Any feedback?
Literature summary for 5.6.1.6 extracted from
- Mutating the conserved Q-loop glutamine 1291 selectively disrupts adenylate kinase-dependent channel gating of the ATP-binding cassette (ABC) adenylate kinase cystic fibrosis transmembrane conductance regulator (CFTR) and reduces channel function in prima (2015), J. Biol. Chem., 290, 14140-14153.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | adenosine 5'-(beta,gamma-imido)triphosphate, AMP-PNP, is a non-hydrolyzable ATP analogue that increases wild-type CFTR current by delaying channel closing and inducing prolonged open bursts | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| transient expression of wild-type and mutant enzymes in HeLa cell membranes using a vaccinia virus/T7 RNA polymerase expression system, recombinant expression of wild-type and mutant enzymes in CHO cells and in HEK-293T cells, also using a vaccinia virus-T7 hybrid expression system for the latter cell type | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | human bronchial airway epithelia derived from cystic fibrosis donors are homozygous for the F508del mutation in the enzyme. Photolabeling of CFTR with 8-N3-[32P]AMP or 8-N3-[32P]ATP. Cell surface biotinylation of wild-type and mutant enzyme CFTR | Homo sapiens |
| additional information | influence of Gln1291 mutations on single-channel gating, overview | Homo sapiens |
| Q1291A | mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current | Homo sapiens |
| Q1291F | mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current. The Q1291F mutation disrupts photolabeling of the AMP-binding site with 8-N3-AMP | Homo sapiens |
| Q1291G | mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current | Homo sapiens |
| Q1291H | mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current | Homo sapiens |
| Q1291W | mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current | Homo sapiens |
| Q1291Y | mutating Gln1291 disrupts adenylate kinase- but not ATPase-dependent gating, and reduces channel activity in airway epithelia. The mutant displays significantly reduced Cl- channel function in well differentiated primary human airway epithelia. Gln1291 mutations interfere with Ap5A inhibition of CFTR current | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| P1,P5-di(adenosine-5') pentaphosphate | Ap5A, an adenylate kinase inhibitor that partially inhibits wild-type CFTR, and inhibition can be attenuated by high ATP concentrations | Homo sapiens |  |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| plasma membrane | - |
Homo sapiens | 5886 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + closed Cl- channel | Homo sapiens | - |
ADP + phosphate + open Cl- channel | - |
? | |
| additional information | Homo sapiens | cystic fibrosis transmembrane conductance regulator (CFTR) channels have ATPase and adenylate kinase activity. In presence of ATP and physiologically relevant concentrations of AMP, the enzyme exhibits adenylate kinase activity, converting ATP and AMP into 2 ADP and vice versa. The enzyme interacts with AMP in an ATP-dependent manner | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P13569 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| glycoprotein | enzyme CFTR core glycosylation occurs in the endoplasmic reticulum | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| airway epithelium | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + closed Cl- channel | - |
Homo sapiens | ADP + phosphate + open Cl- channel | - |
? | |
| ATP + H2O + closed Cl- channel | using inside-out membrane patches from HeLa cells recombinantly and transiently expressing either wild-type or mutant enzyme CFTR | Homo sapiens | ADP + phosphate + open Cl- channel | - |
? | |
| additional information | cystic fibrosis transmembrane conductance regulator (CFTR) channels have ATPase and adenylate kinase activity. In presence of ATP and physiologically relevant concentrations of AMP, the enzyme exhibits adenylate kinase activity, converting ATP and AMP into 2 ADP and vice versa. The enzyme interacts with AMP in an ATP-dependent manner | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| CFTR | - |
Homo sapiens |
| cystic fibrosis transmembrane conductance regulator | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 23 | 26 | gating assay at room temperature | Homo sapiens |
| 37 | - |
adenylate kinase assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.3 | - |
gating assay at | Homo sapiens |
| 7.5 | - |
adenylate kinase assay at | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | human bronchial airway epithelia derived from cystic fibrosis donors are homozygous for the F508del mutation in the enzyme | Homo sapiens |
| additional information | highly conserved residue Gln1291 of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Photolabeling of CFTR with 8-N3-[32P]AMP or 8-N3-[32P]ATP, with a photoactivatable azido (N3)-group attached to the adenine ring | Homo sapiens |
| physiological function | the enzyme function in airway epithelia may depend on its adenylate kinase activity. Adenylate kinase activity is important for the function of an ATP-binding cassette transporter. Both the ATPase and adenylate kinase activities of CFTR can gate the channel. When ATP is the only nucleotide present, ATPase activity gates the channel, when AMP is present as well, adenylate kinase activity can also gate the channel | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
