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Information on EC 5.6.1.6 - channel-conductance-controlling ATPase and Organism(s) Mus musculus and UniProt Accession P26361
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5.6.1.6 channel-conductance-controlling ATPaseIUBMB Comments
ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. The enzyme is found in animals, and in humans its absence brings about cystic fibrosis. Unlike most of the ABC transporters, chloride pumping is not directly coupled to ATP hydrolysis. Instead, the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains. The enzyme is also involved in the functioning of other transmembrane channels.
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Word Map
- 5.6.1.6
- airway
- pulmonary
- camp
- epithelium
- pancreatic
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gate
-
gating
- forskolin
- bronchial
-
transepithelial
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nasal
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deltaf508
- na+
-
f508del
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mucus
-
camp-dependent
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short-circuit
-
blocker
-
nucleotide-binding
- deferens
-
patch-clamp
-
caucasian
-
cotransporter
- bicarbonate
- glibenclamide
-
ussing
-
mucociliary
-
camp-activated
-
non-cf
- infertility
-
electrolyte
-
camp-stimulated
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single-channel
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calu-3
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camp-regulated
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electrogenic
- bumetanide
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outwardly
-
forskolin-stimulated
-
current-voltage
- bronchiectasis
- amiloride
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inside-out
- azoospermia
-
cell-attached
-
amiloride-sensitive
- ibmx
- trypsinogen
-
spink1
- medicine
-
meconium
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
+
closed Cl- channel
=
+
+
open Cl- channel
Synonyms
cystic fibrosis transmembrane conductance regulator, cystic fibrosis transmembrane regulator, cftr channel, cftr cl- channel, cystic fibrosis conductance regulator, abcc7, epithelial basolateral chloride conductance regulator, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CFTR
cystic fibrosis transmembrane conductance regulator
cystic-fibrosis membrane-conductance protein
-
-
-
-
CFTR
-
-
-
-
cystic fibrosis transmembrane conductance regulator
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + closed Cl- channel = ADP + phosphate + open Cl- channel
the conformation of nucleotide-binding domain 1 changes before that of nucleotide-binding domain 2 during channel opening. Nucleotide-binding domain dimerization does not proceed by a symmetric tweezer-like motion, but instead in an asymmetric fashion led by nucleotide-binding domain1
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
transmembrane transport
-
-
-
-
hydrolysis of phosphate bond
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (channel-conductance-controlling)
ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. The enzyme is found in animals, and in humans its absence brings about cystic fibrosis. Unlike most of the ABC transporters, chloride pumping is not directly coupled to ATP hydrolysis. Instead, the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains. The enzyme is also involved in the functioning of other transmembrane channels.
CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
-
chloride channel
-
-
?
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
-
the enzyme is an ATP-binding cassette transporter that functions as a chloride channel. Channel gating occurs through ATP binding in an nucleotide-binding domain 1-nucleotide-binding domain 2 nucleotide sandwich that forms upon displacement of nucleotide-binding domain 1 regulatory segments
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-
?
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
-
CFTR is a Cl- channel
-
-
?
additional information
?
-
-
enzyme defects or inhibition lead to cystic fibrosis
-
-
?
additional information
?
-
-
neither channel activation nor inhibition influence the pH in recycling endosomes nor immature phagosomes. Perturbations of the endo-lysosomal organelles pH homeostasis cannot be linked to the etiology of the cystic fibrosis lung disease, effect of CFTR deficiency in genetically matched respiratory epithelia and alveolar macrophages, overview. CFTR-independent endosomal and phagosomal acidification occurs in RAW macrophages
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
-
the enzyme is an ATP-binding cassette transporter that functions as a chloride channel. Channel gating occurs through ATP binding in an nucleotide-binding domain 1-nucleotide-binding domain 2 nucleotide sandwich that forms upon displacement of nucleotide-binding domain 1 regulatory segments
-
-
?
ATP + H2O + closed Cl- channel
ADP + phosphate + open Cl- channel
-
CFTR is a Cl- channel
-
-
?
additional information
?
-
-
enzyme defects or inhibition lead to cystic fibrosis
-
-
?
additional information
?
-
-
neither channel activation nor inhibition influence the pH in recycling endosomes nor immature phagosomes. Perturbations of the endo-lysosomal organelles pH homeostasis cannot be linked to the etiology of the cystic fibrosis lung disease, effect of CFTR deficiency in genetically matched respiratory epithelia and alveolar macrophages, overview. CFTR-independent endosomal and phagosomal acidification occurs in RAW macrophages
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
inhibition of the enzyme with inhibitor CFTRinh172 and transfection with CFTR-specific siRNAs in DC2 cells reduces basal and forskolin-activated ATP release
-
additional information
-
4,4'-diisothiocyano-2,29-stilbenedisulfonic acid and tamoxifen have little effect on enzyme activity
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lubiprostone
-
lubiprostone enhances Cl- secretion across mouse ileum through a CFTR-dependent pathway and induces the secretory response in intestinal epithelium involving the enzyme. Lubiprostone enhances intestinal Cl- and fluid secretion via prostanoid receptor signaling, triggering activation of CFTR. The EP4-type prostanoid receptor antagonist L-161982 blocks the lubiprostone response
additional information
-
the channel activity of both wild type and G551D mutant enzyme is directly stimulated by mechanical perturbation induced by cell swelling at the single-channel, cellular, and tissue levels. The enzyme is also activated by membrane stretch
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
an immortalized epididymal cell line, quantitative enzyme expression analysis, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
inhibition or knockdown of CFTR inhibits ATP release from mouse epididymal principal cells. Inhibition of CFTR reduces ATP release into the lumen of cauda epididymis in mice in vivo. Defective ATP signalling in the epididymis might contribute to dysfunction of the male reproductive tract associated with CFTR mutations. Given that mutations in CFTR are a leading cause of male infertility, defective ATP signalling in the epididymis might contribute to dysfunction of the male reproductive tract associated with these mutations
physiological function
involvement of the enzyme in the regulation of ATP release from epithelial principal cells in the cauda epididymidis, ATP secretion into the lumen of the cauda epididymal tubule. Extracellular ATP is a key modulator of epididymal function, regulating both transepithelial transport
physiological function
-
the channel activity of the enzyme is required for epithelial regulatory volume decrease
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CFTR_MOUSE
1476
11
167870
Swiss-Prot
other Location (Reliability: 4), other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native and selenomethionyl nucleotide-binding domain 1, hanging-drop vapor-diffusion method
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G551D
-
the mutation impairs ATP hydrolysis and thereby makes the enzyme refractory to cAMP stimulation
additional information
additional information
-
CFTR knockout mice B6, aortas significantly more constricted than control arteries, less sensitive to the relaxing action of VIP, and fail to relax in the presence of CFTR activators
additional information
-
construction of human-murine CFTR chimeras with sequences from nucleotide-binding domain 1, nucleotide-binding domain 2, or the regulatory domain of human CFTR replaced by the equivalent regions of murine CFTR. The gating behavior of human-murine regulatory domain and human CFTR are indistinguishable, whereas human-murine nucleotide-binding domain 1 and human-murine nucleotide-binding domain 2 have subtle effects on channel gating, prolonging both burst duration and interburst interval. By contrast, human-murine nucleotide-binding domain1-2, containing both nucleotide-binding domains of murine CFTR, reproduces the gating behavior of the subconductance state of murine CFTR, which has dramatically prolonged channel openings
additional information
-
CFTR complementation of cystic fibrosis respiratory epithelia has no effect on the endosomal pH
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type nucleotide-binding domain 1 und a mutated version, K464A, in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
novel mechanism for regulation of the vascular tone by cAMP-dependent CFTR chloride channels in vascular smooth muscle cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sheppard, D.N.; Welsh, M.J.
Structure and function of the CFTR chloride channel
Physiol. Rev.
79
S23-45
1999
Homo sapiens, Mus musculus, shark, Xenopus sp.
Lewis, H.A.; Buchanan, S.G.; Burley, S.K.; Conners, K.; Dickey, M.; Dorwart, M.; Fowler, R.; Gao, X.; Guggino, W.B.; Hendrickson, W.A.; Hunt, J.F.; Kearins, M.C.; Lorimer, D.; Maloney, P.C.; Post, K.W.; Rajashankar, K.R.; Rutter, M.E.; Sauder, J.M.; Shriver, S.; Thibodeau, P.H.; Thomas, P.J.; Zhang, M.; Zhao, X.; Emtage, S.
Structure of nucleotide-binding domain 1 of the cystic fibrosis transmembrane conductance regulator
EMBO J.
23
282-293
2004
Mus musculus
Robert, R.; Norez, C.; Becq, F.
Disruption of CFTR chloride channel alters mechanical properties and cAMP-dependent Cl- transport of mouse aortic smooth muscle cells
J. Physiol.
568
483-495
2005
Mus musculus
Scott-Ward, T.S.; Cai, Z.; Dawson, E.S.; Doherty, A.; Da Paula, A.C.; Davidson, H.; Porteous, D.J.; Wainwright, B.J.; Amaral, M.D.; Sheppard, D.N.; Boyd, A.C.
Chimeric constructs endow the human CFTR Cl- channel with the gating behavior of murine CFTR
Proc. Natl. Acad. Sci. USA
104
16365-16370
2007
Homo sapiens, Mus musculus
Bijvelds, M.J.; Bot, A.G.; Escher, J.C.; de Jonge, H.R.
Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator
Gastroenterology
137
976-985
2009
Homo sapiens, Mus musculus
Barriere, H.; Bagdany, M.; Bossard, F.; Okiyoneda, T.; Wojewodka, G.; Gruenert, D.; Radzioch, D.; Lukacs, G.L.
Revisiting the role of CFTR and counterion permeability in the pH regulation of endocytic organelles
Mol. Biol. Cell
20
3125-3141
2009
Homo sapiens, Mus musculus
Ruan, Y.C.; Shum, W.W.; Belleannee, C.; Da Silva, N.; Breton, S.
ATP secretion in the male reproductive tract: essential role of CFTR
J. Physiol.
590
4209-4222
2012
Mus musculus (P26361), Mus musculus C57BL/6 (P26361)
Xie, C.; Cao, X.; Chen, X.; Wang, D.; Zhang, W.K.; Sun, Y.; Hu, W.; Zhou, Z.; Wang, Y.; Huang, P.
Mechanosensitivity of wild-type and G551D cystic fibrosis transmembrane conductance regulator (CFTR) controls regulatory volume decrease in simple epithelia
FASEB J.
30
1579-1589
2016
Homo sapiens, Mus musculus
EXTERNAL LINKS (specific for EC-Number 5.6.1.6)
Transporter Classification Database (TCDB): 3.A.1.202.2, 3.A.1.202.1
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