| Tchem | Gamma-secretase-activating protein |
Regulator of gamma-secretase activity, which specifically activates the production of beta-amyloid protein (beta-amyloid protein 40 and beta-amyloid protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate beta-amyloid, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD.
Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]
Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]
Comments
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Alzheimer's disease | 644 | 3.482 | 1.7 |
| Echinococcosis | 28 | 3.292 | 1.6 |
| Disease | log2 FC | p |
|---|---|---|
| Waldenstrons macroglobulinemia | 1.240 | 0.009 |
| malignant mesothelioma | -5.400 | 0.000 |
| psoriasis | -1.200 | 0.000 |
| glioblastoma | 2.000 | 0.000 |
| osteosarcoma | -1.521 | 0.031 |
| medulloblastoma | -2.300 | 0.000 |
| cystic fibrosis | 2.234 | 0.000 |
| atypical teratoid / rhabdoid tumor | -2.500 | 0.000 |
| medulloblastoma, large-cell | -2.400 | 0.001 |
| non-small cell lung cancer | -2.193 | 0.000 |
| intraductal papillary-mucinous adenoma (... | 1.700 | 0.002 |
| intraductal papillary-mucinous carcinoma... | 1.600 | 0.007 |
| intraductal papillary-mucinous neoplasm ... | 2.100 | 0.004 |
| lung cancer | -3.700 | 0.000 |
| subependymal giant cell astrocytoma | 2.801 | 0.008 |
| Breast cancer | 1.200 | 0.005 |
| invasive ductal carcinoma | 1.236 | 0.005 |
| Pick disease | -1.800 | 0.000 |
| progressive supranuclear palsy | -1.500 | 0.019 |
| ulcerative colitis | 1.900 | 0.000 |
| ovarian cancer | -3.000 | 0.000 |
| PMID | Text |
|---|---|
| 26076991 | GSAP cleavage via caspase-3 is regulated and depend upon the availability of 5-Lipoxygenase in Alzheimer's disease. |
| 25037285 | Its promoter variant contributes to Alzheimer's disease liability. |
| 23209290 | gamma-secretase activating protein (GSAP) and imatinib have roles in the regulation of gamma-secretase activity and amyloid-beta generation |
| 22681044 | Protocols for recombinant bacterial expression and purification of potentially important protein GSAP are not successful in generating soluble forms of GSAP that contain well-ordered and homogeneous tertiary structure. |
| 21718343 | Aberrant regulation of gamma-secretase activating protein expression plays a key role in acceleration of gamma-cleavage of beta-secretase-cleaved C-terminal fragment of amyloid precursor protein and accumulation of Abeta in AD brains |
| 20811458 | A gamma-secretase activating protein (GSAP) that selectively increases amyloid-beta production via interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment. |
MALRLVADFDLGKDVLPWLRAQRAVSEASGAGSGGADVLENDYESLHVLNVERNGNIIYTYKDDKGNVVF 1 - 70 GLYDCQTRQNELLYTFEKDLQVFSCSVNSERTLLAASLVQSTKEGKRNELQPGSKCLTLLVEIHPVNNVK 71 - 140 VLKAVDSYIWVQFLYPHIESHPLPENHLLLISEEKYIEQFRIHVAQEDGNRVVIKNSGHLPRDRIAEDFV 141 - 210 WAQWDMSEQRLYYIDLKKSRSILKCIQFYADESYNLMFEVPLDISLSNSGFKLVNFGCDYHQYRDKFSKH 211 - 280 LTLCVFTNHTGSLCVCYSPKCASWGQITYSVFYIHKGHSKTFTTSLENVGSHMTKGITFLNLDYYVAVYL 281 - 350 PGHFFHLLNVQHPDLICHNLFLTGNNEMIDMLPHCPLQSLSGSLVLDCCSGKLYRALLSQSSLLQLLQNT 351 - 420 CLDCEKMAALHCALYCGQGAQFLEAQIIQWISENVSACHSFDLIQEFIIASSYWSVYSETSNMDKLLPHS 421 - 490 SVLTWNTEIPGITLVTEDIALPLMKVLSFKGYWEKLNSNLEYVKYAKPHFHYNNSVVRREWHNLISEEKT 491 - 560 GKRRSAAYVRNILDNAVKVISNLEARNLGPRLTPLLQEEDSHQRLLMGLMVSELKDHFLRHLQGVEKKKI 561 - 630 EQMVLDYISKLLDLICHIVETNWRKHNLHSWVLHFNSRGSAAEFAVFHIMTRILEATNSLFLPLPPGFHT 631 - 700 LHTILGVQCLPLHNLLHCIDSGVLLLTETAVIRLMKDLDNTEKNEKLKFSIIVRLPPLIGQKICRLWDHP 701 - 770 MSSNIISRNHVTRLLQNYKKQPRNSMINKSSFSVEFLPLNYFIEILTDIESSNQALYPFEGHDNVDAEFV 771 - 840 EEAALKHTAMLLGL 841 - 854 //
| PMID | Year | Title |
|---|---|---|
| 26076991 | 2015 | Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence. |
| 25037285 | 2014 | Common GSAP promoter variant contributes to Alzheimer's disease liability. |
| 23209290 | 2013 | The role of ?-secretase activating protein (GSAP) and imatinib in the regulation of ?-secretase activity and amyloid-? generation. |
| 22681044 | 2012 | Purification and characterization of the human ?-secretase activating protein. |
| 21718343 | 2012 | Immunohistochemical characterization of ?-secretase activating protein expression in Alzheimer's disease brains. |
| 20811458 | 2010 | Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. |
| 17974005 | 2007 | The full-ORF clone resource of the German cDNA Consortium. |
| 16341674 | 2005 | Transcriptome analysis of human gastric cancer. |
| 15489334 | 2004 | The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |
| 14702039 | 2004 | Complete sequencing and characterization of 21,243 full-length human cDNAs. |
| More... |
