Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0271742 (AAA)
 3,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A member of the AAA family of Mg2(+)-ATPases from the archaeon Thermoplasma acidophilum has been cloned and expressed in Escherichia coli. The protein, VCP-like ATPase of Thermoplasma acidophilum (VAT), is a homologue of SAV from Sulfolobus acidocaldarius and CdcH of Halobacterium salinarium, and belongs to the CDC48/VCP/p97 subfamily. The deduced product of the vat gene is 745 residues long (Mr 83,000), which has an optimal Mg2(+)-ATPase activity at 70 degrees C. Electron microscopy shows the purified protein to form single and double homo-hexameric rings. Although the symmetry is different, the appearance of the complexes formed of two rings resembles the 20S proteasome and Hsp60/GroEL.
 ...
PMID:Cloning, sequencing and expression of VAT, a CDC48/p97 ATPase homologue from the archaeon Thermoplasma acidophilum. 911 75

In the yeast Saccharomyces cerevisiae, autophagy, a bulk protein degradation in the vacuole, is induced in response to nutrient starvation. In a screen for mutations that result in induction of autophagy even in the presence of nutrients, we have isolated four mutants representing two csc complementation groups. These mutants induce autophagy of which activity is represented by activation of truncated alkaline phosphatase that is designed to be expressed in the cytosol. CSC1 was cloned by complementation of loss of viability phenotype of csc1-1 mutant and shown to be identical to END13/VPS4/GRD13. Though csc1-1 mutation is recessive, cells of delta csc1 do not induce autophagy in rich media, suggesting that csc1-1 allele is not a complete loss-of-function. Csc1p is a member of novel ATPase family named AAA protein including Sec18p/NSF, Cdc48p/p97, and Pas8p. Mutation site in csc1-1 is found in the SRH region that is highly conserved among AAA proteins. Cells of csc1-1 show sorting defect of CPY and the appearance of the class E compartment. These mutant phenotypes suggest the role of the protein that is involved in the traffic among the Golgi, endosome, and the vacuole in autophagy.
 ...
PMID:Mutational analysis of Csc1/Vps4p: involvement of endosome in regulation of autophagy in yeast. 943 54

The highly conserved ATPase p97, a member of the AAA-ATPases, is found in a complex with its co-factor p47 in rat liver cytosol. Previously it had been shown that p97-mediated reassembly of Golgi cisternae from mitotic Golgi fragments requires p47 which mediates the binding of p97 to a Golgi t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment factor receptor), syntaxin 5. Here we show that it also suppresses the ATPase activity of p97 by up to 85% in a dose-dependent and saturable manner suggesting that it has other roles in the membrane fusion cycle.
 ...
PMID:The p47 co-factor regulates the ATPase activity of the membrane fusion protein, p97. 982 2

Here we present the first description of the genomic organization, transcriptional regulatory sequences, and adult and embryonic gene expression for the mouse p97(CDC48) AAA ATPase. Clones representing two distinct p97 genes were isolated in a genomic library screen, one of them likely representing a non-functional processed pseudogene. The coding region of the gene encoding the functional mRNA is interrupted by 16 introns and encompasses 20.4 kilobase pairs. Definition of the transcriptional initiation site and sequence analysis showed that the gene contains a TATA-less, GC-rich promoter region with an initiator element spanning the transcription start site. Cis-acting elements necessary for basal transcription activity reside within 410 base pairs of the flanking region as determined by transient transfection assays. In immunohistological analyses, p97 was widely expressed in embryos and adults, but protein levels were tightly controlled in a cell type- and cell differentiation-dependent manner. A remarkable heterogeneity in p97 immunostaining was found on a cellular level within a given tissue, and protein amounts in the cytoplasm and nucleus varied widely, suggesting a highly regulated and intermittent function for p97. This study provides the basis for a detailed analysis of the complex regulation of p97 and the reagents required for assessing its functional significance using targeted gene manipulation in the mouse.
 ...
PMID:The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene. 1018 99

Members of the AAA family of ATPases have been implicated in chaperone-like activities. We used the archaeal Cdc48/p97 homologue VAT as a model system to investigate the effect of an AAA protein on the folding and unfolding of two well-studied, heterologous substrates, cyclophilin and penicillinase. We found that, depending on the Mg2+ concentration, VAT assumes two states with maximum rates of ATP hydrolysis that differ by an order of magnitude. In the low-activity state, VAT accelerated the refolding of penicillinase, whereas in the high-activity state, it accelerated its unfolding. Both reactions were ATP-dependent. In its interaction with cyclophilin, VAT was ATP-independent and only promoted refolding. The N-terminal domain of VAT, which lacks ATPase activity, also accelerated the refolding of cyclophilin but showed no effect on penicillinase. VAT appears to be structurally equivalent over its entire length to Sec18/NSF, suggesting that these results apply more broadly to group II AAA proteins.
 ...
PMID:The Janus face of the archaeal Cdc48/p97 homologue VAT: protein folding versus unfolding. 1054 42

Transport between intracellular compartments requires the activity of an N-ethylmaleimide-sensitive fusion protein (NSF). NSF is a member of a growing family of ATPases regulating several membrane fusion reactions. We have cloned the NSF ortholog from the moth, Manduca sexta (MsNSF). MsNSF is highly conserved in domains critical for NSF function in vertebrates. MsNSF codes for a protein of 745 amino acids, translating to a M(r) of 83kDa in vitro. MsNSF is 72% and 61% similar in amino acid sequence to Drosophila and vertebrate NSFs, respectively. We expressed the D1 ATP domain of MsNSF toward which antibodies selective to MsNSF were generated. Affinity purified alpha-MsNSF antibodies detect a 83kDa protein which is highly enriched in nervous tissues. Levels of MsNSF expression are substantially lower in other tissues examined. Anti-MsNSF antibodies are capable of inhibiting vertebrate intra-Golgi transport of a cargo protein in vitro. The identification of NSF ortholog from Manduca, whose neuroendocrine system is well studied, should facilitate isolation of complexes involved in protein trafficking from insect models. Phylogenetic analysis of NSF and related proteins suggests that the members of the AAA family arose from different ancestors, since the ingroup was not monophyletic. Proteasomal subunits and p97 homologs form two distinct subfamilies, while NSF homologs branch in to the third.
 ...
PMID:Identification of a Manduca sexta NSF ortholog, a member of the AAA family of ATPases. 1058 Jan 54

The AAA-ATPase, p97/Cdc48p, has been implicated in many different pathways ranging from membrane fusion to ubiquitin-dependent protein degradation. Binding of the p47 complex directs p97 to act in the post-mitotic fusion of Golgi membranes. We now describe another binding complex comprising mammalian Ufd1 and Npl4. Yeast Ufd1p is required for ubiquitin-dependent protein degradation whereas yeast Npl4p has been implicated in nuclear transport. In rat liver cytosol, Ufd1 and Npl4 form a binary complex, which exists either alone or bound to p97. Ufd1/Npl4 competes with p47 for binding to p97 and so inhibits Golgi membrane fusion. This suggests that it is involved in another cellular function catalysed by p97, the most likely being ubiquitin-dependent events during mitosis. The fact that the binding of p47 and Ufd1/Npl4 is mutually exclusive suggests that these protein complexes act as adapters, directing a basic p97 activity into different cellular pathways.
 ...
PMID:A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways. 1081 9

Two AAA family ATPases, NSF and p97, have been implicated in membrane fusion during assembly and inheritance of organelles of the secretory pathway. We have now investigated the roles of AAA ATPases in membrane fusion during assembly of the peroxisome, an organelle outside the classical secretory system. Here, we show that peroxisomal membrane fusion in the yeast Yarrowia lipolytica requires two AAA ATPases, Pex1p and Pex6p. Release of membrane- associated Pex1p and Pex6p drives the asymmetric priming of two fusion partners. The next step, peroxisome docking, requires release of Pex1p from one partner. Subsequent fusion of the peroxisomal membranes is independent of both Pex1p and Pex6p.
 ...
PMID:Peroxisomal membrane fusion requires two AAA family ATPases, Pex1p and Pex6p. 1095 11

p97, an abundant hexameric ATPase of the AAA family, is involved in homotypic membrane fusion. It is thought to disassemble SNARE complexes formed during the process of membrane fusion. Here, we report two structures: a crystal structure of the N-terminal and D1 ATPase domains of murine p97 at 2.9 A resolution, and a cryoelectron microscopy structure of full-length rat p97 at 18 A resolution. Together, these structures show that the D1 and D2 hexamers pack in a tail-to-tail arrangement, and that the N domain is flexible. A comparison with NSF D2 (ATP complex) reveals possible conformational changes induced by ATP hydrolysis. Given the D1 and D2 packing arrangement, we propose a ratchet mechanism for p97 during its ATP hydrolysis cycle.
 ...
PMID:Structure of the AAA ATPase p97. 1116 19

AAA ATPases play central roles in cellular activities. The ATPase p97, a prototype of this superfamily, participates in organelle membrane fusion. Cryoelectron microscopy and single-particle analysis revealed that a major conformational change of p97 during the ATPase cycle occurred upon nucleotide binding and not during hydrolysis as previously hypothesized. Furthermore, our study indicates that six p47 adaptor molecules bind to the periphery of the ring-shaped p97 hexamer. Taken together, these results provide a revised model of how this and possibly other AAA ATPases can translate nucleotide binding into conformational changes of associated binding partners.
 ...
PMID:A major conformational change in p97 AAA ATPase upon ATP binding. 1116 20


1 2 3 4 5 6 7 8 9 10 Next >>