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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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti39 – 391A → G in PVNH1. 1 Publication
Corresponds to variant rs137853313 [ dbSNP | Ensembl ].
VAR_022734
Natural varianti82 – 821E → V in PVNH1. 1 Publication
Corresponds to variant rs28935169 [ dbSNP | Ensembl ].
VAR_015699
Natural varianti102 – 1021M → V in PVNH1. 1 Publication
VAR_031305
Natural varianti128 – 1281A → V in PVNH1. 1 Publication
Corresponds to variant rs137853315 [ dbSNP | Ensembl ].
VAR_031306
Natural varianti149 – 1491S → F in PVNH1. 1 Publication
VAR_031307
Natural varianti528 – 5281V → M in PVNH1. 1 Publication
Corresponds to variant rs143873938 [ dbSNP | Ensembl ].
VAR_031309
Natural varianti656 – 6561L → F in PVNH1. 1 Publication
Corresponds to variant rs137853311 [ dbSNP | Ensembl ].
VAR_012834
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti172 – 1721L → F in OPD1. 1 Publication
VAR_015714
Natural varianti196 – 1961R → W in OPD1. 1 Publication
Corresponds to variant rs137853317 [ dbSNP | Ensembl ].
VAR_015716
Natural varianti203 – 2031D → Y in OPD1. 1 Publication
Corresponds to variant rs137853314 [ dbSNP | Ensembl ].
VAR_031308
Natural varianti207 – 2071P → L in OPD1. 2 Publications
Corresponds to variant rs28935469 [ dbSNP | Ensembl ].
VAR_015700
Natural varianti267 – 2671A → T in OPD1; unknown pathological significance. 1 Publication
VAR_076501
Natural varianti804 – 8041V → D in OPD1; unknown pathological significance. 1 Publication
VAR_076502
Natural varianti2391 – 23911R → H in OPD1; unknown pathological significance. 1 Publication
VAR_076506
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti170 – 1701Q → P in OPD2. 1 Publication
VAR_015713
Natural varianti187 – 1871N → S in OPD2; unknown pathological significance. 1 Publication
VAR_076500
Natural varianti196 – 1961R → G in OPD2. 2 Publications
VAR_015715
Natural varianti200 – 2001A → S in OPD2. 1 Publication
VAR_015717
Natural varianti210 – 2101C → F in OPD2. 1 Publication
Corresponds to variant rs137853318 [ dbSNP | Ensembl ].
VAR_058720
Natural varianti254 – 2541E → K in OPD2. 1 Publication
Corresponds to variant rs28935470 [ dbSNP | Ensembl ].
VAR_015701
Natural varianti273 – 2731A → P in OPD2. 1 Publication
VAR_015718
Natural varianti555 – 5551T → K in OPD2. 1 Publication
Corresponds to variant rs782611953 [ dbSNP | Ensembl ].
VAR_015719
Natural varianti1645 – 16451C → F in OPD2. 1 Publication
VAR_015723
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1142 – 11421D → V in FMD; unknown pathological significance. 1 Publication
VAR_076503
Natural varianti1159 – 11591D → A in FMD; does not inhibit interaction with MIS18BP1. 2 Publications
Corresponds to variant rs28935471 [ dbSNP | Ensembl ].
VAR_015702
Natural varianti1186 – 11861S → L in FMD. 3 Publications
Corresponds to variant rs137853312 [ dbSNP | Ensembl ].
VAR_015721
Natural varianti1620 – 16201Missing in FMD. 1 Publication
VAR_015722
Natural varianti1728 – 17281G → C in FMD. 1 Publication
Corresponds to variant rs137853316 [ dbSNP | Ensembl ].
VAR_031312
Natural varianti1840 – 18401H → R in FMD; unknown pathological significance. 1 Publication
VAR_076505
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1163 – 11631V → L in MNS; unknown pathological significance. 1 Publication
VAR_076504
Natural varianti1184 – 11841D → E in MNS. 1 Publication
Corresponds to variant rs80338837 [ dbSNP | Ensembl ].
VAR_015720
Natural varianti1188 – 11881A → T in MNS; does not inhibit interaction with MIS18BP1. 3 Publications
Corresponds to variant rs28935472 [ dbSNP | Ensembl ].
VAR_015703
Natural varianti1199 – 11991S → L in MNS; does not inhibit interaction with MIS18BP1. 2 Publications
Corresponds to variant rs28935473 [ dbSNP | Ensembl ].
VAR_015704
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1291 – 12911P → L in FGS2. 1 Publication
Corresponds to variant rs137853319 [ dbSNP | Ensembl ].
VAR_058721
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1724 – 173916Missing in TOD. 1 Publication
VAR_064159Add
BLAST
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti288 – 2881G → R in CVDX. 1 Publication
Corresponds to variant rs267606816 [ dbSNP | Ensembl ].
VAR_064156
Natural varianti637 – 6371P → Q in CVDX. 1 Publication
Corresponds to variant rs267606815 [ dbSNP | Ensembl ].
VAR_064157
Natural varianti711 – 7111V → D in CVDX. 1 Publication
Corresponds to variant rs267606817 [ dbSNP | Ensembl ].
VAR_064158

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi42 – 421K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-43 and R-135. 1 Publication
Mutagenesisi43 – 431K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-135. 1 Publication
Mutagenesisi135 – 1351K → R: Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-43. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiFLNA.
MIMi300048. phenotype.
300049. phenotype.
300244. phenotype.
300321. phenotype.
304120. phenotype.
305620. phenotype.
309350. phenotype.
311300. phenotype.
314400. phenotype.
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)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources1 Publication
Chaini2 – 26472646Filamin-APRO_0000087296Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources1 Publication
Modified residuei11 – 111PhosphoserineCombined sources
Cross-linki42 – 42Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki43 – 43Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki135 – 135Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki299 – 299Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki299 – 299Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei376 – 3761N6-acetyllysineBy similarity
Modified residuei508 – 5081N6-acetyllysineCombined sources
Modified residuei700 – 7001N6-acetyllysineCombined sources
Modified residuei781 – 7811N6-acetyllysineCombined sources
Modified residuei837 – 8371N6-acetyllysineCombined sources
Modified residuei865 – 8651N6-acetyllysineBy similarity
Modified residuei906 – 9061N6-acetyllysineBy similarity
Modified residuei968 – 9681PhosphoserineBy similarity
Modified residuei1055 – 10551PhosphoserineCombined sources
Modified residuei1071 – 10711N6-acetyllysine; alternateBy similarity
Modified residuei1071 – 10711N6-succinyllysine; alternateBy similarity
Modified residuei1081 – 10811PhosphoserineCombined sources
Modified residuei1084 – 10841PhosphoserineCombined sources
Modified residuei1089 – 10891PhosphothreonineCombined sources
Modified residuei1301 – 13011PhosphoserineCombined sources
Modified residuei1338 – 13381PhosphoserineCombined sources
Modified residuei1372 – 13721N6-acetyllysineBy similarity
Modified residuei1459 – 14591PhosphoserineCombined sources
Modified residuei1533 – 15331PhosphoserineCombined sources
Modified residuei1538 – 15381N6-acetyllysineBy similarity
Modified residuei1630 – 16301PhosphoserineCombined sources
Modified residuei1734 – 17341PhosphoserineCombined sources
Modified residuei1835 – 18351PhosphoserineCombined sources
Modified residuei1967 – 19671PhosphoserineCombined sources
Modified residuei2053 – 20531PhosphoserineCombined sources
Modified residuei2128 – 21281PhosphoserineCombined sources
Modified residuei2152 – 21521PhosphoserineCombined sources2 Publications
Modified residuei2158 – 21581PhosphoserineCombined sources
Modified residuei2163 – 21631PhosphoserineCombined sources
Modified residuei2180 – 21801PhosphoserineBy similarity
Modified residuei2284 – 22841PhosphoserineCombined sources
Modified residuei2327 – 23271PhosphoserineCombined sources
Modified residuei2329 – 23291PhosphoserineBy similarity
Modified residuei2336 – 23361PhosphothreonineCombined sources1 Publication
Modified residuei2338 – 23381PhosphoserineCombined sources
Modified residuei2370 – 23701PhosphoserineBy similarity
Modified residuei2414 – 24141PhosphoserineCombined sources
Modified residuei2510 – 25101PhosphoserineCombined sources
Modified residuei2523 – 25231PhosphoserineBy similarity
Modified residuei2526 – 25261PhosphoserineBy similarity
Modified residuei2569 – 25691N6-acetyllysine; alternateBy similarity
Modified residuei2569 – 25691N6-succinyllysine; alternateBy similarity
Modified residuei2575 – 25751N6-acetyllysineBy similarity
Modified residuei2599 – 25991PhosphothreonineBy similarity
Modified residuei2607 – 26071N6-acetyllysineCombined sources
Modified residuei2621 – 26211N6-acetyllysineCombined sources

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei1761 – 17622Cleavage; by calpain

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP21333.
MaxQBiP21333.
PaxDbiP21333.
PeptideAtlasiP21333.
PRIDEiP21333.

2D gel databases

OGPiP21333.

PTM databases

iPTMnetiP21333.
PhosphoSiteiP21333.
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).By similarity17 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
  • glycoprotein 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 interactions.
DIPiDIP-1136N.
IntActiP21333. 211 interactions.
MINTiMINT-118283.
STRINGi9606.ENSP00000358866.

Structurei

Secondary structure

1
2647
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi40 – 434Combined sources
Helixi44 – 5714Combined sources
Helixi58 – 603Combined sources
Turni67 – 737Combined sources
Helixi75 – 8511Combined sources
Helixi100 – 11617Combined sources
Helixi126 – 1305Combined sources
Helixi134 – 14916Combined sources
Beta strandi157 – 1593Combined sources
Helixi168 – 17912Combined sources
Beta strandi181 – 1833Combined sources
Helixi190 – 1923Combined sources
Beta strandi193 – 1953Combined sources
Helixi196 – 20510Combined sources
Helixi213 – 2153Combined sources
Helixi221 – 23616Combined sources
Helixi244 – 2474Combined sources
Helixi254 – 2618Combined sources
Helixi263 – 2664Combined sources
Helixi480 – 4823Combined sources
Beta strandi484 – 4874Combined sources
Helixi488 – 4903Combined sources
Beta strandi501 – 5066Combined sources
Beta strandi515 – 5217Combined sources
Beta strandi529 – 5346Combined sources
Beta strandi537 – 5426Combined sources
Beta strandi548 – 5569Combined sources
Beta strandi565 – 5717Combined sources
Beta strandi579 – 5835Combined sources
Helixi584 – 5863Combined sources
Beta strandi588 – 5903Combined sources
Beta strandi595 – 60410Combined sources
Beta strandi609 – 6179Combined sources
Beta strandi620 – 6256Combined sources
Beta strandi627 – 63610Combined sources
Beta strandi639 – 64911Combined sources
Beta strandi658 – 6647Combined sources
Helixi672 – 6743Combined sources
Beta strandi676 – 6794Combined sources
Helixi680 – 6823Combined sources
Beta strandi683 – 6853Combined sources
Beta strandi693 – 6986Combined sources
Beta strandi707 – 7126Combined sources
Beta strandi714 – 7163Combined sources
Beta strandi721 – 7255Combined sources
Beta strandi727 – 7359Combined sources
Beta strandi739 – 74911Combined sources
Beta strandi758 – 7625Combined sources
Helixi1160 – 11623Combined sources
Beta strandi1164 – 11674Combined sources
Helixi1168 – 11703Combined sources
Beta strandi1172 – 11743Combined sources
Beta strandi1179 – 11846Combined sources
Beta strandi1193 – 11986Combined sources
Beta strandi1206 – 12116Combined sources
Beta strandi1213 – 122210Combined sources
Beta strandi1225 – 123511Combined sources
Beta strandi1244 – 12507Combined sources
Turni1785 – 17873Combined sources
Beta strandi1791 – 17966Combined sources
Beta strandi1804 – 18096Combined sources
Beta strandi1819 – 18224Combined sources
Beta strandi1824 – 18329Combined sources
Beta strandi1838 – 18469Combined sources
Beta strandi1855 – 18606Combined sources
Beta strandi1865 – 18673Combined sources
Beta strandi1869 – 18724Combined sources
Helixi1873 – 18753Combined sources
Beta strandi1877 – 18793Combined sources
Beta strandi1884 – 18896Combined sources
Turni1891 – 18933Combined sources
Beta strandi1895 – 190612Combined sources
Beta strandi1909 – 19146Combined sources
Beta strandi1916 – 192510Combined sources
Beta strandi1930 – 19389Combined sources
Beta strandi1947 – 19537Combined sources
Beta strandi1959 – 19679Combined sources
Beta strandi1980 – 19889Combined sources
Beta strandi1998 – 20014Combined sources
Beta strandi2007 – 20104Combined sources
Beta strandi2014 – 202512Combined sources
Beta strandi2034 – 20396Combined sources
Helixi2041 – 20433Combined sources
Helixi2047 – 20493Combined sources
Beta strandi2051 – 20544Combined sources
Helixi2055 – 20573Combined sources
Beta strandi2059 – 20613Combined sources
Beta strandi2066 – 20716Combined sources
Beta strandi2075 – 20773Combined sources
Beta strandi2080 – 20889Combined sources
Beta strandi2091 – 20966Combined sources
Beta strandi2100 – 21078Combined sources
Beta strandi2112 – 21209Combined sources
Beta strandi2129 – 21368Combined sources
Beta strandi2139 – 214810Combined sources
Beta strandi2161 – 21655Combined sources
Helixi2171 – 21733Combined sources
Beta strandi2174 – 21796Combined sources
Beta strandi2185 – 21873Combined sources
Beta strandi2189 – 21924Combined sources
Beta strandi2194 – 22018Combined sources
Beta strandi2208 – 22169Combined sources
Beta strandi2225 – 22295Combined sources
Beta strandi2234 – 22363Combined sources
Helixi2238 – 22403Combined sources
Beta strandi2242 – 22454Combined sources
Helixi2246 – 22483Combined sources
Beta strandi2257 – 22626Combined sources
Helixi2264 – 22663Combined sources
Beta strandi2271 – 22799Combined sources
Beta strandi2282 – 22876Combined sources
Beta strandi2293 – 22986Combined sources
Beta strandi2303 – 23119Combined sources
Beta strandi2320 – 23267Combined sources
Turni2429 – 24313Combined sources
Beta strandi2433 – 24364Combined sources
Helixi2437 – 24393Combined sources
Beta strandi2441 – 24433Combined sources
Beta strandi2448 – 24536Combined sources
Turni2455 – 24573Combined sources
Beta strandi2462 – 24709Combined sources
Beta strandi2472 – 24798Combined sources
Beta strandi2482 – 24898Combined sources
Beta strandi2491 – 250616Combined sources
Beta strandi2511 – 25188Combined sources
Beta strandi2561 – 25644Combined sources
Helixi2565 – 25673Combined sources
Beta strandi2576 – 25816Combined sources
Beta strandi2590 – 25956Combined sources
Beta strandi2597 – 25993Combined sources
Beta strandi2602 – 26109Combined sources
Beta strandi2613 – 26197Combined sources
Beta strandi2624 – 26329Combined sources
Beta strandi2641 – 26466Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 39-374, 478-766, 1044-1643, 1772-2329, 2331-2522, 2559-2647.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21333.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 274273Actin-bindingAdd
BLAST
Domaini43 – 149107CH 1PROSITE-ProRule annotationAdd
BLAST
Domaini166 – 266101CH 2PROSITE-ProRule annotationAdd
BLAST
Repeati276 – 37499Filamin 1Add
BLAST
Repeati376 – 47499Filamin 2Add
BLAST
Repeati475 – 57096Filamin 3Add
BLAST
Repeati571 – 66393Filamin 4Add
BLAST
Repeati667 – 76397Filamin 5Add
BLAST
Repeati764 – 866103Filamin 6Add
BLAST
Repeati867 – 96599Filamin 7Add
BLAST
Repeati966 – 106196Filamin 8Add
BLAST
Repeati1062 – 115493Filamin 9Add
BLAST
Repeati1155 – 124995Filamin 10Add
BLAST
Repeati1250 – 1349100Filamin 11Add
BLAST
Repeati1350 – 144293Filamin 12Add
BLAST
Repeati1443 – 153997Filamin 13Add
BLAST
Repeati1540 – 163697Filamin 14Add
BLAST
Repeati1649 – 174092Filamin 15Add
BLAST
Repeati1779 – 186082Filamin 16Add
BLAST
Repeati1861 – 195090Filamin 17Add
BLAST
Repeati1951 – 203989Filamin 18Add
BLAST
Repeati2042 – 213190Filamin 19Add
BLAST
Repeati2132 – 223099Filamin 20Add
BLAST
Repeati2233 – 232593Filamin 21Add
BLAST
Repeati2327 – 242094Filamin 22Add
BLAST
Repeati2424 – 251693Filamin 23Add
BLAST
Repeati2552 – 264695Filamin 24Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1490 – 1607118Interaction with furinBy similarityAdd
BLAST
Regioni1741 – 177838Hinge 1Add
BLAST
Regioni2517 – 2647131Self-association site, tailAdd
BLAST
Regioni2517 – 255135Hinge 2Add
BLAST

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

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
211