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Literature summary extracted from

  • Wei, S.; Roessler, B.C.; Chauvet, S.; Guo, J.; Hartman, J.L.; Kirk, K.L.
    Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps (2014), J. Biol. Chem., 289, 19942-19957.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
5.6.1.6 transient recombinant expression of wild-type and mutant enzymes in HEK-293T cells Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
5.6.1.6 additional information each class of gain-of-function mutation in the transmembrane segements functionally rescues ATP binding mutants the enzyme presumably by enhancing ATP occupancy of the nucleotide-binding domains (i.e. by allosteric rescue of ATP binding defects in the nucleotide-binding domains), overview Homo sapiens
5.6.1.6 P355A gain of function mutation of a conserved proline at the base of the pore-lining transmembrane segment 6. Multiple substitutions of this proline promote ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-beta/gamma-imidodiphosphate (AMP-PNP) Homo sapiens
5.6.1.6 P355F gain of function mutation of a conserved proline at the base of the pore-lining transmembrane segment 6. Multiple substitutions of this proline promote ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-beta/gamma-imidodiphosphate (AMP-PNP) Homo sapiens
5.6.1.6 P355S gain of function mutation of a conserved proline at the base of the pore-lining transmembrane segment 6. Multiple substitutions of this proline promote ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-beta/gamma-imidodiphosphate (AMP-PNP) Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
5.6.1.6 membrane transmembrane protein Homo sapiens 16020
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5.6.1.6 ATP + H2O + closed Cl- channel Homo sapiens
-
 ADP + phosphate + open Cl- channel
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
5.6.1.6 Homo sapiens P13569
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5.6.1.6 ATP + H2O + closed Cl- channel
-
 Homo sapiens ADP + phosphate + open Cl- channel
-
 ?
5.6.1.6 ATP + H2O + closed Cl- channel ATP binding gates open enzyme CFTR by an allosteric mechanism, ATP binding biases the equilibrium toward the CFTR open state but is not absolutely required for channel opening Homo sapiens ADP + phosphate + open Cl- channel
-
 ?

Synonyms

EC Number Synonyms Comment Organism
5.6.1.6 CFTR
-
 Homo sapiens
5.6.1.6 CFTR channel
-
 Homo sapiens
5.6.1.6 transmembrane domains of cystic fibrosis transmembrane conductance regulator
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 Homo sapiens
5.6.1.6 transmembrane domains of cystic fibrosis transmembrane conductance regulator channel
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
5.6.1.6 evolution ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters and a unique ATP-gated ion channel, the cystic fibrosis transmembrane conductance regulator. CFTR channels and MRP efflux pumps share a conserved allosteric mechanism for coupling ATP binding to the translocation pathway, and reinforce the view that the CFTR gating mechanism is similar to the activation mechanisms of conventional ligand-gated channels. A proline (Pro355) at the base of pore-lining transmembrane segment 6 in enzyme CFTR is well conserved among the ABCC subfamily of ABC transporters Homo sapiens
5.6.1.6 additional information molecular dynamics simulations of the enzyme in closed and open conformation, overview Homo sapiens
5.6.1.6 physiological function the enzyme is a ATP-gated chloride channel. The enzyme shares gating principles with conventional ligand-gated ion channels, but the allosteric network couples ATP binding at its nucleotide binding domains with conformational changes in its transmembrane helices Homo sapiens