Presenilin-2

UniProt P49810 Organism Homo sapiens Gene AD4, PS2, PSEN2, PSNL2, STM2 EC 3.4.23.-

Also known as: AD4, PS2, PSEN2, PSNL2, STM2

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). Selectively cleaves late endosomal/lysosomal localized substrates and generates the prominent pool of intracellular amyloid beta that contains longer amyloid beta. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis. Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria.

Classification

Family (Pfam): PF01080 Presenilin
InterPro: Pept_A22A_PS2, Peptidase_A22A, Preselin/SPP, Presenilin_C
Functional cluster: Membrane Transporters & GPCRs

Experimental structures · PDB · 2

7Y5X EM 3.00A
7Y5Z EM 3.40A

A predicted model is available from AlphaFold.

Gene Ontology · 32

Disease associations

Alzheimer disease 4 MONDO:0011743
dilated cardiomyopathy 1V MONDO:0013373

Drugs targeting this protein · 7

AVAGACESTAT inhibitor
NIROGACESTAT inhibitor
TARENFLURBIL modulator
RG-4733 inhibitor
NIROGACESTAT HYDROBROMIDE inhibitor
BEGACESTAT inhibitor
SEMAGACESTAT inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Presenilin-1 14 shared papers
Presenilin-2 1 shared papers
AP-1 complex subunit gamma-1 1 shared papers
Dedicator of cytokinesis protein 3 1 shared papers
Presenilin-2 1 shared papers
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein 1 shared papers
Presenilin-associated rhomboid-like protein, mitochondrial 1 shared papers
Dedicator of cytokinesis protein 3 1 shared papers
Presenilin-1 1 shared papers
Major prion protein 1 shared papers
Adapter molecule crk 1 shared papers
Filamin-B 1 shared papers

Literature · 35 cited papers

Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560. Nat. Commun. · 2022
Restricted Location of PSEN2/gamma-Secretase Determines Substrate Specificity and Generates an Intracellular Abeta Pool. Cell · 2016
Previously unrecognized missense mutation E126K of PSEN2 segregates with early onset Alzheimer's disease in a family. J. Alzheimers Dis. · 2014
Novel mutation in the PSEN2 gene (N141Y) associated with early-onset autosomal dominant Alzheimer's disease in a Chinese Han family. Neurobiol. Aging · 2014
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients. Neurobiol. Aging · 2012
Presenilin 2 mutation R71W in an Italian early-onset sporadic Alzheimer's disease case. J. Neurol. · 2011
Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk. Proc. Natl. Acad. Sci. U.S.A. · 2011
Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
… and 23 more in the literature graph

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