Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Filamin-A

Gene

FLNA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 FLNA 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 maintainance (By similarity).By similarity1 Publication

GO - Molecular functioni

  • actin filament binding Source: BHF-UCL
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • Fc-gamma receptor I complex binding Source: BHF-UCL
  • glycoprotein binding Source: BHF-UCL
  • G-protein coupled receptor binding Source: UniProtKB
  • GTPase binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL
  • Rac GTPase binding Source: BHF-UCL
  • Ral GTPase binding Source: BHF-UCL
  • Rho GTPase binding Source: BHF-UCL
  • signal transducer activity Source: UniProtKB
  • 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
  • cilium assembly Source: UniProtKB
  • cytoplasmic sequestering of protein Source: BHF-UCL
  • establishment of protein localization Source: BHF-UCL
  • mitotic spindle assembly Source: MGI
  • mRNA transcription from RNA polymerase II promoter Source: Ensembl
  • negative regulation of apoptotic process Source: CACAO
  • negative regulation of protein catabolic process Source: BHF-UCL
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • negative regulation of transcription from RNA polymerase I promoter Source: CACAO
  • platelet activation Source: Reactome
  • platelet aggregation Source: UniProtKB
  • platelet degranulation Source: Reactome
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of integrin-mediated signaling pathway Source: CACAO
  • positive regulation of substrate adhesion-dependent cell spreading Source: CACAO
  • positive regulation of transcription factor import into nucleus Source: UniProtKB
  • protein localization to cell surface Source: BHF-UCL
  • protein stabilization Source: BHF-UCL
  • receptor clustering Source: BHF-UCL
  • regulation of cell migration Source: UniProtKB
  • semaphorin-plexin signaling pathway Source: WormBase
  • wound healing, spreading of cells Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cilium biogenesis/degradation

Keywords - Ligandi

Actin-binding

Enzyme and pathway databases

BioCyciZFISH:G66-31130-MONOMER.
ReactomeiR-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.
SignaLinkiP21333.
SIGNORiP21333.

Names & Taxonomyi

Protein namesi
Recommended name:
Filamin-A
Short 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:3754. FLNA.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: BHF-UCL
  • actin filament Source: Ensembl
  • apical dendrite Source: Ensembl
  • cell-cell adherens junction Source: BHF-UCL
  • cell-cell junction Source: UniProtKB
  • cortical cytoskeleton Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • dendritic shaft Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: BHF-UCL
  • extracellular region Source: Reactome
  • focal adhesion Source: UniProtKB
  • membrane Source: UniProtKB
  • Myb complex Source: MGI
  • neuronal cell body Source: Ensembl
  • nucleolus Source: CACAO
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Periventricular nodular heterotopia 1 (PVNH1)7 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.
See also OMIM:300049
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02273439A → G in PVNH1. 1 PublicationCorresponds to variant rs137853313dbSNPEnsembl.1
Natural variantiVAR_01569982E → V in PVNH1. 1 PublicationCorresponds to variant rs28935169dbSNPEnsembl.1
Natural variantiVAR_031305102M → V in PVNH1. 1 Publication1
Natural variantiVAR_031306128A → V in PVNH1. 1 PublicationCorresponds to variant rs137853315dbSNPEnsembl.1
Natural variantiVAR_031307149S → F in PVNH1. 1 Publication1
Natural variantiVAR_031309528V → M in PVNH1. 1 PublicationCorresponds to variant rs143873938dbSNPEnsembl.1
Natural variantiVAR_012834656L → F in PVNH1. 1 PublicationCorresponds to variant rs137853311dbSNPEnsembl.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.
See also OMIM:311300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015714172L → F in OPD1. 1 Publication1
Natural variantiVAR_015716196R → W in OPD1. 1 PublicationCorresponds to variant rs137853317dbSNPEnsembl.1
Natural variantiVAR_031308203D → Y in OPD1. 1 PublicationCorresponds to variant rs137853314dbSNPEnsembl.1
Natural variantiVAR_015700207P → L in OPD1. 2 PublicationsCorresponds to variant rs28935469dbSNPEnsembl.1
Natural variantiVAR_076501267A → T in OPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_076502804V → D in OPD1; unknown pathological significance. 1 Publication1
Natural variantiVAR_0765062391R → H in OPD1; unknown pathological significance. 1 PublicationCorresponds to variant rs727503930dbSNPEnsembl.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.
See also OMIM:304120
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015713170Q → P in OPD2. 1 Publication1
Natural variantiVAR_076500187N → S in OPD2; unknown pathological significance. 1 Publication1
Natural variantiVAR_015715196R → G in OPD2. 2 Publications1
Natural variantiVAR_015717200A → S in OPD2. 1 Publication1
Natural variantiVAR_058720210C → F in OPD2. 1 PublicationCorresponds to variant rs137853318dbSNPEnsembl.1
Natural variantiVAR_015701254E → K in OPD2. 1 PublicationCorresponds to variant rs28935470dbSNPEnsembl.1
Natural variantiVAR_015718273A → P in OPD2. 1 Publication1
Natural variantiVAR_015719555T → K in OPD2. 1 PublicationCorresponds to variant rs782611953dbSNPEnsembl.1
Natural variantiVAR_0157231645C → F in OPD2. 1 Publication1
Frontometaphyseal dysplasia (FMD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCongenital bone disease characterized by supraorbital hyperostosis, deafness and digital anomalies.
See also OMIM:305620
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0765031142D → V in FMD; unknown pathological significance. 1 Publication1
Natural variantiVAR_0157021159D → A in FMD; does not inhibit interaction with MIS18BP1. 2 PublicationsCorresponds to variant rs28935471dbSNPEnsembl.1
Natural variantiVAR_0157211186S → L in FMD. 3 PublicationsCorresponds to variant rs137853312dbSNPEnsembl.1
Natural variantiVAR_0157221620Missing in FMD. 1 Publication1
Natural variantiVAR_0313121728G → C in FMD. 1 PublicationCorresponds to variant rs137853316dbSNPEnsembl.1
Natural variantiVAR_0765051840H → R in FMD; unknown pathological significance. 1 Publication1
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.
See also OMIM:309350
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0765041163V → L in MNS; unknown pathological significance. 1 Publication1
Natural variantiVAR_0157201184D → E in MNS. 1 PublicationCorresponds to variant rs80338837dbSNPEnsembl.1
Natural variantiVAR_0157031188A → T in MNS; does not inhibit interaction with MIS18BP1. 3 PublicationsCorresponds to variant rs28935472dbSNPEnsembl.1
Natural variantiVAR_0157041199S → L in MNS; does not inhibit interaction with MIS18BP1. 2 PublicationsCorresponds to variant rs28935473dbSNPEnsembl.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.
See also OMIM:300048
FG 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.
See also OMIM:300321
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0587211291P → L in FGS2. 1 PublicationCorresponds to variant rs137853319dbSNPEnsembl.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.
See also OMIM:300244
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0641591724 – 1739Missing in TOD. 1 PublicationAdd BLAST16
Cardiac valvular dysplasia X-linked (CVDX)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.
See also OMIM:314400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064156288G → R in CVDX. 1 PublicationCorresponds to variant rs267606816dbSNPEnsembl.1
Natural variantiVAR_064157637P → Q in CVDX. 1 PublicationCorresponds to variant rs267606815dbSNPEnsembl.1
Natural variantiVAR_064158711V → D in CVDX. 1 PublicationCorresponds to variant rs267606817dbSNPEnsembl.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).

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.
See also OMIM:300048

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-43 and R-135. 1 Publication1
Mutagenesisi43K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-135. 1 Publication1
Mutagenesisi135K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-43. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2316.
MalaCardsiFLNA.
MIMi300048. phenotype.
300049. phenotype.
300244. phenotype.
300321. phenotype.
304120. phenotype.
305620. phenotype.
309350. phenotype.
311300. phenotype.
314400. phenotype.
OpenTargetsiENSG00000196924.
Orphaneti2301. Congenital short bowel syndrome.
1864. Congenital valvular dysplasia.
82004. Ehlers-Danlos syndrome with periventricular heterotopia.
323. FG syndrome.
1826. Frontometaphyseal dysplasia.
99811. Neuronal intestinal pseudoobstruction.
2484. Osteodysplasty, Melnick-Needles type.
90650. Otopalatodigital syndrome type 1.
90652. Otopalatodigital syndrome type 2.
98892. Periventricular nodular heterotopia.
88630. Terminal osseous dysplasia - pigmentary defects.
PharmGKBiPA28172.

Polymorphism and mutation databases

BioMutaiFLNA.
DMDMi116241365.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000872962 – 2647Filamin-AAdd BLAST2646

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei11PhosphoserineCombined sources1
Cross-linki42Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki43Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki135Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki299Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki299Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei376N6-acetyllysineBy similarity1
Modified residuei508N6-acetyllysineCombined sources1
Modified residuei700N6-acetyllysineCombined sources1
Modified residuei781N6-acetyllysineCombined sources1
Modified residuei837N6-acetyllysineCombined sources1
Modified residuei865N6-acetyllysineBy similarity1
Modified residuei906N6-acetyllysineBy similarity1
Modified residuei968PhosphoserineBy similarity1
Modified residuei1055PhosphoserineCombined sources1
Modified residuei1071N6-acetyllysine; alternateBy similarity1
Modified residuei1071N6-succinyllysine; alternateBy similarity1
Modified residuei1081PhosphoserineCombined sources1
Modified residuei1084PhosphoserineCombined sources1
Modified residuei1089PhosphothreonineCombined sources1
Modified residuei1301PhosphoserineCombined sources1
Modified residuei1338PhosphoserineCombined sources1
Modified residuei1372N6-acetyllysineBy similarity1
Modified residuei1459PhosphoserineCombined sources1
Modified residuei1533PhosphoserineCombined sources1
Modified residuei1538N6-acetyllysineBy similarity1
Modified residuei1630PhosphoserineCombined sources1
Modified residuei1734PhosphoserineCombined sources1
Modified residuei1835PhosphoserineCombined sources1
Modified residuei1967PhosphoserineCombined sources1
Modified residuei2053PhosphoserineCombined sources1
Modified residuei2128PhosphoserineCombined sources1
Modified residuei2152PhosphoserineCombined sources2 Publications1
Modified residuei2158PhosphoserineCombined sources1
Modified residuei2163PhosphoserineCombined sources1
Modified residuei2180PhosphoserineBy similarity1
Modified residuei2284PhosphoserineCombined sources1
Modified residuei2327PhosphoserineCombined sources1
Modified residuei2329PhosphoserineBy similarity1
Modified residuei2336PhosphothreonineCombined sources1 Publication1
Modified residuei2338PhosphoserineCombined sources1
Modified residuei2370PhosphoserineBy similarity1
Modified residuei2414PhosphoserineCombined sources1
Modified residuei2510PhosphoserineCombined sources1
Modified residuei2523PhosphoserineBy similarity1
Modified residuei2526PhosphoserineBy similarity1
Modified residuei2569N6-acetyllysine; alternateBy similarity1
Modified residuei2569N6-succinyllysine; alternateBy similarity1
Modified residuei2575N6-acetyllysineBy similarity1
Modified residuei2599PhosphothreonineBy similarity1
Modified residuei2607N6-acetyllysineCombined sources1
Modified residuei2621N6-acetyllysineCombined sources1

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1761 – 1762Cleavage; by calpain2

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP21333.
MaxQBiP21333.
PaxDbiP21333.
PeptideAtlasiP21333.
PRIDEiP21333.

2D gel databases

OGPiP21333.

PTM databases

iPTMnetiP21333.
PhosphoSitePlusiP21333.
SwissPalmiP21333.

Miscellaneous databases

PMAP-CutDBP21333.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000196924.
CleanExiHS_FLNA.
ExpressionAtlasiP21333. baseline and differential.
GenevisibleiP21333. HS.

Organism-specific databases

HPAiCAB000356.
HPA000368.
HPA001115.
HPA002925.

Interactioni

Subunit structurei

Homodimer. Interacts with PDLIM2 (By similarity). Interacts with FAM101A and FAM101B (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).By similarity18 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q9WMX26EBI-350432,EBI-6863748From a different organism.
ADAMTSL4Q6UY14-33EBI-9641086,EBI-10173507
ARHGAP24Q8N2646EBI-350432,EBI-988764
CCNB2O950678EBI-350432,EBI-375024
CRKP461083EBI-350432,EBI-886
FABP1P071483EBI-9641086,EBI-2115989
FAM101AQ6ZTI63EBI-9641086,EBI-10200920
FLNBO753695EBI-350432,EBI-352089
FOXC1Q129488EBI-350432,EBI-1175253
GRB2P629932EBI-350432,EBI-401755
HSP90AB1P082382EBI-350432,EBI-352572
HSPB7Q9UBY93EBI-9641086,EBI-739361
ITGB1P055565EBI-350432,EBI-703066
ITGB1P072282EBI-350432,EBI-5606437From a different organism.
ITGB7P260106EBI-350432,EBI-702932
KLHL12Q53G593EBI-9641086,EBI-740929
LGALS14Q8TCE93EBI-9641086,EBI-10274069
NRP1O147862EBI-350432,EBI-1187100
OPRM1P353725EBI-350432,EBI-2624570
PHLDB2Q86SQ03EBI-350432,EBI-2798483
RELQ048643EBI-9641086,EBI-307352
TCF4P158843EBI-9641086,EBI-533224

GO - Molecular functioni

  • actin filament binding Source: BHF-UCL
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • Fc-gamma receptor I complex binding Source: BHF-UCL
  • G-protein coupled receptor binding Source: UniProtKB
  • GTPase binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL
  • Rac GTPase binding Source: BHF-UCL
  • Ral GTPase binding Source: BHF-UCL
  • Rho GTPase binding Source: BHF-UCL
  • small GTPase binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108605. 280 interactors.
DIPiDIP-1136N.
IntActiP21333. 213 interactors.
MINTiMINT-118283.
STRINGi9606.ENSP00000358866.

Structurei

Secondary structure

12647
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi40 – 43Combined sources4
Helixi44 – 57Combined sources14
Helixi58 – 60Combined sources3
Turni67 – 73Combined sources7
Helixi75 – 85Combined sources11
Helixi100 – 116Combined sources17
Helixi126 – 130Combined sources5
Helixi134 – 149Combined sources16
Beta strandi157 – 159Combined sources3
Helixi168 – 179Combined sources12
Beta strandi181 – 183Combined sources3
Helixi190 – 192Combined sources3
Beta strandi193 – 195Combined sources3
Helixi196 – 205Combined sources10
Helixi213 – 215Combined sources3
Helixi221 – 236Combined sources16
Helixi244 – 247Combined sources4
Helixi254 – 261Combined sources8
Helixi263 – 266Combined sources4
Helixi480 – 482Combined sources3
Beta strandi484 – 487Combined sources4
Helixi488 – 490Combined sources3
Beta strandi501 – 506Combined sources6
Beta strandi515 – 521Combined sources7
Beta strandi529 – 534Combined sources6
Beta strandi537 – 542Combined sources6
Beta strandi548 – 556Combined sources9
Beta strandi565 – 571Combined sources7
Beta strandi579 – 583Combined sources5
Helixi584 – 586Combined sources3
Beta strandi588 – 590Combined sources3
Beta strandi595 – 604Combined sources10
Beta strandi609 – 617Combined sources9
Beta strandi620 – 625Combined sources6
Beta strandi627 – 636Combined sources10
Beta strandi639 – 649Combined sources11
Beta strandi658 – 664Combined sources7
Helixi672 – 674Combined sources3
Beta strandi676 – 679Combined sources4
Helixi680 – 682Combined sources3
Beta strandi683 – 685Combined sources3
Beta strandi693 – 698Combined sources6
Beta strandi707 – 712Combined sources6
Beta strandi714 – 716Combined sources3
Beta strandi721 – 725Combined sources5
Beta strandi727 – 735Combined sources9
Beta strandi739 – 749Combined sources11
Beta strandi758 – 762Combined sources5
Helixi1160 – 1162Combined sources3
Beta strandi1164 – 1167Combined sources4
Helixi1168 – 1170Combined sources3
Beta strandi1172 – 1174Combined sources3
Beta strandi1179 – 1184Combined sources6
Beta strandi1193 – 1198Combined sources6
Beta strandi1206 – 1211Combined sources6
Beta strandi1213 – 1222Combined sources10
Beta strandi1225 – 1235Combined sources11
Beta strandi1244 – 1250Combined sources7
Turni1785 – 1787Combined sources3
Beta strandi1791 – 1796Combined sources6
Beta strandi1804 – 1809Combined sources6
Beta strandi1819 – 1822Combined sources4
Beta strandi1824 – 1832Combined sources9
Beta strandi1838 – 1846Combined sources9
Beta strandi1855 – 1860Combined sources6
Beta strandi1865 – 1867Combined sources3
Beta strandi1869 – 1872Combined sources4
Helixi1873 – 1875Combined sources3
Beta strandi1877 – 1879Combined sources3
Beta strandi1884 – 1889Combined sources6
Turni1891 – 1893Combined sources3
Beta strandi1895 – 1906Combined sources12
Beta strandi1909 – 1914Combined sources6
Beta strandi1916 – 1925Combined sources10
Beta strandi1930 – 1938Combined sources9
Beta strandi1947 – 1953Combined sources7
Beta strandi1959 – 1967Combined sources9
Beta strandi1980 – 1988Combined sources9
Beta strandi1998 – 2001Combined sources4
Beta strandi2007 – 2010Combined sources4
Beta strandi2014 – 2025Combined sources12
Beta strandi2034 – 2039Combined sources6
Helixi2041 – 2043Combined sources3
Helixi2047 – 2049Combined sources3
Beta strandi2051 – 2054Combined sources4
Helixi2055 – 2057Combined sources3
Beta strandi2059 – 2061Combined sources3
Beta strandi2066 – 2071Combined sources6
Beta strandi2075 – 2077Combined sources3
Beta strandi2080 – 2088Combined sources9
Beta strandi2091 – 2096Combined sources6
Beta strandi2100 – 2107Combined sources8
Beta strandi2112 – 2120Combined sources9
Beta strandi2129 – 2136Combined sources8
Beta strandi2139 – 2148Combined sources10
Beta strandi2161 – 2165Combined sources5
Helixi2171 – 2173Combined sources3
Beta strandi2174 – 2179Combined sources6
Beta strandi2185 – 2187Combined sources3
Beta strandi2189 – 2192Combined sources4
Beta strandi2194 – 2201Combined sources8
Beta strandi2208 – 2216Combined sources9
Beta strandi2225 – 2229Combined sources5
Beta strandi2234 – 2236Combined sources3
Helixi2238 – 2240Combined sources3
Beta strandi2242 – 2245Combined sources4
Helixi2246 – 2248Combined sources3
Beta strandi2257 – 2262Combined sources6
Helixi2264 – 2266Combined sources3
Beta strandi2271 – 2279Combined sources9
Beta strandi2282 – 2287Combined sources6
Beta strandi2293 – 2298Combined sources6
Beta strandi2303 – 2311Combined sources9
Beta strandi2320 – 2326Combined sources7
Turni2429 – 2431Combined sources3
Beta strandi2433 – 2436Combined sources4
Helixi2437 – 2439Combined sources3
Beta strandi2441 – 2443Combined sources3
Beta strandi2448 – 2453Combined sources6
Turni2455 – 2457Combined sources3
Beta strandi2462 – 2470Combined sources9
Beta strandi2472 – 2479Combined sources8
Beta strandi2482 – 2489Combined sources8
Beta strandi2491 – 2506Combined sources16
Beta strandi2511 – 2518Combined sources8
Beta strandi2561 – 2564Combined sources4
Helixi2565 – 2567Combined sources3
Beta strandi2576 – 2581Combined sources6
Beta strandi2590 – 2595Combined sources6
Beta strandi2597 – 2599Combined sources3
Beta strandi2602 – 2610Combined sources9
Beta strandi2613 – 2619Combined sources7
Beta strandi2624 – 2632Combined sources9
Beta strandi2641 – 2646Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AAVNMR-A1863-1956[»]
2BP3X-ray2.32A/B1863-1956[»]
2BRQX-ray2.10A/B2236-2329[»]
2J3SX-ray2.50A/B2045-2329[»]
2JF1X-ray2.20A2236-2329[»]
2K3TNMR-A2427-2522[»]
2K7PNMR-A1772-1956[»]
2K7QNMR-A1954-2141[»]
2MTPNMR-A2236-2330[»]
2W0PX-ray1.90A/B2236-2329[»]
2WFNX-ray3.20A/B1-278[»]
3CNKX-ray1.65A/B2559-2647[»]
3HOCX-ray2.30A/B2-269[»]
3HOPX-ray2.30A/B2-269[»]
3HORX-ray2.70A/B2-269[»]
3ISWX-ray2.80A/B2236-2329[»]
3RGHX-ray2.44A/B1158-1252[»]
4M9PX-ray1.72A478-766[»]
4P3WX-ray2.00A/B/C/D/E/F2152-2329[»]
ProteinModelPortaliP21333.
SMRiP21333.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21333.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 274Actin-bindingAdd BLAST273
Domaini43 – 149CH 1PROSITE-ProRule annotationAdd BLAST107
Domaini166 – 266CH 2PROSITE-ProRule annotationAdd BLAST101
Repeati276 – 374Filamin 1Add BLAST99
Repeati376 – 474Filamin 2Add BLAST99
Repeati475 – 570Filamin 3Add BLAST96
Repeati571 – 663Filamin 4Add BLAST93
Repeati667 – 763Filamin 5Add BLAST97
Repeati764 – 866Filamin 6Add BLAST103
Repeati867 – 965Filamin 7Add BLAST99
Repeati966 – 1061Filamin 8Add BLAST96
Repeati1062 – 1154Filamin 9Add BLAST93
Repeati1155 – 1249Filamin 10Add BLAST95
Repeati1250 – 1349Filamin 11Add BLAST100
Repeati1350 – 1442Filamin 12Add BLAST93
Repeati1443 – 1539Filamin 13Add BLAST97
Repeati1540 – 1636Filamin 14Add BLAST97
Repeati1649 – 1740Filamin 15Add BLAST92
Repeati1779 – 1860Filamin 16Add BLAST82
Repeati1861 – 1950Filamin 17Add BLAST90
Repeati1951 – 2039Filamin 18Add BLAST89
Repeati2042 – 2131Filamin 19Add BLAST90
Repeati2132 – 2230Filamin 20Add BLAST99
Repeati2233 – 2325Filamin 21Add BLAST93
Repeati2327 – 2420Filamin 22Add BLAST94
Repeati2424 – 2516Filamin 23Add BLAST93
Repeati2552 – 2646Filamin 24Add BLAST95

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1490 – 1607Interaction with furinBy similarityAdd BLAST118
Regioni1741 – 1778Hinge 1Add BLAST38
Regioni2517 – 2647Self-association site, tailAdd BLAST131
Regioni2517 – 2551Hinge 2Add BLAST35

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
Contains 1 actin-binding domain.Curated
Contains 2 CH (calponin-homology) domains.PROSITE-ProRule annotation
Contains 24 filamin repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0518. Eukaryota.
COG5069. LUCA.
GeneTreeiENSGT00660000095431.
HOGENOMiHOG000044235.
HOVERGENiHBG004163.
InParanoidiP21333.
KOiK04437.
OMAiVQDNEGC.
OrthoDBiEOG091G00U5.
PhylomeDBiP21333.
TreeFamiTF313685.

Family and domain databases

CDDicd00014. CH. 2 hits.
Gene3Di1.10.418.10. 2 hits.
2.60.40.10. 24 hits.
InterProiIPR001589. Actinin_actin-bd_CS.
IPR001715. CH-domain.
IPR017868. Filamin/ABP280_repeat-like.
IPR001298. Filamin/ABP280_rpt.
IPR028559. FLN_A.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
[Graphical view]
PANTHERiPTHR11915:SF173. PTHR11915:SF173. 1 hit.
PfamiPF00307. CH. 2 hits.
PF00630. Filamin. 23 hits.
[Graphical view]
SMARTiSM00033. CH. 2 hits.
SM00557. IG_FLMN. 24 hits.
[Graphical view]
SUPFAMiSSF47576. SSF47576. 1 hit.
SSF81296. SSF81296. 24 hits.
PROSITEiPS00019. ACTININ_1. 1 hit.
PS00020. ACTININ_2. 1 hit.
PS50021. CH. 2 hits.
PS50194. FILAMIN_REPEAT. 24 hits.
[Graphical view]

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 basket

Isoform 1 (identifier: P21333-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Checksum:i6C1A07041DF50142
GO
Isoform 2 (identifier: P21333-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1649-1656: Missing.

Note: No experimental confirmation available.
Show »
Length:2,639
Mass (Da):280,018
Checksum:i862625C6FEA39075
GO

Sequence cautioni

The sequence BAC03408 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti44I → T AA sequence (PubMed:2248958).Curated1
Sequence conflicti1772A → G in CAA49687 (PubMed:7689010).Curated1
Sequence conflicti2341Q → R in BAC03408 (PubMed:14702039).Curated1
Sequence conflicti2634D → H in CAA37495 (PubMed:8088819).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02273439A → G in PVNH1. 1 PublicationCorresponds to variant rs137853313dbSNPEnsembl.1
Natural variantiVAR_01569982E → V in PVNH1. 1 PublicationCorresponds to variant rs28935169dbSNPEnsembl.1
Natural variantiVAR_031305102M → V in PVNH1. 1 Publication1
Natural variantiVAR_031306128A → V in PVNH1. 1 Publication