Summary

Name PSEN1
Full Name Presenilin-1
Synonyms PS-1, Protein S182 | AD3, PS1, PSNL1
Primary ID P49768
Links - -
Type protein
Relations 40
Pathways Alzheimer
Inhibitors DAPT; 4-[2-[(1R)-1-(N-(4-chlorophenyl)sulfonyl-2,5-difluoroanilino)ethyl]-5-fluorophenyl]butanoic acid
Function Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:15274632, PubMed:10545183, PubMed:10593990, PubMed:10206644, PubMed:10899933, PubMed:10811883, PubMed:12679784, PubMed:12740439, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874, PubMed:28269784, PubMed:20460383). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335, PubMed:30598546, PubMed:30630874). Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (PubMed:9738936, PubMed:10593990, PubMed:10899933, PubMed:10811883). Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin) (PubMed:11953314). Under conditions of apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling (PubMed:9738936, PubMed:11953314). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (By similarity). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis (PubMed:25394380, PubMed:16959576). Involved in the regulation of neurite outgrowth (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression (By similarity).

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▶Modifications Tables

Relations


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Regulator Mechanism target score ℹ
+ SCAF11up-regulates activity img/direct-activation.png cleavage PSEN1 0.288
Publications: 2 Organism: In Vitro
+ CASP6up-regulates activity img/direct-activation.png cleavage PSEN1 0.364
Publications: 2 Organism: In Vitro
+ CASP8up-regulates activity img/direct-activation.png cleavage PSEN1 0.361
Publications: 2 Organism: In Vitro
Pathways:Alzheimer
+ CASP3up-regulates activity img/direct-activation.png cleavage PSEN1 0.445
Publications: 1 Organism: In Vitro
Pathways:Alzheimer
+ CASP1up-regulates activity img/direct-activation.png cleavage PSEN1 0.377
Publications: 1 Organism: In Vitro
+ CASP7up-regulates activity img/direct-activation.png cleavage PSEN1 0.336
Publications: 1 Organism: In Vitro
+ PRKACA