| Tchem | Gamma-secretase-activating protein |
Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta 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 (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid-beta, 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 | P-value |
|---|---|---|
| non-small cell lung cancer | 2890 | 6.4e-18 |
| ovarian cancer | 8520 | 4.7e-08 |
| malignant mesothelioma | 3232 | 9.4e-08 |
| cystic fibrosis | 1696 | 1.2e-06 |
| Pick disease | 1894 | 8.2e-06 |
| atypical teratoid / rhabdoid tumor | 5112 | 1.2e-05 |
| ulcerative colitis | 1819 | 2.2e-05 |
| psoriasis | 6694 | 3.1e-05 |
| glioblastoma | 5792 | 4.8e-04 |
| medulloblastoma, large-cell | 6241 | 5.6e-04 |
| lung cancer | 4740 | 6.3e-04 |
| group 4 medulloblastoma | 1855 | 9.7e-04 |
| intraductal papillary-mucinous adenoma (IPMA) | 2955 | 3.3e-03 |
| invasive ductal carcinoma | 2951 | 4.8e-03 |
| Breast cancer | 3578 | 4.9e-03 |
| intraductal papillary-mucinous neoplasm (IPMN) | 3291 | 5.2e-03 |
| subependymal giant cell astrocytoma | 2287 | 7.9e-03 |
| Waldenstrons macroglobulinemia | 765 | 1.1e-02 |
| intraductal papillary-mucinous carcinoma (IPMC) | 2989 | 1.4e-02 |
| progressive supranuclear palsy | 676 | 1.9e-02 |
| osteosarcoma | 7950 | 4.4e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Alzheimer's disease | 658 | 3.505 | 1.8 |
| Echinococcosis | 26 | 3.253 | 1.6 |
| Disease | log2 FC | p |
|---|---|---|
| atypical teratoid / rhabdoid tumor | -2.400 | 1.2e-05 |
| Breast cancer | 1.200 | 4.9e-03 |
| cystic fibrosis | 2.234 | 1.2e-06 |
| glioblastoma | 2.000 | 4.8e-04 |
| group 4 medulloblastoma | -1.700 | 9.7e-04 |
| intraductal papillary-mucinous adenoma (... | 1.500 | 3.3e-03 |
| intraductal papillary-mucinous carcinoma... | 1.400 | 1.4e-02 |
| intraductal papillary-mucinous neoplasm ... | 2.000 | 5.2e-03 |
| invasive ductal carcinoma | 1.236 | 4.8e-03 |
| lung cancer | -2.300 | 6.3e-04 |
| malignant mesothelioma | -5.100 | 9.4e-08 |
| medulloblastoma, large-cell | -2.400 | 5.6e-04 |
| non-small cell lung cancer | -2.135 | 6.4e-18 |
| osteosarcoma | -1.285 | 4.4e-02 |
| ovarian cancer | -3.000 | 4.7e-08 |
| Pick disease | -1.800 | 8.2e-06 |
| progressive supranuclear palsy | -1.500 | 1.9e-02 |
| psoriasis | -1.200 | 3.1e-05 |
| subependymal giant cell astrocytoma | 2.440 | 7.9e-03 |
| ulcerative colitis | 1.800 | 2.2e-05 |
| Waldenstrons macroglobulinemia | 1.223 | 1.1e-02 |
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 //
