gamma-secretase-activating protein; GSAP; protein pigeon homolog; GSAP-16K (GSAP, PION, LOC392943)

Function

• regulator of gamma-secretase activity
  • specifically activates the production of beta-amyloid protein (beta-amyloid protein 40 & beta-amyloid protein 42), without affecting the cleavage of other gamma-secretase targets such as notch.
  • specifically promotes the gamma-cleavage of APP CTF-alpha (C-terminal fragment of APP after beta secretase cleavage) to generate beta-amyloid
  • reduces the epsilon-cleavage of APP CTF-alpha, leading to low production of AICD
• GSAP is first synthesized as a holoprotein form of 98 kD & rapidly processed into the gamma-secretase-activating protein 16 kD C-terminal form, which constitutes the predominant form
• interacts with APP; specifically interacts with the CTF-alpha product of APP
• interacts with the gamma-secretase complex

Structure

belongs to the GSAP family

Compartment

Golgi apparatus, trans-Golgi network

Alternative splicing

named isoforms=4

Expression

widely expressed

Pharmacology

• activity is specifically inhibited by imatinib (Gleevec)
• imatinib binds PION/GSAP & acts by preventing PION/GSAP interaction with the gamma-secretase substrate, APP CTF-alpha (C-terminal fragment of APP after beta secretase cleavage)
• thus imatinib may inhibit beta-amyloid production

More general terms

• other protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=54103
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:54103
• OMIM: https://mirror.omim.org/entry/613552
• UniProt: http://www.uniprot.org/uniprot/A4D1B5.html