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PR01352

Identifier
GHRHRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01352
No. of Motifs
9
Creation Date
06-MAY-2000
Title
Growth hormone-releasing hormone receptor signature
Database References

GCRDB; GCR_0467; GCR_0485; GCR_0481; GCR_0461; GCR_0516; GCR_0650

GCRDB; GCR_1560
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. HSIUNG, H.M., SMITH, D.P., ZHANG, X.Y., BENNETT, T., ROSTECK, P.R. 
AND LAI, M.H.
Structure and functional expression of a complementary DNA for porcine 
growth hormone-releasing hormone receptor. 
NEUROPEPTIDES 25 1-10 (1993). 
 
7. GAYLINN, B.D., HARRISON, J.K., ZYSK, J.R., LYONS, C.E., LYNCH, K.R.
AND THORNER, M.O.
Molecular cloning and expression of a human anterior pituitary receptor for growth
hormone-releasing hormone.
MOL.ENDOCRINOL. 7 77-84 (1993). 

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.
 
Growth hormone (GH)-releasing hormone (GHRH) belongs to the family of gut-
neuropeptide hormones that includes glucagon, secretin and vasoactive 
intestinal peptide (VIP) [6]. The receptors for this peptide family involve
similar signal transduction pathways - on hormone binding, they interact
with G protein `Gs' and cause stimulation of adenylate cyclase [6]. Acting
through the GHRH receptor (GHRHR), GH plays a pivotal role in the regulation
of GH synthesis and secretion in the pituitary, possibly serving other roles
in different tissues [6]. The human pituitary GHRHR is a 423-amino acid 
protein that has the characteristic 7TM signature of the secretin-like GPCR
superfamily, sharing 47%, 42%, 35%, and 28% identity with receptors for 
VIP, secretin, calcitonin and PTH, respectively [7]. 
 
GHRHRECEPTOR is a 9-element fingerprint that provides a signature for the
growth hormone-releasing hormone receptors. The fingerprint was derived 
from an initial alignment of 3 sequences: the motifs were drawn from 
conserved regions spanning the full alignment length, focusing on those
sections that characterise the GHRH receptors but distinguish them from the
rest of the secretin-like GPCR superfamily - motifs 1-5 span the N-terminal
putative extracellular domain; motif 6 spans the second cytoplasmic loop,
leading into the fourth TM domain; motif 7 lies in the third cytoplasmic
loop; and motifs 8 and 9 reside in the cytoplasmic C-terminus. Two 
iterations on SPTR37_10f were required to reach convergence, at which point
a true set comprising 4 sequences was identified.
Summary Information
4 codes involving  9 elements
0 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
9444444444
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
GRFR_HUMAN    GRFR_MOUSE    GRFR_PIG      GRFR_RAT      
Sequence Titles
GRFR_HUMAN  GROWTH HORMONE-RELEASING HORMONE RECEPTOR PRECURSOR (GHRH RECEPTOR) (GRF RECEPTOR) (GRFR) - HOMO SAPIENS (HUMAN). 
GRFR_MOUSE GROWTH HORMONE-RELEASING HORMONE RECEPTOR PRECURSOR (GHRH RECEPTOR) (GRF RECEPTOR) (GRFR) - MUS MUSCULUS (MOUSE).
GRFR_PIG GROWTH HORMONE-RELEASING HORMONE RECEPTOR PRECURSOR (GHRH RECEPTOR) (GRF RECEPTOR) (GRFR) - SUS SCROFA (PIG).
GRFR_RAT GROWTH HORMONE-RELEASING HORMONE RECEPTOR PRECURSOR (GHRH RECEPTOR) (GRF RECEPTOR) (GRFR) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_10f 2  40   NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
DSLLWATWVLCLLNLWGVALGHLH GRFR_RAT 2 2 -
DGLMWATRILCLLSLCGVTLGHLH GRFR_MOUSE 2 2 -
DRRMWGAHVFCVLSPLPTVLGHMH GRFR_HUMAN 2 2 -

Motif 2 width=21
Element Seqn Id St Int Rpt
FITQLRDDELACLQAAEGTNN GRFR_RAT 30 4 -
FITQLRDDELACLQAAEGTNN GRFR_MOUSE 30 4 -
FITQLREDESACLQAAEEMPN GRFR_HUMAN 30 4 -

Motif 3 width=13
Element Seqn Id St Int Rpt
WPPTGSGQWVSLP GRFR_RAT 65 14 -
WPPTGSGQWVSLP GRFR_MOUSE 65 14 -
WPTAGSGEWVTLP GRFR_HUMAN 65 14 -

Motif 4 width=19
Element Seqn Id St Int Rpt
FFSHFGSDPGAVKRDCTIT GRFR_RAT 81 3 -
FFSHFGSDTGFVKRDCTIT GRFR_MOUSE 81 3 -
FFSHFSSESGAVKRDCTIT GRFR_HUMAN 81 3 -

Motif 5 width=18
Element Seqn Id St Int Rpt
PVPLELLTEEKSYFSTVK GRFR_RAT 113 13 -
PVPLELLTKEKSYFSTVK GRFR_MOUSE 113 13 -
PVPLELLAEEESYFSTVK GRFR_HUMAN 113 13 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ASTSPRSKPAFWWLV GRFR_RAT 232 101 -
ASTSPRSKPAFWWLV GRFR_MOUSE 232 101 -
ASTSPSSRRAFWWLV GRFR_HUMAN 232 101 -

Motif 7 width=16
Element Seqn Id St Int Rpt
RKLGPAQGGLHTRAQY GRFR_RAT 309 62 -
RKLEPAQGGLHTRAQY GRFR_MOUSE 309 62 -
RKLEPAQGSLHTQSQY GRFR_HUMAN 309 62 -

Motif 8 width=16
Element Seqn Id St Int Rpt
GHDPELLPARRTCTEW GRFR_RAT 434 109 -
GHDPELLPARRTCTEW GRFR_MOUSE 393 68 -
GHDPELLPAWRTRAKW GRFR_HUMAN 393 68 -

Motif 9 width=16
Element Seqn Id St Int Rpt
WTTPPRSRVKVLTSEC GRFR_RAT 449 -1 -
WTTPPRSRLKVLTSEC GRFR_MOUSE 408 -1 -
WTTPSRSAAKVLTSMC GRFR_HUMAN 408 -1 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
DSLLWATWVLCLLNLWGVALGHLH GRFR_RAT 2 2 -
DGLMWATRILCLLSLCGVTLGHLH GRFR_MOUSE 2 2 -
DRRMWGAHVFCVLSPLPTVLGHMH GRFR_HUMAN 2 2 -
DSGVWAACIFCLLSSLPVALGHVH GRFR_PIG 2 2 -

Motif 2 width=21
Element Seqn Id St Int Rpt
FITQLRDDELACLQAAEGTNN GRFR_RAT 30 4 -
FITQLRDDELACLQAAEGTNN GRFR_MOUSE 30 4 -
FITQLREDESACLQAAEEMPN GRFR_HUMAN 30 4 -
FITQLREDERTCLQAADRMAN GRFR_PIG 30 4 -

Motif 3 width=13
Element Seqn Id St Int Rpt
WPPTGSGQWVSLP GRFR_RAT 65 14 -
WPPTGSGQWVSLP GRFR_MOUSE 65 14 -
WPTAGSGEWVTLP GRFR_HUMAN 65 14 -
WPTAGPGEWVTLP GRFR_PIG 65 14 -

Motif 4 width=19
Element Seqn Id St Int Rpt
FFSHFGSDPGAVKRDCTIT GRFR_RAT 81 3 -
FFSHFGSDTGFVKRDCTIT GRFR_MOUSE 81 3 -
FFSHFSSESGAVKRDCTIT GRFR_HUMAN 81 3 -
FFSHFSSEPGALKRDCTTT GRFR_PIG 81 3 -

Motif 5 width=18
Element Seqn Id St Int Rpt
PVPLELLTEEKSYFSTVK GRFR_RAT 113 13 -
PVPLELLTKEKSYFSTVK GRFR_MOUSE 113 13 -
PVPLELLAEEESYFSTVK GRFR_HUMAN 113 13 -
PVPLELLTDEKSYFSTVR GRFR_PIG 113 13 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ASTSPRSKPAFWWLV GRFR_RAT 232 101 -
ASTSPRSKPAFWWLV GRFR_MOUSE 232 101 -
ASTSPSSRRAFWWLV GRFR_HUMAN 232 101 -
ASTSPSTRRAFWWLV GRFR_PIG 232 101 -

Motif 7 width=16
Element Seqn Id St Int Rpt
RKLGPAQGGLHTRAQY GRFR_RAT 309 62 -
RKLEPAQGGLHTRAQY GRFR_MOUSE 309 62 -
RKLEPAQGSLHTQSQY GRFR_HUMAN 309 62 -
RKLEPAQGSLHTQPQY GRFR_PIG 309 62 -

Motif 8 width=16
Element Seqn Id St Int Rpt
GHDPELLPARRTCTEW GRFR_RAT 434 109 -
GHDPELLPARRTCTEW GRFR_MOUSE 393 68 -
GHDPELLPAWRTRAKW GRFR_HUMAN 393 68 -
GHDPELLPAWRTHAKW GRFR_PIG 393 68 -

Motif 9 width=16
Element Seqn Id St Int Rpt
WTTPPRSRVKVLTSEC GRFR_RAT 449 -1 -
WTTPPRSRLKVLTSEC GRFR_MOUSE 408 -1 -
WTTPSRSAAKVLTSMC GRFR_HUMAN 408 -1 -
WAKPSRSRAKVLTTVC GRFR_PIG 408 -1 -