SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01355

Identifier
GLUCAGNLIKER  [View Relations]  [View Alignment]  
Accession
PR01355
No. of Motifs
8
Creation Date
06-MAY-2000
Title
Glucagon-like peptide 1 receptor signature
Database References
PRINTS; PR01353 GLUCAGNFAMLY
GCRDB; GCR_0370; GCR_2593; GCR_0771; GCR_0833; GCR_2057; GCR_2059
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. VAN EYLL, B., LANKAT-BUTTGEREIT, B., BODE, H.P., GOKE, R. AND GOKE, B.
Signal transduction of the GLP-1-receptor cloned from a human insulinoma. 
FEBS LETT. 348 7-13 (1994).
 
7. WEI, Y. AND MOJSOV, S.
Tissue-specific expression of the human receptor for glucagon-like
peptide-I: brain, heart and pancreatic forms have the same deduced amino
acid sequences.
FEBS LETT. 358 219-224 (1995).  
 
8. THORENS, B.
Expression cloning of the pancreatic beta cell receptor for the gluco- 
incretin hormone glucagon-like peptide 1.
PROC.NATL.ACAD.SCI.U.S.A. 89 8641-8645 (1992). 

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 inter-
act with G proteins. However, while a similar 3D framework has been
proposed to account for this, there is no significant sequence similarity
between these families: the secretin-like receptors thus bear their own
unique `7TM' signature.
 
Glucagon-like peptide-1 (GLP-1), which is encoded by the glucagon gene and
released from the gut in response to nutrients, is a potent stimulator of
glucose-induced insulin secretion and proinsulin gene expression of
pancreatic beta-cells [6,7]. In humans, GLP-I exerts its physiological
effect as an incretin. Patients with insulinoma tumors show uncontrolled 
insulin hypersecretion [6]. The GLP-I receptor binds GLP-1 with high 
affinity and couples to activation of adenylate cyclase [8]. The receptor
specifically binds GLP-1 and not peptides of related structure and function,
such as glucagon, gastric inhibitory peptide, VIP or secretin [8]. It is
thought that GLP-I might have effects beyond the pancreas, including the 
cardiovascular and central nervous systems, where a receptor with the same
ligand-binding specificity is found [7].  
 
GLUCAGNLIKER is an 8-element fingerprint that provides a signature for the
glucagon-like peptide 1 receptors. The fingerprint was derived from an
initial alignment of 3 sequences: the motifs were drawn from conserved 
regions spanning virtually the full alignment length, focusing on those
sections that characterise the glucagon-like peptide 1 receptors, but
distinguish them from the rest of the glucagon receptor family - motifs 1-5
span the N-terminal putative extracellular domain; motif 6 lies in the first
extracellular loop; and motifs 7 and 8 reside at the cytoplasmic C-terminus.
A single iteration on SPTR37_10f was required to reach convergence, no 
further sequences being identified beyond the starting set.
Summary Information
3 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
833333333
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
GLPR_HUMAN    GLPR_MOUSE    GLPR_RAT      
Sequence Titles
GLPR_HUMAN  GLUCAGON-LIKE PEPTIDE 1 RECEPTOR PRECURSOR (GLP-1 RECEPTOR) (GLP-1-R) - HOMO SAPIENS (HUMAN). 
GLPR_MOUSE GLUCAGON-LIKE PEPTIDE 1 RECEPTOR PRECURSOR (GLP-1 RECEPTOR) (GLP-1-R) - MUS MUSCULUS (MOUSE).
GLPR_RAT GLUCAGON-LIKE PEPTIDE 1 RECEPTOR PRECURSOR (GLP-1 RECEPTOR) (GLP-1-R) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_10f 1  40   NSINGLE    
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
GAVGRAGPRPQGATVSLSETVQ GLPR_RAT 16 16 -
GAVGRAGPRPQGTTVSLSETVQ GLPR_MOUSE 16 16 -
GMVGRAGPRPQGATVSLWETVQ GLPR_HUMAN 16 16 -

Motif 2 width=15
Element Seqn Id St Int Rpt
QRFLTEAPLLATGLF GLPR_RAT 47 9 -
QHFLTEAPLLATGLF GLPR_MOUSE 47 9 -
QRSLTEDPPPATDLF GLPR_HUMAN 47 9 -

Motif 3 width=12
Element Seqn Id St Int Rpt
WASSVLQGHVYR GLPR_RAT 91 29 -
WASSVLQGHVYR GLPR_MOUSE 91 29 -
WASSVPQGHVYR GLPR_HUMAN 91 29 -

Motif 4 width=10
Element Seqn Id St Int Rpt
WLHKDNSSLP GLPR_RAT 110 7 -
WLHKDNSSLP GLPR_MOUSE 110 7 -
WLQKDNSSLP GLPR_HUMAN 110 7 -

Motif 5 width=22
Element Seqn Id St Int Rpt
EESKQGERNSPEEQLLSLYIIY GLPR_RAT 127 7 -
EESKRGERNFPEEQLLSLYIIY GLPR_MOUSE 127 7 -
EESKRGERSSPEEQLLFLYIIY GLPR_HUMAN 127 7 -

Motif 6 width=21
Element Seqn Id St Int Rpt
YSTAAQQHQWDGLLSYQDSLG GLPR_RAT 205 56 -
YSTAAQQHQWDGLLSYQDSLG GLPR_MOUSE 205 56 -
YSTAAQQHQWDGLLSYQDSLS GLPR_HUMAN 205 56 -

Motif 7 width=14
Element Seqn Id St Int Rpt
RLERLNIQRDSSMK GLPR_RAT 421 195 -
RLEHLNIQRDCSMK GLPR_MOUSE 421 195 -
RLEHLHIQRDSSMK GLPR_HUMAN 421 195 -

Motif 8 width=16
Element Seqn Id St Int Rpt
KPLKCPTSSVSSGATV GLPR_RAT 434 -1 -
KPLKCPTSSVSSGATV GLPR_MOUSE 434 -1 -
KPLKCPTSSLSSGATA GLPR_HUMAN 434 -1 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
GAVGRAGPRPQGATVSLSETVQ GLPR_RAT 16 16 -
GAVGRAGPRPQGTTVSLSETVQ GLPR_MOUSE 16 16 -
GMVGRAGPRPQGATVSLWETVQ GLPR_HUMAN 16 16 -

Motif 2 width=15
Element Seqn Id St Int Rpt
QRFLTEAPLLATGLF GLPR_RAT 47 9 -
QHFLTEAPLLATGLF GLPR_MOUSE 47 9 -
QRSLTEDPPPATDLF GLPR_HUMAN 47 9 -

Motif 3 width=12
Element Seqn Id St Int Rpt
WASSVLQGHVYR GLPR_RAT 91 29 -
WASSVLQGHVYR GLPR_MOUSE 91 29 -
WASSVPQGHVYR GLPR_HUMAN 91 29 -

Motif 4 width=10
Element Seqn Id St Int Rpt
WLHKDNSSLP GLPR_RAT 110 7 -
WLHKDNSSLP GLPR_MOUSE 110 7 -
WLQKDNSSLP GLPR_HUMAN 110 7 -

Motif 5 width=22
Element Seqn Id St Int Rpt
EESKQGERNSPEEQLLSLYIIY GLPR_RAT 127 7 -
EESKRGERNFPEEQLLSLYIIY GLPR_MOUSE 127 7 -
EESKRGERSSPEEQLLFLYIIY GLPR_HUMAN 127 7 -

Motif 6 width=21
Element Seqn Id St Int Rpt
YSTAAQQHQWDGLLSYQDSLG GLPR_RAT 205 56 -
YSTAAQQHQWDGLLSYQDSLG GLPR_MOUSE 205 56 -
YSTAAQQHQWDGLLSYQDSLS GLPR_HUMAN 205 56 -

Motif 7 width=14
Element Seqn Id St Int Rpt
RLERLNIQRDSSMK GLPR_RAT 421 195 -
RLEHLNIQRDCSMK GLPR_MOUSE 421 195 -
RLEHLHIQRDSSMK GLPR_HUMAN 421 195 -

Motif 8 width=16
Element Seqn Id St Int Rpt
KPLKCPTSSVSSGATV GLPR_RAT 434 -1 -
KPLKCPTSSVSSGATV GLPR_MOUSE 434 -1 -
KPLKCPTSSLSSGATA GLPR_HUMAN 434 -1 -