{PDOC00425}
{PS00452; GUANYLATE_CYCLASE_1}
{PS50125; GUANYLATE_CYCLASE_2}
{BEGIN}
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* Guanylate cyclase domain signature and profile *
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Guanylate cyclases (EC 4.6.1.2) [1 to 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, alpha and beta are  proteins of  from 70 to 82 Kd  which are  highly
related. Two forms of beta subunits are currently known: beta-1 which seems to
be expressed in  lung and brain,  and beta-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.

-Consensus pattern: [GD]-[VI]-[LIVM]-x(0,1)-[GS]-x(5)-[FY]-x-[LIVM]-[FYWL]-
                    [GS]-[DNTHKWE]-[DNTAS]-[IV]-[DNTAY]-x(5)-[DEC]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for the sea urchin Arbacia punctulata resact receptor which lack this domain.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: The pattern will detect both domains of adenylate cyclases class-III.

-Last update: December 2004 / Pattern and text revised.

[ 1] Koesling D., Boehme E., Schultz G.
     "Guanylyl cyclases, a growing family of signal-transducing enzymes."
     FASEB J. 5:2785-2791(1991).
     PubMed=1680765
[ 2] Garbers D.L.
     "The guanylyl cyclase receptor family."
     New Biol. 2:499-504(1990).
     PubMed=1982420
[ 3] Garbers D.L.
     "Guanylyl cyclase receptors and their endocrine, paracrine, and
     autocrine ligands."
     Cell 71:1-4(1992).
     PubMed=1356629
[ 4] Yuen P.S.T., Garbers D.L.
     "Guanylyl cyclase-linked receptors."
     Annu. Rev. Neurosci. 15:193-225(1992).
     PubMed=1349465; DOI=10.1146/annurev.ne.15.030192.001205
[ 5] Iyengar R.
     "Molecular and functional diversity of mammalian Gs-stimulated
     adenylyl cyclases."
     FASEB J. 7:768-775(1993).
     PubMed=8330684
[ 6] Barzu O., Danchin A.
     "Adenylyl cyclases: a heterogeneous class of ATP-utilizing enzymes."
     Prog. Nucleic Acid Res. Mol. Biol. 49:241-283(1994).
     PubMed=7863008

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