Disease relevance of ATP5AL1

• A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II [1].
• Binding sites for one Pi and two ATP or ADP molecules have been identified on the isolated, reconstitutively active beta subunit from the Rhodospirillum rubrum F0.F1 ATP synthase [2].
• Evaluation of gene expression profiles in a panel of leukemias revealed a strong correlation between the expression level of the gene encoding subunit 6 of the mitochondrial F(0)F(1) ATP synthase (known to be the binding site of members of this class of macrolides) and their sensitivity to these natural products [3].
• Immunologic identification of Na+,K(+)-ATPase isoforms in myocardium. Isoform change in deoxycorticosterone acetate-salt hypertension [4].
• We report a new type of fatal mitochondrial disorder caused by selective deficiency of mitochondrial ATP synthase (ATPase) [5].

Psychiatry related information on ATP5AL1

• Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3 [6].
• Prohibitin and ATP synthase protein levels were examined in the substantia nigra and frontal cortex (area 8) in five cases of Parkinson's disease (PD), five cases of dementia with Lewy bodies pure form (pDLB), five cases of early Alzheimer's disease (AD stage IIA, B), nine cases with advanced AD (stages V/VIC), and nine controls [7].
• This indicates that ATP synthase maintained its ATP synthesis and therefore its motor activity in the artificial membranes [8].

High impact information on ATP5AL1

• Other structural and mutational probes of the F1 and F0 portions of the ATP synthase are reviewed, together with kinetic and other evaluations of catalytic site occupancy and behavior during hydrolysis or synthesis of ATP [9].
• It lacks the pentose phosphate cycle and, more unexpectedly, ATP-synthase subunits, which are thought to be essential for life [10].
• Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface [11].
• We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase [11].
• This has been confirmed in the direction of hydrolysis after isolation of the soluble F1 portion of the protein and visualization of the actual rotation of the central 'shaft' of the enzyme with respect to the rest of the molecule, making ATP synthase the world's smallest rotary engine [12].

Chemical compound and disease context of ATP5AL1

• Measurement of activity and immunoblot results showed that ALDH2 and ATP synthase were also inhibited through oxidative modification of their cysteine or tyrosine residues in alcoholic fatty livers of rats [13].
• When 5-FU sensitivity was compared with ATP synthase activity in six different human colon cancer cell lines, a positive correlation has been found [14].
• The membrane topology of the a subunit of the F1F0 ATP synthase from Escherichia coli has been probed by surface labeling using 3-(N-maleimidylpropionyl) biocytin [15].
• The mRNA and protein products produced by an alpha-subunit-secreting pituitary tumor were studied to further characterize the early steps in glycoprotein hormone biosynthesis. alpha-Subunit mRNA was readily detected by RNA blot hybridization to alpha-subunit cDNA and was qualitatively normal, with a length of about 800 bases [16].
• Recombinant human 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthetase, isoform 1 (brain), was purified to near-homogeneity from an Escherichia coli expression system and kinetically characterized [17].

Biological context of ATP5AL1

• We have now studied the second avian gene known to exist in a copy on the nonrecombining regions of both the Z and the W chromosome, viz., the ATP synthase alpha-subunit (ATP5A1) [18].
• Three nuclear genome encoded membrane proteins, namely, the phosphate carrier (PHC), the adenine nucleotide carrier (ANT), and the ATP synthase complex, consisting of at least 13 individual subunits, catalyze these reactions [19].
• The locations of the alpha and gamma subunits of the mitochondrial ATP synthase complex and the mitochondrial phosphate carrier, PHC, on human chromosomes were determined using cloned rat liver cDNA as probes [19].
• We report here that the amino acid sequence surrounding this residue is highly homologous to the beta-subunit of mitochondrial and bacterial ATP-synthase in the region of the polypeptide that is believed to contribute to nucleotide binding [20].
• Homology between human bladder carcinoma oncogene product and mitochondrial ATP-synthase [20].

Anatomical context of ATP5AL1

• The enzyme ATP synthase, or F-ATPase, is present in the membranes of bacteria, chloroplasts and mitochondria [21].
• A 51.5-kD protein (p51.5) bearing structural and immunologic characteristics of the beta subunit of H+ transporting ATP synthase (E.C. 3.6.1.34, beta-H+ATPase, published molecular mass of 51.6 kD) was detected on the plasma membrane of three different human tumor cell lines studied [22].
• A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines [22].
• Structural and immunogold-assisted assignment of two of these complexes, photosystem I (PS I) and ATP synthase, allowed direct determination of their surface density, which, for both, was found to be highest in grana margins [23].
• The purified chloroplast ATP synthase (CF(0)-CF(1)) was reconstituted into azolectin liposomes from which bilayer membranes on the tip of a glass pipette ('dip stick technique')and planar bilayer membranes were form ed [24].

Associations of ATP5AL1 with chemical compounds

• PHLPP and a Second Isoform, PHLPP2, Differentially Attenuate the Amplitude of Akt Signaling by Regulating Distinct Akt Isoforms [25].
• The proton gradient may be used to synthesize adenosine triphosphate via an ATP synthase enzyme [26].
• The purified H(+)-translocating ATP synthase from chloroplasts was reconstituted into phosphatidylcholine/phosphatidic acid liposomes [27].
• Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes [28].
• Treatment with oligomycin and/or bongkrekic acid indicated that the maintenance of Deltapsi(m) during exposure to NO is caused by reversal of the ATP synthase and other electrogenic pumps [29].

Physical interactions of ATP5AL1

• The major storage component in CLN2 is the subunit c of mitochondrial ATP synthase complex and its accumulation is the direct result of lack of CLN2p in this disease [30].
• Amino-terminal sequencing coupled with peptide mass fingerprinting and immunologic analyses identified the plasminogen binding protein as annexin II and the angiostatin binding protein as the alpha/beta-subunits of ATP synthase [31].
• NRF-1 and NRF-2 can bind to some of the subunits of both CCO and ATP synthase to regulate gene expression [32].
• Small-angle X-ray scattering studies of Mg.AT(D)P-induced hexamer to dimer dissociation in the reconstituted alpha 3 beta 3 complex of ATP synthase from thermophilic bacterium PS3 [33].
• Purified AKAP121 KH domain binds the 3' untranslated regions (3'UTRs) of transcripts encoding the Fo-f subunit of mitochondrial ATP synthase and manganese superoxide dismutase (MnSOD) [34].

Enzymatic interactions of ATP5AL1

• The beta subunit of chloroplast ATP synthase (CF0CF1-ATPase) is phosphorylated by casein kinase II [35].

Co-localisations of ATP5AL1

• In addition to the expected mitochondria localization, ATP-2 and other ATP synthase components colocalize with LOV-1 and PKD-2 in cilia [36].

Regulatory relationships of ATP5AL1

• In these cells, UCP1 acts as a proton carrier activated by free fatty acids and creates a shunt between complexes of the respiratory chain and ATP synthase [37].
• Inhibitors of electron-transport chain complex III, antimycin A and myxothiazol, the ATP synthase inhibitor oligomycin and ATP depletion with 2-deoxyglucose or glucosamine also blocked HO-1 induction [38].
• Paclitaxel induces apoptosis via protein kinase A- and p38 mitogen-activated protein-dependent inhibition of the Na+/H+ exchanger (NHE) NHE isoform 1 in human breast cancer cells [39].
• Upstream stimulatory factor 2 activates the mammalian F1F0 ATP synthase alpha-subunit gene through an initiator element [40].
• Transcript levels of mitochondrial-encoded ATP synthase 6/8 were similarly upregulated in these tissues whereas transcript levels of the nuclear encoded subunits Cox4 and ATP synthase alpha did not change during hibernation [41].

Other interactions of ATP5AL1

• The four mitochondrial ATP synthase alpha-subunit (ATP5A) genes map to chromosomes 2, 9, 16, and 18 [42].
• Angiostatin also bound to the recombinant alpha-subunit of human ATP synthase, and this binding was not inhibited by a 2,500-fold molar excess of plasminogen [31].
• Coexpression of RNPS1 with p54 cooperatively stimulated exon inclusion in an ATP synthase gamma-subunit pre-mRNA [43].
• RT-PCR and Western blot analyses with a specific antibody against UGT1A1 indicate that isoform 2 is differentially expressed in liver, kidney, colon, and small intestine at levels that reach or exceed, for some tissues, those of isoform 1 [44].
• The low-serum component of this microenvironment confers increased motility and invasion in breast cancer cells by activating the Na+/H+ exchanger isoform 1 (NHE1) [45].

Analytical, diagnostic and therapeutic context of ATP5AL1

• ATP synthase: an electrochemical transducer with rotatory mechanics [46].
• In this study, we have determined NHE kinetics in cultured lymphoblasts from diabetic patients with and without nephropathy, with nondiabetic controls, using fluorometry with the pH indicator 2,7'-bis-(carboxyethyl)-5,6-carboxyfluorescein and estimation of NHE isoform 1 (NHE-1) density with specific polyclonal antibodies [47].
• RNA editing of subunit 9 of the wheat mitochondrial ATP synthase has been studied by cDNA and protein sequence analysis [48].
• Western blotting showed that expression of other ATP synthase complex subunits was also lower in 5-FU-resistant cell lines and that these resistant cells also showed decreased ATP synthase activity and reduced intracellular ATP content [14].
• Two-dimensional gel electrophoresis data showed there was lower expression of the alpha subunit of mitochondrial F(1)F(0)-ATP synthase (ATP synthase) in 5-FU-resistant cells compared with parent cells [14].

References