InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FLNA

Summary

InnateDB Protein

IDBP-91019.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FLNA

Protein Name

filamin A, alpha

Synonyms

ABP-280; ABPX; CSBS; CVD1; FLN; FLN-A; FLN1; FMD; MNS; NHBP; OPD; OPD1; OPD2; XLVD; XMVD;

Species

Homo sapiens

Ensembl Protein

ENSP00000358866

InnateDB Gene

IDBG-91003 (FLNA)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000250, ECO:0000269PubMed:22121117}.

Subcellular Localization

Cytoplasm, cell cortex. Cytoplasm, cytoskeleton.

Disease Associations

Periventricular nodular heterotopia 1 (PVNH1) [MIM:300049]: A 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. {ECO:0000269PubMed:11532987, ECO:0000269PubMed:11914408, ECO:0000269PubMed:12410386, ECO:0000269PubMed:15249610, ECO:0000269PubMed:16299064}. Note=The disease is caused by mutations affecting the gene represented in this entry.Periventricular nodular heterotopia 4 (PVNH4) [MIM:300537]: A disorder characterized by nodular brain heterotopia, joint hypermobility and development of aortic dilation in early adulthood. {ECO:0000269PubMed:15668422, ECO:0000269PubMed:15994863}. Note=The disease is caused by mutations affecting the gene represented in this entry.Otopalatodigital syndrome 1 (OPD1) [MIM:311300]: X-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. {ECO:0000269PubMed:12612583, ECO:0000269PubMed:15940695}. Note=The disease is caused by mutations affecting the gene represented in this entry.Otopalatodigital syndrome 2 (OPD2) [MIM:304120]: Congenital 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. {ECO:0000269PubMed:12612583, ECO:0000269PubMed:17431908}. Note=The disease is caused by mutations affecting the gene represented in this entry.Frontometaphyseal dysplasia (FMD) [MIM:305620]: Congenital bone disease characterized by supraorbital hyperostosis, deafness and digital anomalies. {ECO:0000269PubMed:12612583, ECO:0000269PubMed:16596676}. Note=The disease is caused by mutations affecting the gene represented in this entry.Melnick-Needles syndrome (MNS) [MIM:309350]: Severe 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. {ECO:0000269PubMed:12612583}. Note=The disease is caused by mutations affecting the gene represented in this entry.Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked (IPOX) [MIM:300048]: A 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. {ECO:0000269PubMed:17357080}. Note=The disease is caused by mutations affecting the gene represented in this entry.FG syndrome 2 (FGS2) [MIM:300321]: FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. {ECO:0000269PubMed:17632775}. Note=The disease is caused by mutations affecting the gene represented in this entry.Terminal osseous dysplasia (TOD) [MIM:300244]: A 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. {ECO:0000269PubMed:20598277}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cardiac valvular dysplasia X-linked (CVDX) [MIM:314400]: A 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. {ECO:0000269PubMed:17190868}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in FLNA may be a cause of macrothrombocytopenia, a disorder characterized by subnormal levels of blood platelets. Blood platelets are abnormally enlarged.Congenital short bowel syndrome, X-linked (CSBSX) [MIM:300048]: A 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. {ECO:0000269PubMed:23037936}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 167 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.

Experimentally validated
Total	167 [view]
Protein-Protein	165 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001948	glycoprotein binding
GO:0004871	signal transducer activity
GO:0005080	protein kinase C binding
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0017048	Rho GTPase binding
GO:0017160	Ral GTPase binding
GO:0031267	small GTPase binding
GO:0031852	mu-type opioid receptor binding
GO:0034988	Fc-gamma receptor I complex binding
GO:0042803	protein homodimerization activity
GO:0044822	poly(A) RNA binding
GO:0046332	SMAD binding
GO:0048365	Rac GTPase binding
GO:0051015	actin filament binding

Biological Process

GO:0001837	epithelial to mesenchymal transition
GO:0002576	platelet degranulation
GO:0007195	adenylate cyclase-inhibiting dopamine receptor signaling pathway
GO:0007596	blood coagulation
GO:0030036	actin cytoskeleton organization
GO:0030168	platelet activation
GO:0031532	actin cytoskeleton reorganization
GO:0034329	cell junction assembly
GO:0034394	protein localization to cell surface
GO:0042177	negative regulation of protein catabolic process
GO:0042384	cilium assembly
GO:0042789	mRNA transcription from RNA polymerase II promoter
GO:0042993	positive regulation of transcription factor import into nucleus
GO:0043113	receptor clustering
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045022	early endosome to late endosome transport
GO:0045184	establishment of protein localization
GO:0050821	protein stabilization
GO:0051220	cytoplasmic sequestering of protein
GO:0051764	actin crosslink formation
GO:0090307	spindle assembly involved in mitosis

Cellular Component

GO:0005576	extracellular region
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005802	trans-Golgi network
GO:0005829	cytosol
GO:0005884	actin filament
GO:0005886	plasma membrane
GO:0015629	actin cytoskeleton
GO:0016020	membrane
GO:0030863	cortical cytoskeleton
GO:0031523	Myb complex
GO:0043025	neuronal cell body
GO:0043198	dendritic shaft
GO:0043234	protein complex
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome
GO:0097440	apical dendrite