Cyclic nucleotide turnover

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Cyclic nucleotides are second messengers generated by cyclase enzymes from precursor triphosphates and hydrolysed by phosphodiesterases. The cellular actions of these cyclic nucleotides are mediated through activation of protein kinases (cAMP- and cGMP-dependent protein kinases), ion channels (cyclic nucleotide-gated, CNG, and hyperpolarization and cyclic nucleotide-gated, HCN) and guanine nucleotide exchange factors (GEFs, Epac).

Adenylyl cyclases

Overview

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Adenylyl cyclase (ENSF00000000188), E.C. 4.6.1.1, converts ATP to cAMP and pyrophosphate. Mammalian membrane-bound adenylyl cyclases are typically made up of two clusters of six TM domains separating two intracellular, overlapping catalytic domains that are the target for the nonselective activators forskolin, NKH477 (except AC9, [52]) and Gαs (the stimulatory G protein α subunit). adenosine and its derivatives (e.g. 2',5'-dideoxyadenosine), acting through the P-site, appear to be physiological inhibitors of adenylyl cyclase activity [67]. Three families of adenylyl cyclase are distinguishable: calmodulin (CALM2, CALM3, CALM1, P62158)-stimulated (AC1, AC3 and AC8), Ca2+-inhibitable (AC5, AC6 and AC9) and Ca2+-insensitive (AC2, AC4 and AC7) forms.

Enzymes

AC1 Show summary »

AC2 Show summary »

AC3 Show summary »

AC4 Show summary »

AC5 Show summary »

AC6 Show summary »

AC7 Show summary »

AC8 Show summary »

AC9 Show summary »

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Soluble guanylyl cyclase

Overview

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Soluble guanylyl cyclase (GTP diphosphate-lyase (cyclising)), E.C. 4.6.1.2, is a heterodimer comprising α and β chains, both of which have two subtypes in man (predominantly α1β1; [74]). A haem group is associated with the β chain and is the target for the endogenous ligand nitric oxide (NO•), and, potentially, carbon monoxide [21]. The enzyme converts guanosine-5'-triphosphate (GTP) to the intracellular second messenger 3',5'-guanosine monophosphate (cGMP).

Enzymes

sGC (Soluble guanylyl cyclase ) Show summary » More detailed page

Subunits

Soluble guanylyl cyclase α 1 subunit Show summary »

Soluble guanylyl cyclase α 2 subunit Show summary »

Soluble guanylyl cyclase β 1 subunit Show summary »

Soluble guanylyl cyclase β 2 subunit Show summary »

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Exchange protein activated by cyclic AMP (Epac)

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Epacs are members of a family of guanine nucleotide exchange factors (ENSFM00250000000899), which also includes RapGEF5 (GFR, KIAA0277, MR-GEF, Q92565) and RapGEFL1 (Link-GEFII, Q9UHV5). They are activated endogenously by cAMP and with some pharmacological selectivity by 8-pCPT-2'-O-Me-cAMP [15]. Once activated, Epacs induce an enhanced activity of the monomeric G proteins, Rap1 and Rap2 by facilitating binding of GTP in place of GDP, leading to activation of phospholipase C [57].

Enzymes

Epac1 Show summary »

Epac2 Show summary »

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Phosphodiesterases, 3',5'-cyclic nucleotide

Overview

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3',5'-Cyclic nucleotide phosphodiesterases (PDEs, 3',5'-cyclic-nucleotide 5'-nucleotidohydrolase), E.C. 3.1.4.17, catalyse the hydrolysis of a 3',5'-cyclic nucleotide (usually cAMP or cGMP). IBMX is a nonselective inhibitor with an IC50 value in the millimolar range for all isoforms except PDE 8A, 8B and 9A. A 2',3'-cyclic nucleotide 3'-phosphodiesterase (E.C. 3.1.4.37 CNPase) activity is associated with myelin formation in the development of the CNS.

Enzymes

PDE1A Show summary »

PDE1B Show summary »

PDE1C Show summary »

PDE2A Show summary »

PDE3A Show summary » More detailed page

PDE3B Show summary »

PDE4A Show summary »

PDE4B Show summary » More detailed page

PDE4C Show summary »

PDE4D Show summary »

PDE5A Show summary » More detailed page

PDE6A Show summary »

PDE6B Show summary »

PDE6C Show summary »

PDE6D Show summary »

PDE6G Show summary »

PDE6H Show summary »

PDE7A Show summary »

PDE7B Show summary » More detailed page

PDE8A Show summary »

PDE8B Show summary »

PDE9A Show summary »

PDE10A Show summary »

PDE11A Show summary »

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Further reading

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References

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