Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AAA domain-containing 3A (ATAD3A) is a member of the AAA-ATPase family. Three forms of ATAD3 have been identified: ATAD3A, ATAD3B and ATAD3C. In this study, we examined the type and expression of ATAD3 in lung adenocarcinoma (LADC). Expression of ATAD3A was detected by reverse transcription-polymerase chain reaction, immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy. Our results show that ATAD3A is the major form expressed in LADC. Silencing of ATAD3A expression increased mitochondrial fragmentation and cisplatin sensitivity. Serum deprivation increased ATAD3A expression and drug resistance. These results suggest that ATAD3A could be an anti-apoptotic marker in LADC.
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PMID:ATPase family AAA domain-containing 3A is a novel anti-apoptotic factor in lung adenocarcinoma cells. 2033 22

ATAD3 (ATPase family AAA domain-containing protein 3) is a mitochondrial membrane bound ATPase whose function has not yet been discovered but its role is essential for the embryonic development. The ATAD3 gene exists since the pluri-cellular organisms with specialized tissues and remains unique until vertebrates. In primates and humans, two other genes have appeared (called ATAD3B and ATAD3C versus ATAD3A the ancestral gene). ATAD3 knock down in different non-transformed cell lines is associated with drastic changes in the mitochondrial network, inhibition of proliferation and modification of the functional interactions between mitochondria and endoplasmic reticulum. However, the analysis of the functions of ATAD3A and ATAD3B in different human cancer cell lines shows on the contrary that they can have anti-proliferative effects and induce chemoresistant properties. ATAD3 may therefore be implicated in an unknown but essential and growth-linked mitochondrial function existing since pluri-cellular -organization and involved in tumorigenesis.
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PMID:[ATAD3, a vital membrane-bound mitochondrial ATPase involved in tumor progression]. 2219 48

ATAD3 (ATPase family AAA Domain-containing protein 3) is a mitochondrial membrane bound ATPase whose function has not yet been discovered but its role is essential for embryonic development. The ATAD3 gene has existed since the pluri-cellular organisms with specialized tissues and has remained unique until vertebrates. In primates and human, two other genes have appeared (called ATAD3B and ATAD3C versus ATAD3A the ancestral gene). ATAD3 knock-down in different non-transformed cell lines is associated with drastic changes in the mitochondrial network, inhibition of proliferation and modification of the functional interactions between mitochondria and endoplasmic reticulum. However, the analysis of the cellular properties of ATAD3A and ATAD3B in different human cancer cell lines shows on the contrary that they can present anti-proliferative and chemoresistant properties. ATAD3 may therefore be implicated in an unknown but essential and growth-linked mitochondrial function existing since pluri-cellular organization and involved in tumorigenesis.
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PMID:ATAD3, a vital membrane bound mitochondrial ATPase involved in tumor progression. 2231 59

Here we report on the identification of a human pluripotent embryonic stem cell (hESC) specific mitochondrial protein that is re-expressed in cancer cells, ATAD3B. ATAD3B belongs to the AAA+ ATPase ATAD3 protein family of mitochondrial proteins specific to multicellular eukaryotes. Using loss- and gain-of-function approaches, we show that ATAD3B associates with the ubiquitous ATAD3A species, negatively regulates the interaction of ATAD3A with matrix nucleoid complexes and contributes to a mitochondria fragmentation phenotype. We conclude that ATAD3B is a negative regulator of ATAD3A and may function as an adaptor of mitochondrial homeostasis and metabolism in hESCs and cancer cells.
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PMID:ATAD3B is a human embryonic stem cell specific mitochondrial protein, re-expressed in cancer cells, that functions as dominant negative for the ubiquitous ATAD3A. 2266 26

ATAD3 (ATPase family AAA-Domain containing protein 3) is a mitochondrial inner membrane ATPase with unknown but vital functions. Initial researches have focused essentially on the major p66-ATAD3 isoform, but other proteins and mRNAs are described in the data banks. Using a set of anti-peptide antibodies and by the use of rodent and human cell lines and organs, we tried to detail ATAD3 gene expression profiles and to verify the existence of the various ATAD3 isoforms. In rodent, the single ATAD3 gene is expressed as a major isoform of 67 kDa, (ATAD3l; long), in all cells and organs studied. A second isoform, p57-ATAD3s (small), is expressed specifically throughout brain development and in adult, and overexpressed around the peri-natal period. p57-ATAD3s is also expressed in neuronal and glial rodent cell lines, and during in vitro differentiation of primary cultured rat oligodendrocytes. Other smaller isoforms were also detected in a tissue-specific manner. In human and primates, ATAD3 paralogues are encoded by three genes (ATAD3A, 3B and 3C), each of them presenting several putative variants. Analyzing the expression of ATAD3A and ATAD3B with four specific anti-peptide antibodies, and comparing their expressions with in vitro expressed ATAD3 cDNAs, we were able to observe and define five isoforms. In particular, the previously described p72-ATAD3B is confirmed to be in certain cases a phosphorylated form of ATAD3As. Moreover, we observed that the ATAD3As phosphorylation level is regulated by insulin and serum. Finally, exploring ATAD3 mRNA expression, we confirmed the existence of an alternative splicing in rodent and of several mRNA isoforms in human. Considering these observations, we propose the development of a uniform denomination for ATAD3 isoforms in rodent and human.
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PMID:Expression analysis of ATAD3 isoforms in rodent and human cell lines and tissues. 2423 51

ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane protein implicated in mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. We identified a recurrent de novo ATAD3A c.1582C>T (p.Arg528Trp) variant by whole-exome sequencing (WES) in five unrelated individuals with a core phenotype of global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. We also describe two families with biallelic variants in ATAD3A, including a homozygous variant in two siblings, and biallelic ATAD3A deletions mediated by nonallelic homologous recombination (NAHR) between ATAD3A and gene family members ATAD3B and ATAD3C. Tissue-specific overexpression of borR534W, the Drosophila mutation homologous to the human c.1582C>T (p.Arg528Trp) variant, resulted in a dramatic decrease in mitochondrial content, aberrant mitochondrial morphology, and increased autophagy. Homozygous null bor larvae showed a significant decrease of mitochondria, while overexpression of borWT resulted in larger, elongated mitochondria. Finally, fibroblasts of an affected individual exhibited increased mitophagy. We conclude that the p.Arg528Trp variant functions through a dominant-negative mechanism that results in small mitochondria that trigger mitophagy, resulting in a reduction in mitochondrial content. ATAD3A variation represents an additional link between mitochondrial dynamics and recognizable neurological syndromes, as seen with MFN2, OPA1, DNM1L, and STAT2 mutations.
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PMID:Recurrent De Novo and Biallelic Variation of ATAD3A, Encoding a Mitochondrial Membrane Protein, Results in Distinct Neurological Syndromes. 2764 Mar 7

In yeast, a sequence of physical and genetic interactions termed the endoplasmic reticulum (ER)-mitochondria organizing network (ERMIONE) controls mitochondria-ER interactions and mitochondrial biogenesis. Several functions that characterize ERMIONE complexes are conserved in mammalian cells, suggesting that a similar tethering complex must exist in metazoans. Recent studies have identified a new family of nuclear-encoded ATPases associated with diverse cellular activities (AAA+-ATPase) mitochondrial membrane proteins specific to multicellular eukaryotes, called the ATPase family AAA domain-containing protein 3 (ATAD3) proteins (ATAD3A and ATAD3B). These proteins are crucial for normal mitochondrial-ER interactions and lie at the heart of processes underlying mitochondrial biogenesis. ATAD3A orthologues have been studied in flies, worms, and mammals, highlighting the widespread importance of this gene during embryonic development and in adulthood. ATAD3A is a downstream effector of target of rapamycin (TOR) signalling in Drosophila and exhibits typical features of proteins from the ERMIONE-like complex in metazoans. In humans, mutations in the ATAD3A gene represent a new link between altered mitochondrial-ER interaction and recognizable neurological syndromes. The primate-specific ATAD3B protein is a biomarker of pluripotent embryonic stem cells. Through negative regulation of ATAD3A function, ATAD3B supports mitochondrial stemness properties.
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PMID:ATAD3 proteins: brokers of a mitochondria-endoplasmic reticulum connection in mammalian cells. 2894 Oct 10

Identification of novel proteins with changed expression in resistant cancer cells could be helpful in elucidation mechanisms involved in the development of acquired resistance to paclitaxel. In this study, we carried out a 2D-PAGE using the mitochondrial-enriched fraction from paclitaxel-resistant MCF7/PacR cells compared to original paclitaxel-sensitive MCF7 breast cancer cells. Differentially expressed proteins were identified employing mass spectrometry. We found that lysosomal cathepsin D and mitochondrial abhydrolase-domain containing protein 11 (ABHD11) had decreased expression in MCF7/PacR cells. On the other hand, mitochondrial carbamoyl-phosphate synthetase 1 (CPS1) and ATPase family AAA-domain containing protein 3A and 3B (ATAD3A, ATAD3B) were overexpressed in MCF7/PacR cells. Further, we showed that there was no difference in localization of CPS1 in MCF7 and MCF7/PacR cells. We demonstrated a significant increase in the number of CPS1 positive MCF7/PacR cells, using FACS analysis, compared to the number of CPS1 positive MCF7 cells. Silencing of CPS1 expression by specific siRNA had no significant effect on the resistance of MCF7/PacR cells to paclitaxel. To summarize, we identified several novel proteins of a mitochondrial fraction whose role in acquired resistance to paclitaxel in breast cancer cells should be further assessed.
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PMID:Differentially Expressed Mitochondrial Proteins in Human MCF7 Breast Cancer Cells Resistant to Paclitaxel. 3124 89

ATPase family AAA domain-containing protein 3 (ATAD3) is a mitochondrial membrane-bound ATPase that is involved in a number of cellular processes and is linked with the progression of various types of malignancies. In primates, the ATAD3 gene cluster contains ATAD3A, ATAD3B and ATAD3C. The association between ATAD3 gene cluster expression and hepatocellular carcinoma (HCC) remains unknown. Therefore, the present study examined the prognostic significance of ATAD3 gene cluster expression in patients with HCC. Box plots of expression differences between HCC and normal liver tissues for the ATAD3 family genes were obtained from the online tool Gene Expression Profiling Interactive Analysis. Data from 360 patients with HCC in The Cancer Genome Atlas database were analyzed. Kaplan-Meier analysis and a Cox regression model were used to calculate median survival time (MST) and overall survival (OS). ATAD3A and ATAD3B expression levels were higher in HCC compared with normal liver tissues (P<0.05). However, ATAD3C expression was significantly decreased in HCC tissues compared with normal liver tissues (P<0.05). ATAD3A [P=0.017, hazard ratio (HR)=1.54, 95% confidence interval (CI)=1.08-2.20; adjusted P=0.032; adjusted HR=1.52; 95% CI=1.04-2.22] and ATAD3B (P=0.026, HR=1.49, 95% CI=1.05-2.13; adjusted P=0.031, adjusted HR=1.52, 95% CI=1.04-2.21) expression levels were significantly associated with OS. A joint-effects analysis revealed that patients with high ATAD3A and ATAD3B expression had reduced OS rates compared with patients with low ATAD3A and ATAD3B expression (P=0.007, HR=1.77, 95% CI=1.16-2.69; adjusted P=0.013, adjusted HR=1.76, 95% CI=1.13-2.75). In conclusion, ATAD3A and ATAD3B may serve as potential prognostic biomarkers for patients with HCC.
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PMID:Prognostic value of ATAD3 gene cluster expression in hepatocellular carcinoma. 3142 90