Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase), a membrane bound Ca(2+)- /Mg(2+)- dependent ATPase that sequesters Ca(2+) into the SR/ER lumen, is one of the essential components for the maintenance of intracellular Ca(2+) homeostasis. Here we describe the identification and functional characterization of a C. elegans SERCA gene (ser-1). ser-1 is a single gene alternatively spliced at its carboxyl terminus to form two isoforms (SER-1A and SER-1B) and displays a high homology (70% identity, 80% similarity) with mammalian SERCAs. Green fluorescent protein (GFP) and whole-mount immunostaining analyses reveal that SER-1 expresses in neuronal cells, body-wall muscles, pharyngeal and vulval muscles, excretory cells, and vulva epithelial cells. Furthermore, SER-1::GFP expresses during embryonic stages and the expression is maintained through the adult stages. Double-stranded RNA injection (also known as RNAi) targeted to each SER-1 isoform results in severe phenotypic defects: ser-1A(RNAi) animals show embryonic lethality, whereas ser-1B(RNAi) results in L1 larval arrest phenotype. These findings suggest that both isoforms of C. elegans SERCA, like in mammals, are essential for embryonic development and post-embryonic growth and survival.
...
PMID:Two isoforms of sarco/endoplasmic reticulum calcium ATPase (SERCA) are essential in Caenorhabditis elegans. 1116 7

Dyneins are multisubunit protein complexes that couple ATPase activity with conformational changes. They are involved in the cytoplasmatic movement of organelles (cytoplasmic dyneins) and the bending of cilia and flagella (axonemal dyneins). Here we present the first complete cDNA and genomic sequences of a human axonemal dynein beta heavy chain gene, DNAH9, which maps to 17p12. The 14-kb-long cDNA is divided into 69 exons spread over 390 kb. The cDNA sequence of DNAH9 was determined using a combination of methods including 5' rapid amplification of cDNA ends, RT-PCR, and cDNA library screening. RT-PCR using nasal epithelium and testis RNA revealed several alternatively spliced transcripts. The genomic structure was determined using three overlapping BACs sequenced by the Whitehead Institute/MIT Center for Genome Research. The predicted protein, of 4486 amino acids, is highly homologous to sea urchin axonemal beta heavy chain dyneins (67% identity). It consists of an N-terminal stem and a globular C-terminus containing the four P-loops that constitute the motor domain. Lack of proper ciliary and flagellar movement characterizes primary ciliary dyskinesia (PCD), a genetically heterogeneous autosomal recessive disorder with respiratory tract infections, bronchiectasis, male subfertility, and, in 50% of cases, situs inversus (Kartagener syndrome, KS). Dyneins are excellent candidate genes for PCD and KS because in over 50% of cases the ultrastructural defects of cilia are related to the dynein complex. Genotype analysis was performed in 31 PCD families with two or more affected siblings using a highly informative dinucleotide polymorphism located in intron 26 of DNAH9. Two families with concordant inheritance of DNAH9 alleles in affected individuals were observed. A mutation search was performed in these two "candidate families," but only polymorphic variants were found. In the absence of pathogenic mutations, the DNAH9 gene has been excluded as being responsible for autosomal recessive PCD in these families.
...
PMID:Axonemal beta heavy chain dynein DNAH9: cDNA sequence, genomic structure, and investigation of its role in primary ciliary dyskinesia. 1124 63

We have identified a cDNA encoding the mouse homologue of the yeast V-ATPase 21-kDa subunit c" (Vma16p). The encoded protein contains 205 amino acid residues with five putative membrane spanning segments and shows 48% identity and 64% similarity to the yeast protein. Despite this homology, however, the mouse cDNA does not complement the phenotype of a yeast strain in which the VMA16 gene has been disrupted. Northern blot analysis demonstrated that the 21-kDa subunit is expressed in most tissues examined and showed an expression pattern almost identical to that of the 16-kDa proteolipid subunit (subunit c). The presence of multiple mRNA species suggests the existence of alternatively spliced forms of the 21-kDa subunit which, from Southern blot analysis, are derived from a single gene. Promoter analysis using the luciferase reporter gene revealed that a region 186 bases upstream of the initiation site is sufficient to show a low level of transcriptional activity but that transcription is significantly enhanced by inclusion of the region -186 to -706. The 21-kDa protein was Myc-tagged and the 16-kDa protein was HA-tagged and the tagged proteins were co-expressed in COS-1 cells in order to study their intracellular localization by immunofluorescence microscopy. Both proteins showed significant punctate and perinuclear staining and were predominantly co-localized throughout the cell, consistent with their presence in the same V(0) complexes. Selective permeabilization of cells with digitonin (to permeabilize the plasma membrane) or Triton X-100 (to permeabilize both intracellular and plasma membranes) followed by immunofluorescence microscopy revealed that the carboxyl terminus of the 21-kDa subunit is exposed on the cytoplasmic side of the membrane whereas the carboxyl terminus of the 16-kDa subunit is located on the lumenal side of the membrane.
...
PMID:Expression and localization of the mouse homologue of the yeast V-ATPase 21-kDa Subunit c" (Vma16p). 1144 Oct 17

Recently the gene encoding a member of the RecQ helicase family, RecQ5, was cloned from the fruit fly, Drosophila melanogaster [J.J.Sekelsky, M.H.Brodsky, G.M. Rubin and R.S. Hawley (1999) Nucleic Acids Res., 27, 3762-3769]. The Drosophila RecQ5 transcript is alternatively spliced, like its human counterpart, to yield three protein isoforms. Two of these isoforms are almost identical and have a predicted molecular weight of 54 kDa. The third isoform is larger and contains, in addition to the helicase domain shared by all three isoforms, a long highly charged C-terminal region. A small isoform of the Drosophila RecQ5 protein (RECQ5) has been expressed in Escherichia coli and purified. The purified protein is a single-stranded DNA-stimulated ATPase (dATPase) and a 3'-->5' DNA helicase. Hydrolysis of the nucleotide cofactor is required for unwinding activity and dATP supported the unwinding reaction better than other NTPs. The turnover number for the single-stranded DNA-stimulated dATPase activity was 1380 min(-1), approximately 1.5-fold higher than that observed for the ATPase activity (900 min(-1)). The purified protein catalyzed unwinding of partial duplex substrates up to at least 93 bp, however, unwinding of an 89 bp blunt duplex substrate was not detected.
...
PMID:Biochemical characterization of the small isoform of Drosophila melanogaster RECQ5 helicase. 1145 23

The sarco-endoplasmic reticulum Ca(2+)-transport ATPase (SERCA) loads intracellular releasable Ca(2+) stores by transporting cytosolic Ca(2+) into the endoplasmic (ER) or sarcoplasmic reticulum (SR). We characterized the only SERCA homologue of the nematode Caenorhabditis elegans, which is encoded by the sca-1 gene. The sca-1 transcript is alternatively spliced in a similar mode as the vertebrate SERCA2 transcript, giving rise to two protein variants: CeSERCAa and CeSERCAb. These proteins showed structural and functional conservation to the vertebrate SERCA2a/b proteins. The CeSERCAs were primarily expressed in contractile tissues. Loss of CeSERCA through gene ablation or RNA interference resulted in contractile dysfunctioning and in early larval or embryonic lethality, respectively. Similar defects could be induced pharmacologically using the SERCA-specific inhibitor thapsigargin, which bound CeSERCA at a conserved site. The conservation of SERCA2 homologues in C. elegans will allow genetic and chemical suppressor analyses to identify promising drug targets and lead molecules for treatment of SERCA-related diseases such as heart disease.
...
PMID:The sarco-endoplasmic reticulum Ca2+ ATPase is required for development and muscle function in Caenorhabditis elegans. 1155 1

In apicomplexan parasites, actin-disrupting drugs and the inhibitor of myosin heavy chain ATPase, 2,3-butanedione monoxime, have been shown to interfere with host cell invasion by inhibiting parasite gliding motility. We report here that the actomyosin system of Toxoplasma gondii also contributes to the process of cell division by ensuring accurate budding of daughter cells. T. gondii myosins B and C are encoded by alternatively spliced mRNAs and differ only in their COOH-terminal tails. MyoB and MyoC showed distinct subcellular localizations and dissimilar solubilities, which were conferred by their tails. MyoC is the first marker selectively concentrated at the anterior and posterior polar rings of the inner membrane complex, structures that play a key role in cell shape integrity during daughter cell biogenesis. When transiently expressed, MyoB, MyoC, as well as the common motor domain lacking the tail did not distribute evenly between daughter cells, suggesting some impairment in proper segregation. Stable overexpression of MyoB caused a significant defect in parasite cell division, leading to the formation of extensive residual bodies, a substantial delay in replication, and loss of acute virulence in mice. Altogether, these observations suggest that MyoB/C products play a role in proper daughter cell budding and separation.
...
PMID:Toxoplasma gondii myosins B/C: one gene, two tails, two localizations, and a role in parasite division. 1170 51

The sequence of the pig cDNA encoding the muscle-specific betam-protein, a member of the X,K-ATPase beta-subunits family, was determined. Two alternatively spliced transcripts encoding polypeptide chains of 355 and 351 residues were identified. The tissue specificity of expression of betam and other X,K-ATPase beta-subunit genes was studied by RT-PCR performed on 24 tissues from newborn pigs. The betam expression was shown to be highly tissue-specific, being detected at the highest level in skeletal muscle, at a lower level in heart, and at much lower level in skin. The betam transcripts are more abundant in the tissues from the newborn than adult. Immunoblotting and deglycosylation shift assay indicated that skeletal muscle membranes of newborn pigs contain betam protein with an electrophoretic mobility and carbohydrate content very similar to that of human betam. Fractionation of membranes from both newborn and adult pig skeletal muscles by isopycnic centrifugation revealed that the majority of the betam protein is concentrated in the sarcoplasmic reticulum-containing fractions. This intracellular location is a unique property that distinguishes the betam protein from other members of the X,K-ATPase beta-subunit family.
...
PMID:The betam protein, a member of the X,K-ATPase beta-subunits family, is located intracellularly in pig skeletal muscle. 1171 65

Steady-state and transient-kinetic studies were conducted to characterize the overall and partial reactions of the Ca(2+)-transport cycle mediated by the human sarco(endo)plasmic reticulum Ca(2+)-ATPase 3 (SERCA3) isoforms: SERCA3a, SERCA3b, and SERCA3c. Relative to SERCA1a, all three human SERCA3 enzymes displayed a reduced apparent affinity for cytosolic Ca(2+) in activation of the overall reaction due to a decreased E(2) to E(1)Ca(2) transition rate and an increased rate of Ca(2+) dissociation from E(1)Ca(2). At neutral pH, the ATPase activity of the SERCA3 enzymes was not significantly enhanced upon permeabilization of the microsomal vesicles with calcium ionophore, indicating a difference from SERCA1a with respect to regulation of the lumenal Ca(2+) level (either an enhanced efflux of lumenal Ca(2+) through the pump in E(2) form or insensitivity to inhibition by lumenal Ca(2+)). Other differences from SERCA1a with respect to the overall ATPase reaction were an alkaline shift of the pH optimum, increased catalytic turnover rate at pH optimum (highest for SERCA3b, the isoform with the longest C terminus), and an increased sensitivity to inhibition by vanadate that disappeared under equilibrium conditions in the absence of Ca(2+) and ATP. The transient-kinetic analysis traced several of the differences from SERCA1a to an enhancement of the rate of dephosphorylation of the E(2)P phosphoenzyme intermediate, which was most pronounced at alkaline pH and increased with the length of the alternatively spliced C terminus.
...
PMID:Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 3 isoforms by steady-state and transient kinetic analyses. 1220 29

In several plant species, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activase consists of two isoforms that are produced by alternative splicing of a pre-mRNA. Two forms of activase corresponding to the longer, redox-regulated alpha and the shorter, beta forms were detected immunologically in cotton (Gossypium hirsutum L.) leaves, but their N-termini differed in 4 of 14 residues. The cDNAs for the alpha and beta forms of cotton activase diverged throughout the translated and 3'-untranslated regions, including variations that accounted for the differences in N-terminal amino acid sequence. Analysis of genomic DNA confirmed that separate genes encoded the alpha and beta forms of cotton activase. Separate activase genes were also detected in diploid species of cotton containing the different progenitor genomes of the cultivated allotetraploid, indicating that the occurrence of separate alpha- and beta-form genes in cotton predates the merger of the diploid genomes. The deduced amino acid sequences of the two forms of cotton activase exhibited 84% identity and both forms were active after expression in Escherichia coli. The recombinant alpha and beta forms exhibited similar affinities for ATP and only minor differences in thermotolerance, but their ATPase specific activities differed. The results show for the first time a plant species with two forms of activase that are structurally and functionally equivalent to the alternatively spliced alpha and beta forms in other plants, but that are encoded by separate genes. That cotton still expresses both forms of activase, even without alternative splicing, suggests that each form has a required function in photosynthesis.
...
PMID:Two isoforms of Rubisco activase in cotton, the products of separate genes not alternative splicing. 1262 60

The AU-rich element (ARE) in the 3' untranslated region of unstable mRNAs mediate their rapid degradation. ARE binding proteins (AUBPs) have been described that either stabilize or otherwise degrade ARE-mRNAs by recruiting the exosome, a complex of 3'-to-5' exoribonucleases. We have identified RHAU, a putative DExH RNA helicase that was isolated in association with the ARE of urokinase plasminogen activator mRNA (ARE(uPA)). RHAU physically interacts with the deadenylase PARN and the human exosome and enhances the deadenylation and decay of ARE(uPA)-mRNAs. An alternatively spliced isoform of RHAU that localized to the cytoplasm had a more pronounced effect on ARE(uPA)-mRNA destabilization than full-length RHAU. Furthermore, the ATPase activity of RHAU is essential for its mRNA-destabilizing function. ARE(uPA)-mRNA recognition by RHAU may be mediated through its RNA-dependent interaction with the AUBPs HuR and NFAR1. A model is presented to describe the action of RHAU in ARE(uPA)-directed mRNA turnover.
...
PMID:Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU. 1473 98


<< Previous 1 2 3 4 5 6 Next >>

---