to cell surface
Protein localization to plasma membrane
Protein stabilization
Receptor clustering
Regulation of cell migration
Regulation of membrane repolarization during atrial cardiac muscle cell action potential
Regulation of membrane repolarization during cardiac muscle cell action potential
Semaphorin-plexin signaling pathway
Synapse organization
Tubulin deacetylation
Wound healing, spreading of cells
Cellular Component
Actin cytoskeleton
Actin filament
Actin filament bundle
Apical dendrite
Axonal growth cone
Brush border
Cell-cell junction
Cortical cytoskeleton
Cytoplasm
Cytosol
Dendritic shaft
Extracellular exosome
Extracellular matrix
Extracellular region
Focal adhesion
Glutamatergic synapse
Growth cone
Membrane
Myb complex
Neuronal cell body
Nucleolus
Nucleus
Perikaryon
Perinuclear region of cytoplasm
Plasma membrane
Postsynapse
Trans-Golgi network
Z disc
Molecular Function
Actin filament binding
Cadherin binding
Fc-gamma receptor I complex binding
G protein-coupled receptor binding
Glycoprotein binding
GTPase binding
Ion channel binding
Kinase binding
Mu-type opioid receptor binding
Obsolete signal transducer activity
Poly(A) RNA binding
Potassium channel regulator activity
Protein homodimerization activity
Protein kinase C binding
Rac GTPase binding
Ral GTPase binding
Rho GTPase binding
RNA binding
SMAD binding
Small GTPase binding
Transcription factor binding
The reference OMIM entry for this protein is 300017
Filamin a; flna
Filamin, alpha
Filamin 1; fln1
Fln
Actin-binding protein 280; abp280
DESCRIPTION
The FLNA gene encodes filamin A, a widely expressed 280-kD actin-binding protein that regulates reorganization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes, and second messengers. Filamins crosslink actin filaments into orthogonal networks in the cytoplasm and participate in the anchoring of membrane proteins to the actin cytoskeleton. Remodeling of the cytoskeleton is central to the modulation of cell shape and migration (Maestrini et al., 1993; Fox et al., 1998).CLONING
By analysis of the native ABP280 protein and cloning of the human endothelial ABP280 cDNA, Gorlin et al. (1990) demonstrated that ABP280 is a 2,647-amino acid protein with 3 functional domains: an N-terminal filamentous actin-binding domain, a C-terminal self-association domain, and a membrane glycoprotein-binding domain. The N-terminal actin-binding domain of ABP280 displays strong structural and functional similarity to the N-terminal domains of dystrophin (300377), alpha-actinin (102575), and beta-spectrin (182870). In a search for muscle- and heart-specific isoforms that might be involved in Emery muscular dystrophy (EDMD; 310300), Maestrini et al. (1993) identified several different ABP280 mRNAs. Two were X-linked and were produced by alternative splicing of a small exon of 24 nucleotides. Both of these were ubiquitous in distribution. At least 1 additional gene encoding an RNA more than 70% identical to ABP280 was found and was shown to map to chromosome 7 by study of human/hamster somatic cell hybrids (FLNC; 102565).GENE FUNCTION
Vadlamudi et al. (2002) identified FLNA as a binding partner of PAK1 (602590) in a yeast 2-hybrid screen of a mammary gland cDNA library. By mutation analysis, they localized the PAK1-binding region in FLNA to tandem repeat 23 in the C terminus, and the FLNA-binding region in PAK1 between amino acids 52 and 132 in the conserved CDC42 (116952)/RAC (602048)-interacting domain. Endogenous FLNA was phosphorylated by PAK1 on ser2152 following stimulation with physiologic signaling molecules. Following stimulation, FLNA colocalized with PAK1 in membrane ruffles. The ruffle-forming activity of PAK1 was found in FLNA-expressing cells, but not in cells deficient in FLNA. Androgen receptor (AR; 313700), a nuclear transcription factor, mediates male sexual differentiation. Loy et al. (2003) characterized a negative regulatory domain in the AR hinge region that interacts with filamin A. Filamin A interferes with AR interdomain interactions and competes with the coactivator transcriptional intermediary factor-2 (TIF2; 601993) to downregulate AR function specifically. Although full-length filamin A is predominantly cytoplasmic, a C-terminal 100-kD fragment colocalized with AR to the nucleus. This naturally occurring filamin A fragment repressed AR transactivation and disrupted AR interdomain interactions and TIF2-activated AR function in a manner reminiscent of full-length filamin A, raising the possibility that the inhibitory effects of cytoplasmic filamin A may be transduced through this fragment, which can localize to the nucleus and form part of the preinitiation complex. This unanticipated role of filamin A added to the evidence for the involvement of cytoskeletal proteins in transcription regulation. Mutation in the X-linked FLNA gene can cause the neurologic disorder periventricular heterotopia (300049). Although periventricular heterotopia is character ... More on the omim web site
Dec. 2, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300017 was added.