ERAB contains a putative noncleavable signal peptide.
The 42-residue amyloid beta protein (Abeta42) has been shown to be toxic to neurons and is believed to play a key causative role in Alzheimer's disease (AD). A search for Abeta binding proteins that can mediate its toxicity resulted in the identification of the endoplasmic-reticulum (ER) associated Abeta binding protein (ERAB) which was also shown to be involved in Abeta induced apoptosis. The primary report indicated that a signal sequence is absent in ERAB suggesting that it is bound to the cytoplasmic aspect of cellular membranes. Abeta is generated in the lumen of secretory organelles and released into the medium resulting in its separation from ERAB by a membrane barrier. After computer analysis of the ERAB sequence, we have detected a putative signal peptide that can direct the protein into the secretory pathway. This signal sequence was found in human, rodent, and bovine ERAB suggesting that it is a type II integral membrane protein in vertebrates. This topology can explain the binding of Abeta to ERAB. Our finding that an integral membrane form of ERAB can bind to Abeta in the lumen of transport vesicles and other cytoplasmic receptors provides a basis for understanding its role in AD.
Department of Pharmacology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida, 32224, USA.
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D015094:3-Hydroxyacyl CoA Dehydrogenases; D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D002417:Cattle; D004330:Drosophila; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008830:Microbodies / Q000737:chemistry; D008928:Mitochondria / Q000737:chemistry; D021382:Protein Sorting Signals / Q000032:analysis*; D012984:Software
D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; C458480:Hsd17b10 protein, mouse