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EC Tree
IUBMB Comments Also acts on dATP to form 3',5'-cyclic dAMP. Requires pyruvate. Activated by NAD+ in the presence of EC 2.4.2.31 NAD(P)+---arginine ADP-ribosyltransferase.
The taxonomic range for the selected organisms is: Bos taurus The enzyme appears in selected viruses and cellular organisms
Synonyms
adenylate cyclase, adenylyl cyclase, adenyl cyclase, pituitary adenylate cyclase, edema factor, adenylylcyclase, soluble adenylyl cyclase, adenylate cyclase toxin, adcy5, aciii,
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3',5'-cyclic AMP synthetase
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Adenylate cyclase, olfactive type
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adenylate cyclases IV
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adenylate cyclases VI
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Adenylyl cyclase type 10
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ATP pyrophosphate-lyase
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Ca(2+)-inhibitable adenylyl cyclase
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Ca(2+)/calmodulin activated adenylyl cyclase
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cyclase, adenylate
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soluble adenylyl cyclase
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AC2
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AC3
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P-O bond cleavage
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ATP diphosphate-lyase (cyclizing; 3',5'-cyclic-AMP-forming)
Also acts on dATP to form 3',5'-cyclic dAMP. Requires pyruvate. Activated by NAD+ in the presence of EC 2.4.2.31 NAD(P)+---arginine ADP-ribosyltransferase.
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ATP
3',5'-cAMP + diphosphate
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ATP
3',5'-cAMP + diphosphate
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Mg2+
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2',5'-dideoxyadenosine
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inhibitor significantly inhibits heparin-induced capacitation of sperm cells
beta, gamma subunit of the guanine-nucleotide binding regulatory protein
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Gbetagamma
a second isoform- and regulator-specific contact site in C2 is necessary to render enzyme activity susceptible to Gbetagamma modulation. In addition to the PFAHL-motif in C1b of ACII, Gbetagamma contacts the KF-loop in C2
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5'-guanylimidodiphosphate
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activation
alpha subunit of the guanine-nucleotide binding regulatory protein
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activation
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BIM-1
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specific protein-kinase C inhibitor, significantly increases cumulus cell cAMP concentrations
clonidine
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slight stimulatory effect on cAMP concentrations
EGTA
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significantly increases cumulus cell cAMP concentrations
guanosine 5'-(beta,gamma-imido)triphosphate
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activation
H89
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specific inhibitor of protein-kinase A, significantly increases cumulus cell cAMP concentrations at 0.0001 and 0.03 mM
ionomycin
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increases intracellular Ca2+ concentrations, significantly increases cumulus cell cAMP concentrations
pertussis toxin
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catalyses ADP-ribosylation of a cysteine residue on GalphaI, causing the G-protein complex to become uncoupled from the receptor, significantly increases cAMP concentrations
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staurosporine
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non-specific protein-kinase C inhibitor, significantly increases cumulus cell cAMP concentrations
thapsigargin
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increases intracellular Ca2+ concentrations, significantly increases cumulus cell cAMP concentrations
additional information
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cholera toxin, KN-62, phorbol-12-myristate-13-acetate and BAPTA-am or a combination of 3 mM EGTA plus BAPTA-am have no effect on cAMP concentrations
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Calmodulin
a second isoform- and regulator-specific contact site in C2 is necessary to render enzyme activity susceptible to calmodulin modulation. In addition to the PFAHL-motif in C1b of ACII, calmodulin requires not only the Ca2+-independent AC28-region in C1b but also a Ca2+-dependent domain in C2a of ACI with the VLG-loop to stimulate this adenylyl cyclase isoform
Calmodulin
calmodulin activation of isoform Adcy1 can be regulated by selctive oxidation of the C-terminal Met residues in calmodulin, and by two N-terminal Met residues, M36 and M51. CaM with all Met residues oxidized is unable to activate the enzyme
forskolin
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activation
forskolin
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increases substantially cAMP concentrations
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0.07
ATP
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5
ATP
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recombinant protein
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additional information
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SwissProt
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isoform Adcy1
SwissProt
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AC isoforms 3, 4, 6, 8, and 9
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sAC
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additional information
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AC isoforms 1, 3, 4, 6, and 9 in cumulus cells. AC1, AC4 and AC6 predominate
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cerebral cortex
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mictrotubule
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all nine membrane-associated isoforms
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membrane-associated
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physiological function
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hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a membrane-associated adenylate cyclase. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by membrane-associated adenylate cyclase
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ADCY1_BOVIN
1134
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123979
Swiss-Prot
other Location (Reliability: 2 )
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115000
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catalytic unit, SDS-PAGE
358000
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sucrose density gradient centrifugation
150000
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sucrose density gradient centrifugation
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V1027A/L1031A
is not catalytically active under basal, Galphas- or forskolin-stimulated conditions
additional information
ACI-deletion mutants ACI.lambda1057 with reduced catalytic activity and ACI.lambda1094, which like mutant ACIlambda1057 is active and stimulated by Ca/CaM as well as ACI. Mutant ACII.lambda928 is catalytically inactive, mutant ACII.AA930 shows diminished activity, mutants ACII.AA925 or ACII.AA932 show no significant change in Gbetagamma-regulation
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recombinant adenylyl cyclase
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expression in HEK 293 cells
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expression in Sf9 cells
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medicine
isoform Adcy1 catalytic activity can be delicately adjusted by mediating calmodulin activation of Adcy1 by reversible Met oxidation in calmodulin
medicine
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cumulus cells possess multiple active isoforms of adenylyl cyclase, each isoform may have a specific role at a specific time during oocyte growth and maturation
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Shattuck, R.L.; Oldenburg, D.J.; Storm, D.R.
Purification and characterization of a calmodulin-sensitive adenylate cyclase from Bordetella pertussis
Biochemistry
24
6356-6362
1985
Bordetella pertussis, Bos taurus
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Yeager, R.E.; Heideman, W.; Rosenberg, G.B.; Storm, D.R.
Purification of the calmodulin-sensitive adenylate cyclase from bovine cerebral cortex
Biochemistry
24
3776-3783
1985
Bos taurus
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Wolff, J.; Cook, G.H.
Microtubule-associated adenylate cyclase
Biochim. Biophys. Acta
844
34-41
1985
Bos taurus
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Asbury, R.F.; Cook, G.H.; Wolff, J.
Soluble adenylate cyclase from thyroid membranes
J. Biol. Chem.
253
5286-5292
1978
Bos taurus
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Herman, C.A.; Zahler, W.L.; Doak, G.A.; Campbell, B.J.
Bull sperm adenylate cyclase: localization and partial characterization
Arch. Biochem. Biophys.
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622-629
1976
Bos taurus
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Tang, W.J.; Krupinski, J.; Gilman, A.G.
Expression and characterization of calmodulin-activated (type I) adenylylcyclase
J. Biol. Chem.
266
8595-8603
1991
Bos taurus
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Moos Jr., M.; Morris, D.I.; Robbins, J.; Appel, L.; Seamon, K.B.
Purification of bovine brain adenylyl cyclase with a novel derivative of forskolin: evidence for a high specific activity form of the enzyme
Prep. Biochem. Biotechnol.
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155-167
1996
Bos taurus
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Wang, P.; Storm, D.R.
Purification and characterization of calmodulin-sensitive adenylyl cyclase from bovine brain
Methods Enzymol.
195
65-82
1991
Bos taurus
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Diel, S.; Beyermann, M.; Navarro Llorens, J.M.; Wittig, B.; Kleuss, C.
Two Interaction Sites on Mammalian Adenylyl Cyclase Type I and II: modulation by calmodulin and Gbetagamma
Biochem. J.
411
449-456
2008
Bos taurus (P19754)
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Lastro, M.; Collins, S.; Currie, W.B.
Adenylyl cyclases in oocyte maturation: a characterization of AC isoforms in bovine cumulus cells
Mol. Reprod. Dev.
73
1202-1210
2006
Bos taurus
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Fernandez, S.; Cordoba, M.
A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid
Anim. Reprod. Sci.
179
80-87
2017
Bos taurus
brenda
Luebker, C.; Urbauer, R.; Moskovitz, J.; Dove, S.; Weisemann, J.; Fedorova, M.; Urbauer, J.; Seifert, R.
Membranous adenylyl cyclase 1 activation is regulated by oxidation of N- and C-terminal methionine residues in calmodulin
Biochem. Pharmacol.
93
196-209
2015
Bos taurus (P19754)
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Transporter Classification Database (TCDB):
8.A.85.1.4