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* G-protein coupled receptors family 2 signatures *
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A number of peptide hormones bind to  G-protein coupled  receptors that, while
structurally similar to the majority of G-protein coupled receptors (R7G) (see
the relevant entry <PDOC00210>),  do not show any  similarity  at the level of
their sequence,  thus  representing  a  new family whose current known members
[1,2] are listed below:

 - Calcitonin receptor.
 - Calcitonin gene-related peptide receptor.
 - Corticotropin releasing factor receptor types 1 and 2.
 - Gastric inhibitory polypeptide receptor.
 - Glucagon receptor.
 - Glucagon-like peptide 1 receptor.
 - Growth hormone-releasing hormone receptor.
 - Parathyroid hormone / parathyroid hormone-related peptide types 1 and 2.
 - Pituitary adenylate cyclase activating polypeptide receptor.
 - Secretin receptor.
 - Vasoactive intestinal peptide receptor types 1 and 2.
 - Insects diuretic hormone receptor.

In addition to the above characterized receptors, this family also includes:

 - Caenorhabditis elegans putative receptor C13B9.4.
 - Caenorhabditis elegans putative receptor ZK643.3.
 - Human  leucocyte  antigen  CD97, a protein that contains, in its N-terminal
   section, 3 EGF-like domains (see <PDOC00021>).
 - Human cell surface glycoprotein EMR1,  a protein  that  contains, in its N-
   terminal section, 6 EGF-like domains (see <PDOC00021>).
 - Mouse  cell  surface glycoprotein F4/80, a protein that contains, in its N-
   terminal section, 7 EGF-like domains (see <PDOC00021>).

All the  characterized receptors are coupled to G-proteins which activate both
adenylyl cyclase and the phosphatidylinositol-calcium pathway.

Like classical R7G they  seem  to  contain seven transmembrane regions.  Their
N-terminus is probably located on the extracellular side of the  membrane  and
potentially glycosylated, while their C-terminus is probably cytoplasmic.  But
apart from these topological similarities they do share any region of sequence
similarity and are therefore probably not evolutionary related.

Every receptor  gene  in this family is encoded on multiple exons, and several
of these  genes  are  alternatively  spliced  to  yield  functionally distinct
products.

The N-terminal extracellular domain of these receptors contains five conserved
cysteines  residues  which  could  be  involved in  disulfide  bonds;  we have
developed a pattern in the region that spans the first three cysteines.

One of the most highly conserved regions spans the C-terminal part of the last
transmembrane  region and the  beginning of the adjacent intracellular region.
We have used this region as a second signature pattern.

-Consensus pattern: C-x(3)-[FYWLIV]-D-x(3,4)-C-[FW]-x(2)-[STAGV]-x(8,9)-C-[PF]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for CD97, EMR1 and F4/80.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Consensus pattern: Q-G-[LMFCA]-[LIVMFT]-[LIV]-x-[LIVFST]-[LIF]-[VFYH]-C-
                    [LFY]-x-N-x(2)-V
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Expert(s) to contact by email:
           Kolakowski L.F. Jr.; kolakowski@uthsca.edu

-Last update: July 1998 / Patterns and text revised.

[ 1] Jueppner H., Abou-Samra A.-B., Freeman M., Kong X.-F., Schipani E.,
     Richards J., Kolakowski L.F. Jr., Hock J., Potts J.T. Jr.,
     Kronenberg H.M., Segre G.V.
     Science 254:1024-1026(1991).
[ 2] Hamann J., Hartmann E., Van Lier R.A.W.
     Genomics 32:144-147(1996).
