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PR00818

Identifier
ISLETAMYLOID  [View Relations]  [View Alignment]  
Accession
PR00818
No. of Motifs
4
Creation Date
05-MAR-1998  (UPDATE 10-JUN-1999)
Title
Islet amyloid protein (amylin) signature
Database References

PROSITE; PS00258 CALCITONIN
BLOCKS; BL00258
INTERPRO; IPR000443
Literature References
1. JORDAN, K., MURTAUGH, M.P., O'BRIEN, T.D., WESTERMARK, P., BETSHOLTZ,C.
AND JOHNSON, K.H.
Canine IAPP cDNA sequence provides important clues regarding diabetogenesis
and amyloidogenesis in Type 2 diabetes. 
BIOCHEM.BIOPHYS.RES.COMMUN. 169 502-508 (1990). 
 
2. ROBERTS, A.N., LEIGHTON, B., TODD, J.A., COCKBURN, D., SCHOFIELD, P.N.,
SUTTON, R., HOLT, S., BOYD, Y., DAY, A.J., FOOT, E.A., WILLIS, A.C.,
REID, K.B.M. AND COOPER, G.J.S.
Molecular and functional characterization of amylin, a peptide associated
with type 2 diabetes mellitus. 
PROC.NATL.ACAD.SCI.U.S.A. 86 9662-9666 (1989). 
 
3. HUBBARD, J.A., MARTIN, S.R., CHAPLIN, L.C., BOSE, C., KELLY, S.M.
AND PRICE, N.C.
Solution structures of calcitonin-gene-related-peptide analogues of
calcitonin-gene-related peptide and amylin. 
BIOCHEM.J. 275 785-788 (1991). 

Documentation
Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide
or amylin) is a pancreatic islet hormone that is stored with insulin in beta
cell granules [1]. IAPP has a propensity to form islet cell-disrupting 
amyloid deposits, and opposes the action of insulin in peripheral tissues; 
the peptide may therefore have a significant role in the development of Type
2 diabetes mellitus [1]. It is thought that an intrinsic structural motif of
IAPP, which only occurs in species that develop age-associated or Type 2 
diabetes (e.g., humans and cats), is linked to its amyloidogenicity [1].
 
IAPP is a short, 37-residue peptide. The hormone selectively inhibits 
insulin-stimulated glucose utilisation and glycogen deposition in muscle,
but does not affect adipocyte glucose metabolism. The sequences of amylin
and the calcitonin gene-related peptides (CGRPs) show strong similarity:
both peptides have a conserved N-terminal intramolecular disulphide bridge,
and both have a C-terminal glycine, which suggests that the C-terminal
residue of amylin, like that of CGRP, is amidated [2].
 
Near- and far-UV CD spectra of human alpha CGRP, analogues and fragments of
CGRP, and amylin have been recorded in aqueous solution and in trifluoro-
ethanol/water mixtures [3]. The peptides were shown to contain significant
amounts of alpha-helix in aqueous solution, this amount increasing upon 
addition of TFE. Amylin appears to contain less helix than CGRP [3].
 
ISLETAMYLOID is a 4-element fingerprint that provides a signature for
islet amyloid peptides. The fingerprint was derived from an initial
alignment of 9 sequences: the motifs were drawn from conserved regions
spanning the full alignment length - motif 1 encodes the putative signal
sequence; and motifs 2-4 span the amyloid peptide, motif 2 including part of
the region encoded by PROSITE pattern CALCITONIN (PS00258), which contains 
the two N-terminal Cys residues that form a disulphide-linked loop. A single
iteration on OWL30.0 was required to reach convergence, no further sequences
being identified beyond the starting set. Several partial matches were also
found, all of which are related calcitonins that match motifs 2 and 4. 
 
An update on SPTR37_9f identified a true set of 9 sequences.
Summary Information
9 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
49999
30000
20000
1234
True Positives
IAPP_CANFA    IAPP_CAVPO    IAPP_FELCA    IAPP_HUMAN    
IAPP_MESAU IAPP_MOUSE IAPP_OCTDE IAPP_RAT
Q90743
Sequence Titles
IAPP_CANFA  ISLET AMYLOID POLYPEPTIDE PRECURSOR (AMYLIN) - CANIS FAMILIARIS (DOG). 
IAPP_CAVPO ISLET AMYLOID POLYPEPTIDE PRECURSOR (AMYLIN) - CAVIA PORCELLUS (GUINEA PIG).
IAPP_FELCA ISLET AMYLOID POLYPEPTIDE PRECURSOR (AMYLIN) - FELIS SILVESTRIS CATUS (CAT).
IAPP_HUMAN ISLET AMYLOID POLYPEPTIDE PRECURSOR (DIABETES-ASSOCIATED PEPTIDE) (DAP) (AMYLIN) (INSULINOMA AMYLOID PEPTIDE) - HOMO SAPIENS (HUMAN).
IAPP_MESAU ISLET AMYLOID POLYPEPTIDE PRECURSOR (AMYLIN) - MESOCRICETUS AURATUS (GOLDEN HAMSTER).
IAPP_MOUSE ISLET AMYLOID POLYPEPTIDE PRECURSOR (DIABETES-ASSOCIATED PEPTIDE) (DAP) (AMYLIN) - MUS MUSCULUS (MOUSE).
IAPP_OCTDE ISLET AMYLOID POLYPEPTIDE PRECURSOR (AMYLIN) - OCTODON DEGUS (DEGU).
IAPP_RAT ISLET AMYLOID POLYPEPTIDE PRECURSOR (DIABETES-ASSOCIATED PEPTIDE) (DAP) (AMYLIN) - RATTUS NORVEGICUS (RAT).
Q90743 AMYLOID PROTEIN PRECURSOR - GALLUS GALLUS (CHICKEN).
Scan History
OWL30_0    1  50   NSINGLE    
SPTR37_9f 2 10 NSINGLE
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
HISKLPAALLIFSVALNHLKAT IAPP_MESAU 2 2 -
CLLRLPVTLLVLCVALNELKAT IAPP_CAVPO 2 2 -
CNLKLSAFFIVLSVTLNCLEAT A56855 2 2 -
CLLQLPVVLLLLSAALNTLKAT IAPP_OCTDE 2 2 -
CLLKLPVVLIILSVALNHLKAT IAPP_CANFA 2 2 -
CISKLPAVLLILSVALNHLRAT IAPP_MOUSE 3 3 -
CLLKLPVVLIVLLVALHHLKAT IAPP_FELCA 2 2 -
CISRLPAVLLILSVALGHLRAT IAPP_RAT 3 3 -
GILKLQVFLIVLSVALNHLKAT IAPP_HUMAN 2 2 -

Motif 2 width=17
Element Seqn Id St Int Rpt
HQVGKRKCNTATCATQR IAPP_CAVPO 31 7 -
HQLEKRKCNTATCVTQR A56855 74 50 -
HQMEKRKCNTATCATQR IAPP_CANFA 28 4 -
PQMDKRKCNTATCATQR IAPP_MOUSE 32 7 -
NQVEKRKCNTATCATQR IAPP_FELCA 28 4 -
PQVDKRKCNTATCATQR IAPP_RAT 32 7 -
HQVEKRKCNTATCATQR IAPP_HUMAN 28 4 -
HQMDKRKCNTATCATQR IAPP_MESAU 31 7 -
HRVDKRKCNTATCATQR IAPP_OCTDE 31 7 -

Motif 3 width=17
Element Seqn Id St Int Rpt
RLADFLVRSSSNIGAIY A56855 90 -1 -
RLANFLVRTSNNLGAIL IAPP_CANFA 44 -1 -
RLANFLVRSSNNLGPVL IAPP_MOUSE 48 -1 -
RLANFLIRSSNNLGAIL IAPP_FELCA 44 -1 -
RLANFLVRSSNNLGPVL IAPP_RAT 48 -1 -
RLANFLVHSSNNFGAIL IAPP_HUMAN 44 -1 -
RLANFLVHSNNNLGPVL IAPP_MESAU 47 -1 -
RLTNFLVRSSHNLGAAL IAPP_CAVPO 47 -1 -
RLTNFLVRSSHNLGAAL IAPP_OCTDE 47 -1 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LLPTDVGSNTYGKRNA IAPP_CAVPO 63 -1 -
LPPTKVGSNTYGRRNA IAPP_OCTDE 63 -1 -
LSPTNVGSNTYGKRNT IAPP_CANFA 60 -1 -
YSPTNVGSNTYGKRDT A56855 106 -1 -
LPPTNVGSNTYGKRNA IAPP_MOUSE 64 -1 -
LSPTNVGSNTYGKRST IAPP_FELCA 60 -1 -
LPPTNVGSNTYGKRNV IAPP_RAT 64 -1 -
LSSTNVGSNTYGKRNA IAPP_HUMAN 60 -1 -
LSPTNVGSNTYGKRSA IAPP_MESAU 63 -1 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
CLLKLPVVLIILSVALNHLKAT IAPP_CANFA 2 2 -
CISKLPAVLLILSVALNHLRAT IAPP_MOUSE 3 3 -
CLLKLPVVLIVLLVALHHLKAT IAPP_FELCA 2 2 -
CISRLPAVLLILSVALGHLRAT IAPP_RAT 3 3 -
GILKLQVFLIVLSVALNHLKAT IAPP_HUMAN 2 2 -
HISKLPAALLIFSVALNHLKAT IAPP_MESAU 2 2 -
CLLRLPVTLLVLCVALNELKAT IAPP_CAVPO 2 2 -
CLLQLPVVLLLLSAALNTLKAT IAPP_OCTDE 2 2 -
CNLKLSAFFIVLSVTLNCLEAT Q90743 2 2 -

Motif 2 width=17
Element Seqn Id St Int Rpt
HQMEKRKCNTATCATQR IAPP_CANFA 28 4 -
PQMDKRKCNTATCATQR IAPP_MOUSE 32 7 -
NQVEKRKCNTATCATQR IAPP_FELCA 28 4 -
PQVDKRKCNTATCATQR IAPP_RAT 32 7 -
HQVEKRKCNTATCATQR IAPP_HUMAN 28 4 -
HQMDKRKCNTATCATQR IAPP_MESAU 31 7 -
HQVGKRKCNTATCATQR IAPP_CAVPO 31 7 -
HRVDKRKCNTATCATQR IAPP_OCTDE 31 7 -
HQLEKRKCNTATCVTQR Q90743 74 50 -

Motif 3 width=17
Element Seqn Id St Int Rpt
RLANFLVRTSNNLGAIL IAPP_CANFA 44 -1 -
RLANFLVRSSNNLGPVL IAPP_MOUSE 48 -1 -
RLANFLIRSSNNLGAIL IAPP_FELCA 44 -1 -
RLANFLVRSSNNLGPVL IAPP_RAT 48 -1 -
RLANFLVHSSNNFGAIL IAPP_HUMAN 44 -1 -
RLANFLVHSNNNLGPVL IAPP_MESAU 47 -1 -
RLTNFLVRSSHNLGAAL IAPP_CAVPO 47 -1 -
RLTNFLVRSSHNLGAAL IAPP_OCTDE 47 -1 -
RLADFLVRSSSNIGAIY Q90743 90 -1 -

Motif 4 width=16
Element Seqn Id St Int Rpt
LSPTNVGSNTYGKRNT IAPP_CANFA 60 -1 -
LPPTNVGSNTYGKRNA IAPP_MOUSE 64 -1 -
LSPTNVGSNTYGKRST IAPP_FELCA 60 -1 -
LPPTNVGSNTYGKRNV IAPP_RAT 64 -1 -
LSSTNVGSNTYGKRNA IAPP_HUMAN 60 -1 -
LSPTNVGSNTYGKRSA IAPP_MESAU 63 -1 -
LLPTDVGSNTYGKRNA IAPP_CAVPO 63 -1 -
LPPTKVGSNTYGRRNA IAPP_OCTDE 63 -1 -
YSPTNVGSNTYGKRDT Q90743 106 -1 -