|PROSITE documentation PDOC00425 [for PROSITE entry PS00452]|
Guanylate cyclases (EC 22.214.171.124) [1,2,3,4] catalyze the formation of cyclic GMP (cGMP) from GTP. cGMP acts as an intracellular messenger, activating cGMP-dependent kinases and regulating CGMP-sensitive ion channels. The role of cGMP as a second messenger in vascular smooth muscle relaxation and retinal photo-transduction is well established. Guanylate cyclase is found both in the soluble and particular fraction of eukaryotic cells. The soluble and plasma membrane-bound forms differ in structure, regulation and other properties.
Most currently known plasma membrane-bound forms are receptors for small polypeptides. The topology of such proteins is the following: they have a N-terminal extracellular domain which acts as the ligand binding region, then a transmembrane domain, followed by a large cytoplasmic C-terminal region that can be subdivided into two domains: a protein kinase-like domain that appears important for proper signalling and a cyclase catalytic domain. This topology is schematically represented below.
+-----------------------xxxxx----------------------+---------------+ | Ligand-binding XXXXX Protein Kinase like | Cyclase | +-----------------------xxxxx----------------------+---------------+ Extracellular Transmembrane Cytoplasmic
The known guanylate cyclase receptors are:
The soluble forms of guanylate cyclase are cytoplasmic heterodimers. The two subunits, α and β are proteins of from 70 to 82 Kd which are highly related. Two forms of β subunits are currently known: β-1 which seems to be expressed in lung and brain, and β-2 which is more abundant in kidney and liver.
The membrane and cytoplasmic forms of guanylate cyclase share a conserved domain which is probably important for the catalytic activity of the enzyme. Such a domain is also found twice in the different forms of membrane-bound adenylate cyclases (also known as class-III) [5,6] from mammals, slime mold or Drosophila. We have derived a consensus pattern from the most conserved region in that domain. We also developed a profile which covers the domain.Note:
The pattern will detect both domains of adenylate cyclases class-III.Last update:
December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Koesling D. Boehme E. Schultz G.|
|Title||Guanylyl cyclases, a growing family of signal-transducing enzymes.|
|Source||FASEB J. 5:2785-2791(1991).|
|Title||The guanylyl cyclase receptor family.|
|Source||New Biol. 2:499-504(1990).|
|Title||Guanylyl cyclase receptors and their endocrine, paracrine, and autocrine ligands.|
|4||Authors||Yuen P.S.T. Garbers D.L.|
|Title||Guanylyl cyclase-linked receptors.|
|Source||Annu. Rev. Neurosci. 15:193-225(1992).|
|Title||Molecular and functional diversity of mammalian Gs-stimulated adenylyl cyclases.|
|Source||FASEB J. 7:768-775(1993).|
|6||Authors||Barzu O. Danchin A.|
|Title||Adenylyl cyclases: a heterogeneous class of ATP-utilizing enzymes.|
|Source||Prog. Nucleic Acid Res. Mol. Biol. 49:241-283(1994).|