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PR00490

Identifier
SECRETINR  [View Relations]  [View Alignment]  
Accession
PR00490
No. of Motifs
8
Creation Date
04-MAR-1996  (UPDATE 24-JUN-1999)
Title
Secretin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN

INTERPRO; IPR002144
GCRDB; GCR_0242
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.   
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ISHIHARA T., NAKAMURA S., KAZIRO, Y., TAKAHASHI, T., TAKAHASHI, K.
AND NAGATA, S.  
Molecular cloning and expression of a cDNA encoding the secretin receptor.
EMBO J. 10 1635-1641 (1991).
 
3. LIN, H.Y., HARRIS, T.L., FLANNERY, M.S., ARUFFO, A., KAJI, E.H.,
GORN, A., KOLAKOWSKI, L.F., LODISH, H.F. AND GOLDRING, S.R.
Expression cloning of adenylate cyclase-coupled calcitonin receptor.
SCIENCE 254 1022-1024 (1991). 
 
4. JUEPPNER, H., ABOU-SAMRA, A.-B., FREEMAN, M., KONG, X.F.,
SCHIPANI, E., RICHARDS, J., KOLALOWSKI, L.F., HOCK, J., POTTS, J.T.,
KRONENBERG, H.M. AND SEGRE, G.E.
A G protein linked receptor for parathyroid hormone and parathyroid
hormone-related peptide.
SCIENCE 254 1024-1026 (1991).
 
5. ISHIHARA, T., SHIGEMOTO, R., MORI, K., TAKAHASHI, K. AND NAGATA, S.
Functional expression and tissue distribution of a novel receptor for
vasoactive intestinal polypeptide.
NEURON 8(4) 811-819 (1992).
 
6. WATSON, S. AND ARKINSTALL, S.
Vasoactive intestinal polypeptide family.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.278-283.

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that   
encompasses a wide range of functions (including various autocrine, para-   
crine and endocrine processes). They show considerable diversity at the   
sequence level, on the basis of which they can be separated into distinct   
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship,   
but between which there is no statistically significant similarity in   
sequence [1]. The currently known clan members include the rhodopsin-like   
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating   
pheromone receptors, and the metabotropic glutamate receptor family.       
 
The secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid   
hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal
peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-   
inositol-calcium pathway. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, in a manner
reminiscent of the rhodopsins and other receptors believed to interact with
G proteins. However, while a similar 3D framework has been proposed to
account for this, there is no significant sequence identity between these
families: the secretin-like receptors thus bear their own unique `7TM'
signature.      
 
Secretin stimulates secretion of enzymes and ions in the pancreas and
intestine, and is present in small amounts in the brain (e.g., in the
hypothalamus, brainstem and cerebral cortex) [6]. Secretin receptors are
found in high levels in the pancreas, stomach and heart [6]. They activate
adenylyl cyclase through stimulation of Gs.
 
SECRETINR is an 8-element fingerprint that provides a signature for the
secretin receptors. The fingerprint was derived from an initial alignment
of 4 sequences: the motifs were drawn from conserved sections within the
N- and C-termini, focusing on those areas of the alignment that 
characterise the secretin receptors but distinguish them from the
rest of the secretin-like family - motifs 1-6 lie in the N-terminal region
preceding the first TM domain, and motifs 7 and 8 lie at the C-terminus.
A single iteration on OWL27.0 was required to reach convergence, no further
sequences being identified beyond the starting set. 
 
An update on SPTR37_9f identified a true set of 2 sequences, and 1
partial match.
Summary Information
   2 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
1 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
822222222
700000000
600000000
501101110
400000000
300000000
200000000
12345678
True Positives
SCRC_HUMAN    SCRC_RAT      
True Positive Partials
Codes involving 5 elements
SCRC_RABIT
Sequence Titles
SCRC_HUMAN  SECRETIN RECEPTOR PRECURSOR (SCT-R) - HOMO SAPIENS (HUMAN). 
SCRC_RAT SECRETIN RECEPTOR PRECURSOR (SCT-R) - RATTUS NORVEGICUS (RAT).

SCRC_RABIT SECRETIN RECEPTOR PRECURSOR (SCT-R) - ORYCTOLAGUS CUNICULUS (RABBIT).
Scan History
OWL27_0    1  50   NSINGLE    
SPTR37_9f 1 40 NSINGLE
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
RPHLSPPLQQLLL HSU13989 2 2 -
RPRLSLLLLRLLL SCRC_RAT 6 6 -
RPHLSPPLQQLLL HSU28281 2 2 -
RPHLSPPLQQLLL JC2532 2 2 -

Motif 2 width=17
Element Seqn Id St Int Rpt
LACAAHSTGALPRLCDV HSU13989 18 3 -
LTKAAHTVGVPPRLCDV SCRC_RAT 19 0 -
LACAAHSTGALPRLCDV HSU28281 18 3 -
LACAAHSTGALPRLCDV JC2532 18 3 -

Motif 3 width=16
Element Seqn Id St Int Rpt
VLWEEQDQCLQELSRE JC2532 37 2 -
VLLEERAHCLQQLSKE SCRC_RAT 38 2 -
VLWEEQDQCLQELSRE HSU13989 37 2 -
VLWEEQDQCLQELSRE HSU28281 37 2 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EKKGALGPETAS SCRC_RAT 53 -1 -
EQTGDLGTEQPV JC2532 52 -1 -
EQTGDLGTEQPV HSU13989 52 -1 -
EQTGDLGTEQPV HSU28281 52 -1 -

Motif 5 width=15
Element Seqn Id St Int Rpt
PRFLRMLTSRNGSLF HSU28281 90 26 -
PRFLRMLTSRNGSLF HSU13989 90 26 -
PKFLLMLSNKNGSLF SCRC_RAT 90 25 -
PRFLRMLTSRNGSLF JC2532 90 26 -

Motif 6 width=14
Element Seqn Id St Int Rpt
CGVNVNDSSNEKRH HSU13989 123 18 -
CAVNVNDSSNEKRH JC2532 123 18 -
CGVNVNDSSNEKRH HSU28281 123 18 -
CGVNINNSFNERRH SCRC_RAT 123 18 -

Motif 7 width=13
Element Seqn Id St Int Rpt
QWHLREFPLHPVA JC2532 405 268 -
QWHLREFPLHPVA HSU28281 405 268 -
QWHLQEFPLRPVA SCRC_RAT 405 268 -
QWHLREFPLHPVA HSU13989 405 268 -

Motif 8 width=11
Element Seqn Id St Int Rpt
EQSQGTCRTSI HSU28281 429 11 -
EQSQGTCRTSI JC2532 429 11 -
EQSRSIPRASI SCRC_RAT 438 20 -
EQSQGTCRTSI HSU13989 429 11 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
RPHLSPPLQQLLL SCRC_HUMAN 2 2 -
RPRLSLLLLRLLL SCRC_RAT 6 6 -

Motif 2 width=17
Element Seqn Id St Int Rpt
LACAAHSTGALPRLCDV SCRC_HUMAN 18 3 -
LTKAAHTVGVPPRLCDV SCRC_RAT 19 0 -

Motif 3 width=16
Element Seqn Id St Int Rpt
VLWEEQDQCLQELSRE SCRC_HUMAN 37 2 -
VLLEERAHCLQQLSKE SCRC_RAT 38 2 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EQTGDLGTEQPV SCRC_HUMAN 52 -1 -
EKKGALGPETAS SCRC_RAT 53 -1 -

Motif 5 width=15
Element Seqn Id St Int Rpt
PRFLRMLTSRNGSLF SCRC_HUMAN 90 26 -
PKFLLMLSNKNGSLF SCRC_RAT 90 25 -

Motif 6 width=14
Element Seqn Id St Int Rpt
CGVNVNDSSNEKRH SCRC_HUMAN 123 18 -
CGVNINNSFNERRH SCRC_RAT 123 18 -

Motif 7 width=13
Element Seqn Id St Int Rpt
QWHLREFPLHPVA SCRC_HUMAN 405 268 -
QWHLQEFPLRPVA SCRC_RAT 405 268 -

Motif 8 width=11
Element Seqn Id St Int Rpt
EQSQGTCRTSI SCRC_HUMAN 429 11 -
EQSRSIPRASI SCRC_RAT 438 20 -