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)

The positions, with respect to the plasma membrane, of lysine 905, contained in the peptide QRKIVE, and of lysine 1012, contained in the carboxy-terminal peptide, RPGGWVEKETYY, of ovine Na+/K(+)-transporting ATPase have been reported to be cytoplasmic and extracytoplasmic, respectively [Bayer, R. (1990) Biochemistry 29, 2551-2256]. These results from our laboratory have been reexamined using an extension of the same procedure. Sealed right-side-out vesicles were modified with pyridoxal phosphate and sodium [3H]borohydride in the presence and absence of saponin or cholate. The modified alpha polypeptide was isolated and digested with the proteinase from Staphylococcus aureus strain V8 or trypsin to produce one or the other of these two peptides. These digests were passed over immunoadsorbents, identical to those used by Bayer, directed against pyroglutamylRXIVE or -ETYY. Unlike in the earlier studies, however, in the present studies the modified, radioactive peptides bound and eluted from the immunoadsorbents were submitted to HPLC, and their respective mobilities were compared to those of the synthetic peptides that had also been modified with pyridoxal phosphate. In this manner, the correct, modified peptide could be positively identified, and its specific radioactivity could be estimated. When cholate was added to sealed vesicles, prior to modification, there was at least a 3-fold increase in the incorporation of radioactivity into lysine 1012, consistent with a cytoplasmic location for this residue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The carboxy terminus of sodium and potassium ion transporting ATPase is located on the cytoplasmic surface of the membrane. 838 80

In addition to the three isoforms of the catalytic subunit of the Na, K-ATPase originally identified (alpha1, alpha2, and alpha3), a fourth alpha polypeptide (alpha4) has recently been found in mammalian cells. This novel alpha-subunit of the Na,K-ATPase is selectively expressed in male gonadal tissues. In the testes, alpha4 is functionally active and comprises approximately half of the Na, K-ATPase activity of the organ. At present, the pattern of expression of the alpha4 polypeptide within the cells of the male gonad is unknown. By in situ hybridization, immunocytochemistry, and the ouabain inhibition profile of Na,K-ATPase activity, we show that the alpha4-subunit is expressed in the germ cells of rat testes. The highest amounts of the isoform are found in spermatozoa, where it constitutes two thirds of the Na,K-ATPase activity of the gametes. The other Na pump present in the cells is the ubiquitously expressed alpha1 polypeptide. The characteristic localization of alpha4 in the gonad is further supported by the drastic reduction of the polypeptide in mice that are infertile as a consequence of arrest in maturation of the germ cells. In addition, GC-1spg cells, a murine cell line derived from testis spermatogonia, also contain the Na, K-ATPase alpha4 polypeptide. However, the level of expression of the isoform in these cells is much lower than in the spermatozoa, a fact that may depend on the limited ability of the GC-1spg cells to differentiate in vitro. The particular expression of the Na,K-ATPase alpha4 isoform we encounter and the specific enzymatic properties of the polypeptide suggests its importance for ionic homeostasis of the germ cells of the testes.
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PMID:The alpha4 isoform of the Na,K-ATPase is expressed in the germ cells of the testes. 1089 97

Menkes disease (MD) is a rare and severe X-linked recessive disorder of copper metabolism. The MD gene, ATP7A (ATPase Cu++ transporting alpha polypeptide), encodes an ATP-dependent copper-binding membrane protein. In this report, we describe a girl with typical clinical features of MD, carrying a balanced translocation between the chromosomes X and 16 producing the disruption of one copy of ATP7A gene and the silencing of the other copy because of the chromosome X inactivation. Fluorescence in situ hybridization experiments with bacterial derived artificial chromosome probes revealed that the breakpoints were located within Xq13.3 and 16p11.2. Replication pattern analysis demonstrated that the normal X chromosome was late replicating and consequently inactivated, whereas the der(X)t(X;16), bearing the disrupted ATP7A gene, was active. An innovative approach, based on FMR1 (fragile X mental retardation 1) gene polymorphism, has been used to disclose the paternal origin of the rearrangement providing a new diagnostic tool for determining the parental origin of defects involving the X chromosome and clarifying the mechanism leading to the cytogenetic rearrangement that occurred in our patient.
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PMID:Lyonization effects of the t(X;16) translocation on the phenotypic expression in a rare female with Menkes disease. 1909 23

The homoeostasis of metal ions in cells is the result of the contribution of several cellular pathways that involve transient, often weak, protein-protein interactions. Metal transfer typically implies the formation of adducts where the metal itself acts as a bridge between proteins, by co-ordinating residues of both interacting partners. In the present study we address the interaction between the human copper(I)-chaperone HAH1 (human ATX1 homologue) and a metal-binding domain in one of its partners, namely the P-type copper-transporting ATPase, ATP7A (ATPase, Cu+ transporting, alpha polypeptide). The adduct was structurally characterized in solution, in the presence of copper(I), and through X-ray crystallography, upon replacing copper(I) with cadmium(II). Further insight was obtained through molecular modelling techniques and site-directed mutagenesis. It was found that the interaction involves a relatively small interface (less than 1000 A(2), 1 A=0.1 nm) with a low fraction of non-polar atoms. These observations provide a possible explanation for the low affinity of the two apoproteins. It appears that electrostatics is important in selecting which domain of the ATPase is able to form detectable amounts of the metal-mediated adduct with HAH1.
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PMID:Copper(I)-mediated protein-protein interactions result from suboptimal interaction surfaces. 1945 93

Octylphenol (OP) and bisphenol A (BPA) are known as endocrine-disrupting chemicals (EDCs). During pregnancy, the expression of steroid hormone receptors is controlled by maternal and fetal nutrition. To evaluate the impact of EDCs during pregnancy, ethinyl estradiol (EE, 0.2 mg/kg/day), OP (50 mg/kg/day), and BPA (50 mg/kg/day) were administered to pregnant mice. The mRNA levels of TRPV6 (transient receptor potential cation channels in subfamily V, member 6) decreased significantly by EE and OP. The PMCA1 (ATPase, Ca++ transporting, plasma membrane 1) mRNA and protein levels decreased significantly by EE, OP, and BPA. CTR1 (solute carrier family 31, member 1) and ATP7A (ATPase, Cu++ transporting, alpha polypeptide) expression decreased significantly by EE, OP, and BPA. The mRNA levels of IREG1 (iron-regulated transporter, member 1) decreased significantly by EE. Hephaestin (HEPH) mRNA levels decreased significantly by EE, OP, and BPA, and protein levels decreased significantly by BPA. As a result of immunohistochemistry analysis, all cation transporter proteins were found in labyrinth of placenta. To confirm the cytosolic level of cations, levels of cation level in fetal serum were measured. EE, OP, and BPA significantly reduced serum calcium and copper levels, and iron levels were reduced by BPA. Taken together, some EDCs, such as OP and BPA, could modulate the calcium, copper, and iron ion-transporting channels during pregnancy. The fetus relies on the mother for ionic transportation, and, therefore, pregnant women should avoid exposure to cation-channel-disrupting chemicals.
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PMID:Effects of Octylphenol and Bisphenol A on the Metal Cation Transporter Channels of Mouse Placentas. 2769 74

Pancreatic cancer is regarded as the most fatal and aggressive malignancy cancer due to its low 5-year survival rate and poor prognosis. The approaches of early diagnosis and treatment are limited, which makes it urgent to identify the complex mechanism of pancreatic oncogenesis. In this study, we used RNA-seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in paired tumor and normal pancreatic samples from ten patients. More than 1000 differentially expressed genes were identified, nearly half of which were also found to be differentially expressed in the majority of examined patients. Functional enrichment analysis revealed that these genes were significantly enriched in multicellular organismal and metabolic process, secretion, mineral transport, and intercellular communication. In addition, only 24 differentially expressed miRNAs were found, all of which have been reported to be associated with pancreatic cancer. Furthermore, an integrated miRNA-mRNA interaction network was generated using multiple resources. Based on the calculation of disease correlation scores developed here, several genes present in the largest connected subnetwork, such as albumin, ATPase H+ /K+ exchanging alpha polypeptide and carcinoembryonic antigen-related cell adhesion molecule 1, were considered as novel genes that play important roles in the development of pancreatic cancer. Overall, our data provide new insights into further understanding of key molecular mechanisms underlying pancreatic tumorigenesis.
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PMID:Network-based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer. 3029 29


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