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)

The Saccharomyces cerevisiae vacuolar H(+)-ATPase (V-ATPase) is a multi-subunit complex that can be structurally and functionally divided into peripheral (V1) and integral membrane (V0) sectors. The vma22-1 mutation was isolated in a screen for mutants defective in V-ATPase function vma22 delta cells contain no V-ATPase activity due to a failure to assemble the enzyme complex; V1 subunits accumulate in the cytosol, and the V0 100-kDa subunit is rapidly degraded. Turnover of the 100-kDa integral membrane protein was found to occur in the endoplasmic reticulum (ER) of vma22 delta cells. The product of the VMA22 gene, Vma22p, is a 21-kDa hydrophilic protein that is not a subunit of the V-ATPase but rather is associated with ER membranes. The association of Vma22p with ER membranes was perturbed by mutations in VMA12, a gene that encodes an ER membrane protein (Vma12p) that is also required for V-ATPase assembly. These results indicate that Vma22p, along with Vma21p and Vma12p, form a set of ER proteins required for V-ATPase assembly.
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PMID:Vma22p is a novel endoplasmic reticulum-associated protein required for assembly of the yeast vacuolar H(+)-ATPase complex. 767 16

The yeast vacuolar proton-translocating ATPase (V-ATPase) is a multisubunit complex comprised of peripheral membrane subunits involved in ATP hydrolysis and integral membrane subunits involved in proton pumping. The yeast vma21 mutant was isolated from a screen to identify mutants defective in V-ATPase function. vma21 mutants fail to assemble the V-ATPase complex onto the vacuolar membrane: peripheral subunits accumulate in the cytosol and the 100-kDa integral membrane subunit is rapidly degraded. The product of the VMA21 gene (Vma21p) is an 8.5-kDa integral membrane protein that is not a subunit of the purified V-ATPase complex but instead resides in the endoplasmic reticulum. Vma21p contains a dilysine motif at the carboxy terminus, and mutation of these lysine residues abolishes retention in the endoplasmic reticulum and results in delivery of Vma21p to the vacuole, the default compartment for yeast membrane proteins. Our findings suggest that Vma21p is required for assembly of the integral membrane sector of the V-ATPase in the endoplasmic reticulum and that the unassembled 100-kDa integral membrane subunit present in delta vma21 cells is rapidly degraded by nonvacuolar proteases.
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PMID:Vma21p is a yeast membrane protein retained in the endoplasmic reticulum by a di-lysine motif and is required for the assembly of the vacuolar H(+)-ATPase complex. 784 20

Three previously identified genes from Saccharomyces cerevisiae, VMA12, VMA21, and VMA22, encode proteins localized to the endoplasmic reticulum (ER). These three proteins are required for the biogenesis of a functional vacuolar ATPase (V-ATPase), but are not part of the final enzyme complex. Subcellular fractionation and chemical cross-linking studies have revealed that Vma12p and Vma22p form a stable membrane associated complex. Cross-linking analysis also revealed a direct physical interaction between the Vma12p/Vma22p assembly complex and Vph1p, the 100-kD integral membrane subunit of the V-ATPase. The interaction of the Vma12p/Vma22p complex with Vph1p was transient (half-life of approximately 5 min), reflecting trafficking of this V-ATPase subunit through the ER en route to the vacuolar membrane. Analysis of these protein-protein interactions in ER-blocked sec12 mutant cells indicated that the Vph1p-Vma12p/Vma22p interactions are quite stable when transport of the V-ATPase out of the ER is blocked. Fractionation of solubilized membrane proteins on a density gradient revealed comigration of Vma22p and Vma12p, indicating that they form a complex even in the absence of cross-linker. Vma12p and Vma22p migrated to fractions separate from Vma21p. Loss of Vph1p caused the Vma12p/Vma22p complex to sediment to less dense fractions, consistent with association of Vma12p/ Vma22p with nascent Vph1p in ER membranes. This is the first evidence for a dedicated assembly complex in the ER required for the assembly of an integral membrane protein complex (V-ATPase) as it is transported through the secretory pathway.
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PMID:Assembly of the yeast vacuolar H+-ATPase occurs in the endoplasmic reticulum and requires a Vma12p/Vma22p assembly complex. 966 Aug 61

The yeast vacuolar proton-translocating ATPase (V-ATPase) is the best characterized member of the V-ATPase family. Biochemical and genetic screens led to the identification of a large number of genes in yeast, designated VMA, encoding proteins required to assemble a functional V-ATPase. A total of thirteen genes encode subunits of the final enzyme complex. In addition to subunit-encoding genes, we have identified three genes that code for proteins that are not part of the final V-ATPase complex yet required for its assembly. We refer to these nonsubunit Vma proteins as assembly factors, since their function is dedicated to assembling the V-ATPase. The assembly factors, Vma12p, Vma21p, and Vma22p are localized to the endoplasmic reticulum (ER) and aid the assembly of newly synthesized V-ATPase subunits that are translocated into the ER membrane. At least two of these proteins, Vma12p and Vma22p, function together in an assembly complex and interact directly with nascent V-ATPase subunits.
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PMID:Assembly of the yeast vacuolar proton-translocating ATPase. 1034 Aug 47

Plasma membrane V-ATPase isolated from midgut and Malpighian tubules of the tobacco hornworm, Manduca sexta, contains a novel prominent 20-kDa polypeptide. Based on N-terminal protein sequencing, we cloned a corresponding cDNA. The deduced hydrophobic protein consisted of 88 amino acids with a molecular mass of only 9.7 kDa. Immunoblots of the recombinant 9.7-kDa polypeptide, using a monoclonal anti- body to the 20-kDa polypeptide, confirmed that the correct cDNA had been cloned. The 20-kDa polypeptide is glycosylated, as deduced from lectin staining. Treatment with N-glycosidase A resulted in the appearance of two additional protein bands of 16 and 10 kDa which both were immunoreactive to the 20-kDa polypeptide-specific monoclonal antibody. Thus, extensive N-glycosylation of the novel Vo subunit M9.7 accounts for half of its molecular mass observed in SDS-polyacrylamide gel electrophoresis. M9.7 exhibits some similarities to the yeast protein Vma21p which resides in the endoplasmic reticulum and is required for the assembly of the Vo complex. However, as deduced from immunoblots as well as from activities of the V-ATPase and endoplasmic reticulum marker enzymes in different membrane preparations, M9.7 is, in contrast to the yeast polypeptide, a constitutive subunit of the mature plasma membrane V-ATPase of M. sexta.
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PMID:A novel insect V-ATPase subunit M9.7 is glycosylated extensively. 1035 99

The proton-translocating ATPase (H(+)-ATPase) found on the membrane of the yeast vacuole is the best characterized member of the V-type ATPase family. Biochemical and genetic screens have led to the identification of 14 genes, the majority designated VMA (for vacuolar membrane ATPase) encoding subunits of the enzyme complex. At least eight genes encode for proteins comprising the peripherally associated catalytic V(1) subcomplex, and six genes code for proteins forming the proton-translocating membrane V(o) subcomplex. Several additional genes have been identified that encode proteins that are not part of the final V-ATPase complex yet are required for its assembly. These non-subunit Vma proteins function as dedicated V-ATPase assembly factors since their absence appears to inhibit assembly of the V-ATPase only. The assembly factors designated Vma12p, Vma21p and Vma22p have been localized to the membrane of the endoplasmic reticulum and aid the association of newly synthesized V-ATPase subunits translocated into the endoplasmic reticulum membrane. Two of these proteins, Vma12p and Vma22p, function together in an assembly complex that interacts directly with nascent V-ATPase subunits.
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PMID:Composition and assembly of the yeast vacuolar H(+)-ATPase complex. 1060 Jun 74

To obtain insight into the molecular mechanisms underlying the metabolism and functions of endogenous d-serine, we have explored d-serine-regulated transcripts in the neocortex of the infant rat treated with acute d-serine administration by using an RNA fingerprinting technique. Cloning and sequence analysis of the corresponding cDNAs to the identified transcripts have revealed that the dsr-1 (d-serine responsive transcript-1) mRNA is presumed to contain a novel sequence at the 5'-region, while the 631-base nucleotide sequence of its 3'-end is identical with that of rat M9.2 mRNA encoding a subunit of vacuolar type proton-ATPase. The predicted two open reading frames and their deduced amino acid sequences suggest that the dsr-1 product has a membrane spanning domain. The dsr-1 transcript was detected as a single band around 2.1 kb on the Northern blot. RT-PCR analyses have indicated that the dsr-1 transcript is expressed predominantly in the brain, lung, and testis, and that acute intraperitoneal injection of d-serine significantly upregulates dsr-1 expression in the neocortex 3 and 15 h later without affecting the levels of the M9.2 gene transcript. These results suggest that dsr-1 products may be involved in the d-serine-related metabolic or signaling pathways in mammalian brains.
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PMID:Cloning of a D-serine-regulated transcript dsr-1 from the rat cerebral cortex. 1116 53

We have identified a cDNA encoding a novel putative neuron-specific isoform of vacuolar proton-translocating ATPase (V-ATPase), NM9.2, from rat and mouse. Sequence analysis revealed that NM9.2 conserved similar characteristic amino acid sequences with 60-70% identity to M9.2 previously isolated from V-ATPase in chromaffin granules. Using Northern blot analysis, NM9.2 mRNA was specifically detected in the brain, whereas M9.2 mRNA was widely expressed in various tissues. In situ hybridization showed that NM9.2 gene expression was restricted mainly to neuronal cells and consistent with that of the a1/Ac116 subunit of V-ATPase. NM9.2 is a putative neuronal isoform of the 9.2 kDa subunit in V-ATPase.
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PMID:A novel putative M9.2 isoform of V-ATPase expressed in the nervous system. 1254 25

The yeast V-ATPase belongs to a family of V-type ATPases present in all eucaryotic organisms. In Saccharomyces cerevisiae the V-ATPase is localized to the membrane of the vacuole as well as the Golgi complex and endosomes. The V-ATPase brings about the acidification of these organelles by the transport of protons coupled to the hydrolysis of ATP. In yeast, the V-ATPase is composed of 13 subunits consisting of a catalytic V1 domain of peripherally associated proteins and a proton-translocating V0 domain of integral membrane proteins. The regulatory subunit, Vma13p, was the first V-ATPase subunit to have its crystal structure determined. In addition to proteins forming the functional V-ATPase complex, three ER-localized proteins facilitate the assembly of the V0 subunits following their translation and insertion into the membrane of the ER. Homologues of the Vma21p assembly factor have been identified in many higher eukaryotes supporting a ubiquitous assembly pathway for this important enzyme complex.
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PMID:Structure and assembly of the yeast V-ATPase. 1463 76

The Saccharomyces cerevisiae vacuolar H+-ATPase (V-ATPase) is a multisubunit complex composed of a peripheral membrane sector (V1) responsible for ATP hydrolysis and an integral membrane sector (V0) required for proton translocation. Biogenesis of V0 requires an endoplasmic reticulum (ER)-localized accessory factor, Vma21p. We found that in vma21Delta cells, the major proteolipid subunit of V0 failed to interact with the 100-kDa V0 subunit, Vph1p, indicating that Vma21p is necessary for V0 assembly. Immunoprecipitation of Vma21p from wild-type membranes resulted in coimmunoprecipitation of all five V0 subunits. Analysis of vmaDelta strains showed that binding of V0 subunits to Vma21p was mediated by the proteolipid subunit Vma11p. Although Vma21p/proteolipid interactions were independent of Vph1p, Vma21p/Vph1p association was dependent on all other V0 subunits, indicating that assembly of V0 occurs in a defined sequence, with Vph1p recruitment into a Vma21p/proteolipid/Vma6p complex representing the final step. An in vitro assay for ER export was used to demonstrate preferential packaging of the fully assembled Vma21p/proteolipid/Vma6p/Vph1p complex into COPII-coated transport vesicles. Pulse-chase experiments showed that the interaction between Vma21p and V0 was transient and that Vma21p/V0 dissociation was concomitant with V0/V1 assembly. Blocking ER export in vivo stabilized the interaction between Vma21p and V0 and abrogated assembly of V0/V1. Although a Vma21p mutant lacking an ER-retrieval signal remained associated with V0 in the vacuole, this interaction did not affect the assembly of vacuolar V0/V1 complexes. We conclude that Vma21p is not involved in regulating the interaction between V0 and V1 sectors, but that it has a crucial role in coordinating the assembly of V0 subunits and in escorting the assembled V0 complex into ER-derived transport vesicles.
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PMID:Role of Vma21p in assembly and transport of the yeast vacuolar ATPase. 1535 64


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