PSEN2
entrez
5664
canonical
uniprot
P49810
canonical
ensembl
ENSG00000143801
resolver
ensembl
ENSG00000288674
resolver
ensp
ENSP00000355747
resolver
ensp
ENSP00000403737
resolver
ensp
ENSP00000503116
resolver
ensp
ENSP00000570131
resolver
ensp
ENSP00000610921
resolver
ensp
ENSP00000610923
resolver
ensp
ENSP00000638822
resolver
ensp
ENSP00000638833
resolver
genesymbol
PSEN2
resolver
genesymbol_syn
AD4
resolver
genesymbol_syn
PS2
resolver
genesymbol_syn
PSNL2
resolver
genesymbol_syn
STM2
resolver
hgnc
HGNC:9509
resolver
uniprot
A8K8D4
resolver
uniprot
B1AP21
resolver
uniprot
Q96P32
resolver
uniprot_entry
PSN2_HUMAN
resolver
uniprot_sec
A8K8D4
resolver
uniprot_sec
B1AP21
resolver
uniprot_sec
Q96P32
resolver
amino_acid_sequence
MLTFMASDSEEEVCDERTSLMSAESPTPRSCQEGRQGPEDGENTAQWRSQENEEDGEEDPDRYVCSGVPGRPPGLEEELTLKYGAKHVIMLFVPVTLCMIVVVATIKSVRFYTEKNGQLIYTPFTEDTPSVGQRLLNSVLNTLIMISVIVVMTIFLVVLYKYRCYKFIHGWLIMSSLMLLFLFTYIYLGEVLKTYNVAMDYPTLLLTVWNFGAVGMVCIHWKGPLVLQQAYLIMISALMALVFIKYLPEWSAWVILGAISVYDLVAVLCPKGPLRMLVETAQERNEPIFPALIYSSAMVWTVGMAKLDPSSQGALQLPYDPEMEEDSYDSFGEPSYPEVFEPPLTGYPGEELEEEEERGVKLGLGDFIFYSVLVGKAAATGSGDWNTTLACFVAILIGLCLTLLLLAVFKKALPALPISITFGLIFYFSTDNLVRPFMDTLASHQLYI
uniprot
proteins
disease_involvement
DISEASE: Alzheimer disease 4 (AD4) [MIM:606889]: A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10732806, ECO:0000269|PubMed:14681895, ECO:0000269|PubMed:16752394, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:21285369, ECO:0000269|PubMed:21544564, ECO:0000269|PubMed:22503161, ECO:0000269|PubMed:24838186, ECO:0000269|PubMed:24844686, ECO:0000269|PubMed:27293189, ECO:0000269|PubMed:7638622, ECO:0000269|PubMed:7651536, ECO:0000269|PubMed:9384602}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated, 1V (CMD1V) [MIM:613697]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:17186461}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.4.23.-
uniprot
proteins
function
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:10497236, PubMed:10652302, PubMed:16752394, PubMed:27293189, PubMed:36272978). Selectively cleaves late endosomal/lysosomal localized substrates and generates the prominent pool of intracellular amyloid beta that contains longer amyloid beta (PubMed:27293189). 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 (PubMed:16959576). Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria (PubMed:21285369). {ECO:0000269|PubMed:10497236, ECO:0000269|PubMed:10652302, ECO:0000269|PubMed:16752394, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:21285369, ECO:0000269|PubMed:27293189, ECO:0000269|PubMed:36272978}.
uniprot
proteins
mass_dalton
50140
uniprot
proteins
mutagenesis
MUTAGEN 16..21; /note="ERTSLM->ARTSAA: Impairs AP1G1 interaction. Does not affect aspartic endopeptidase activity, intramembrane cleaving. Does not affect gamma-secretase complex assemlby. Significantly decreases localization at late endosome/lysosome."; /evidence="ECO:0000269|PubMed:27293189"; MUTAGEN 19; /note="S->A: Does not affect AP1G1 interaction. Does not affect aspartic endopeptidase activity, intramembrane cleaving. Does not affect gamma-secretase complex assemlby. Does not affect localization at late endosome/lysosome."; /evidence="ECO:0000269|PubMed:27293189"; MUTAGEN 19; /note="S->D: Impairs AP1G1 interaction. Does not affect aspartic endopeptidase activity, intramembrane cleaving. Does not affect gamma-secretase complex assembly. Decreases localization at late endosome/lysosome."; /evidence="ECO:0000269|PubMed:27293189"; MUTAGEN 263; /note="D->A: Reduces production of amyloid-beta in APP processing."; /evidence="ECO:0000269|PubMed:10652302"; MUTAGEN 366; /note="D->A: Reduces production of amyloid-beta in APP processing and of NICD in NOTCH1 processing. Increased mitochondrion-endoplasmic reticulum membrane tethering resulting in increased calcium transfer to mitochondria."; /evidence="ECO:0000269|PubMed:10497236, ECO:0000269|PubMed:10652302, ECO:0000269|PubMed:21285369
uniprot
proteins
post_translational_modification
PTM: Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments. {ECO:0000269|PubMed:10497236, ECO:0000269|PubMed:10652302, ECO:0000269|PubMed:36272978}.; PTM: Phosphorylated on serine residues (PubMed:27293189). Phosphorylation at Ser-19 affects PSEN2 sorting (PubMed:27293189). {ECO:0000269|PubMed:27293189}.
uniprot
proteins
protein_family
Peptidase A22A family
uniprot
proteins
pubmed
10497236
uniprot
proteins
pubmed
10631141
uniprot
proteins
pubmed
10652302
uniprot
proteins
pubmed
10732806
uniprot
proteins
pubmed
10854253
uniprot
proteins
pubmed
11799129
uniprot
proteins
pubmed
12214059
uniprot
proteins
pubmed
14681895
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15274632
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16752394
uniprot
proteins
pubmed
16959576
uniprot
proteins
pubmed
17186461
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21285369
uniprot
proteins
pubmed
21544564
uniprot
proteins
pubmed
22503161
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24838186
uniprot
proteins
pubmed
24844686
uniprot
proteins
pubmed
27293189
uniprot
proteins
pubmed
36272978
uniprot
proteins
pubmed
7638622
uniprot
proteins
pubmed
7651536
uniprot
proteins
pubmed
8574969
uniprot
proteins
pubmed
8618867
uniprot
proteins
pubmed
8661049
uniprot
proteins
pubmed
9384602
uniprot
proteins
pubmed
9437013
uniprot
proteins
pubmed
9521418
uniprot
proteins
sequence_length
448
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:8574969}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:8574969}; Multi-pass membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:27293189}. Lysosome membrane {ECO:0000269|PubMed:27293189}. Note=Late endosome/lysosome localization is dependent of the phosphorylation-mediated interaction with the AP1G1 (PubMed:27293189). Also highly enriched in mitochondria-associated endoplasmic reticulum membrane contact site (By similarity). {ECO:0000250|UniProtKB:Q61144, ECO:0000269|PubMed:27293189}.
uniprot
proteins
transmembrane_region
TRANSMEM 88..108; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 139..159; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 167..187; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 201..221; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 224..244; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 250..270; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 362..382; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 389..409; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins