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Information on EC 4.6.1.1 - adenylate cyclase and Organism(s) Homo sapiens and UniProt Accession O43306

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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.
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Homo sapiens
UNIPROT: O43306
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
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, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
adenylyl cyclase
-
adenylyl cyclase type VI
-
type 6 adenylyl cyclase
-
3',5'-cyclic AMP synthetase
-
-
-
-
AC 1
-
-
AC 2
-
-
AC 3
-
-
AC 4
-
-
AC 5
-
-
AC 7
-
-
AC 8
-
-
AC 9
-
-
ACI
-
isoform
ACII
-
isoform
ACTP10
-
-
-
-
ACVI
-
-
ADCY10
-
-
adenyl cyclase
-
-
-
-
adenylate cyclase
-
-
adenylate cyclase 1
-
-
adenylate cyclase 10
-
-
adenylate cyclase 6
-
-
adenylate cyclase type 10
-
Adenylate cyclase, olfactive type
-
-
-
-
adenylyl cyclase
Adenylyl cyclase type 10
-
-
-
-
adenylyl cyclase VII
-
adenylylcyclase
-
-
-
-
ATP pyrophosphate-lyase
-
-
-
-
Ca(2+)-inhibitable adenylyl cyclase
-
-
-
-
Ca(2+)/calmodulin activated adenylyl cyclase
-
-
-
-
cyclase, adenylate
-
-
-
-
Edema factor
-
-
-
-
Rutabaga protein
-
-
-
-
soluble AC
-
soluble adenylate cyclase
soluble adenylyl cyclase
-
-
transmembrane adenylyl cyclase type 1
-
-
transmembrane adenylyl cyclase type 3
-
-
transmembrane adenylyl cyclase type 8
-
-
type 3 adenylyl cyclase
-
type 6 adenylyl cyclase
-
-
type 8 adenylyl cyclase
-
-
type I adenylate cyclase
-
-
type V adenylyl cyclase
-
isoform
type VI adenylyl cyclase
xlAC
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
P-O bond cleavage
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
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.
CAS REGISTRY NUMBER
COMMENTARY hide
9012-42-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP
3',5'-cyclic-AMP + diphosphate
show the reaction diagram
ATP
3',5'-cAMP + diphosphate
show the reaction diagram
ATP
3',5'-cyclic AMP + diphosphate
show the reaction diagram
ATP
3',5'-cyclic-AMP + diphosphate
show the reaction diagram
ATP
cAMP + diphosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP
3',5'-cyclic-AMP + diphosphate
show the reaction diagram
ATP
3',5'-cyclic AMP + diphosphate
show the reaction diagram
ATP
3',5'-cyclic-AMP + diphosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
bicarbonate
activates
NaF
-
activates
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2',5'-dideoxyadenosine
massive inhibition of cAMP formation with a combination of enzyme inhibitors 9-(tetrahydro-29-furyl)adenine and 2',5'-dideoxyadenosine
inhibitory G protein
-
-
SQ 22536
i.e. 9-(tetrahydro-29-furyl)adenine, massive inhibition of cAMP formation with a combination of enzyme inhibitors 9-(tetrahydro-29-furyl)adenine and 2',5'-dideoxyadenosine
1alpha,9alpha-dihydroxy-labd-13(E)-ene-8a,15-diol
-
a derivative of each of the two stereoisomers of labd-13(E)-ene-8a,15-diol, overview
1alpha-hydroxy-labd-13(E)-ene-8a,15-diol
-
a derivative of each of the two stereoisomers of labd-13(E)-ene-8a,15-diol, overview
2',3'-O-(2,4,6-trinitrophenyl)-ADP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-AMP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-ATP
-
most potent inhibitor for isoform ACV
2',3'-O-(2,4,6-trinitrophenyl)-CTP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-GDP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-GTP
-
-
2',3'-O-(2,4,6-trinitrophenyl)-UTP
-
most potent inhibitor for isoforms ACI and ACII
2',3'-O-(N-anthraniloyl)-ADP
-
-
2',3'-O-(N-anthraniloyl)-ATP
-
-
2',3'-O-(N-anthraniloyl)-IMP
-
-
2',3'-O-(N-methylanthraniloyl)-ADP
-
-
2',3'-O-(N-methylanthraniloyl)-ATP
-
-
2',3'-O-(N-methylanthraniloyl)-CDP
-
-
2',3'-O-(N-methylanthraniloyl)-CTP
-
-
2',3'-O-(N-methylanthraniloyl)-GTP
-
-
2',3'-O-(N-methylanthraniloyl)-GTPgammaS
-
potent inhibitor of isoform AC5
2',3'-O-(N-methylanthraniloyl)-IDP
-
-
2',3'-O-(N-methylanthraniloyl)-IMP
-
-
2',3'-O-(N-methylanthraniloyl)-ITP
-
-
2',3'-O-(N-methylanthraniloyl)-ITPgammaS
-
potent inhibitor of isoform AC5
2',3'-O-(N-methylanthraniloyl)-UDP
-
-
2',3'-O-(N-methylanthraniloyl)-UTP
-
-
2',3'-O-(N-methylanthraniloyl)-XTP
-
-
2',5'-dideoxyadenosine
massive inhibition of cAMP formation with a combination of enzyme inhibitors 9-(tetrahydro-29-furyl)adenine and 2',5'-dideoxyadenosine
2'-d3'-AMP
P-site inhibitor, uncompetitive. A complemented state of the enzyme is strongly stabilized by the presence of the inhibitor and diphosphate
2'-deoxy-3'-O-[2-(methylamino)benzoyl]adenosine 5'-triphosphate
-
-
2'-deoxy-3'-O-[2-(methylamino)benzoyl]guanosine 5'-triphosphate
-
-
2-hydroxy-17beta-estradiol
-
specific sAC inhibitor, blocks CO2/HCO3- mediated cAMP production
2-hydroxyestradiol
-
reversible inhibition of recombinant soluble enzyme in dose dependent manner, IC50 in low micromolar range, trans-membrane enzyme VII IC50 of about 2 microM
2-hydroxyestrone
-
reversible inhibition of recombinant soluble enzyme in dose dependent manner, IC50 in low micromolar range
2OH-17beta estradiol
-
inhibits bicarbonate-induced cAMP production
3'-deoxy-2'-O-[2-(methylamino)benzoyl]adenosine 5'-triphosphate
-
-
3'-deoxy-2'-O-[2-(methylamino)benzoyl]guanosine 5'-triphosphate
-
-
4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
-
-
4-hydroxyestradiol
-
reversible inhibition of recombinant soluble enzyme in dose dependent manner, IC50 in low micromolar range
arginine-vasopressin
-
-
ATP
-
substrate inhibition at high concentrations, inhibition is relieved in the presence of HCO3-, no substrate inhibition in the presence of 50 mM HCO3-
bithionol
potent, isoform Adcy10-specific inhibitor, noncompetitive with respect to ATP
buprenorphine
-
a low-efficacy partial mu-opioid agonist
Ca2+/calcineurin
-
-
-
Carbachol
-
increases intracellular calcium, inhibits A2bR mediated increase in cAMP by 53%
DAMGO
-
a higher efficacy mu-opioid agonist
diphosphate
-
non-competitive inhibitor with respect to ATP
EDTA
-
-
Galphai
-
inhibits Galphas-stimulated activities of ACVI, Gbetagamma does not alter the ability of Galphai to inhibit the activities of ACVI
GALPHAI protein
-
inhibits basal activity of isoform V, not the basal activity of isoform VI
-
Hexachlorophene
potent, isoform Adcy10-specific inhibitor, noncompetitive with respect to ATP
inhibitory G protein
-
both alpha and betagamma subunits, activated by GTP binding, can modulate activity of effectors in transduction signaling, including adenylyl cyclase. In depressed patients, the expression of stimulatory G protein is increased and of inhibitory G protein is decreased, which suggests greater stimulation of the cAMP pathway
-
L-(+)-2,3-butanediol
-
isoform AC7 activity is inhibited to about 50% with 100 mM L-(+)-2,3-butanediol
labd-13(E)-ene-8a,15-diol
-
isolated from the resin Ladano of the plant Cistus creticus subsp. creticus that grows in the island of Crete, Greece. Docking calculations of the two stereoisomers of the compound and derivatives to the enzyme at the forskolin binding site, overview
lubrol-PX
-
-
morphine
-
a higher efficacy mu-opioid agonist
nalbuphine
-
a low-efficacy partial mu-opioid agonist
NO
-
NO functions either via an as yet unidentified regulator of adenylyl cyclase or the enzyme itself is the target of NO, inhibition is reversed by reducing agents
Oxytocin
-
-
PAPANANOATE
-
nitric oxide donor, completely abolishes A2bR mediated cAMP production
phosphocreatine
-
-
prostaglandin E1
-
-
putrescine
-
-
quinpirole
-
-
S-nitroso-N-acetylpenicillamine
-
nitric oxide donor, inhibits A2bR mediated increase in cAMP by 64%
spermidine
-
-
spermine
-
-
SQ 22536
i.e. 9-(tetrahydro-29-furyl)adenine, massive inhibition of cAMP formation with a combination of enzyme inhibitors 9-(tetrahydro-29-furyl)adenine and 2',5'-dideoxyadenosine
SQ22536
thrombin
-
thrombin transiently inhibits adenylyl cyclase 6
-
tyrphostin A25
-
IC50 0.119mM, IC50 forskolin-stimulated adenylyl cyclase 1 mM, 37°C, pH 7.5
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
isoproterenol
-
stimulating G protein
GalphaS, and Gbeta1 and Ggamma2 subunits, G-protein-coupled receptors couple Galphas and activate isozyme ACVI
-
1,2,3-propanetriol
-
isoform AC6 shows about 10% stimulation of activity with 100 mM 1,2,3-propanetriol, isoform AC7 shows about 18% stimulation of activity with 100 mM 1,2,3-propanetriol, isoform AC9 shows about 15% stimulation of activity with 100 mM 1,2,3-propanetriol
1,2-Butanediol
-
isoform AC6 shows about 37% stimulation of activity with 100 mM 1,2-butanediol, isoform AC7 shows about 38% stimulation of activity with 100 mM 1,2-butanediol, isoform AC9 shows about 32% stimulation of activity with 100 mM 1,2-butanediol
1,3-butanediol
-
isoforms AC6 and AC7 show about 22% stimulation of activity with 100 mM 1,3-butanediol, isoform AC9 shows about 17% stimulation of activity with 100 mM 1,3-butanediol
1,3-Propanediol
-
isoform AC6 shows about 17% stimulation of activity with 100 mM 1,3-propanediol, isoform AC7 shows about 20% stimulation of activity with 100 mM 1,3-propanediol, isoform AC9 shows about 17% stimulation of activity with 100 mM 1,3-propanediol
1,4-Butanediol
-
isoform AC6 shows about 30% stimulation of activity with 100 mM 1,4-butanediol, isoform AC7 shows about 25% stimulation of activity with 100 mM 1,4-butanediol, isoform AC9 shows about 40% stimulation of activity with 100 mM 1,4-butanediol
1-butanol
-
isoform AC6 shows about 85% stimulation of activity with 100 mM 1-butanol, isoform AC7 shows about 110% stimulation of activity with 100 mM 1-butanol, isoform AC9 shows about 105% stimulation of activity with 100 mM 1-butanol
1-propanol
-
isoform AC6 shows about 31% stimulation of activity with 100 mM 1-propanol, isoform AC7 shows about 50% stimulation of activity with 100 mM 1-propanol, isoform AC9 shows about 44% stimulation of activity with 100 mM 1-propanol
2,3-Butanediol
-
isoform AC6 shows about 30% stimulation of activity with 100 mM 2,3-butanediol, isoform AC7 shows about 35% stimulation of activity with 100 mM 2,3-butanediol, isoform AC9 shows about 41% stimulation of activity with 100 mM 2,3-butanediol
2-butanol
-
isoform AC6 shows about 60% stimulation of activity with 100 mM 2-butanol, isoform AC7 shows about 70% stimulation of activity with 100 mM 2-butanol, isoform AC9 shows about 60% stimulation of activity with 100 mM 2-butanol
2-propanol
-
isoform AC6 shows about 20% stimulation of activity with 100 mM 2-propanol, isoform AC7 shows about 35% stimulation of activity with 100 mM 2-propanol, isoform AC9 shows about 40% stimulation of activity with 100 mM 2-propanol
A2B adenosine receptor
-
activates the enzyme and regulates its activity and the cAMP signaling pathway in mast and microvascular cell, role of the C-terminus of the A2B receptor in stimulation of adenylate cyclase, which is important for A2B receptor coupling to Gs-adenylate cyclase, overview
-
A2bR
-
-
-
Calmodulin
Carbachol
-
carbachol-induced capacitative Ca2+ entry clearly stimulates AC8-mediated cAMP production at the single-cell level
catecholamine
-
activation
CO2
-
induces acidification of cells, accompanied by a rise in intracellular HCO3-
D-(-)-2,3-butanediol
-
isoforms AC6 and AC7show about 30% stimulation of activity with 100 mM D-(-)-2,3-butanediol, isoform AC9 shows about 10% stimulation of activity with 100 mM D-(-)-2,3-butanediol
D1A dopamine receptor
-
-
-
ethanol
forskolin
G-protein
-
G-protein alpha-subunit
-
-
-
Galphas
-
GALPHAS protein
-
250fold stimulation isoform V, 500fold stimulation isoform VI
-
Gbeta1gamma2
-
increases the activation of ACV and ACVI by forskolin or Galphas. Gbetagamma subunits derived from sources other than Gi participate in mediating the full activation of ACVI by the beta-adrenergic receptor agonist, isoproterenol
-
Gsalpha
-
AC5 undergoes a cooperative activation by Gsalpha
-
GTPgammaS
guanosine 5'-(beta,gamma-imido)triphosphate
-
activation
HCO3-
isoprenaline
-
-
isoproterenol
L-(+)-2,3-butanediol
-
isoform AC6 shows about 55% stimulation of activity with 100 mM L-(+)-2,3-butanediol, isoform AC9 shows about 45% stimulation of activity with 100 mM L-(+)-2,3-butanediol
meso-2,3-butanediol
-
isoform AC6 shows about 15% stimulation of activity with 100 mM meso-2,3-butanediol, isoform AC7 shows about 28% stimulation of activity with 100 mM meso-2,3-butanediol, isoform AC9 shows about 10% stimulation of activity with 100 mM meso-2,3-butanediol
NaF
-
activation
NaHCO3
-
10 mM, 30fold activation, half-maximal activation at 11 mM
PKC
-
-
-
prostaglandin E1
-
-
protein kinase A
-
stimulates cAMP in the brain, the activation is increased in brains of patients with bipolar mood disorders, overview
-
Protein kinase C
phosphorylation
-
relaxin
-
AC5 activity is potentiated by PKCzeta after exposure to relaxin
-
Sodium fluoride
-
-
sphingosine 1-phosphate
stimulates
stimulating G protein
-
thapsigargin
-
thapsigargin-induced capacitative Ca2+ entry clearly stimulates AC8-mediated cAMP production at the single-cell level
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011 - 0.8
ATP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00014 - 0.0011
2',3'-O-(2,4,6-trinitrophenyl)-ADP
0.0048 - 0.0074
2',3'-O-(2,4,6-trinitrophenyl)-AMP
0.0000037 - 0.000099
2',3'-O-(2,4,6-trinitrophenyl)-ATP
0.000024 - 0.00011
2',3'-O-(2,4,6-trinitrophenyl)-CTP
0.00041 - 0.0034
2',3'-O-(2,4,6-trinitrophenyl)-GDP
0.000023 - 0.00022
2',3'-O-(2,4,6-trinitrophenyl)-GTP
0.0000071 - 0.000024
2',3'-O-(2,4,6-trinitrophenyl)-UTP
0.00064 - 0.0029
2',3'-O-(N-anthraniloyl)-ADP
0.00012 - 0.00064
2',3'-O-(N-anthraniloyl)-ATP
0.0043 - 0.0075
2',3'-O-(N-anthraniloyl)-IMP
0.00079 - 0.0029
2',3'-O-(N-methylanthraniloyl)-ADP
0.0001 - 0.00033
2',3'-O-(N-methylanthraniloyl)-ATP
0.00058 - 0.0037
2',3'-O-(N-methylanthraniloyl)-CDP
0.00015 - 0.00069
2',3'-O-(N-methylanthraniloyl)-CTP
0.000053 - 0.00061
2',3'-O-(N-methylanthraniloyl)-GTP
0.000034 - 0.00037
2',3'-O-(N-methylanthraniloyl)-GTPgammaS
0.000031 - 0.000086
2',3'-O-(N-methylanthraniloyl)-IDP
0.0044 - 0.0085
2',3'-O-(N-methylanthraniloyl)-IMP
0.0000012 - 0.000014
2',3'-O-(N-methylanthraniloyl)-ITP
0.000032 - 0.00012
2',3'-O-(N-methylanthraniloyl)-ITPgammaS
0.00034 - 0.0027
2',3'-O-(N-methylanthraniloyl)-UDP
0.000032 - 0.00046
2',3'-O-(N-methylanthraniloyl)-UTP
0.0011 - 0.003
2',3'-O-(N-methylanthraniloyl)-XTP
0.00032 - 0.0048
2'-deoxy-3'-O-[2-(methylamino)benzoyl]adenosine 5'-triphosphate
0.00027 - 0.0013
2'-deoxy-3'-O-[2-(methylamino)benzoyl]guanosine 5'-triphosphate
0.000065 - 0.00054
3'-deoxy-2'-O-[2-(methylamino)benzoyl]adenosine 5'-triphosphate
0.0018 - 0.0087
3'-deoxy-2'-O-[2-(methylamino)benzoyl]guanosine 5'-triphosphate
1
GTP
-
in 50 mM Tris-HCl (pH 8.0), 50 mM NaCl, 10 mM MgCl2, 10 mM CaCl2, at 37°C
additional information
additional information
-
inhibition of forskolin-stimulated adenylyl cyclase by mu-opioid recptor agonists in cells expressing different forms of G proteins, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002
2-hydroxyestradiol
Homo sapiens
-
reversible inhibition of recombinant soluble enzyme in dose dependent manner, IC50 in low micromolar range, trans-membrane enzyme VII IC50 of about 2 microM
0.043
4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
Homo sapiens
-
in 50 mM Tris-HCl (pH 8.0), 50 mM NaCl, 10 mM MgCl2, 10 mM CaCl2, at 37°C
0.000022
arginine-vasopressin
Homo sapiens
-
-
0.0000034
Oxytocin
Homo sapiens
-
-
0.119
tyrphostin A25
Homo sapiens
-
IC50 0.119mM, IC50 forskolin-stimulated adenylyl cyclase 1 mM, 37°C, pH 7.5
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
ciliary beat frequency is stimulated by cAMP independently of intracellular pH
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
forskolin-insensitive AC isoforms in various B cell populations
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
erythroleukemia cell line, high expression of isozyme AC7
Manually annotated by BRENDA team
-
cardiac
Manually annotated by BRENDA team
a macrophage-like cell line
Manually annotated by BRENDA team
-
specific localization of the 50 kDa isoform to the axoneme of ciliated airway epithelial cells
Manually annotated by BRENDA team
-
expresses all nine adenylate cyclase isoforms
Manually annotated by BRENDA team
additional information
-
AC1 and AC8 present at the apical pool of airway epithelial cells, specifically in ciliated cells, AC3 mainly present on the basolateral aspect
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
in SH-SY5Y cells AC9 mainly in irregular discrete punctae which are distinct from lysosomes, early endosomes or tubulovesicular endosomes
-
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ADCY6_HUMAN
1168
12
130615
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
190000
192000
-
AC9, Western blot analysis
50000
-
sAC form in axonemes, Western blot analysis
75000
-
Western blot analysis
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
glycosylation at N955 and N964
phosphoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallized in complex with substrate and Ca2+ or Mg2+
-
hanging drop vapor diffusion method, using 100 mM sodium acetate (pH 4.8), 200 mM trisodium-citrate, 18% (w/v) PEG 4000, 20% (v/v) glycerol
-
in complex with inhibitor bithionol. The inhibitor binds to the isoform Adcy10-specific, allosteric binding site for the physiological activator bicarbonate. Inhibition follows an allosteric mechanism, the compound induces rearrangements of substrate binding residues and of Arg176, a trigger between the active site and allosteric site
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F1078S
-
isoform VI, mutation within the GALPHAS binding pocket
N1090D
-
isoform V, mutation within the GALPHAS binding pocket
N955A
-
mutation prevents glycosylation
N964A
-
mutation prevents glycosylation
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ACV purified by gel filtration
-
by gel filtration
-
glutathione-Sepharose 4B resin column chromatography, Q-Sepharose column chromatography, and Talon resin column chromatography
-
nickel affinity column chromatography and gel filtration
-
recombinant sAC
-
soluble isozyme
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of isozyme ACVI in Spodoptera frugiperda Sf9 cell membranes, with a combination of four recombinant baculoviruses individually encoding the dopamine D1 receptor, G-protein alphaS-subunit, G-protein beta1gamma2 subunit dimer, and adenylyl cyclase type VI, ACVI. The recovered budded virus fraction produces cAMP in response to the stimulation with dopamine. Co-expression of all three G-protein subunits inaddition to receptor and ACVI led to amaximal response. Budded virusses co-expressingthel proteins also respond to dopamine agonists fenoldopam and SKF38393 and the antagonist flupenthixol, overview
transient expression of tagged isozyme AC6 in HEK-PR1 cells
ACV fused with a GST tag and expressed in Escherichia coli, wild-type and mutant ACVIdeltaN enzymes expressed in Sf9 cells, COS-7 cells overexpressing ACVI, binding domain vector pGBKT7 together with pGADT7-beta1 or the activating vector pGADT7 together with pGBKT7-N-terminal region of ACV or ACVI co-transformed into AH109 cells
-
chimeras inserted into the mammalian expression vector pCMV-SK, wild-type and chimeric mutants expressed in HEK-293 cells
cloning of AC7 cDNA from HEL cells
expressed in C6 glioma cells
-
expressed in Escherichia coli in Hi5 cells
-
expressed in Sf9 insect cells
-
expression in Sf9 cells
-
expression of GST-sAC fusion protein in SF9 cells
-
expression of isoenzymes ACI-ACVIII in COS cells
-
expression of transmembrane isozymes in HEK293T cells, expression of GST-tagged soluble isozyme
gene Adcy7 encoding isozyme AC7
HEK-293 cells stably transfected with AC9
-
ligated into pGEM-T Easy vector and expanded in DH5alpha Escherichia coli
-
polymorphism genotyping, and ADRB2 and ADCY6 gene interaction. The effect of ADRB2 on adhesion of erythrocytes in the sickle cell disease is different depending on the genotype of ADCY6. Sickle red cells from patients who were homozygous for either the G allele at single nucleotide polymorphism rs3730070 of ADCY6 demonstrate significantly increased adhesion to laminin compared to red cells from control patients, overview
-
the ADCY10 gene is located in the region linked to spinal bone mineral density
-
transfection of Sf9 cell
transient expression of fluorescent EGFP-tagged AC6 truncation mutants, expression of isozyme AC6 in COS-7 cells, expressing caveolin-1, and in HEK-293 cells or cardiac fibroblasts isolated from caveolin-1 knock-out mice, localization of AC6 in lipid rafts in all cell types, association via the AC6 C-terminal domains, expression analysis, overview
-
transient expression of tagged isozyme AC3 in HEK-PR1 cells, AC6 forms complexes with the IP3 R2 receptor
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in SK-N-SH human neuroblastoma cells, morphine significantly increases RNA transcript and protein levels of type I adenylate cyclase
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
the enzyme activity is useful as a marker for determination of G-protein-coupled receptor function mediating adenylyl cylcase activation by extracellular baculovirus particles, usage of this budded virus display system to detect G-protein-coupled receptor signaling, method development, overview
analysis
medicine
additional information
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Read, L.K.; Mikkelsen, R.B.
Plasmodium falciparum-infected erythrocytes contain an adenylate cyclase with properties which differ from those of the host enzyme
Mol. Biochem. Parasitol.
45
109-120
1991
Homo sapiens, Plasmodium falciparum
Manually annotated by BRENDA team
Reddy, N.B.; Oliver, K.L.; Festoff, B.W.; Engel, W.K.
Adenylate cyclase system of human skeletal muscle subcellular distribution and general problems
Biochim. Biophys. Acta
540
371-388
1978
Homo sapiens
-
Manually annotated by BRENDA team
Wedner, H.J.; Parker, C.W.
Adenylate cyclase activity in lymphocyte subcellular fractions. Characterization of a nuclear adenylate cyclase
Biochem. J.
162
483-491
1977
Homo sapiens
Manually annotated by BRENDA team
Hellevuo, K.; Yoshimura, M.; Mons, N.; Hoffman, P.L.; Cooper, D.M.F.; Tabakoff, B.
The characterization of a novel human adenylyl cyclase which is present in brain and other tissues
J. Biol. Chem.
270
11581-11589
1995
Homo sapiens
Manually annotated by BRENDA team
Khan, N.A.; Quemener, V.; Moulinoux, J.P.
Inhibition of adenylate cyclase activity by polyamines in human erythrocyte plasma membranes
Life Sci.
46
43-47
1990
Homo sapiens
Manually annotated by BRENDA team
Wadman, I.A.; Farndale, R.W.; Martin, B.R.
Evidence for regulation of human platelet adenylate cyclase by phosphorylation. Inhibition by ATP and guanosine 5 -[beta-thio]diphosphate occur by distinct mechanisms
Biochem. J.
276
621-630
1991
Homo sapiens
Manually annotated by BRENDA team
Hanoune, J.; Defer, N.
Regulation and role of adenylyl cyclase isoforms
Annu. Rev. Pharmacol. Toxicol.
41
145-174
2001
Homo sapiens
Manually annotated by BRENDA team
McVey, M.; Hill, J.; Howlett, A.; Klein, C.
Adenylyl cyclase, a coincidence detector for nitric oxide
J. Biol. Chem.
274
18887-18892
1999
Homo sapiens
Manually annotated by BRENDA team
Litvin, T.N.; Kamenetsky, M.; Zarifyan, A.; Buck, J.; Levin, L.R.
Kinetic Properties of "Soluble" Adenylyl Cyclase. Synergism between calcium and bicarbonate
J. Biol. Chem.
278
15922-15926
2003
Homo sapiens
Manually annotated by BRENDA team
Cumbay, M.G.; Watts, V.J.
Novel Regulatory Properties of Human Type 9 Adenylate Cyclase (AC9)
J. Pharmacol. Exp. Ther.
310
108-115
2004
Homo sapiens
Manually annotated by BRENDA team
Rhee, M.H.; Nevo, I.; Avidor-Reiss, T.; Levy, R.; Vogel, Z.
Differential superactivation of adenylyl cyclase isozymes after chronic activation of the CB1 cannabinoid receptor
Mol. Pharmacol.
57
746-752
2000
Homo sapiens
Manually annotated by BRENDA team
Bernatchez, R.; Belkacemi, L.; Rassart, E.; Daoud, G.; Simoneau, L.; Lafond, J.
Differential expression of membrane and soluble adenylyl cyclase isoforms in cytotrophoblast cells and syncytiotrophoblasts of human placenta
Placenta
24
648-657
2003
Homo sapiens, Homo sapiens (O43306), Homo sapiens (O60266), Homo sapiens (O95622), Homo sapiens (P40145), Homo sapiens (P51828), Homo sapiens (Q08462), Homo sapiens (Q08828), Homo sapiens (Q96PN6)
Manually annotated by BRENDA team
Asboth, G.; Price, S.A.; Bellinger, J.; Ledger, W.; Barlow, D.H.; Bernal, A.L.
Characterization of adenylyl cyclases in cultured human granulosa cells
Reproduction
121
217-228
2001
Homo sapiens
Manually annotated by BRENDA team
Jaleel, M.; Shenoy, A.R.; Visweswariah, S.S.
Tyrphostins Are Inhibitors of Guanylyl and Adenylyl Cyclases
Biochemistry
43
8247-8255
2004
Homo sapiens
Manually annotated by BRENDA team
Chen-Goodspeed, M.; Lukan, A.N.; Dessauer, C.W.
Modeling of Gas and Gai Regulation of Human Type V and VI Adenylyl Cyclase
J. Biol. Chem.
280
1808-1816
2005
Homo sapiens
Manually annotated by BRENDA team
Steegborn, C.; Litvin, T.N.; Hess, K.C.; Capper, A.B.; Taussig, R.; Buck, J.; Levin, L.R.; Wu, H.
A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen
J. Biol. Chem.
280
31754-31759
2005
Homo sapiens, Arthrospira platensis
Manually annotated by BRENDA team
Yoshimura, M.; Pearson, S.; Kadota, Y.; Gonzalez, C.E.
Identification of ethanol responsive domains of adenylyl cyclase
Alcohol. Clin. Exp. Res.
30
1824-1832
2006
Rattus norvegicus (P21932), Rattus norvegicus (P26769), Homo sapiens (P51828)
Manually annotated by BRENDA team
Kolachala, V.L.; Obertone, T.S.; Wang, L.; Merlin, D.; Sitaraman, S.V.
Adenosine 2b receptor (A2bR) signals through adenylate cyclase (AC) 6 isoform in the intestinal epithelial cells
Biochim. Biophys. Acta
1760
1102-1108
2006
Cricetulus griseus, Homo sapiens
Manually annotated by BRENDA team
Baudouin-Legros, M.; Hamdaoui, N.; Borot, F.; Fritsch, J.; Ollero, M.; Planelles, G.; Edelman, A.
Control of Basal CFTR Gene Expression by Bicarbonate-Sensitive Adenylyl Cyclase in Human Pulmonary Cells
Cell. Physiol. Biochem.
21
75-86
2008
Homo sapiens
Manually annotated by BRENDA team
Beazely, M.A.; Watts, V.J.
Regulatory properties of adenylate cyclases type 5 and 6: A progress report
Eur. J. Pharmacol.
535
1-12
2006
Cricetulus griseus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Nlend, M.C.; Schmid, A.; Sutto, Z.; Ransford, G.A.; Conner, G.E.; Fregien, N.; Salathe, M.
Calcium-mediated, purinergic stimulation and polarized localization of calcium-sensitive adenylyl cyclase isoforms in human airway epithelia
FEBS Lett.
581
3241-3246
2007
Homo sapiens
Manually annotated by BRENDA team
Gao, X.; Sadana, R.; Dessauer, C.W.; Patel, T.B.
Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits
J. Biol. Chem.
282
294-302
2007
Canis lupus familiaris, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Willoughby, D.; Cooper, D.M.
Ca2+ stimulation of adenylyl cyclase generates dynamic oscillations in cyclic AMP
J. Cell Sci.
119
828-836
2006
Homo sapiens
Manually annotated by BRENDA team
Schmid, A.; Sutto, Z.; Nlend, M.C.; Horvath, G.; Schmid, N.; Buck, J.; Levin, L.R.; Conner, G.E.; Fregien, N.; Salathe, M.
Soluble adenylyl cyclase is localized to cilia and contributes to ciliary beat frequency regulation via production of cAMP
J. Gen. Physiol.
130
99-109
2007
Homo sapiens
Manually annotated by BRENDA team
Antoni, F.A.; Wiegand, U.K.; Black, J.; Simpson, J.
Cellular localisation of adenylyl cyclase: a post-genome perspective
Neurochem. Res.
31
287-295
2006
Homo sapiens, Macaca sp., Mus musculus, Rattus norvegicus, Mus musculus C57BL/6
Manually annotated by BRENDA team
Willoughby, D.; Cooper, D.M.
Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains
Physiol. Rev.
87
965-1010
2007
Aplysia sp., Canis lupus familiaris, Oryctolagus cuniculus, Dictyostelium discoideum, Drosophila sp. (in: flies), Homo sapiens, Mus musculus, Paramecium sp., Rattus norvegicus, Tetrahymena sp., Plasmodium sp.
Manually annotated by BRENDA team
Cooper, D.M.; Crossthwaite, A.J.
Higher-order organization and regulation of adenylyl cyclases
Trends Pharmacol. Sci.
27
426-431
2006
Homo sapiens
Manually annotated by BRENDA team
Koukoulitsa, C.; Zervou, M.; Demetzos, C.; Mavromoustakos, T.
Comparative docking studies of labdane-type diterpenes with forskolin at the active site of adenylyl cyclase
Bioorg. Med. Chem.
16
8237-8243
2008
Homo sapiens
Manually annotated by BRENDA team
Eyler, C.E.; Jackson, T.; Elliott, L.E.; De Castro, L.M.; Jonassaint, J.; Ashley-Koch, A.; Telen, M.J.
beta2-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion
Br. J. Haematol.
141
105-108
2008
Homo sapiens
Manually annotated by BRENDA team
Wann, B.P.; DAnjou, B.; Bah, T.M.; Webster, H.H.; Godbout, R.; Rousseau, G.
Effect of olfactory bulbectomy on adenylyl cyclase activity in the limbic system
Brain Res. Bull.
79
32-36
2009
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Ichikawa, S.; Koller, D.L.; Curry, L.R.; Lai, D.; Xuei, X.; Edenberg, H.J.; Hui, S.L.; Peacock, M.; Foroud, T.; Econs, M.J.
Association of adenylate cyclase 10 (ADCY10) polymorphisms and bone mineral density in healthy adults
Calcif. Tissue Int.
84
97-102
2009
Homo sapiens
Manually annotated by BRENDA team
Kloster, M.M.; Hafte, T.T.; Moltzau, L.R.; Naderi, E.H.; Dahle, M.K.; Skalhegg, B.S.; Gaudernack, G.; Levy, F.O.; Naderi, S.; Blomhoff, H.K.
EBV infection renders B cells resistant to growth inhibition via adenylyl cyclase
Cell. Signal.
20
1169-1178
2008
Homo sapiens
Manually annotated by BRENDA team
Thangavel, M.; Liu, X.; Sun, S.Q.; Kaminsky, J.; Ostrom, R.S.
The C1 and C2 domains target human type 6 adenylyl cyclase to lipid rafts and caveolae
Cell. Signal.
21
301-308
2009
Homo sapiens
Manually annotated by BRENDA team
Jiang, L.I.; Collins, J.; Davis, R.; Fraser, I.D.; Sternweis, P.C.
Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII
J. Biol. Chem.
283
23429-23439
2008
Homo sapiens (P51828), Homo sapiens (P51829)
Manually annotated by BRENDA team
Sakihama, T.; Masuda, K.; Sato, T.; Doi, T.; Kodama, T.; Hamakubo, T.
Functional reconstitution of G-protein-coupled receptor-mediated adenylyl cyclase activation by a baculoviral co-display system
J. Biotechnol.
135
28-33
2008
Homo sapiens (O43306)
Manually annotated by BRENDA team
Tovey, S.C.; Dedos, S.G.; Taylor, E.J.; Church, J.E.; Taylor, C.W.
Selective coupling of type 6 adenylyl cyclase with type 2 IP3 receptors mediates direct sensitization of IP3 receptors by cAMP
J. Cell Biol.
183
297-311
2008
Homo sapiens (O43306), Homo sapiens (O60266), Homo sapiens
Manually annotated by BRENDA team
Schlicker, C.; Rauch, A.; Hess, K.C.; Kachholz, B.; Levin, L.R.; Buck, J.; Steegborn, C.
Structure-based development of novel adenylyl cyclase inhibitors
J. Med. Chem.
51
4456-4464
2008
Rattus norvegicus, Arthrospira platensis (O32393), Homo sapiens (Q96PN6), Homo sapiens
Manually annotated by BRENDA team
Donati, R.J.; Dwivedi, Y.; Roberts, R.C.; Conley, R.R.; Pandey, G.N.; Rasenick, M.M.
Postmortem brain tissue of depressed suicides reveals increased Gs alpha localization in lipid raft domains where it is less likely to activate adenylyl cyclase
J. Neurosci.
28
3042-3050
2008
Homo sapiens
Manually annotated by BRENDA team
Brown, J.T.; Kant, A.; Mailman, R.B.
Rapid, semi-automated, and inexpensive radioimmunoassay of cAMP: Application in GPCR-mediated adenylate cyclase assays
J. Neurosci. Methods
177
261-266
2009
Homo sapiens
Manually annotated by BRENDA team
Clark, M.J.; Linderman, J.J.; Traynor, J.R.
Endogenous regulators of G protein signaling differentially modulate full and partial mu-opioid agonists at adenylyl cyclase as predicted by a collision coupling model
Mol. Pharmacol.
73
1538-1548
2008
Homo sapiens
Manually annotated by BRENDA team
Dwivedi, Y.; Pandey, G.N.
Adenylyl cyclase-cyclicAMP signaling in mood disorders: Role of the crucial phosphorylating enzyme protein kinase A
Neuropsychiatr. Disease Treat.
4
161-176
2008
Homo sapiens
Manually annotated by BRENDA team
Ryzhov, S.; Zaynagetdinov, R.; Goldstein, A.E.; Matafonov, A.; Biaggioni, I.; Feoktistov, I.
Differential role of the carboxy-terminus of the A(2B) adenosine receptor in stimulation of adenylate cyclase, phospholipase Cbeta, and interleukin-8
Purinergic Signal.
5
289-298
2009
Cricetulus griseus, Homo sapiens
Manually annotated by BRENDA team
Rhim, J.H.; Jang, I.S.; Song, K.Y.; Ha, M.K.; Cho, S.C.; Yeo, E.J.; Park, S.C.
Lysophosphatidic acid and adenylyl cyclase inhibitor increase proliferation of senescent human diploid fibroblasts by inhibiting adenosine monophosphate-activated protein kinase
Rejuvenation Res.
11
781-792
2008
Homo sapiens
Manually annotated by BRENDA team
Koshimizu, T.A.; Tsuchiya, H.; Tsuda, H.; Fujiwara, Y.; Shibata, K.; Hirasawa, A.; Tsujimoto, G.; Fujimura, A.
Inhibition of heat shock protein 90 attenuates adenylate cyclase sensitization after chronic morphine treatment
Biochem. Biophys. Res. Commun.
392
603-607
2010
Homo sapiens
Manually annotated by BRENDA team
Mou, T.C.; Masada, N.; Cooper, D.M.; Sprang, S.R.
Structural basis for inhibition of mammalian adenylyl cyclase by calcium
Biochemistry
48
3387-3397
2009
Homo sapiens
Manually annotated by BRENDA team
Oener, S.S.; Kaya, A.I.; Onaran, H.O.; Oezcan, G.; Ugur, O.
beta2-Adrenoceptor, Gs and adenylate cyclase coupling in purified detergent-resistant, low density membrane fractions
Eur. J. Pharmacol.
630
42-52
2010
Homo sapiens
Manually annotated by BRENDA team
Macdougall, D.A.; Wachten, S.; Ciruela, A.; Sinz, A.; Cooper, D.M.
Separate elements within a single IQ-like motif in adenylyl cyclase type 8 impart Ca2+/calmodulin binding and autoinhibition
J. Biol. Chem.
284
15573-15588
2009
Homo sapiens
Manually annotated by BRENDA team
Suryanarayana, S.; Goettle, M.; Huebner, M.; Gille, A.; Mou, T.C.; Sprang, S.R.; Richter, M.; Seifert, R.
Differential inhibition of various adenylyl cyclase isoforms and soluble guanylyl cyclase by 2,3-O-(2,4,6-trinitrophenyl)-substituted nucleoside 5-triphosphates
J. Pharmacol. Exp. Ther.
330
687-695
2009
Homo sapiens
Manually annotated by BRENDA team
Werthmann, R.C.; von Hayn, K.; Nikolaev, V.O.; Lohse, M.J.; Buenemann, M.
Real-time monitoring of cAMP levels in living endothelial cells: thrombin transiently inhibits adenylyl cyclase 6
J. Physiol.
587
4091-4104
2009
Homo sapiens
Manually annotated by BRENDA team
Taylor, M.; Grundt, P.; Griffin, S.A.; Newman, A.H.; Luedtke, R.R.
Dopamine D3 receptor selective ligands with varying intrinsic efficacies at adenylyl cyclase inhibition and mitogenic signaling pathways
Synapse
64
251-266
2010
Homo sapiens
Manually annotated by BRENDA team
Hasanuzzaman, M.; Yoshimura, M.
Effects of straight chain alcohols on specific isoforms of adenylyl cyclase
Alcohol. Clin. Exp. Res.
34
743-749
2010
Homo sapiens
Manually annotated by BRENDA team
Pinto, C.; Lushington, G.H.; Richter, M.; Gille, A.; Geduhn, J.; Koenig, B.; Mou, T.C.; Sprang, S.R.; Seifert, R.
Structure-activity relationships for the interactions of 2'- and 3'-(O)-(N-methyl)anthraniloyl-substituted purine and pyrimidine nucleotides with mammalian adenylyl cyclases
Biochem. Pharmacol.
82
358-370
2011
Homo sapiens
Manually annotated by BRENDA team
Kleinboelting, S.; Diaz, A.; Moniot, S.; van den Heuvel, J.; Weyand, M.; Levin, L.R.; Buck, J.; Steegborn, C.
Crystal structures of human soluble adenylyl cyclase reveal mechanisms of catalysis and of its activation through bicarbonate
Proc. Natl. Acad. Sci. USA
111
3727-3732
2014
Homo sapiens
Manually annotated by BRENDA team
Kleinboelting, S.; Ramos-Espiritu, L.; Buck, H.; Colis, L.; van den Heuvel, J.; Glickman, J.F.; Levin, L.R.; Buck, J.; Steegborn, C.
Bithionol potently inhibits human soluble adenylyl cyclase through binding to the allosteric activator site
J. Biol. Chem.
291
9776-9784
2016
Homo sapiens (Q96PN6), Homo sapiens
Manually annotated by BRENDA team
Ritt, M.; Sivaramakrishnan, S.
Correlation between activity and domain complementation in adenylyl cyclase demonstrated with a novel fluorescence resonance energy transfer sensor
Mol. Pharmacol.
89
407-412
2016
Homo sapiens (O95622), Homo sapiens (Q08462)
Manually annotated by BRENDA team