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

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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)

Screening a rat colon cDNA library for aldosterone-induced genes resulted in the molecular cloning of a cDNA whose corresponding mRNA is strongly induced in the colon by dexamethasone, aldosterone, and a low NaCl diet. A similar mRNA was detected in kidney papilla but not in brain, heart, or skeletal muscle. Xenopus laevis oocytes injected with cRNA synthesized from this clone, designated CHIF (channel-inducing factor), express a K(+)-specific channel activity. The biophysical, pharmacological, and regulatory characteristics of this channel are very similar to those reported before for IsK (minK). These include: slow (tau > 20 s) activation by membrane depolarization with a threshold potential above -50 mV, blockade by clofilium, inhibition by phorbol ester, and activation by 8-bromoadenosine 3',5'-cyclic monophosphate and high cytoplasmic Ca2+. The primary structure of this clone, however, shows no homology to IsK. Instead, CHIF exhibits > 50% similarity to two other short bitopic membrane proteins, phospholemman and the gamma subunit of Na+K(+)-ATPase. The data are consistent with the possibility that CHIF is a member of a family of transmembrane regulators capable of activating endogenous oocyte transport proteins.
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PMID:A corticosteroid-induced gene expressing an "IsK-like" K+ channel activity in Xenopus oocytes. 759 86

CHIF is a recently cloned, corticosteroid-induced gene which evokes K+ channel activity in oocytes (B. Attali, H. Latter, N. Rachamim, and H. Garty. Proc. Natl. Acad. Sci. USA 92: 6092-6096, 1995). To further characterize the possible role of this gene in epithelial ion transport, we have studied its epithelial distribution and hormonal induction. Northern hybridizations indicate that the zonal distribution of CHIF mRNA in kidney is: papilla >>medulla>> cortex. High levels of CHIF were also detected in a primary culture from inner medullary collecting duct (IMCD). Perfusing rats with < 20 nM aldosterone through osmotic minipumps evoked a 22.4 +/- 1.9-fold increase in colonic CHIF. A significant increase was observed 3 h after administrating the corticosteroid, but maximal response was detected only after a 72-h incubation. This response appears to be mineralocorticoid specific; perfusing or injecting rats with maximal doses of dexamethasone did not evoke a further increase in CHIF mRNA. In contrast, high levels of CHIF are expressed in kidney papilla and IMCD primary culture, irrespective of corticosteroid treatment. Thus, like the apical Na+ channel and the H(+)-K(+)-adenosinetriphosphatase, CHIF is mineralocorticoid induced in the colon but constitutively expressed in kidney.
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PMID:Aldosterone induction and epithelial distribution of CHIF. 877 Jan 63

Previous reports have demonstrated that the phospholemman (PLM), a 72-residue plasma-membrane protein enriched in skeletal muscle and heart, is a major substrate phosphorylated in response to insulin and adrenergic stimulation. Here we describe the isolation and characterization of human and rat PLM cDNA from the heart. Both PLM proteins share significant nucleotide and amino acid sequence and structural similarities with the previously published canine PLM and, to a lesser degree, with Na+/K(+)-ATPase gamma subunit, Mat-8 protein, and CHIF protein. Despite the functional diversity, all these proteins are quite small and possess a single transmembrane domain. Human PLM appears to be a unique gene localized on chromosome 19q13.1. The PLM mRNA is widely distributed in human tissues, with the highest expression in skeletal muscle and heart, suggesting a functional role in muscle contraction. Like canine PLM, both human and rat PLM induce a hyperpolarization-activated chloride current when expressed in Xenopus oocytes. The high degree of sequence and functional conservation among the mammalian PLM proteins indicates that this gene is conserved throughout evolution.
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PMID:Characterization of the human and rat phospholemman (PLM) cDNAs and localization of the human PLM gene to chromosome 19q13.1. 916 43

Recently, an IsK-like potassium (K+) channel corticosteroid-induced gene (CHIF) was cloned. A high-K+ diet enhances, while a low-K+ diet decreases the expression of this gene. The major expression of CHIF in the adult rat kidney is in the papilla, where it is constitutive, in contrast to its inducibility by corticosteroids and a low-salt diet in the rat colon. In order to further understand the ontogeny of K+ clearance, we studied the presence of CHIF in the kidney papilla in different stages of rat development. Total RNA from rat kidney papillae of 1- to 3-day pre-labor unborn offspring, 2- to 3-day-old newborns, 10-day-old, 6-week-old, and 43-week-old rats underwent northern hybridization for CHIF and the alpha-subunit of the Na+-K+-ATPase mRNA. Minor expression of CHIF mRNA was found in fetal and newborn rat papillae, while older rats showed an age-related increase in gene expression. The expression of the alpha-sub unit of the Na+-K+-ATPase was not age related. We conclude that CHIF is present in the rat kidney papilla and the expression is related to age. The relative deficiency of CHIF in the newborn may be one of the factors responsible for the reduced K+ clearance in is period.
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PMID:The ontogeny of the expression of K+ channel-like gene (CHIF) in the rat kidney papilla. 976 51

The molecular mechanisms by which corticosteroids affect fluid and electrolyte balance are unclear. Though glucocorticoid-responsive genes have been identified, genes regulated by aldosterone have not. CHIF (channel-inducing factor gene) is a recently identified gene that is up-regulated in the distal colon by chronic corticosteroid exposure, is expressed in the kidney, and induces a K+-specific current in Xenopus oocytes. The predicted protein shows similarity to gammaNa.K-ATPase, phospholemman, and Mat-8; all seem to be involved in ion transport. CHIF thus presents as a potential aldosterone target gene. In this study, CHIF expression was examined in rats in the acute timeframe of 0.5-4 h after corticosteroid administration. CHIF messenger RNA showed up-regulation by both mineralocorticoid and glucocorticoid receptor agonists in the distal colon, which was not diminished by cycloheximide. Corticosteroid regulation was not observed in the kidney. Basal and induced expression was absent in the lung and in all gastrointestinal tissues except colon, with expression increasing proximal to distal. CHIF is the first gene to show acute regulation by aldosterone and thus encodes a candidate aldosterone-induced protein. In addition, gammaNa.K-ATPase gene expression was found to be very low in colon and significantly higher in kidney. Regulation by corticosteroids was not evident in either tissue.
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PMID:Acute regulation by corticosteroids of channel-inducing factor gene messenger ribonucleic acid in the distal colon. 1006 46

P-type ATPases (E1E2-ATPases) are primary active transporters which form phospho-intermediates during their catalytic cycle. They are classified into P1 to P4 based on the primary structure and potential transmembrane segments. Although the classic P-type ATPases are cation transporters, two new members have recently been found; one is a flippase catalyzing the flip-flop movement of aminophospholipids, but the substrate and function of the other one remain unknown. It would be interesting to determine whether the cations and aminophospholipids are transported by similar or different mechanisms. P-type ATPases are believed to have been derived from a common ancestor, and their genes are found to be distributed in various chromosomal loci. However, gene duplication events can be traced from the tandem arrangement of genes and their linkage map. Na+/K+- and H+/K+-ATPases have not only closely related a subunits but also similar beta subunits. Renal Na+/K+-ATPase has an additional subunit gamma. Similar small polypeptides (phospholemman, Mat-8 and CHIF), which induce Cl- and K+ currents, have been found. The idea of their functional and structural coupling with P-type ATPases, especially with H+/K+-ATPase, is intriguing. Each P-type ATPase must have specific domains or sequences for its intracellular trafficking (sorting, retention and recycling). Identification of such regions and studies on the molecules playing role in their recognition may facilitate the unveiling of various cellular processes regulated by P-type ATPases.
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PMID:Structures of P-type transporting ATPases and chromosomal locations of their genes. 1020 33

A gene family of small membrane proteins, represented by phospholemman and the gamma subunit of Na,K-ATPase, was defined and characterized by the analysis of more than 1000 related ESTs (expressed sequence tags). In addition to new and more complete cDNA sequence for known family members (including MAT-8, CHIF, and RIC), the findings included two new family members and new splicing variants. A large number of EST replicates made it possible to derive curated DNA sequence with higher confidence and accuracy than from the sequencing of individual clones. The family has a core motif of 35 invariant and conserved amino acids centered on a single transmembrane span. Features of each predicted protein product were compared, and tissue distributions were determined. The gene family was named FXYD (pronounced fix-id) in recognition of invariant amino acids in its signature motif. The abundant proteins are involved in the control of ion transport.
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PMID:The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence, and expression. 1095 Sep 25

The biological role of small membrane proteins of the new FXYD family is largely unknown. The best characterized FXYD protein is the gamma-subunit of the Na,K-ATPase (NKA) that modulates the Na,K-pump function in the kidney. Here, we report that, similarly to gamma(a) and gamma(b) splice variants, the FXYD protein CHIF (corticosteroid-induced factor) is a type I membrane protein which is associated with NKA in renal tissue, and modulates the Na,K-pump transport when expressed in Xenopus oocytes. In contrast to gamma(a) and gamma(b), which both decrease the apparent Na+ affinity of the Na,K-pump, CHIF significantly increases the Na+ affinity and decreases the apparent K+ affinity due to an increased Na+ competition at external binding sites. The extracytoplasmic FXYD motif is required for stable gamma-subunit and CHIF interaction with NKA, while cytoplasmic, positively charged residues are necessary for the gamma-subunit's association efficiency and for CHIF's functional effects. These data document that CHIF is a new tissue-specific regulator of NKA which probably plays a crucial role in aldosterone-responsive tissues responsible for the maintenance of body Na+ and K+ homeostasis.
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PMID:CHIF, a member of the FXYD protein family, is a regulator of Na,K-ATPase distinct from the gamma-subunit. 1148 3

1. The gamma subunit is a specific component of the plasmalemmal Na(+),K(+)-ATPase. Like structurally related single-spanning membrane proteins such as cardiac phospholemman, Mat-8 and renal CHIF, large ion conductances are activated when gamma subunits are expressed in Xenopus oocytes. 2. Here we report critical properties of the gamma-activated conductance. The gamma-activated conductance showed non-selective cationic and anionic permeation, and extremely slow kinetics, with an activation time constant > 1 s following steps to -100 mV. 3. The gamma-activated conductance was inhibited by extracellular divalent ions including Ba(2+) (K(i) = 0.7 mM) and Ca(2+) (K(i) = 0.4 mM). 4. 2-Deoxyglucose (MW approximately 180), inulin (MW approximately 5000) and spermidine (MW approximately 148) efflux could occur through the gamma-activated conductance pathway, indicating a large pore diameter. In contrast, dextran-70 (MW approximately 70 000) did not pass through the gamma-activated channel, indicating an upper limit to the pore size of approximately 50 A (5 nm). 5. Similar conductances that are permeable to large molecules were activated by extreme hyperpolarization (> -150 mV) of uninjected oocytes. 6. We conclude that the Na(+),K(+)-ATPase gamma subunits activate Ca(2+)- and voltage-gated, non-selective, large diameter pores that are intrinsically present within the oocyte membrane.
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PMID:Heterologous expression of the Na(+),K(+)-ATPase gamma subunit in Xenopus oocytes induces an endogenous, voltage-gated large diameter pore. 1153 33

Maintenance of the Na+ and K+ gradients between the intracellular and extracellular milieus of animal cells is a prerequisite for basic cellular homeostasis and for functions of specialized tissues. The Na,K-ATPase, an oligomeric P-type adenosine triphosphatase (ATPase), is composed of a catalytic alpha subunit and a regulatory beta subunit and is the main player that fulfils these tasks. A variety of regulatory mechanisms are necessary to guarantee appropriate Na,K-ATPase expression and activity adapted to changing physiological demands. Recently, a regulatory mechanism was defined that is mediated by interaction of Na,K-ATPase with small proteins of the FXYD family, which possess a single transmembrane domain and so far have been considered as channels or regulators of ion channels. The mammalian FXYD proteins FXYD1 through FXYD7 exhibit tissue-specific distribution. Phospholemman (FXYD1) in heart and skeletal muscle, the gamma subunit of Na,K-ATPase (FXYD2) and corticosteroid hormone-induced factor (FXYD4, also known as CHIF) in the kidney, and FXYD7 in the brain associate preferentially with the widely expressed Na,K-ATPase alpha1-beta1 isozyme and modulate its transport activity in a way that conforms to tissue-specific requirements. Thus, tissue- and isozyme-specific interaction of Na,K-ATPase with FXYD proteins contributes to proper handling of Na+ and K+ by the Na,K-ATPase, and ensures correct function in such processes as renal Na+-reabsorption, muscle contraction, and neuronal excitability.
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PMID:FXYD proteins: new tissue-specific regulators of the ubiquitous Na,K-ATPase. 1253 82


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