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PR01624

Identifier
GHRELIN  [View Relations]  [View Alignment]  
Accession
PR01624
No. of Motifs
4
Creation Date
07-DEC-2001
Title
Preproghrelin peptide signature
Database References
Literature References
1. KOJIMA, M., HOSODA, H., MATSUO, H. AND KANGAWA, K.
Ghrelin: discovery of the natural endogenous lignad for the growth hormone
secretagogue receptor.
TRENDS ENDOCRINOL.METAB. 12(3) 118-122 (2001).
 
2. KOJIMA, M., HOSODA, H., DATE, Y., NAKAZATO, M., MATSUO, H. AND KANGAWA, K.
Ghrelin is a growth-hormone-releasing acylated peptide from stomach.
NATURE 402 656-660 (1999).
 
3. INUI, A.
Ghrelin: an orexigenic and somatotrophic signal from the stomach.
NAT.REV.NEUROSCI. 2(8) 551-560 (2001).

Documentation
Growth hormone (GH) is a pituitary hormone involved in cell and overall body
growth, carbohydrate-protein-lipid metabolism and osmotic homeostasis.
Control of GH release was initially ascribed to 2 pathways: stimulation by
hypothalamic GH-releasing hormone (GHRH) and inhibition by somatostatin.
More recently, synthetic compounds, termed GH secretagogues (GHS), were 
shown to stimulate GH release strongly. This effect is elicited by an orphan
G protein-coupled receptor (GPCR), subsequently named the GHS receptor
(GHS-R). The endogenous ligand for this receptor was purified from rat and
human stomach and named ghrelin [1].
 
The purified cDNA for ghrelin encodes a 117 amino acid prepropeptide. The
first 23 amino acid residues form a signal peptide that is cleaved to leave
proghrelin. Residues 24-51 are cleaved to yield active ghrelin, discarding
the C-terminal fragment [2]. The 28-residue ghrelin peptide that is left is
biologically inactive. Esterification with n-octanoic acid at Ser3 is 
required for biological activity. Ghrelin mRNA is expressed mainly in the
stomach in a distinct endocrine cell type in the submucosal layer, known as
X/A-like cells. The active peptide is secreted into the bloodstream rather
than the stomach. Ghrelin responsive cells are found in abundance in a 
limited area of the hypothalamic arcuate nucleus (ARC), a region involved in
control of food intake. As well as releasing GH indirectly via its action 
on the ARC region of the hypothalamus, ghrelin also appears to be able to
stimulate GH release via direct action on the pituitary [3].
 
A further variant of the ghrelin peptide exists in rat stomach, des-Gln14-
ghrelin. This is produced by alternative splicing and does not require the
esterification by n-octanoic acid for biological activity. However, its 
presence in only small quantities in the stomach suggests ghrelin is the
major active form. The ghrelin active peptide and the GHS receptor share
sequence similarity with motilin and the motilin receptor, respectively, 
suggesting an evolutionary relationship.
 
GHRELIN is a 4-element fingerprint that provides a signature for the
preproghrelin peptides. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length - motif 1 spans the C-termius
of the signal peptide and the N-terminus of the active peptide; motif 2
spans the C-terminal region of the active peptide; and motifs 3 and 4 span
the C-terminal region of the peptide that is discarded upon cleavage of
proghrelin. Two iterations on SPTR40_18f were required to reach convergence,
at which point a true set comprising 11 sequences was identified.
Summary Information
11 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
411111111
30000
20000
1234
True Positives
Q9BDG8        Q9BDJ6        Q9BEF7        Q9BEF8        
Q9EQX0 Q9ET69 Q9GKY4 Q9GKY5
Q9H3R3 Q9QYH7 Q9WUZ1
Sequence Titles
Q9BDG8      PREPROGHRELIN DES14Q - Sus scrofa (Pig).      
Q9BDJ6 GHRELIN PREPROPROTEIN PRECURSOR - Bos taurus (Bovine).
Q9BEF7 PREPRO DELTA GLN14 MTLRP PRECURSOR - Canis familiaris (Dog).
Q9BEF8 PREPROMTLRP PRECURSOR - Canis familiaris (Dog).
Q9EQX0 PREPROGHRELIN PRECURSOR (2210006E23RIK PROTEIN) - Mus musculus (Mouse).
Q9ET69 PREPRO-DES-GLN14-GHRELIN PRECURSOR - Rattus norvegicus (Rat).
Q9GKY4 PREPROGHRELIN-27 PRECURSOR - Sus scrofa (Pig).
Q9GKY5 PREPROGHRELIN PRECURSOR - Sus scrofa (Pig).
Q9H3R3 PREPROGHRELIN-27 PRECURSOR - Homo sapiens (Human).
Q9QYH7 GHRELIN PRECURSOR - Rattus norvegicus (Rat).
Q9WUZ1 M46 PROTEIN PRECURSOR - Mus musculus (Mouse).
Scan History
SPTR40_18f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
DMAMAGSSFLSPEHQKAQ Q9QYH7 19 19 -
DLAMAGSSFLSPEHQKVQ Q9BDG8 20 20 -
DLAMAGSSFLSPEHQRVQ Q9H3R3 19 19 -
DLAMAGSSFLSPEHQKLQ Q9BDJ6 19 19 -

Motif 2 width=14
Element Seqn Id St Int Rpt
RKESKKPPAKLQPR Q9QYH7 38 1 -
RKESKKPAAKLKPR Q9BDG8 38 0 -
RKESKKPPAKLQPR Q9H3R3 37 0 -
RKEAKKPSGRLKPR Q9BDJ6 37 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
EEELEIRFNAPFDVGIKL Q9QYH7 69 17 -
EDELEIRFNAPCDVGIKL Q9BDG8 69 17 -
EDELEVRFNAPFDVGIKL Q9H3R3 68 17 -
EDELEIRFNAPFNIGIKL Q9BDJ6 68 17 -

Motif 4 width=13
Element Seqn Id St Int Rpt
LGKFLQDILWEEV Q9QYH7 98 11 -
LGKFLQDILWEEV Q9BDG8 98 11 -
LGKFLQDILWEEA Q9H3R3 97 11 -
LGKFLQDILWEEA Q9BDJ6 97 11 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
DMAMAGSSFLSPEHQKAQ Q9EQX0 19 19 -
DMAMAGSSFLSPEHQKAQ Q9WUZ1 19 19 -
DMAMAGSSFLSPEHQKAQ Q9QYH7 19 19 -
DMAMAGSSFLSPEHQKAQ Q9ET69 19 19 -
DLAMAGSSFLSPEHQKVQ Q9BDG8 20 20 -
DLAMAGSSFLSPEHQKVQ Q9GKY4 20 20 -
DLAMAGSSFLSPEHQKVQ Q9GKY5 20 20 -
DLAMAGSSFLSPEHQRVQ Q9H3R3 19 19 -
DLAMAGSSFLSPEHQKLQ Q9BEF7 19 19 -
DLAMAGSSFLSPEHQKLQ Q9BEF8 19 19 -
DLAMAGSSFLSPEHQKLQ Q9BDJ6 19 19 -

Motif 2 width=14
Element Seqn Id St Int Rpt
RKESKKPPAKLQPR Q9EQX0 38 1 -
RKESKKPPAKLQPR Q9WUZ1 37 0 -
RKESKKPPAKLQPR Q9QYH7 38 1 -
RKESKKPPAKLQPR Q9ET69 37 0 -
RKESKKPAAKLKPR Q9BDG8 38 0 -
RKESKKPAAKLKPR Q9GKY4 38 0 -
RKESKKPAAKLKPR Q9GKY5 39 1 -
RKESKKPPAKLQPR Q9H3R3 37 0 -
RKESKKPPAKLQPR Q9BEF7 37 0 -
RKESKKPPAKLQPR Q9BEF8 38 1 -
RKEAKKPSGRLKPR Q9BDJ6 37 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
EEELEIRFNAPFDVGIKL Q9EQX0 69 17 -
EEELEIRFNAPFDVGIKL Q9WUZ1 68 17 -
EEELEIRFNAPFDVGIKL Q9QYH7 69 17 -
EEELEIRFNAPFDVGIKL Q9ET69 68 17 -
EDELEIRFNAPCDVGIKL Q9BDG8 69 17 -
EDKLEIRFNAPCDVGIKL Q9GKY4 69 17 -
EDKLEIRFNAPCDVGIKL Q9GKY5 70 17 -
EDELEVRFNAPFDVGIKL Q9H3R3 68 17 -
EDELEIRFNAPFDVGIKL Q9BEF7 68 17 -
EDELEIRFNAPFDVGIKL Q9BEF8 69 17 -
EDELEIRFNAPFNIGIKL Q9BDJ6 68 17 -

Motif 4 width=13
Element Seqn Id St Int Rpt
LGKFLQDILWEEV Q9EQX0 98 11 -
LGKFLQDILWEEV Q9WUZ1 97 11 -
LGKFLQDILWEEV Q9QYH7 98 11 -
LGKFLQDILWEEV Q9ET69 97 11 -
LGKFLQDILWEEV Q9BDG8 98 11 -
LGKFLQDILWEEV Q9GKY4 98 11 -
LGKFLQDILWEEV Q9GKY5 99 11 -
LGKFLQDILWEEA Q9H3R3 97 11 -
LGKFLQEVLWEDT Q9BEF7 97 11 -
LGKFLQEVLWEDT Q9BEF8 98 11 -
LGKFLQDILWEEA Q9BDJ6 97 11 -