Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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actinin alpha 1(ACTN1) actinin alpha 1(ACTN1) Related Genes Homo sapiens
CHROMOSOME 14,
CYTOBAND 14q24.1-q24.2, 14q24.1-q24.2|14q24|14q22-q24,
ENSEMBL_GENE_ID ENSG00000072110,
GENERIF_SUMMARY Identification of a 31 kD amino-terminal fragment of alpha-actinin protein, named mactinin, that promotes monocyte/macrophage maturation in vitro., the focal adhesion component alpha-actinin interacts with syndecan-4 in a beta-integrin-independent manner, an alpha-actinin-dependent association between the actin cytoskeleton and A2AR trafficking, the dynamics of alpha-actinin are important for PI 3-kinase-induced reorganization of the actin cytoskeleton, GluR4 may regulate its synaptic targeting through phosphorylation-dependent interactions with alpha-Actinin-1 and IQGAP1, S1P-induced recruitment of S1P1 to CEM fractions promotes PI3 kinase-mediated Tiam1/Rac1 activation required for alpha-actinin-1/4-regulated cortical actin rearrangement and EC barrier enhancement, Results show that the interaction between two species with weak affinity in solution, such as vinculin and alpha-actinin, can be visualized in a membrane-like environment., Alpha-actinin plays a role in regulating cell survival through stabilization of focal adhesions and regulation of TNF-alpha-induced survival signaling., Results show that the interaction between ICAM-5 and alpha-actinin is mediated through binding of positively charged amino acids near the transmembrane domain of ICAM-5, and this interaction may play an important role in neuronal differentiation., Interaction of alpha 1 actinin with ICAM-1 is required for leukocyte extravasation., Molecular dynamics method was applied to investigate the mechanical behaviour of the human skeletal muscle alpha-actinin., there is an alpha-actinin-1-dependent mGlu(5b) receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning, ACT1 is de-expressed in endometriosis and endometrioid carcinoma compared with normal uterine epithelium., Alpha-actinin-1 phosphorylation at Y12 plays a crucial role in pressure-activated cell adhesion and mechanotransduction by facilitating Src recruitment to beta(1)-integrin, and consequently the association of focal adhesion kinase with Src., Taken together, alpha-actinin not only attaches TRPP3 to the cytoskeleton but also up-regulates TRPP3 channel function., study examines the mechanism by which phosphoinositide binding regulates alpha-actinin function, A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three organs and may represent general cancer-related splicing events., alpha-actinin-1 may play a role in human glomerular disease, two sm-titin Zq domains interact with each other and with the two R2-R3 sites in the alpha-actinin central rod, interaction of GNE with alpha-actinin 1 might point to its involvement in alpha-actinin mediated processes, ICAM-2 mediates suppression of metastatic phenotype and the interaction of ICAM-2/alpha-actinin/actin represents the first complete membrane-linker protein-actin linkage to impact tumor cell motility in vitro and metastatic potential in an in vivo model., Data describe alterations of myocardial intercellular and cell-matrix contacts in hypertrophic tissue, and show intracellular translocation of beta-catenin, alpha-actinin and chondroitin sulfate proteoglycan 6 in both an animal model and in LVH patients., Mactinin is a novel inducer of Hsp90 activity on monocytes and may serve to perpetuate and augment monocytic activation., cathepsin X overexpression reduced LFA-1 clustering and induced an intermediate affinity LFA-1 conformation that is known to associate with alpha-actinin-1., Both alpha-actinin-1 and alpha-actinin-4 make critical and distinct contributions to cytoskeletal organization, rigidity-sensing, and motility of glioma cells., Alpha-actinin 1 and 4 are differentially regulated during the development and progression of astrocytomas because each of these isoforms uniquely contributes to distinct malignant properties of astrocytoma cells., The results suggest that the interaction between HAMLET and alpha-actinins promotes tumor cell detachment., Actinin-1 and cortactin showed matrix-contact-side localization in adenocarcinoma cells., The C-terminal polybasic region of CYTH2 participates in interacting directly with the EFh2 domain of ACTN1., The alpha-actinin/EWI motif-containing protein 2 (EWI-2) complex is involved in regulation of the actin cytoskeleton at T cell immune and virological synapses, providing a link between membrane microdomains and structures involved in T cell recognition., Loss of dorsal stress fibers either by depleting alpha-actinin-1 or Rac1 results in a beta-actin accumulation at the leading edge in migrating and spreading cells., Alpha actinin 1, a cytoskeleton protein implicated in inflammatory/degenerative autoimmune diseases, might be regarded as a novel multiple sclerosis autoantigen., Transduction of mouse fetal liver-derived megakaryocytes with disease-associated ACTN1 variants caused a disorganized actin-based cytoskeleton in megakaryocytes., The tyrosine phosphorylation of alpha-actinin1 at Y12 and alpha-actinin4 at Y265 is critical for dorsal stress fiber establishment, transverse arc maintenance and focal adhesion maturation., Actinin-alpha1 readily forms heterodimers composed of monomers that may have different properties and interacting proteins, altering our view of non-muscle actinin, thus altering our view of non-muscle actinin function., We conclude that alpha-actinin stabilizes Ca(V)1.2 at the plasma membrane and that its displacement by calcium-calmodulin triggers calcium-induced endocytosis of Ca(V)1.2, thus providing an important negative feedback mechanism for calcium influx., A missense mutation in the alpha-actinin 1 gene (ACTN1) is the cause of autosomal dominant macrothrombocytopenia in a large French family., ACTN1-related thrombocytopenia is characterized by mild course with platelet macrocytosis and low risk for bleeding., ArgBP2 interaction with alpha-actinin and actin stress fibers inhibits cell migration, ACTN1 determines the motility of keratinocytes by regulating the organization of the actin cytoskeleton, focal adhesion, and hemidesmosome proteins complexes, thereby modulating cell speed, lamellipodial dynamics, and directed migration, Data indicate that alpha-actinin (110 kDa) autoantibody was characterized as a major target in lupus nephritis (LN) patients positive for Anti-membrane autoantibodies (MbA)., Host cortactin, PKD1 and actin are recruited by Trypanosoma cruzi extracellular amastigotes based on experiments in fixed and live cells by time lapse confocal microscopy., Drp1 is in dynamic equilibrium on mitochondria in a fission-independent manner, and that fission factors such as actin filaments target productive oligomerization to fission sites., The authors show that the microtubule binding protein EB1 (end-binding protein 1), a key regulator of microtubule dynamics, can bind directly to filamentous actin (F-actin) F-actin., Several dominantly inherited congenital macrothrombocytopenia-associated mutations that are located within the actinin-1 actin-binding domain cause increased binding of actinin-1 to actin filaments and enhance filament bundling in vitro.,
OFFICIAL_GENE_SYMBOL ACTN1,
OMIM_DISEASE Bleeding disorder, platelet-type, 15,
SP_COMMENT function:F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein., similarity:Belongs to the alpha-actinin family., similarity:Contains 1 actin-binding domain., similarity:Contains 2 CH (calponin-homology) domains., similarity:Contains 2 EF-hand domains., similarity:Contains 4 spectrin repeats., subcellular location:Colocalizes with MYOZ2 and PPP3CA at the Z-line of heart and skeletal muscle., subunit:Homodimer; antiparallel. Interacts with DDN, MYOZ2, PDLIM2, TTID and LPP.,
actinin alpha 2(ACTN2) actinin alpha 2(ACTN2) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1q42-q43,
ENSEMBL_GENE_ID ENSG00000077522,
GENERIF_SUMMARY Spectrin-like repeats from dystrophin and alpha-actinin-2 are not functionally interchangeable., Association of Ca2+-activated K+ channel with alpha-actinin2 localizes channel to entry of external Ca(2+) source, which regulates channel function., actinin-2 participate in sequestering parafibromin in the cytoplasmic compartment., ACTN2 expression is affected by the content of alpha-actinin-3., demonstrate that proper membrane localization of a small-conductance Ca(2+)-activated K(+) channel (SK2 or K(Ca)2.2) is dependent on its interacting protein, alpha-actinin2, a major F-actin crosslinking protein., BPAG1-b was detectable in vitro and in vivo as a high molecular mass protein in striated and heart muscle cells, co-localizing with alpha-actinin-2 and partially with the cytolinker plectin as well as with the intermediate filament protein desmin., This is the first genome-wide linkage analysis that shows mutations in ACTN2 cause HCM, This study generated the genomic sequences of K88-positive and F18-positive porcine enteroteoxigenic E. coli (ETEC) strains and examined the phylogenetic distribution of clinical porcine ETEC strains and their plasmid-associated genetic content., data provide functional evidence that the primary sequences of alpha-actinin-2 and alpha-actinin-3 evolved differences to optimize their functions, Findigs show that the F-actin-binding protein alpha-actinin-2 targets CaMKIIalpha to F-actin in cells by binding to the CaMKII regulatory domain., study strengthens the hypothesis that ACTN2 influences caries risk., The novel heterozygous missense sequence variant ACTN2 cosegregated with a complex cardiomyopathic trait, characterized by the interplay of midapical, nonobstructive HCM, early onset of AF and AV block, as well as regional LV noncompaction., Clinical evaluation of an Australian family revealed diverse cardiac pathologies in four affected members and genetic testing of the exome identified a pathogenic ACTN2 heterozygous variant (Ala119Thr) that co-segregated with disease., Study reports a complete high-resolution structure of the 200 kDa alpha-actinin-2 dimer from striated muscle and explore its functional implications on the biochemical and cellular level.,
OFFICIAL_GENE_SYMBOL ACTN2,
OMIM_DISEASE Cardiomyopathy, dilated, 1AA, with or without LVNC, Cardiomyopathy, hypertrophic, 23, with or without LVNC,
SP_COMMENT disease:Defects in ACTN2 are the cause of cardiomyopathy dilated type 1AA (CMD1AA) [MIM:612158]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death., function:F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein., similarity:Belongs to the alpha-actinin family., similarity:Contains 1 actin-binding domain., similarity:Contains 2 CH (calponin-homology) domains., similarity:Contains 2 EF-hand domains., similarity:Contains 4 spectrin repeats., subcellular location:Colocalizes with MYOZ1 and FLNC at the Z-lines of skeletal muscle., subunit:Homodimer; antiparallel. Also forms heterodimers with ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C-terminal region with the LDB3 PDZ domain. Interacts with XIRP2., tissue specificity:Expressed in both skeletal and cardiac muscle.,
actinin alpha 3 (gene/pseudogene)(ACTN3) actinin alpha 3 (gene/pseudogene)(ACTN3) Related Genes Homo sapiens
CHROMOSOME 11,
CYTOBAND 11q13.1,
ENSEMBL_GENE_ID ENSG00000248746,
GENERIF_SUMMARY REIVIEW, ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise., Data report the crystal structure of the actin binding domain of human muscle alpha-actinin-3, which is formed by two consecutive calponin homology domains arranged in a "closed" conformation., Subjects possessing the ACTN3-deficient genotype (XX) had lower baseline CK compared with the heterozygotes (P = 0.035)., We determined mitochondrial DNA (mtDNA) and ACTN3 genotypes in Finnish elite endurance (n = 52) and sprint (n = 89) athletes, and found that the frequencies of mtDNA haplogroups differed significantly between the two groups, In a study of adolescent Greeks there is a significant association between the ACTN3 R577X polymorphism and 40 m sprint time in males that accounts for phenotypic variance, with the 577R allele contributing to faster times in an additive manner., the ACTN3 R577X polymorphism influences the response of quadriceps muscle power to strength training in older adults, In women with McArdle's disease, ACTN3 genotypes might partly explain the large individual variability that exists in the phenotypic manifestation of this disorder, the R577X polymorphism within the ACTN3 gene was not associated with ultra-endurance performance in the 2000 and 2001 South African Ironman Triathlons, The mechanism by which the ACTN3 polymorphism has its effect on muscle power, relies on a control function of fiber type proportions., alpha-actinin-3 deficiency is not a major influence on performance in African athletes, results indicate that the ACTN3 R577X nonsense allele (X) is under-represented in elite strength athletes, consistent with previous reports indicating that alpha-actinin-3 deficiency appears to impair muscle performance, ACTN3 R577X polymorphism was associated with power athlete status in Russians., the shift towards more efficient aerobic muscle metabolism associated with alpha-actinin-3 deficiency also underlies the adaptive benefit of the 577X allele, in world-class cyclists, we only found an association between ACTN3 genotypes and ventilatory threshold and peak power output, and between ACTN3/ACE genotype combinations and respiratory compensation threshold, Knee extensor functional and contractile properties, including high-velocity strength, were not influenced by ACE and ACTN3 polymorphisms in a cohort of United Kingdom Caucasian males., actinin-3 participate in sequestering parafibromin in the cytoplasmic compartment, data suggest that alpha-actinin-3 deficiency may negatively influence sports performance in Russian endurance athletes., ACTN3 genotype is associated with muscle phenotypes in women across the adult age span., The authors observed that Opc-expressing bacteria interacted with a 100 kDa protein in whole-cell lysates of human endothelial and epithelial cells. The identity of the protein was established as alpha-actinin by mass spectrometry., The ACTN3 polymorphism may influence declines in certain measures of physical performance with aging but the influence of the ACTN3 R577X polymorphism does not appear to have a strong effect on skeletal muscle-related phenotypes., ACTN3 genotype may modulate responsiveness to exercise training., Association between the ACTN3 R577X polymorphism and artistic gymnastic performance in Italy is reported., the ACTN3 R allele is associated with top-level sprint performance and the X allele and XX genotypes may not be critical but rather additive to endurance performance, The main finding of our study was that the ACTN3 R577X polymorphism does not seem to influence the ability to produce peak (explosive) power in nonathletic, young adults of both genders., sprinter performance is determined by the interaction between the wild-type HIF1A Pro/Pro genotype and ACTN3 RR genotype, ACTN3 XX genotype is negatively associated with elite sprint athlete status, the underlying low frequency in these populations eliminates the possibility of replicating this association in Jamaican and US African American sprinters., data suggest that ACE ID/ ACTN3 R577X genotype combination is associated with sprint ability. However, ACE ID/ ACTN3 R577X genotype combination is not related to the level of performance, ACTN3 R/X polymorphisms were not associated with muscle function or muscularity phenotypes in older Caucasian men., We propose that the alteration in GPh activity in the absence of alpha-actinin-3 is a fundamental mechanistic link in the association between ACTN3 genotype and human performance., The researchers found no significant evidence that genetic polymorphisms, such as ACTN3, significantly influence muscle phenotypes in a group of nonagenarians., The results show that ACTN3 R577X polymorphism influences the size of the thigh muscles of older women., Study suggests a protective role of alpha-actinin-3 protein in muscle damage after eccentric training and an improved stress-sensor signaling, although effects are small., Examined the association of R577X polymorphism (rs1815739) in the alpha-actinin-3 (ACTN3) gene with "explosive" leg muscle power performance. Findings suggest that the ACTN3 R577X polymorphism does not influence explosive leg muscle power., The presence of alpha-actinin-3 protein is associated with improved sprint/power performance in athletes and the general population--REVIEW, Though the ACE I/D polymorphism is a strong candidate to modulate some exercise-related phenotypes, alone or in combination with the ACTN3 R577X polymorphism, does not seem to exert a major influence in the muscle power, as assessed during exercise tests., in recreationally active individuals, the ACTN3 R577X polymorphism is not associated with muscle performance phenotypes, supporting recent findings that R577X may only be important for predicting performance in elite athletes, In conclusion, our findings indicate that ACTN3 R577X and other SNPs in ACTN3 are not genetic determinants of endurance performance in Caucasian males., results indicated that ACTN3 R577X polymorphism was associated with endurance performance in female athletes but not male athletes in China, functional ACTN3 R577X genotype represents a genetic risk factor for falling in older females., Examined the association between ACE I/D and ACTN3 R577X polymorphisms and muscle-related phenotypes and their adaptation to resistance training in older women. Results suggest these genetic variations may interact to determine muscle mass in older women., ACTN3 was found to have bimodal expression in human skeletal muscle tissue., the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes., the frequencies of ACTN3 577R allele were significantly higher in female international sprint swimmers than among national sprint swimmers or the general population, An association between ACTN3 R577X polymorphism and smaller thigh-muscle cross-sectional area in a group of elderly women but not in a group of middle-aged women., The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population., ACTN3 likely contributes to the regulation of bone mass through alterations in bone turnover., Professional soccer athletes homozygous to ACTN3XX gene are more susceptible to eccentric damage and present a higher catabolic state, demonstrated by metabolic, hormonal and immune responses post an eccentric training., ACTN3 R577X polymorphism is associated with preferred racing distance in speed skaters and muscle fibre type composition., The oxidative enzyme activity of fast muscle fibres was not associated with ACTN3 genotype, Lithuanian athletes who are carriers of the ACE I/I and I/D as well as ACTN3 X/X and R/X genotypes have the potential to achieve better results in power-requiring sports., ACE I/D and ACTN3 R577X polymorphisms are candidates to modulate exercise-related phenotypes in adults, our data suggest that they do not exert a major influence in the muscle phenotypes of old people., Relationships between ACTN3 genotypes and power or body composition-related phenotypes were not significant., The results indicated that the ACTN3 R577X polymorphism is most strongly associated with grip strength in young Chinese male soldiers. A strong association between the ACTN3 R577X genotypes and sprint or endurance phenotypes was not observed., relationships between polymorphisms of the ACE, ACTN3, PPARD, and PPARGC1A genes and performance as measured by six fitness tests in sedentary adolescent girls, data provide functional evidence that the primary sequences of alpha-actinin-2 and alpha-actinin-3 evolved differences to optimize their functions, the ACTN3 577X allele seemed to increase the risk of developing idiopathic inflammatory myopathies, although this was not related to severity of expression of the phenotype., An interaction of two polymorphisms (ACE and ACTN-3) might be able to discriminate quantitative traits crucial for the elite soccer performance, however the contribution of genetic factors to soccer performance is not so high., ACE I/D and ACTN3 R/X polymorphisms are likely factors in modulating exercise-related phenotypes in older women, particularly in response to a resistance training stimuli., The data indicated that ACTN3 polymorphisms were related to athletic performance in Japanese wrestlers., study compared impact of, and recovery from, muscle-damaging eccentric exercise on subjects with or without functional ACTN3 - homozygous for R or X alleles; ACTN3 genotype does not influence the observed repeated-bout effect; but XX homozygotes recover baseline voluntary torque values faster, Data provide comprehensive support for the influence of the ACTN3 R577X polymorphism on elite athletic performance., The ACTN3 R allele was associated with high results of performance tests., Our data suggest that the combination of ACTN3 and ACE gene polymorphisms is associated with the athletic status of Japanese elite wrestlers., ACTN3 alone does not influence endurance performance in triathletes., Genotype for ACTN3 is associated with contractile properties in human muscle fibers., ACTN3 p.R577X genotype was not significantly associated with swimmer status in these samples., The contribution of genetics to sports-related phenotype traits is undeniable with some genotypes, of which ACTN3 R577X is currently the leading candidate, partly distinguishing individuals predisposed to either endurance or power sports., results provide more solid evidence for the associations between ACE II genotype and endurance events and between ACTN3 R allele and power events, results suggest that environmental variables related to latitudinal variation, such as species richness and mean annual temperature, may have influenced the adaptive evolution of ACTN3 577XX during recent human history, We show that the ACTN3 R577X polymorphism is associated with human muscle volume and influences maximal isoinertial strength (1-RM) and maximum power (Wmax)., R577X polymorphism is not associated with team-sport athletic status, compared to endurance athletes and non-athletic controls., Soccer players of genotype ACTN3/RR are the fastest in short distances and present higher jump potential. ACTN3/XX individuals presented the highest aerobic capacity., Report favourable allelic patterns of ACTN3 and CNTF genes on aerobic performance in athletes., Presently, the ACTN3 R577X polymorphism has provided the most consistent results, being the only muscle gene to show an elite power performance association across multiple athlete cohorts., ACTN3 R577X is associated with explosive muscle performance and this phenotype is important in the sport of basketball but the authors found no association with leg explosive power in elite basket players or with the status of being this type of athlete., ACTN3 R577X genotype is associated with sprint/power performance in elite Japanese track and fi eld athletes, especially short sprint performance., Alpinists show significantly higher frequencies of X allele compared to controls., A mechanistic explanation for the effects of the ACTN3 genotype on skeletal muscle performance in elite athletes, No significant differences of R577X polymorphism of ACTN3 gene were observed between the four ethnic groups employed in the Indian Army that requires high levels of physical fitness., ACTN3 R577X polymorphism is a candidate in the modulation of exercise-related gait speed phenotype in older women., These results suggest that the ACTN3 R allele is associated with the relative peak power during the Wingate anaerobic test in male Japanese collegiate athletes., erythropoietin (EPO T --> G) and alpha-actinin-3 (ACTN3 R577X) polymorphisms have roles in nutrigenomic effects on athletes' performance, specifically antioxidant supplementation based on pequi oil, The study showed that ACTN3 and ACE gene polymorphisms have an effect on muscle power., Glycogen utilization during sprint exercise varied across ACTN3 genotypes in type II fibers but not in type I fibers., R577X polymorphism in the ACTN3 gene was independently associated with worse survival in patients with chronic heart failure., These results suggest that factors associated with the ACTN3 XX genotype in canoe and kayak paddlers might provide some competitive advantage in performance at 1000 m, but it seems to limit at 200 m., ACTN3 577XX is overrepresented in skeletal Class II malocclusion; suggests biologic influence during bone growth. ACTN3 577XX is underrepresented in deepbite malocclusion; suggests muscle differences contribute to variations in vertical facial dimensions., These results suggest that the ACTN3 gene may play a significant role in determining muscle phenotypes. However, this gene is only one of many factors which could contribute to athletes' performance and muscle phenotypes., ACTN3 R577X polymorphism modulates VO2 of a homogeneous untrained population, by differentiating VO2rep and VO2peak in XX genotype carriers, who may display higher aerobic capacity., fatigue-resistant muscle fibers with leaky SR would contribute to non-shivering thermogenesis, providing a tentative explanation for the evolutionary advantage of carrying the ACTN3 577xx gene in a cold climate., changes in Ca2+ handling in the absence of alpha-actinin-3 are consistent with cold acclimatisation , and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments ., The ACTN3 R577X is associated with acute ankle sprains in this study., This suggests that the ACTN3 gene has a greater impact on determining dynamic movements than influencing static muscle strength., This study aimed at determining the influence of the ACTN3 R577X polymorphism on muscle strength and muscle endurance in non-athletic young men, Our results suggest that the ACTN3 R577X genotype is associated with lower-extremity muscle function in the Japanese population., Authors present a simple and cost-efficient method to genotype the ACTN3 r577x polymorphism by a single PCR., The present study provides novel findings associating the ACTN3 R577X polymorphism with physiological variables that are connected to endurance performance., The ACTN3 R577X polymorphism is associated with cardiometabolic fitness in healthy young adults., F-actin and cell-matrix adhesions differently affect membrane dynamics and cell migration., New insights that have been made in understanding the molecular mechanisms that underlie the consequences of alpha-actinin-3 deficiency.,
OFFICIAL_GENE_SYMBOL ACTN3,
OMIM_DISEASE Alpha-actinin-3 deficiency, Sprinting performance,
SP_COMMENT function:F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein., polymorphism:About 18% of the world population lack a functional ACTN3 due to a stop codon polymorphism at position 577. The absence of a functional ACTN3 expression is not correlated with a disease state., sequence caution:According to the human genome assembly there is a stop codon in position 577 which is only found in 18% of the world population., similarity:Belongs to the alpha-actinin family., similarity:Contains 1 actin-binding domain., similarity:Contains 2 CH (calponin-homology) domains., similarity:Contains 2 EF-hand domains., similarity:Contains 4 spectrin repeats., subunit:Homodimer; antiparallel. Also forms heterodimers with ACTN2. Interacts with MYOZ1., tissue specificity:Expressed only in a subset of type 2 skeletal muscle fibers.,
actinin alpha 4(ACTN4) actinin alpha 4(ACTN4) Related Genes Homo sapiens
CHROMOSOME 19,
CYTOBAND 19q13,
ENSEMBL_GENE_ID ENSG00000130402,
GENERIF_SUMMARY interaction with tight junction protein MAGI-1, isolated two anti-alpha-actinin-4 T cell clones from the same patient TIL and from his peripheral blood lymphocytes (PBLs) by using tetramers of soluble HLA-A2 molecules loaded with the mutated peptide, Sporadic FSGS is a heterogeneous disease, since ACTN4 and podocin genes are not found in our patients with sporadic FSGS., ACTN4 has a role promoting tumorigenicity and regulating cell motility, Actinin alpha-4 is mainly present intracellularly and is involved in cellular motility via interaction with the actin cytoskeleton, thus probably affecting the metastatic potential of tumor cells., Results suggest that humanin is a novel binding partner of the alpha-actinin-4 R1-R4 domain in podocytes., the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation, No mutations detected in Japanese congenital nephrotic synddrome patients., ACTN4 mutations accounts for about 3.5% of familial focal glomerulosclerosis., Interaction of alpha 4 actinin with ICAM-1 is required for leukocyte extravasation., The role of ACTN4 in MEF2A transcription via HDAC7 antagonism is reported., A critical regulator of AKT1 localization and function., Cytokine activation of MAPK14 and apoptosis is opposed by ACTN4 targeting of protein phosphatase 2A for site-specific dephosphorylation of MEK3., actinin-4...could be a novel prognostic indicator for patients with ovarian carcinomas., exposure of a buried actin-binding site 1 in mutant alpha-actinin-4 causes an increase in its actin-binding affinity, common variants in LRRC7, KIRREL, NPHS2 and ACTN4 do not appeear to contribute to susceptibility to diabetic nephropathy in Finnish patients with type 1 diabetes, Crystal structure of the actin-binding domain of alpha-actininin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis., eNOS activity in vascular endothelial cells is tonically and dynamically regulated by competitive interaction with alpha-actinin-4 and calmodulin., alpha-actinin-4 is important for the NF-kappaB nuclear translocation and its functions inside the nucleus., Motility-related ACTN4 is associated with advanced and metastatic ovarian carcinoma., A novel ACTN4 mutation, p.Ser262Phe, was detected in the patients, and their father was found to have a germline mosaicism for the mutation in these patients with familial focal segmental glomerulosclerosis, low expression levels of alpha-actinin-4 mRNA and protein are linked to the progression of glomerulopathy and proteinuria in human diabetic nephropathy, Actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus., Mutations and single nucleotide polymorphisms of the ACTN4 gene may be associated with Chinese idiopathic focal segmental glomerulosclerosis., The actinin-4 gene may serve as a predictor of poor outcome and tumor chemoresistance in patients with advanced-stage ovarian cancers., Mutations in ACTN4, the gene encoding the actin-binding protein alpha-actinin-4, are a cause of focal segmental glomerulosclerosis., Heterozygous mutations in the promoters of the ACTN4 and SYNPO genes are found in patients with idiopathic focal segmental glomerulosclerosis., Data show that actinin-4 expression levels significantly correlate with worse survival after PDAC resection., expression of alpha-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential., EGF regulates the actin binding activity of ACTN4 by inducing tyrosyl-directed phosphorylation, The absence of mutations of ACTN4 in this study suggests that there are other genetic causes of steroid-resistant nephrotic syndrome, Both alpha-actinin-1 and alpha-actinin-4 make critical and distinct contributions to cytoskeletal organization, rigidity-sensing, and motility of glioma cells., Alpha-actinin 1 and 4 are differentially regulated during the development and progression of astrocytomas because each of these isoforms uniquely contributes to distinct malignant properties of astrocytoma cells., The association of ACTN4 with different ribonucleoproteins suggests that a major function of nuclear ACTN4 may be regulation of mRNA metabolism and signaling., Levels of eEF1A2 and alpha-actinin-4 mRNA appeared to be unrelated to breast tumour size, except for a significant down-regulation of alpha-actinin-4 mRNA in T3 cases., The actin-binding protein, actinin alpha 4 (ACTN4), is a nuclear receptor coactivator that promotes proliferation of MCF-7 breast cancer cells., Epothilone B antagonizes glioma cell motility associated with reorganization of the actin-binding protein alpha-actinin 4., The results suggest that the interaction between HAMLET and alpha-actinins promotes tumor cell detachment., The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, alpha-actin4, and podocin were found to increase with the progression of diabetic nephropathy., Alpha-actinin-4 and CLP36 protein deficiencies contribute to podocyte defects in multiple human glomerulopathies, non-muscle alpha-ACTN4, HSPA5 and cytoplasmic ACTB, should be targeted in idiopathic premature ovarian failure cases, The ACTN4-ABCF2 interaction was markedly enhanced by hypotonic stimulation., In 12 of 23 ACTN4-amplified ovarian clear-cell adenocarcinomas, the better differentiated carcinoma components exhibited fewer alterations than those with poorly differentiated histology., the first link between focal segmental glomerulosclerosis-linked ACTN4 mutants and transcriptional activation by nuclear receptor such as RARalpha and peroxisome proliferator-activated receptor gamma., MTBP also inhibited ACTN4-mediated F-actin bundling., A novel ACTN4 isoform was found in human epidermoid carcinoma cells. Analysis of ACTN4 mRNA showed the presence of a splice variant that lacked the exons 2-8., Depletion of alpha-actinin but not RhoA inhibition causes microtubules-cortex associations during early mitosis, novel extended LXXLL motif that is critical for interactions with both receptors and co-activators. This motif functions more efficiently in a spliced isoform of ACTN4 than it does in the full-length protein., there is limited evidence of association of the ACTN4 gene in African-Americans with non-diabetic end-stage renal disease, these results suggest that D5(H) of high molecular weight kininogen may modulate cell adhesion and invasion together with actinin-4., In actinin-4-knockdown keratinocytes, focal contact area is increased by 25%, and hemidesmosome proteins are mislocalized., The tyrosine phosphorylation of alpha-actinin1 at Y12 and alpha-actinin4 at Y265 is critical for dorsal stress fiber establishment, transverse arc maintenance and focal adhesion maturation., the C-terminal tail of alpha-actinin-4 is essential for its function in cell migration and adhesion to substratum., Data suggest that in the nucleus, ACTN4 functions as a selective transcriptional co-activator of RelA/p65., significant correlation between actinin-4 expression and infiltrating glioma grade, Actinin-alpha4 readily forms heterodimers composed of monomers that may have different properties and interacting proteins, thus altering our view of non-muscle actinin function., Mutations of TRPC6 and ACTN4 occur in only a minor portion of Chinese familial familial focal segmental glomerulosclerosis patients., results demonstrate that monoclonal C-7 antibody exerts an inhibitory effect on endothelium-dependent vasorelaxation induced by acetylcholine and that this response may at least partially result from the inhibition of alpha-actinin 4, Data suggest that ACTN4 plays roles in breast cancer tumorigenesis via promotion of cell proliferation, metastasis, and drug resistance., Increased expression of ACTN4 is associated with invasiveness of bladder cancer., 20 exonic and intronic substitutions were found among 48 Czech FSGS/MCD patients. 2242A>G is a candidate mutation in 1 patient. In IGA nephropathy 3 new substitutions were found, Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death among 290 patients with stage I lung adenocarcinoma., Copy number increase of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma., Actinin-4, a novel interacting partner of influenza A virus nucleoprotein, plays a crucial role in viral replication., High ACTN4 expression is associated with thyroid cancer, The mRNA/protein expressions of ACTN4a was higher in the stenotic colon segment tissue than in the normal colon segment tissue of Hirschsrung disease patients., key regulator of endothelial cell stiffness and of ICAM-1-mediated neutrophil transmigration, Estrogen promotes the invasion of ovarian cancer cells via activation of the PI3K/AKT pathway, downregulation of Ecadherin and upregulation of alphaactinin4., Findings suggest that alpha-Actinin-4 (ACTN4) plays an important role in maintaining the amoeboidal morphology of invasive melanoma and thus promoting dissemination through collagen-rich matrices., Knockdown of ACTN4 protein inhibited cell invasion and migration. These results suggest that ACTN4 is associated with lung cancer cell motility., ACTN4 is a transcriptional coactivator of NF-kappaB., The copy number of ACTN4 is a predictive biomarker for Chemoradiotherapy of locally advanced pancreatic cancer., ACTN4va expression was also significantly related to distant metastasis, ZYX defective binding to ACTN4, which occupies focal adhesions instead of ACTN1, induces the formation of immature focal adhesions, resulting in the enhancement of cell motility and invasion., The contribution of ACTN4 to the process of lung cancer metastasis to the brain could be mainly through regulation of actin cytoskeleton reorganization, cell motility, and focal adhesion., Using fluorescence recovery after photobleaching, we show that an ACTN4 mutation that causes human kidney disease roughly triples the wild-type binding affinity of ACTN4 to F-actin in cells, increasing the dissociation time from 29 +/- 13 to 86 +/- 29 s., alpha-actinin-4 is a novel group 1 mGluR-interacting partner that orchestrates spine dynamics and morphogenesis in neurons., SLK interacts with Tpr and alpha-actinin-4 in cells, and these protein-protein interactions may control the subcellular localization and the biological activity of SLK., This study identified alpha-actinin-4 as a novel NHERF1 interaction partner and provided new insights into the regulatory mechanism of the actin cytoskeleton by NHERF1., Selective regulation of NF-kappaB gene targets may indicate involvement of ACTN4 in determining the specificity of cell response to NF-kappaB activation in cells of different types. (Review),
OFFICIAL_GENE_SYMBOL ACTN4,
OMIM_DISEASE Glomerulosclerosis, focal segmental, 1,
SP_COMMENT disease:Cytoplasmic localization of ACTN4 may be associated with cancer metastases due to enhanced cell motility., disease:Defects in ACTN4 are the cause of focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]. FSGS1 is a common renal lesion characterized by increased urinary protein excretion (proteinuria) and decreasing kidney function (nephrotic syndrome). Renal insufficiency often progresses to end-stage renal disease (ESRD) (also known as end-stage renal failure), a highly morbid state requiring either dialysis therapy or kidney transplantation. FSGS1 is defined by the presence of segmental sclerosis in glomeruli, and is seen in all ethnic groups, although it is particularly common in individuals of African descent. FSGS1 occurs as an isolated primary condition or secondary to disorders as HIV infection, obesity, hypertension and diabetes. FSGS1 may also be inherited as a Mendelian trait., function:F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein., sequence caution:Sequencing errors. Compared to other mammalian sequences., similarity:Belongs to the alpha-actinin family., similarity:Contains 1 actin-binding domain., similarity:Contains 2 CH (calponin-homology) domains., similarity:Contains 2 EF-hand domains., similarity:Contains 4 spectrin repeats., subcellular location:Colocalizes with actin stress fibers. Nuclear translocation can be induced by the PI3 kinase inhibitor wortmannin or by cytochalasin D. Exclusively localized in the nucleus in a limited number of cell lines (breast cancer cell line MCF7, oral floor cancer IMC2, and bladder cancer KU7)., subunit:Homodimer; antiparallel (By similarity). Binds TRIM3 at the N-terminus (By similarity). Interacts with BAIAP1 and PDLIM2., tissue specificity:Widely expressed.,