WORKLIST ENTRIES (1):

BETAAMYLOID View alignment View Structure     Beta-amyloid peptide (beta-APP) signature
 Type of fingerprint: COMPOUND with 3  elements
Links:
   PRINTS; PR00203 AMYLOIDA4
   INTERPRO; IPR001255
   PDB; 1AAP 3Dinfo
   SCOP; 1AAP 
   CATH; 1AAP 

 Creation date 15-SEP-1993; UPDATE 06-JUN-1999

   1. HARDY, J.
   Framing beta-amyloid.
   NAT.GENET. 1(4) 233-234 (1992).

   2. ARISPE, N., ROJAS, E. AND POLLARD, H.B.
   Alzheimer's disease amyloid beta-protein forms calcium channels in bilayer
   membranes: blockade by tromethamine and aluminum.
   PROC.NATL.ACAD.SCI.U.S.A. 90 567-571 (1993).

   3. OTVOS, L., SZENDREI, G.I., LEE, V.M.-Y AND MANTSCH, H.H.
   Human and rodent Alzheimer beta-amyloid peptides acquire distinct 
   conformations in membrane-mimicking solvents.
   EUR.J.BIOCHEM. 211 249-257 (1993).

   Beta-amyloid protein (beta-APP) is a 40-residue peptide implicated in the
   pathogenesis of Alzheimer's disease (AD) and aged Down's Syndrome (which is
   promoted by the acquisition of an additional copy of chromosome 21) [1-3].
   The peptide is a proteolytic product of the much larger amyloid precursor
   protein (APP) encoded by a gene on chromosome 21. In AD, pathologically the
   brain is characterised by extracellular amyloid plaques, intraneuronal
   neurofibrillary tangles, and vascular and neuronal damage. The major
   protein found within these deposits is a small, highly aggregating peptide
   (beta-APP), which is thought to be derived from aberrant catabolism of its
   precursor.
  
   The exact function of APP is unknown, but it may mediate cell-cell inter-
   actions. The protein comprises a large extracellular N-terminal domain, and
   a short hydrophobic membrane-spanning domain, followed by a short
   C-terminal region - beta-APP both precedes and forms part of the trans-
   membrane region. Little is known about its structure, but studies on a 
   synthetic peptide have shown that it can express different proportions of 
   alpha-helix and beta-sheet, depending on physiologically relevant environ-
   mental variables, such as ionic strength, pH and hydrophobicity [2]. The 
   extracellular 28-residue region of the peptide is organised in a cross beta-
   structure, while the C-terminal portion is believed to span the membrane
   via a hydrophobic alpha-helical domain. Assemblies of different numbers of
   such synthetic peptides have been shown to form cation-selective ion
   channels across planar lipid bilayers [2].
  
   Brain deposits of beta-APP in amyloid fibrils are common in humans, 
   monkeys, dogs and bears, but similar accumulations are rare in rodent
   brains. The primary sequence of the rodent peptide differs at only 3
   positions compared with its human counterpart, and it is believed that
   these subtle inter-species differences may account for the inability of
   the rodent peptide to form amyloid fibrils in situ. Specifically, the
   human peptide, but not the rodent homologue, is capable of forming a
   beta-sheet structure at low peptide concentration. Thus, a specific
   amino-acid sequence is a critical determinant of amyloidogenesis [3].
  
   BETAAMYLOID is a 3-element fingerprint that provides a signature for the
   beta-amyloid peptide. The fingerprint was derived from an initial alignment
   of 3 sequences: the motifs completely span the 40-residue peptide, the
   first two corresponding to the sheet-forming hydrophilic region, and the
   third to the alpha-helical hydrophobic C-terminus. Two iterations on
   OWL21.1 were required to reach convergence, at which point a true set
   comprising 7 sequences was identified. A single partial match was also
   found, A44017, a beta-APP fragment lacking the portion of sequence bearing 
   motif 1.
  
   An update on SPTR37_9f identified a true set of 10 sequences.

  SUMMARY INFORMATION
     10 codes involving  3 elements
      0 codes involving  2 elements

   COMPOSITE FINGERPRINT INDEX
  
    3|  10   10   10  
    2|   0    0    0  
   --+----------------
     |   1    2    3  

True positives..
 A4_HUMAN       Q60496         A4_SAISC       P97487         
 A4_RAT         A4_MOUSE       O57394         Q91963         
 O73683         O93279         


  PROTEIN TITLES
   A4_HUMAN         ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN PRECURSOR (PROTEASE N
   Q60496           ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN - CAVIA PORCELLUS (GU
   A4_SAISC         ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN PRECURSOR [CONTAINS: 
   P97487           HIPPOCAMPAL AMYLOID PROTEIN - MUS MUSCULUS (MOUSE).
   A4_RAT           ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN HOMOLOG PRECURSOR (AM
   A4_MOUSE         ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN HOMOLOG PRECURSOR (AM
   O57394           EL AMYLOID PRECURSOR PROTEIN 699 - NARKE JAPONICA (ELECTRIC 
   Q91963           APP747 - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
   O73683           AMYLOID PRECURSOR PROTEIN - TETRAODON FLUVIATILIS (PUFFER FI
   O93279           BETA-AMYLOID PRECURSOR PROTEIN - FUGU RUBRIPES (JAPANESE PUF

SCAN HISTORY OWL21_1 2 50 NSINGLE OWL26_0 1 50 NSINGLE SPTR37_9f 2 11 NSINGLE INITIAL MOTIF SETS BETAAMYLOID1 Length of motif = 14 Motif number = 1 Beta amyloid peptide motif I - 1 PCODE ST INT FRHDSGYEVHHQKL A4_HUMAN 674 674 FGHDSGFEVRHQKL A4_MOUSE 674 674 FGHDSGFEVRHQKL A4_RAT 674 674 BETAAMYLOID2 Length of motif = 13 Motif number = 2 Beta amyloid peptide motif II - 1 PCODE ST INT VFFAEDVGSNKGA A4_HUMAN 688 0 VFFAEDVGSNKGA A4_MOUSE 688 0 VFFAEDVGSNKGA A4_RAT 688 0 BETAAMYLOID3 Length of motif = 13 Motif number = 3 Beta amyloid peptide motif III - 1 PCODE ST INT AIIGLMVGGVVIA A4_HUMAN 700 -1 AIIGLMVGGVVIA A4_MOUSE 700 -1 AIIGLMVGGVVIA A4_RAT 700 -1 FINAL MOTIF SETS BETAAMYLOID1 Length of motif = 14 Motif number = 1 Beta amyloid peptide motif I - 2 PCODE ST INT FRHDSGYEVHHQKL A4_HUMAN 675 675 FRHDSGYEVHHQKL Q60496 600 600 FRHDSGYEVHHQKL A4_SAISC 656 656 FGHDSGFEVRHQKL A4_MOUSE 675 675 FGHDSGFEVRHQKL A4_RAT 675 675 FGHDSGFEVRHQKL P97487 600 600 FQQDSGYEVHHQKL O57394 604 604 YRHDTAYEVHHQKL Q91963 652 652 DRQSTEYEVHHQKL O73683 685 685 KRQSAGYEVYHQKL O93279 642 642 BETAAMYLOID2 Length of motif = 13 Motif number = 2 Beta amyloid peptide motif II - 2 PCODE ST INT VFFAEDVGSNKGA A4_HUMAN 689 0 VFFAEDVGSNKGA Q60496 614 0 VFFAEDVGSNKGA A4_SAISC 670 0 VFFAEDVGSNKGA A4_MOUSE 689 0 VFFAEDVGSNKGA A4_RAT 689 0 VFFAEDVGSNKGA P97487 614 0 VFFPKDVGSNKGA O57394 618 0 VFFAEEVGSNKGA Q91963 666 0 VFFAEDVGSNKGA O73683 699 0 VFFADDVGSNKGA O93279 656 0 BETAAMYLOID3 Length of motif = 13 Motif number = 3 Beta amyloid peptide motif III - 2 PCODE ST INT AIIGLMVGGVVIA A4_HUMAN 701 -1 AIIGLMVGGVVIA Q60496 626 -1 AIIGLMVGGVVIA A4_SAISC 682 -1 AIIGLMVGGVVIA A4_MOUSE 701 -1 AIIGLMVGGVVIA A4_RAT 701 -1 AIIGLMVGGVVIA P97487 626 -1 AIIGLMVGGVVIA O57394 630 -1 AIIGLMVGGVVIA Q91963 678 -1 AIIGLMVGGVVIA O73683 711 -1 AIIGLMVGGVVIA O93279 668 -1

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