MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP001089

UniProt Annotations

Entry Information
Gene Namefilamin A, alpha
Protein EntryFLNA_HUMAN
UniProt IDP21333
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P21333-1; Sequence=Displayed; Name=2; IsoId=P21333-2; Sequence=VSP_035454; Note=No experimental confirmation available.;
CautionVariant Thr-1764 has been originally associated with periventricular nodular heterotopia. It has been subsequently reported as a benign polymorphism. {ECO:0000305|PubMed:12612583}.
DiseaseCardiac 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:0000269|PubMed:17190868}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseCongenital 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:0000269|PubMed:23037936}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseFG syndrome 2 (FGS2) [MIM:300321]: FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. {ECO:0000269|PubMed:17632775}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseFrontometaphyseal dysplasia (FMD) [MIM:305620]: Congenital bone disease characterized by supraorbital hyperostosis, deafness and digital anomalies. {ECO:0000269|PubMed:12612583, ECO:0000269|PubMed:16596676}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseIntestinal 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:0000269|PubMed:17357080}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseMelnick-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:0000269|PubMed:12612583}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNote=Defects in FLNA may be a cause of macrothrombocytopenia, a disorder characterized by subnormal levels of blood platelets. Blood platelets are abnormally enlarged.
DiseaseOtopalatodigital 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:0000269|PubMed:12612583, ECO:0000269|PubMed:15940695}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseOtopalatodigital 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:0000269|PubMed:12612583, ECO:0000269|PubMed:17431908}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseasePeriventricular 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:0000269|PubMed:11532987, ECO:0000269|PubMed:11914408, ECO:0000269|PubMed:12410386, ECO:0000269|PubMed:15249610, ECO:0000269|PubMed:16299064}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseasePeriventricular nodular heterotopia 4 (PVNH4) [MIM:300537]: A disorder characterized by nodular brain heterotopia, joint hypermobility and development of aortic dilation in early adulthood. {ECO:0000269|PubMed:15668422, ECO:0000269|PubMed:15994863}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseTerminal 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:0000269|PubMed:20598277}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainComprised 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.
FunctionPromotes 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:0000269|PubMed:22121117}.
InteractionQ9WMX2:- (xeno); NbExp=6; IntAct=EBI-350432, EBI-6863741; Q8N264:ARHGAP24; NbExp=6; IntAct=EBI-350432, EBI-988764; O95067:CCNB2; NbExp=8; IntAct=EBI-350432, EBI-375024; P46108:CRK; NbExp=3; IntAct=EBI-350432, EBI-886; O75369:FLNB; NbExp=5; IntAct=EBI-350432, EBI-352089; Q12948:FOXC1; NbExp=8; IntAct=EBI-350432, EBI-1175253; P62993:GRB2; NbExp=2; IntAct=EBI-350432, EBI-401755; P05556:ITGB1; NbExp=5; IntAct=EBI-350432, EBI-703066; P07228:ITGB1 (xeno); NbExp=2; IntAct=EBI-350432, EBI-5606437; P26010:ITGB7; NbExp=6; IntAct=EBI-350432, EBI-702932; O14786:NRP1; NbExp=2; IntAct=EBI-350432, EBI-1187100; P35372:OPRM1; NbExp=5; IntAct=EBI-350432, EBI-2624570; Q86SQ0:PHLDB2; NbExp=2; IntAct=EBI-350432, EBI-2798483;
PtmPhosphorylation extent changes in response to cell activation. {ECO:0000269|PubMed:16964243, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17924679, ECO:0000269|PubMed:18088087, ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19367720, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692}.
PtmPolyubiquitination 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. {ECO:0000269|PubMed:24052262}.
Sequence CautionSequence=BAC03408.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the filamin family. {ECO:0000305}.
SimilarityContains 1 actin-binding domain. {ECO:0000305}.
SimilarityContains 24 filamin repeats. {ECO:0000255|PROSITE- ProRule:PRU00087}.
SimilarityContains 2 CH (calponin-homology) domains. {ECO:0000255|PROSITE-ProRule:PRU00044}.
Subcellular LocationCytoplasm, cell cortex. Cytoplasm, cytoskeleton.
SubunitHomodimer. 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). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:11739414, ECO:0000269|PubMed:12393796, ECO:0000269|PubMed:16076904, ECO:0000269|PubMed:16862148, ECO:0000269|PubMed:18322202, ECO:0000269|PubMed:18556573, ECO:0000269|PubMed:19923718, ECO:0000269|PubMed:21228480, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:23890175, ECO:0000269|PubMed:9437013}.
Tissue SpecificityUbiquitous.
  logo