oops. Move "What I don't know:" to below "ADDL complex has_part..."
Corrected message below

-Alan


On Jan 21, 2007, at 9:26 PM, Eric Neumann wrote:

Bill,

I'm trying to understand the central issue here: is it that ADDL is not a full gene product so one cannot use the Entrez URI?


I'm trying to understand this stuff too. Here's my current understanding:

APP gene (for which there is an entrez gene entry)-> precursor protein (~700AA). Two proteases can cleave it into different fragments from 39-42 amino acids. These are collectively called Amyloid beta proteins. I.e. Amyloid beta is a protein family, though in different contexts it might refer to a specific member of that family.

ADDLs are short oligomers of amyloid beta proteins. I've seen it said that they are made of Abeta(1-42) (i.e. the 42 AA cleavage product)


If so, why not just define the necessary set of peptides as new URI's (in HCLS's namespace for now), with predicate ':derived_from A-beta*56' ?


Abeta*56 is also a protein complex of Amyloid beta proteins. 56 here refers to the molecular weight in kDa. It wasn't specifically stated but it looks to me that Abeta*56 fits the definition of an ADDL. A single Abeta1-42 is about 4.5kDa,

The variables are therefore a) which Abeta b) what size complex.

So the relation is more like:

precursor protein_gene_product_of APP
Abeta derived_from precursor (in the BFO sense)
ADDL complex has_part only Abeta (also some sort of cardinality specification)

What I don't know:

Whether APP splice form matters. How mutation matters. Whether ADDL refers specifically to Abeta1-42 complexes. What the comment about Abeta1-40 in the immunogen(epitope) field of the ADDL antibody in Alzforum means. Bill's note suggests that shorter fragments of Abeta might be consituents of ADDLs. I don't know if these are just experimental constructs or whether they occur in vivo. Whether ADDLs are always composed of multiples of a single form of abeta, or whether different species can be mixed.

-Alan

http://en.wikipedia.org/wiki/Amyloid_precursor_protein
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? db=PubMed&cmd=Retrieve&dopt=Citation&list_uids=16541076
http://www.pnas.org/cgi/content/full/95/11/6448
http://www.jbc.org/cgi/content/abstract/271/34/20631


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