UniProtKB - P21333 (FLNA_HUMAN)
Protein
Filamin-A
Gene
FLNA
Organism
Homo sapiens (Human)
Status
Functioni
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).By similarity2 Publications
Caution
Variant Thr-1764 has been originally associated with periventricular nodular heterotopia. It has been subsequently reported as a benign polymorphism.1 Publication
GO - Molecular functioni
- actin filament binding Source: BHF-UCL
- cadherin binding Source: BHF-UCL
- Fc-gamma receptor I complex binding Source: BHF-UCL
- G protein-coupled receptor binding Source: UniProtKB
- GTPase binding Source: UniProtKB
- ion channel binding Source: BHF-UCL
- kinase binding Source: UniProtKB
- mu-type opioid receptor binding Source: Ensembl
- potassium channel regulator activity Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- Rac GTPase binding Source: BHF-UCL
- Ral GTPase binding Source: BHF-UCL
- Rho GTPase binding Source: BHF-UCL
- RNA binding Source: UniProtKB
- SMAD binding Source: Ensembl
- small GTPase binding Source: BHF-UCL
- transcription factor binding Source: UniProtKB
GO - Biological processi
- actin crosslink formation Source: BHF-UCL
- actin cytoskeleton reorganization Source: BHF-UCL
- adenylate cyclase-inhibiting dopamine receptor signaling pathway Source: BHF-UCL
- cell junction assembly Source: Reactome
- cerebral cortex development Source: Ensembl
- cilium assembly Source: UniProtKB
- cytoplasmic sequestering of protein Source: BHF-UCL
- defense response to virus Source: Reactome
- establishment of protein localization Source: BHF-UCL
- establishment of Sertoli cell barrier Source: Ensembl
- formation of radial glial scaffolds Source: Ensembl
- mitotic spindle assembly Source: MGI
- mRNA transcription by RNA polymerase II Source: Ensembl
- negative regulation of apoptotic process Source: CACAO
- negative regulation of DNA-binding transcription factor activity Source: UniProtKB
- negative regulation of protein catabolic process Source: BHF-UCL
- negative regulation of transcription by RNA polymerase I Source: CACAO
- platelet activation Source: Reactome
- platelet aggregation Source: UniProtKB
- platelet degranulation Source: Reactome
- positive regulation of actin filament bundle assembly Source: Ensembl
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of integrin-mediated signaling pathway Source: CACAO
- positive regulation of neural precursor cell proliferation Source: Ensembl
- positive regulation of neuron migration Source: Ensembl
- positive regulation of potassium ion transmembrane transport Source: BHF-UCL
- positive regulation of protein import into nucleus Source: UniProtKB
- positive regulation of substrate adhesion-dependent cell spreading Source: CACAO
- protein localization to bicellular tight junction Source: Ensembl
- protein localization to cell surface Source: BHF-UCL
- protein localization to plasma membrane Source: BHF-UCL
- protein stabilization Source: BHF-UCL
- receptor clustering Source: BHF-UCL
- regulation of cell migration Source: UniProtKB
- regulation of membrane repolarization during atrial cardiac muscle cell action potential Source: BHF-UCL
- regulation of membrane repolarization during cardiac muscle cell action potential Source: BHF-UCL
- semaphorin-plexin signaling pathway Source: WormBase
- tubulin deacetylation Source: CACAO
- wound healing, spreading of cells Source: UniProtKB
Keywordsi
| Molecular function | Actin-binding |
| Biological process | Cilium biogenesis/degradation |
Enzyme and pathway databases
| PathwayCommonsi | P21333 |
| Reactomei | R-HSA-114608, Platelet degranulation R-HSA-430116, GP1b-IX-V activation signalling R-HSA-446353, Cell-extracellular matrix interactions R-HSA-5627123, RHO GTPases activate PAKs R-HSA-8983711, OAS antiviral response |
| SignaLinki | P21333 |
| SIGNORi | P21333 |
Protein family/group databases
| MoonDBi | P21333, Predicted |
| TCDBi | 8.A.66.1.4, the dystrophin (dystrophin) family |
Names & Taxonomyi
| Protein namesi | Recommended name: Filamin-AShort name: FLN-A Alternative name(s): Actin-binding protein 280 Short name: ABP-280 Alpha-filamin Endothelial actin-binding protein Filamin-1 Non-muscle filamin |
| Gene namesi | Name:FLNA Synonyms:FLN, FLN1 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000196924.14 |
| HGNCi | HGNC:3754, FLNA |
| MIMi | 300017, gene |
| neXtProti | NX_P21333 |
Subcellular locationi
Cytoskeleton
- cytoskeleton By similarity
Other locations
- cell cortex 1 Publication
- Perikaryon By similarity
- growth cone By similarity
Note: Colocalizes with CPMR1 in the central region of DRG neuron growth cone (By similarity). Following SEMA3A stimulation of DRG neurons, colocalizes with F-actin (By similarity).By similarity
Cytoskeleton
- actin cytoskeleton Source: WormBase
- actin filament Source: Ensembl
- cortical cytoskeleton Source: Ensembl
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
Nucleus
Plasma Membrane
- plasma membrane Source: BHF-UCL
Other locations
- apical dendrite Source: Ensembl
- cell-cell junction Source: UniProtKB
- cytoplasm Source: UniProtKB
- dendritic shaft Source: Ensembl
- focal adhesion Source: UniProtKB
- glutamatergic synapse Source: Ensembl
- growth cone Source: UniProtKB-SubCell
- membrane Source: UniProtKB
- Myb complex Source: MGI
- perikaryon Source: UniProtKB-SubCell
- perinuclear region of cytoplasm Source: Ensembl
- postsynapse Source: Ensembl
- Z disc Source: BHF-UCL
Keywords - Cellular componenti
Cell projection, Cytoplasm, CytoskeletonPathology & Biotechi
Involvement in diseasei
Periventricular nodular heterotopia 1 (PVNH1)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH1 is an X-linked dominant form. Heterozygous females have normal intelligence but suffer from seizures and various manifestations outside the central nervous system, especially related to the vascular system. Hemizygous affected males die in the prenatal or perinatal period.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_022734 | 39 | A → G in PVNH1. 1 PublicationCorresponds to variant dbSNP:rs137853313EnsemblClinVar. | 1 | |
| Natural variantiVAR_015699 | 82 | E → V in PVNH1. 1 PublicationCorresponds to variant dbSNP:rs28935169EnsemblClinVar. | 1 | |
| Natural variantiVAR_031305 | 102 | M → V in PVNH1. 1 Publication | 1 | |
| Natural variantiVAR_031306 | 128 | A → V in PVNH1. 1 PublicationCorresponds to variant dbSNP:rs137853315EnsemblClinVar. | 1 | |
| Natural variantiVAR_031307 | 149 | S → F in PVNH1. 1 Publication | 1 | |
| Natural variantiVAR_012834 | 656 | L → F in PVNH1. 1 PublicationCorresponds to variant dbSNP:rs137853311EnsemblClinVar. | 1 |
Otopalatodigital syndrome 1 (OPD1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionX-linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias known as oto-palato-digital syndrome spectrum disorders that also include OPD2, Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. FLNA is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. Males with OPD1 have cleft palate, malformations of the ossicles causing deafness and milder bone and limb defects than those associated with OPD2. Obligate female carriers of mutations causing both OPD1 and OPD2 have variable (often milder) expression of a similar phenotypic spectrum.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_015714 | 172 | L → F in OPD1. 1 Publication | 1 | |
| Natural variantiVAR_015716 | 196 | R → W in OPD1. 1 PublicationCorresponds to variant dbSNP:rs137853317EnsemblClinVar. | 1 | |
| Natural variantiVAR_031308 | 203 | D → Y in OPD1. 1 PublicationCorresponds to variant dbSNP:rs137853314EnsemblClinVar. | 1 | |
| Natural variantiVAR_015700 | 207 | P → L in OPD1. 2 PublicationsCorresponds to variant dbSNP:rs28935469EnsemblClinVar. | 1 | |
| Natural variantiVAR_076501 | 267 | A → T in OPD1; unknown pathological significance. 1 Publication | 1 | |
| Natural variantiVAR_076502 | 804 | V → D in OPD1; unknown pathological significance. 1 Publication | 1 | |
| Natural variantiVAR_076506 | 2391 | R → H in OPD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs727503930EnsemblClinVar. | 1 |
Otopalatodigital syndrome 2 (OPD2)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCongenital bone disorder that is characterized by abnormally modeled, bowed bones, small or absent first digits and, more variably, cleft palate, posterior fossa brain anomalies, omphalocele and cardiac defects.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_015713 | 170 | Q → P in OPD2. 1 PublicationCorresponds to variant dbSNP:rs863223628Ensembl. | 1 | |
| Natural variantiVAR_076500 | 187 | N → S in OPD2; unknown pathological significance. 1 Publication | 1 | |
| Natural variantiVAR_015715 | 196 | R → G in OPD2. 2 Publications | 1 | |
| Natural variantiVAR_015717 | 200 | A → S in OPD2. 1 Publication | 1 | |
| Natural variantiVAR_058720 | 210 | C → F in OPD2. 1 PublicationCorresponds to variant dbSNP:rs137853318EnsemblClinVar. | 1 | |
| Natural variantiVAR_015701 | 254 | E → K in OPD2. 1 PublicationCorresponds to variant dbSNP:rs28935470EnsemblClinVar. | 1 | |
| Natural variantiVAR_015718 | 273 | A → P in OPD2. 1 Publication | 1 | |
| Natural variantiVAR_015719 | 555 | T → K in OPD2. 1 PublicationCorresponds to variant dbSNP:rs782611953Ensembl. | 1 | |
| Natural variantiVAR_015723 | 1645 | C → F in OPD2. 1 Publication | 1 |
Frontometaphyseal dysplasia 1 (FMD1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked disease characterized by generalized skeletal dysplasia, deafness, and urogenital defects.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_076503 | 1142 | D → V in FMD1; unknown pathological significance. 1 Publication | 1 | |
| Natural variantiVAR_015702 | 1159 | D → A in FMD1; does not inhibit interaction with MIS18BP1. 2 PublicationsCorresponds to variant dbSNP:rs28935471EnsemblClinVar. | 1 | |
| Natural variantiVAR_015721 | 1186 | S → L in FMD1. 3 PublicationsCorresponds to variant dbSNP:rs137853312EnsemblClinVar. | 1 | |
| Natural variantiVAR_015722 | 1620 | Missing in FMD1. 1 Publication | 1 | |
| Natural variantiVAR_031312 | 1728 | G → C in FMD1. 1 PublicationCorresponds to variant dbSNP:rs137853316EnsemblClinVar. | 1 | |
| Natural variantiVAR_076505 | 1840 | H → R in FMD1; unknown pathological significance. 1 Publication | 1 |
Melnick-Needles syndrome (MNS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSevere congenital bone disorder characterized by typical facies (exophthalmos, full cheeks, micrognathia and malalignment of teeth), flaring of the metaphyses of long bones, s-like curvature of bones of legs, irregular constrictions in the ribs, and sclerosis of base of skull.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_076504 | 1163 | V → L in MNS; unknown pathological significance. 1 Publication | 1 | |
| Natural variantiVAR_015720 | 1184 | D → E in MNS. 1 PublicationCorresponds to variant dbSNP:rs80338837EnsemblClinVar. | 1 | |
| Natural variantiVAR_015703 | 1188 | A → T in MNS; does not inhibit interaction with MIS18BP1. 3 PublicationsCorresponds to variant dbSNP:rs28935472EnsemblClinVar. | 1 | |
| Natural variantiVAR_015704 | 1199 | S → L in MNS; does not inhibit interaction with MIS18BP1. 2 PublicationsCorresponds to variant dbSNP:rs28935473EnsemblClinVar. | 1 |
Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked (IPOX)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by a severe abnormality of gastrointestinal motility due to primary qualitative defects of enteric ganglia and nerve fibers. Affected individuals manifest recurrent signs of intestinal obstruction in the absence of any mechanical lesion.
Related information in OMIMFG syndrome 2 (FGS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionFG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_058721 | 1291 | P → L in FGS2. 1 PublicationCorresponds to variant dbSNP:rs137853319EnsemblClinVar. | 1 |
Terminal osseous dysplasia (TOD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin and recurrent digital fibroma during infancy. A significant phenotypic variability is observed in affected females.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_064159 | 1724 – 1739 | Missing in TOD. 1 PublicationAdd BLAST | 16 |
Cardiac valvular dysplasia, X-linked (CVD1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare X-linked heart disease characterized by mitral and/or aortic valve regurgitation. The histologic features include fragmentation of collagenous bundles within the valve fibrosa and accumulation of proteoglycans, which produces excessive valve tissue leading to billowing of the valve leaflets.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_064156 | 288 | G → R in CVD1. 1 PublicationCorresponds to variant dbSNP:rs267606816EnsemblClinVar. | 1 | |
| Natural variantiVAR_064157 | 637 | P → Q in CVD1. 1 PublicationCorresponds to variant dbSNP:rs267606815EnsemblClinVar. | 1 | |
| Natural variantiVAR_064158 | 711 | V → D in CVD1. 1 PublicationCorresponds to variant dbSNP:rs267606817EnsemblClinVar. | 1 |
Defects in FLNA may be a cause of macrothrombocytopenia, a disorder characterized by subnormal levels of blood platelets. Blood platelets are abnormally enlarged (PubMed:21960593).1 Publication
Congenital short bowel syndrome, X-linked (CSBSX)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by a shortened small intestine, and malabsorption. The mean length of the small intestine in affected individuals is approximately 50 cm, compared with a normal length at birth of 190-280 cm. It is associated with significant mortality and morbidity. Infants usually present with failure to thrive, recurrent vomiting, and diarrhea.
Related information in OMIMMutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 42 | K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-43 and R-135. 1 Publication | 1 | |
| Mutagenesisi | 43 | K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-135. 1 Publication | 1 | |
| Mutagenesisi | 135 | K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-43. 1 Publication | 1 |
Keywords - Diseasei
Deafness, Disease mutationOrganism-specific databases
| DisGeNETi | 2316 |
| GeneReviewsi | FLNA |
| MalaCardsi | FLNA |
| MIMi | 300048, phenotype 300049, phenotype 300244, phenotype 300321, phenotype 304120, phenotype 305620, phenotype 309350, phenotype 311300, phenotype 314400, phenotype |
| OpenTargetsi | ENSG00000196924 |
| Orphaneti | 2301, Congenital short bowel syndrome 555877, FLNA-related X-linked myxomatous valvular dysplasia 1826, Frontometaphyseal dysplasia 2484, Melnick-Needles syndrome 99811, Neuronal intestinal pseudoobstruction 323, NON RARE IN EUROPE: FG syndrome phenotypic spectrum 90650, Otopalatodigital syndrome type 1 90652, Otopalatodigital syndrome type 2 98892, Periventricular nodular heterotopia 88630, Terminal osseous dysplasia-pigmentary defects syndrome 75497, X-linked Ehlers-Danlos syndrome 482606, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome |
| PharmGKBi | PA28172 |
Miscellaneous databases
| Pharosi | P21333, Tbio |
Chemistry databases
| DrugBanki | DB11638, Artenimol |
Polymorphism and mutation databases
| BioMutai | FLNA |
| DMDMi | 116241365 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Initiator methioninei | RemovedCombined sources1 Publication | |||
| ChainiPRO_0000087296 | 2 – 2647 | Filamin-AAdd BLAST | 2646 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 2 | N-acetylserineCombined sources1 Publication | 1 | |
| Modified residuei | 11 | PhosphoserineCombined sources | 1 | |
| Cross-linki | 42 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
| Cross-linki | 43 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
| Cross-linki | 135 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
| Cross-linki | 299 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources | ||
| Cross-linki | 299 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources | ||
| Modified residuei | 376 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 508 | N6-acetyllysineCombined sources | 1 | |
| Modified residuei | 700 | N6-acetyllysineCombined sources | 1 | |
| Modified residuei | 781 | N6-acetyllysineCombined sources | 1 | |
| Modified residuei | 837 | N6-acetyllysineCombined sources | 1 | |
| Modified residuei | 865 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 906 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 968 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1055 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1071 | N6-acetyllysine; alternateBy similarity | 1 | |
| Modified residuei | 1071 | N6-succinyllysine; alternateBy similarity | 1 | |
| Modified residuei | 1081 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1084 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1089 | PhosphothreonineCombined sources | 1 | |
| Modified residuei | 1301 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1338 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1372 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 1459 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1533 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1538 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 1630 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1734 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1835 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1967 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2053 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2128 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2152 | PhosphoserineCombined sources2 Publications | 1 | |
| Modified residuei | 2158 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2163 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2180 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 2284 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2327 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2329 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 2336 | PhosphothreonineCombined sources1 Publication | 1 | |
| Modified residuei | 2338 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2370 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 2414 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2510 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 2523 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 2526 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 2569 | N6-acetyllysine; alternateBy similarity | 1 | |
| Modified residuei | 2569 | N6-succinyllysine; alternateBy similarity | 1 | |
| Modified residuei | 2575 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 2599 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 2607 | N6-acetyllysineCombined sources | 1 | |
| Modified residuei | 2621 | N6-acetyllysineCombined sources | 1 |
Post-translational modificationi
Phosphorylation at Ser-2152 is negatively regulated by the autoinhibited conformation of filamin repeats 19-21. Ligand binding induces a conformational switch triggering phosphorylation at Ser-2152 by PKA.1 Publication
Phosphorylation extent changes in response to cell activation.
Polyubiquitination in the CH1 domain by a SCF-like complex containing ASB2 leads to proteasomal degradation. Prior dissociation from actin may be required to expose the target lysines (PubMed:24052262). Ubiquitinated in endothelial cells by RNF213 downstream of the non-canonical Wnt signaling pathway, leading to its degradation by the proteasome (PubMed:26766444).2 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 1761 – 1762 | Cleavage; by calpain | 2 |
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
| CPTACi | CPTAC-508 CPTAC-509 |
| EPDi | P21333 |
| jPOSTi | P21333 |
| MassIVEi | P21333 |
| MaxQBi | P21333 |
| PaxDbi | P21333 |
| PeptideAtlasi | P21333 |
| PRIDEi | P21333 |
| ProteomicsDBi | 53859 [P21333-1] 53860 [P21333-2] |
2D gel databases
| OGPi | P21333 |
PTM databases
| CarbonylDBi | P21333 |
| GlyGeni | P21333, 2 sites, 1 O-linked glycan (2 sites) |
| iPTMneti | P21333 |
| MetOSitei | P21333 |
| PhosphoSitePlusi | P21333 |
| SwissPalmi | P21333 |
Expressioni
Tissue specificityi
Ubiquitous.
Gene expression databases
| Bgeei | ENSG00000196924, Expressed in esophagogastric junction muscularis propria and 250 other tissues |
| ExpressionAtlasi | P21333, baseline and differential |
| Genevisiblei | P21333, HS |
Organism-specific databases
| HPAi | ENSG00000196924, Tissue enhanced (smooth muscle, urinary bladder) |
Interactioni
Subunit structurei
Homodimer.
Interacts with PDLIM2 (By similarity).
Interacts with RFLNA and RFLNB (By similarity).
Interacts with FCGR1A, FLNB, FURIN, HSPB7, INPPL1, KCND2, MYOT, MYOZ1, ARHGAP24, PSEN1, PSEN2 and ECSCR.
Interacts also with various other binding partners in addition to filamentous actin.
Interacts (via N-terminus) with MIS18BP1 (via N-terminus).
Interacts (via N-terminus) with TAF1B.
Interacts with TMEM67 (via C-terminus) and MKS1.
Interacts (via actin-binding domain) with MICALL2 (via CH domain).
Interacts (via filamin repeat 5) with SYK; docks SYK to the plasma membrane (PubMed:20713593).
Interacts (via filamin repeats 19 and 21) with DRD3; increased PKA-mediated phosphorylation at Ser-2152.
Interacts (via filamin repeat 21) with MAS1, AGTR1 and ADRA1D; increases PKA-mediated phosphorylation of FLNA at Ser-2152 (PubMed:26460884).
Interacts (via filamin repeats 4, 9, 12, 17, 19, 21, and 23) with GP1BA (high affinity), ITGB7, ITGB2 and FBLIM1 (PubMed:19828450, PubMed:21524097, PubMed:25666618).
Interacts with CEACAM1 (via cytoplasmic domain); inhibits cell migration and cell scattering by interfering with the interaction between FLNA and RALA (PubMed:16291724).
Interacts with FOXC1 (PubMed:15684392).
Interacts (via calponin-homology (CH) domain 1 and filamin repeat 24) with CRMP1; the interaction alters FLNA ternary structure and thus promotes FLNA dissociation from F-actin (PubMed:25358863).
Interacts with DPYSL3/CRMP3 and DPYSL4/CRMP4 (PubMed:25358863).
By similarity20 PublicationsBinary interactionsi
Hide detailsP21333
Isoform 2 [P21333-2]
GO - Molecular functioni
- actin filament binding Source: BHF-UCL
- cadherin binding Source: BHF-UCL
- Fc-gamma receptor I complex binding Source: BHF-UCL
- G protein-coupled receptor binding Source: UniProtKB
- GTPase binding Source: UniProtKB
- ion channel binding Source: BHF-UCL
- kinase binding Source: UniProtKB
- mu-type opioid receptor binding Source: Ensembl
- protein homodimerization activity Source: BHF-UCL
- Rac GTPase binding Source: BHF-UCL
- Ral GTPase binding Source: BHF-UCL
- Rho GTPase binding Source: BHF-UCL
- SMAD binding Source: Ensembl
- small GTPase binding Source: BHF-UCL
- transcription factor binding Source: UniProtKB
Protein-protein interaction databases
| BioGRIDi | 108605, 357 interactors |
| ComplexPortali | CPX-117, Glycoprotein Ib-IX-V-Filamin-A complex CPX-122, Filamin A homodimer |
| CORUMi | P21333 |
| DIPi | DIP-1136N |
| IntActi | P21333, 269 interactors |
| MINTi | P21333 |
| STRINGi | 9606.ENSP00000358866 |
Miscellaneous databases
| RNActi | P21333, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| SASBDBi | P21333 |
| SMRi | P21333 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | P21333 |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 43 – 149 | Calponin-homology (CH) 1PROSITE-ProRule annotationAdd BLAST | 107 | |
| Domaini | 166 – 269 | Calponin-homology (CH) 2PROSITE-ProRule annotationAdd BLAST | 104 | |
| Repeati | 276 – 374 | Filamin 1Add BLAST | 99 | |
| Repeati | 376 – 474 | Filamin 2Add BLAST | 99 | |
| Repeati | 475 – 570 | Filamin 3Add BLAST | 96 | |
| Repeati | 571 – 663 | Filamin 4Add BLAST | 93 | |
| Repeati | 667 – 763 | Filamin 5Add BLAST | 97 | |
| Repeati | 764 – 866 | Filamin 6Add BLAST | 103 | |
| Repeati | 867 – 965 | Filamin 7Add BLAST | 99 | |
| Repeati | 966 – 1061 | Filamin 8Add BLAST | 96 | |
| Repeati | 1062 – 1154 | Filamin 9Add BLAST | 93 | |
| Repeati | 1155 – 1249 | Filamin 10Add BLAST | 95 | |
| Repeati | 1250 – 1349 | Filamin 11Add BLAST | 100 | |
| Repeati | 1350 – 1442 | Filamin 12Add BLAST | 93 | |
| Repeati | 1443 – 1539 | Filamin 13Add BLAST | 97 | |
| Repeati | 1540 – 1636 | Filamin 14Add BLAST | 97 | |
| Repeati | 1649 – 1740 | Filamin 15Add BLAST | 92 | |
| Repeati | 1779 – 1860 | Filamin 16Add BLAST | 82 | |
| Repeati | 1861 – 1950 | Filamin 17Add BLAST | 90 | |
| Repeati | 1951 – 2039 | Filamin 18Add BLAST | 89 | |
| Repeati | 2042 – 2131 | Filamin 19Add BLAST | 90 | |
| Repeati | 2132 – 2230 | Filamin 20Add BLAST | 99 | |
| Repeati | 2233 – 2325 | Filamin 21Add BLAST | 93 | |
| Repeati | 2327 – 2420 | Filamin 22Add BLAST | 94 | |
| Repeati | 2424 – 2516 | Filamin 23Add BLAST | 93 | |
| Repeati | 2552 – 2646 | Filamin 24Add BLAST | 95 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 2 – 274 | Actin-bindingAdd BLAST | 273 | |
| Regioni | 1490 – 1607 | Interaction with furinBy similarityAdd BLAST | 118 | |
| Regioni | 1741 – 1778 | Hinge 1Add BLAST | 38 | |
| Regioni | 2517 – 2647 | Self-association site, tailAdd BLAST | 131 | |
| Regioni | 2517 – 2551 | Hinge 2Add BLAST | 35 |
Domaini
Comprised of a NH2-terminal actin-binding domain, 24 immunoglobulin-like internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation. Filamin repeat 20 interacts with filamin repeat 21 masking the ligand binding site on filamin repeat 21, resulting in an autoinhibited conformation (PubMed:17690686). The autoinhibition can be relieved by ligands like ITGB7 or FBLIM1 (PubMed:21524097). Filamin repeats 19 and 21 can simultaneously engage ligands (PubMed:21524097).2 Publications
Sequence similaritiesi
Belongs to the filamin family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
| eggNOGi | KOG0518, Eukaryota |
| GeneTreei | ENSGT00940000153588 |
| InParanoidi | P21333 |
| OMAi | WATDRPV |
| OrthoDBi | 437627at2759 |
| PhylomeDBi | P21333 |
| TreeFami | TF313685 |
Family and domain databases
| CDDi | cd00014, CH, 2 hits |
| DisProti | DP01950 |
| Gene3Di | 1.10.418.10, 2 hits 2.60.40.10, 24 hits |
| InterProi | View protein in InterPro IPR001589, Actinin_actin-bd_CS IPR001715, CH-domain IPR036872, CH_dom_sf IPR017868, Filamin/ABP280_repeat-like IPR001298, Filamin/ABP280_rpt IPR013783, Ig-like_fold IPR014756, Ig_E-set |
| Pfami | View protein in Pfam PF00307, CH, 2 hits PF00630, Filamin, 23 hits |
| SMARTi | View protein in SMART SM00033, CH, 2 hits SM00557, IG_FLMN, 24 hits |
| SUPFAMi | SSF47576, SSF47576, 1 hit SSF81296, SSF81296, 24 hits |
| PROSITEi | View protein in PROSITE PS00019, ACTININ_1, 1 hit PS00020, ACTININ_2, 1 hit PS50021, CH, 2 hits PS50194, FILAMIN_REPEAT, 24 hits |
Sequences (2+)i
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P21333-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MSSSHSRAGQ SAAGAAPGGG VDTRDAEMPA TEKDLAEDAP WKKIQQNTFT
60 70 80 90 100
RWCNEHLKCV SKRIANLQTD LSDGLRLIAL LEVLSQKKMH RKHNQRPTFR
110 120 130 140 150
QMQLENVSVA LEFLDRESIK LVSIDSKAIV DGNLKLILGL IWTLILHYSI
160 170 180 190 200
SMPMWDEEED EEAKKQTPKQ RLLGWIQNKL PQLPITNFSR DWQSGRALGA
210 220 230 240 250
LVDSCAPGLC PDWDSWDASK PVTNAREAMQ QADDWLGIPQ VITPEEIVDP
260 270 280 290 300
NVDEHSVMTY LSQFPKAKLK PGAPLRPKLN PKKARAYGPG IEPTGNMVKK
310 320 330 340 350
RAEFTVETRS AGQGEVLVYV EDPAGHQEEA KVTANNDKNR TFSVWYVPEV
360 370 380 390 400
TGTHKVTVLF AGQHIAKSPF EVYVDKSQGD ASKVTAQGPG LEPSGNIANK
410 420 430 440 450
TTYFEIFTAG AGTGEVEVVI QDPMGQKGTV EPQLEARGDS TYRCSYQPTM
460 470 480 490 500
EGVHTVHVTF AGVPIPRSPY TVTVGQACNP SACRAVGRGL QPKGVRVKET
510 520 530 540 550
ADFKVYTKGA GSGELKVTVK GPKGEERVKQ KDLGDGVYGF EYYPMVPGTY
560 570 580 590 600
IVTITWGGQN IGRSPFEVKV GTECGNQKVR AWGPGLEGGV VGKSADFVVE
610 620 630 640 650
AIGDDVGTLG FSVEGPSQAK IECDDKGDGS CDVRYWPQEA GEYAVHVLCN
660 670 680 690 700
SEDIRLSPFM ADIRDAPQDF HPDRVKARGP GLEKTGVAVN KPAEFTVDAK
710 720 730 740 750
HGGKAPLRVQ VQDNEGCPVE ALVKDNGNGT YSCSYVPRKP VKHTAMVSWG
760 770 780 790 800
GVSIPNSPFR VNVGAGSHPN KVKVYGPGVA KTGLKAHEPT YFTVDCAEAG
810 820 830 840 850
QGDVSIGIKC APGVVGPAEA DIDFDIIRND NDTFTVKYTP RGAGSYTIMV
860 870 880 890 900
LFADQATPTS PIRVKVEPSH DASKVKAEGP GLSRTGVELG KPTHFTVNAK
910 920 930 940 950
AAGKGKLDVQ FSGLTKGDAV RDVDIIDHHD NTYTVKYTPV QQGPVGVNVT
960 970 980 990 1000
YGGDPIPKSP FSVAVSPSLD LSKIKVSGLG EKVDVGKDQE FTVKSKGAGG
1010 1020 1030 1040 1050
QGKVASKIVG PSGAAVPCKV EPGLGADNSV VRFLPREEGP YEVEVTYDGV
1060 1070 1080 1090 1100
PVPGSPFPLE AVAPTKPSKV KAFGPGLQGG SAGSPARFTI DTKGAGTGGL
1110 1120 1130 1140 1150
GLTVEGPCEA QLECLDNGDG TCSVSYVPTE PGDYNINILF ADTHIPGSPF
1160 1170 1180 1190 1200
KAHVVPCFDA SKVKCSGPGL ERATAGEVGQ FQVDCSSAGS AELTIEICSE
1210 1220 1230 1240 1250
AGLPAEVYIQ DHGDGTHTIT YIPLCPGAYT VTIKYGGQPV PNFPSKLQVE
1260 1270 1280 1290 1300
PAVDTSGVQC YGPGIEGQGV FREATTEFSV DARALTQTGG PHVKARVANP
1310 1320 1330 1340 1350
SGNLTETYVQ DRGDGMYKVE YTPYEEGLHS VDVTYDGSPV PSSPFQVPVT
1360 1370 1380 1390 1400
EGCDPSRVRV HGPGIQSGTT NKPNKFTVET RGAGTGGLGL AVEGPSEAKM
1410 1420 1430 1440 1450
SCMDNKDGSC SVEYIPYEAG TYSLNVTYGG HQVPGSPFKV PVHDVTDASK
1460 1470 1480 1490 1500
VKCSGPGLSP GMVRANLPQS FQVDTSKAGV APLQVKVQGP KGLVEPVDVV
1510 1520 1530 1540 1550
DNADGTQTVN YVPSREGPYS ISVLYGDEEV PRSPFKVKVL PTHDASKVKA
1560 1570 1580 1590 1600
SGPGLNTTGV PASLPVEFTI DAKDAGEGLL AVQITDPEGK PKKTHIQDNH
1610 1620 1630 1640 1650
DGTYTVAYVP DVTGRYTILI KYGGDEIPFS PYRVRAVPTG DASKCTVTVS
1660 1670 1680 1690 1700
IGGHGLGAGI GPTIQIGEET VITVDTKAAG KGKVTCTVCT PDGSEVDVDV
1710 1720 1730 1740 1750
VENEDGTFDI FYTAPQPGKY VICVRFGGEH VPNSPFQVTA LAGDQPSVQP
1760 1770 1780 1790 1800
PLRSQQLAPQ YTYAQGGQQT WAPERPLVGV NGLDVTSLRP FDLVIPFTIK
1810 1820 1830 1840 1850
KGEITGEVRM PSGKVAQPTI TDNKDGTVTV RYAPSEAGLH EMDIRYDNMH
1860 1870 1880 1890 1900
IPGSPLQFYV DYVNCGHVTA YGPGLTHGVV NKPATFTVNT KDAGEGGLSL
1910 1920 1930 1940 1950
AIEGPSKAEI SCTDNQDGTC SVSYLPVLPG DYSILVKYNE QHVPGSPFTA
1960 1970 1980 1990 2000
RVTGDDSMRM SHLKVGSAAD IPINISETDL SLLTATVVPP SGREEPCLLK
2010 2020 2030 2040 2050
RLRNGHVGIS FVPKETGEHL VHVKKNGQHV ASSPIPVVIS QSEIGDASRV
2060 2070 2080 2090 2100
RVSGQGLHEG HTFEPAEFII DTRDAGYGGL SLSIEGPSKV DINTEDLEDG
2110 2120 2130 2140 2150
TCRVTYCPTE PGNYIINIKF ADQHVPGSPF SVKVTGEGRV KESITRRRRA
2160 2170 2180 2190 2200
PSVANVGSHC DLSLKIPEIS IQDMTAQVTS PSGKTHEAEI VEGENHTYCI
2210 2220 2230 2240 2250
RFVPAEMGTH TVSVKYKGQH VPGSPFQFTV GPLGEGGAHK VRAGGPGLER
2260 2270 2280 2290 2300
AEAGVPAEFS IWTREAGAGG LAIAVEGPSK AEISFEDRKD GSCGVAYVVQ
2310 2320 2330 2340 2350
EPGDYEVSVK FNEEHIPDSP FVVPVASPSG DARRLTVSSL QESGLKVNQP
2360 2370 2380 2390 2400
ASFAVSLNGA KGAIDAKVHS PSGALEECYV TEIDQDKYAV RFIPRENGVY
2410 2420 2430 2440 2450
LIDVKFNGTH IPGSPFKIRV GEPGHGGDPG LVSAYGAGLE GGVTGNPAEF
2460 2470 2480 2490 2500
VVNTSNAGAG ALSVTIDGPS KVKMDCQECP EGYRVTYTPM APGSYLISIK
2510 2520 2530 2540 2550
YGGPYHIGGS PFKAKVTGPR LVSNHSLHET SSVFVDSLTK ATCAPQHGAP
2560 2570 2580 2590 2600
GPGPADASKV VAKGLGLSKA YVGQKSSFTV DCSKAGNNML LVGVHGPRTP
2610 2620 2630 2640
CEEILVKHVG SRLYSVSYLL KDKGEYTLVV KWGDEHIPGS PYRVVVP
Length:2,647
Mass (Da):280,739
Last modified:January 23, 2007 - v4