Tchem PSEN1 Presenilin-1

Protein Summary

Description

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). Requires the presence of the other members of the gamma-secretase complex for protease activity (PubMed:15274632, PubMed:25043039, PubMed:26280335). 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). Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene, the full-length nature of only some have been determined. [provided by RefSeq, Aug 2008]

Uniprot Accession IDs

• P49768
• B2R6D3
• O95465
• Q14762
• Q15719
• Q15720
• Q96P33
• Q9UIF0
• PS-1

Gene Name

• PSEN1

Ensembl ID

• ENST00000324501
• ENSP00000326366
• ENSG00000080815
• ENST00000357710
• ENSP00000350342
• ENST00000394157
• ENSP00000377712
• ENST00000394164
• ENSP00000377719
• ENST00000553855
• ENSP00000452242
• ENST00000555386
• ENSP00000450845
• ENST00000557511
• ENSP00000451429

Symbol

• AD3
• PS1
• PSNL1
• AD3
• FAD
• PS1
• PS-1
• S182
• ACNINV3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	0.98
molecular function	0.94
disease perturbation	0.93
kinase perturbation	0.91

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Membrane-bound Signaling Molecule / Presenilin-1

Protein / Hydrolase / Protease / Aspartic Protease / Presenilin-1

Protein / Calcium-binding Protein / Presenilin-1

DTO Classes

Protein / Enzyme / Protease / Aspartic Protease / Presenilin-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1933.18   (req: < 5)

Gene RIFs: 594   (req: <= 3)

Antibodies: 853   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1933.18   (req: >= 5)

Gene RIFs: 594   (req: > 3)

Antibodies: 853   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 84

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 91

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0