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PR01422

Identifier
GPR56ORPHANR  [View Relations]  [View Alignment]  
Accession
PR01422
No. of Motifs
5
Creation Date
28-NOV-2000
Title
GPR56 orphan receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN
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. LIU, M., PARKER, R.M.C., DARBY, K., EYRE, H.J., COPELAND, N.G.,
CRAWFORD, J., GILBERT, D.J., SUTHERLAND, G.R., JENKINS, N.A. AND HERZOG, H.
GPR56, a novel secretin-like human G protein-coupled receptor gene.
GENOMICS 55 296-305 (1999).

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.
 
Several 7TM receptors have been cloned but their endogenous ligands are
unknown; these have been termed orphan receptors. GPR56 was isolated from a
human heart cDNA library using oligonucleotide primers corresponding to
TM domains 4 and 7 of the secretin-like receptor family. The mRNA transcript
is widely distributed throughout most tissues, the highest levels being
found in thyroid, brain and heart. Within the brain, the hippocampus and
hypothalamic nuclei express GPR56 in particularly high levels.
 
GPR56ORPHANR is a 5-element fingerprint that provides a signature for the
GPR56 orphan 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 areas of the
alignment that characterise the GPR56 receptors but distinguish them from
the rest of the secretin-like superfamily - motifs 1-3 reside within the
N-terminal domain; motif 4 lies at the C-terminus of TM domain 3, leading
into the second cytoplasmic loop; and motif 5 lies in the second external
loop. A single iteration on SPTR39_14f was required to reach convergence,
no further sequences being identified beyond the starting set.
Summary Information
3 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
533333
400000
300000
200000
12345
True Positives
O95966        Q9QZT2        Q9Y653        
Sequence Titles
O95966      TM7XN1 PROTEIN PRECURSOR - Homo sapiens (Human). 
Q9QZT2 SERPENTINE RECEPTOR - Mus musculus (Mouse).
Q9Y653 G-PROTEIN-COUPLED RECEPTOR - Homo sapiens (Human).
Scan History
SPTR39_14f 1  240  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
RGLYHFCLYWNRHAGR O95966 85 85 -
RGLYHFCLYWNRHAGR Q9Y653 85 85 -
RGLYHFCLYWSRHTGR Q9QZT2 85 85 -

Motif 2 width=17
Element Seqn Id St Int Rpt
TKVANLTEPVVLTFQHQ O95966 320 219 -
TKVANLTEPVVLTFQHQ Q9Y653 320 219 -
TKVTNLSDPVVLTFQHQ Q9QZT2 320 219 -

Motif 3 width=14
Element Seqn Id St Int Rpt
QPKNVTLQCVFWVE O95966 338 1 -
QPKNVTLQCVFWVE Q9Y653 338 1 -
QPKNVTLQCVFWVE Q9QZT2 338 1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
YRLVVEVFGTYVPGY O95966 495 143 -
YRLVVEVFGTYVPGY Q9Y653 501 149 -
YRLVVEVFGTYVPGY Q9QZT2 495 143 -

Motif 5 width=19
Element Seqn Id St Int Rpt
YPSMCWIRDSLVSYITNLG O95966 552 42 -
YPSMCWIRDSLVSYITNLG Q9Y653 558 42 -
YPSMCWIRDSLVSYVTNLG Q9QZT2 552 42 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
RGLYHFCLYWNRHAGR O95966 85 85 -
RGLYHFCLYWNRHAGR Q9Y653 85 85 -
RGLYHFCLYWSRHTGR Q9QZT2 85 85 -

Motif 2 width=17
Element Seqn Id St Int Rpt
TKVANLTEPVVLTFQHQ O95966 320 219 -
TKVANLTEPVVLTFQHQ Q9Y653 320 219 -
TKVTNLSDPVVLTFQHQ Q9QZT2 320 219 -

Motif 3 width=14
Element Seqn Id St Int Rpt
QPKNVTLQCVFWVE O95966 338 1 -
QPKNVTLQCVFWVE Q9Y653 338 1 -
QPKNVTLQCVFWVE Q9QZT2 338 1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
YRLVVEVFGTYVPGY O95966 495 143 -
YRLVVEVFGTYVPGY Q9Y653 501 149 -
YRLVVEVFGTYVPGY Q9QZT2 495 143 -

Motif 5 width=19
Element Seqn Id St Int Rpt
YPSMCWIRDSLVSYITNLG O95966 552 42 -
YPSMCWIRDSLVSYITNLG Q9Y653 558 42 -
YPSMCWIRDSLVSYVTNLG Q9QZT2 552 42 -