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PROSITE documentation PDOC00425 [for PROSITE entry PS50125]

Guanylate cyclase domain signature and profile





Description

Guanylate cyclases (EC 4.6.1.2) [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 sea-urchins receptors for speract and resact, which are small peptides that stimulate sperm motility and metabolism.
  • The receptors for natriuretic peptides (ANF). Two forms of ANF receptors with guanylate cyclase activity are currently known: GC-A (or ANP-A) which seems specific to atrial natriuretic peptide (ANP), and GC-B (or ANP-B) which seems to be stimulated more effectively by brain natriuretic peptide (BNP) than by ANP.
  • The receptor for Escherichia coli heat-stable enterotoxin (GC-C). The endogenous ligand for this intestinal receptor seems to be a small peptide called guanylin.
  • Retinal guanylate cyclase (retGC) which probably plays a specific functional role in the rods and/or cones of photoreceptors. It is not known if this protein acts as receptor, but its structure is similar to that of the other plasma membrane-bound GCs.

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.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

GUANYLATE_CYCLASE_2, PS50125; Guanylate cyclase domain profile  (MATRIX)

GUANYLATE_CYCLASE_1, PS00452; Guanylate cyclase signature  (PATTERN)


References

1AuthorsKoesling D., Boehme E., Schultz G.
TitleGuanylyl cyclases, a growing family of signal-transducing enzymes.
SourceFASEB J. 5:2785-2791(1991).
PubMed ID1680765

2AuthorsGarbers D.L.
TitleThe guanylyl cyclase receptor family.
SourceNew Biol. 2:499-504(1990).
PubMed ID1982420

3AuthorsGarbers D.L.
TitleGuanylyl cyclase receptors and their endocrine, paracrine, and autocrine ligands.
SourceCell 71:1-4(1992).
PubMed ID1356629

4AuthorsYuen P.S.T., Garbers D.L.
TitleGuanylyl cyclase-linked receptors.
SourceAnnu. Rev. Neurosci. 15:193-225(1992).
PubMed ID1349465
DOI10.1146/annurev.ne.15.030192.001205

5AuthorsIyengar R.
TitleMolecular and functional diversity of mammalian Gs-stimulated adenylyl cyclases.
SourceFASEB J. 7:768-775(1993).
PubMed ID8330684

6AuthorsBarzu O., Danchin A.
TitleAdenylyl cyclases: a heterogeneous class of ATP-utilizing enzymes.
SourceProg. Nucleic Acid Res. Mol. Biol. 49:241-283(1994).
PubMed ID7863008



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