{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
{END}