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PROSITE documentation PDOC00204 [for PROSITE entry PS00320]

Amyloidogenic glycoprotein signatures





Description

Amyloidogenic glycoprotein (A4 protein or APP) is an integral, glycosylated membrane brain protein [1,2]. APP is associated with Alzheimer's disease (AD). This responsibility stems from the fact that a small peptide (of 43 residues), called the amyloid β protein, which is part of the sequence of A4, is the major constituent of amyloid deposits in AD and in Down's syndrome. As shown in the schematic representation below, the amyloid β protein both precedes and forms part of the unique transmembrane region of A4.

       +----------------------------------------xxxxxxx-------------+
       |  Extracellular                         XXXXXXX Cytoplasmic |
       +------------------------------------BBBBBBBBxxx-------------+
'X': Transmembrane region.
'B': Position of the amyloid beta protein in A4.

The exact function of A4 protein is not yet known, but it has been suggested that it mediates cell-cell interactions. The sequence of A4 from mammalian species is well conserved and is also similar to that of other proteins:

  • Drosophila APPL (gene vnd) [3].
  • Mammalian protein APLP1 [4].
  • Mammalian protein APLP2 (APPH) (YWK-II) (CDEI-binding protein) [5].

We have derived two patterns specific to these proteins, the first one is a perfectly conserved octapeptide located in the beginning of the extracellular domain; the second is a conserved octapeptide located at the C-terminal end of the cytoplasmic domain.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

A4_INTRA, PS00320; Amyloidogenic glycoprotein intracellular domain signature  (PATTERN)

A4_EXTRA, PS00319; Amyloidogenic glycoprotein extracellular domain signature  (PATTERN)


References

1AuthorsDyrks T., Weidemann A., Multhaup G., Salbaum J.M., Lemaire H.-G., Kang J., Muller-Hill B., Masters C.L., Beyreuther K.
TitleIdentification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease.
SourceEMBO J. 7:949-957(1988).
PubMed ID2900137

2AuthorsAshall F., Goate A.M.
TitleRole of the beta-amyloid precursor protein in Alzheimer's disease.
SourceTrends Biochem. Sci. 19:42-46(1994).
PubMed ID8140621

3AuthorsRosen D.R., Martin-Morris L., Luo L.Q., White K.
TitleA Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor.
SourceProc. Natl. Acad. Sci. U.S.A. 86:2478-2482(1989).
PubMed ID2494667

4AuthorsWasco W., Bupp K., Magendantz M., Gusella J.F., Tanzi R.E., Solomon F.
TitleIdentification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor.
SourceProc. Natl. Acad. Sci. U.S.A. 89:10758-10762(1992).
PubMed ID1279693

5AuthorsSprecher C.A., Grant F.J., Grimm G., O'Hara P.J., Norris F., Norris K., Foster D.C.
TitleMolecular cloning of the cDNA for a human amyloid precursor protein homolog: evidence for a multigene family.
SourceBiochemistry 32:4481-4486(1993).
PubMed ID8485127



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