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

More than 200 genes annotated as Na+/H+ hydrogen exchangers (NHEs) currently reside in bioinformation databases such as GenBank and Pfam. We performed detailed phylogenetic analyses of these NHEs in an effort to better understand their specific functions and physiological roles. This analysis initially required examining the entire monovalent cation proton antiporter (CPA) superfamily that includes the CPA1, CPA2, and NaT-DC families of transporters, each of which has a unique set of bacterial ancestors. We have concluded that there are nine human NHE (or SLC9A) paralogs as well as two previously unknown human CPA2 genes, which we have named HsNHA1 and HsNHA2. The eukaryotic NHE family is composed of five phylogenetically distinct clades that differ in subcellular location, drug sensitivity, cation selectivity, and sequence length. The major subgroups are plasma membrane (recycling and resident) and intracellular (endosomal/TGN, NHE8-like, and plant vacuolar). HsNHE1, the first cloned eukaryotic NHE gene, belongs to the resident plasma membrane clade. The latter is the most recent to emerge, being found exclusively in vertebrates. In contrast, the intracellular clades are ubiquitously distributed and are likely precursors to the plasma membrane NHE. Yeast endosomal ScNHX1 was the first intracellular NHE to be described and is closely related to HsNHE6, HsNHE7, and HsNHE9 in humans. Our results link the appearance of NHE on the plasma membrane of animal cells to the use of the Na+/K(+)-ATPase to generate the membrane potential. These novel observations have allowed us to use comparative biology to predict physiological roles for the nine human NHE paralogs and to propose appropriate model organisms in which to study the unique properties of each NHE subclass.
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PMID:Evolutionary origins of eukaryotic sodium/proton exchangers. 1564 48

Neurospora crassa has been the model filamentous fungus for the study of many fundamental cellular mechanisms of transport and metabolism. The recently completed genome sequence of N. crassa has over 10,000 genes without significant matches for a large number of genes (41%) in the sequence databases, indeed presents many challenges for new discoveries. Using transporter database and BLAST searches a total of 65 open reading frames for putative cation transporter genes have been identified in N. crassa. These were further confirmed by characteristic features of the family like transmembrane domains (TOPPRED 2), conserved motifs (Clustal W) and phylogenetic analysis (TREETOP). In Neurospora cation transporter genes constitute nearly 18.3% of the total membrane transport systems, which is higher than E. coli (8.8%), S. cerevisiae (13.7%), S. pombe (17.2%), A. fumigatus (10.1%), A. thaliana (16.8%) and H. sapiens (15.6%). We refer to the complete complement of metal ion transporter genes as "Metal Transportome". There are a total of 33 putative transporters for alkali and alkaline earth metals constituting 18 for calcium (P-ATPase, VIC, CaCA, Mid1), 7 for sodium (P-ATPase, CPA1, CPA2), 4 for potassium (Trk, VIC, KUP), and 4 for magnesium (MIT). Transition metal ion transporters account for 32 transporters including 7 for zinc (ZIP), 6 for copper (Ctr2, Ctr1), 2 each for manganese (Nramp), iron (OFeT), arsenite (ArsAB, ACR3) and other metal ions (ABC and P-ATPase) and 1 each for nickel (NiCoT) and chromate (CHR). N. crassa has 7 linkage groups of which LGI harbors 21 of metal ion transporters and in contrast LGVII has only 2. Studies on metal transportomes of different organisms will help to unravel the role of metal ion transporters in homeostasis.
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PMID:Metal transportome of Neurospora crassa. 1692 81

The vital task of vectorial solute transport is often energised by a plasma membrane, proton-motive V-ATPase. However, its proposed partner, an apical alkali-metal/proton exchanger, has remained elusive. Here, both FlyAtlas microarray data and in situ analyses demonstrate that the bacterial kefB and kefC (members of the CPA2 family) homologues in Drosophila, CG10806 and CG31052, respectively, are both co-expressed with V-ATPase genes in transporting epithelia. Immunocytochemistry localises endogenous CG10806 and CG31052 to the apical plasma membrane of the Malpighian (renal) tubule. YFP-tagged CG10806 and CG31052 both localise to the plasma membrane of Drosophila S2 cells, and when driven in principal cells of the Malpighian tubule, they localise specifically to the apical plasma membrane. V-ATPase-energised fluid secretion is affected by overexpression of CG10806, but not CG31052; in the former case, overexpression causes higher basal rates, but lower stimulated rates, of fluid secretion compared with parental controls. Overexpression also impacts levels of secreted Na+ and K+. Both genes rescue exchanger-deficient (nha1 nhx1) yeast, but act differently; CG10806 is driven predominantly to the plasma membrane and confers protection against excess K+, whereas CG31052 is expressed predominantly on the vacuolar membrane and protects against excess Na+. Thus, both CG10806 and CG31052 are functionally members of the CPA2 gene family, colocalise to the same apical membrane as the plasma membrane V-ATPase and show distinct ion specificities, as expected for the Wieczorek exchanger.
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PMID:Identification of two partners from the bacterial Kef exchanger family for the apical plasma membrane V-ATPase of Metazoa. 1862 2

We analyzed V-type H+-ATPase (VA) and Na+/K+-ATPase (NKA) along the caeca and midgut of third instar Drosophila larvae using immunohistochemistry and ATPase activity assays. Corresponding H+ and K+ fluxes were characterized using the Scanning Ion-Selective Electrode Technique (SIET), and the roles of transport ATPases in energizing ion transport across the larval gut were investigated by basal application of bafilomycin, a VA inhibitor, and ouabain, a NKA inhibitor. Addition of bafilomycin led to a decrease in H+ absorption along the caeca and midgut except at the copper cells and large flat cell zone of the middle midgut. H+ absorption was decreased by acetazolamide, consistent with carbonic anhydrase activity in all regions except at the large flat cell zone of the middle midgut. Bafilomycin or acetazolamide also led to decreased K+ absorption across the caeca and the anterior midgut. Our data show the dependence of K+ transport on H+ gradients established by the VA in the latter regions, consistent with the presence of a Cation-Proton Antiporter (CPA2) identified in other insect epithelia. Addition of ouabain led to the increase of K+ absorption along the anterior midgut and the large flat cell zone of the middle midgut, suggesting a role for the NKA in these regions. This study shows the importance of both ATPases in driving ion transport across the gut of larval Drosophila.
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PMID:The roles of V-type H+-ATPase and Na+/K+-ATPase in energizing K+ and H+ transport in larval Drosophila gut epithelia. 2818 26