Psen1
entrez
19164
canonical
uniprot
P49769
canonical
ensembl
ENSMUSG00000019969
resolver
ensp
ENSMUSP00000048363
resolver
genesymbol
Psen1
resolver
genesymbol_syn
Ad3h
resolver
genesymbol_syn
Psnl1
resolver
uniprot
Q3UYK2
resolver
uniprot
Q91WK6
resolver
uniprot
Q9JLP9
resolver
uniprot_entry
PSN1_MOUSE
resolver
uniprot_entry
Q3UYK2_MOUSE
resolver
uniprot_sec
Q91WK6
resolver
uniprot_sec
Q9JLP9
resolver
amino_acid_sequence
MTEIPAPLSYFQNAQMSEDSHSSSAIRSQNDSQERQQQHDRQRLDNPEPISNGRPQSNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVIMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYVTVALLIWNFGVVGMIAIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVPKNPKYNTQRAERETQDSGSGNDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSGSILTSEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
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:19834068). Requires the presence of the other members of the gamma-secretase complex for protease activity (By similarity). 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:10421573, PubMed:11517342). 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:11226248). 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:11226248). Required for normal embryonic brain and skeleton development, and for normal angiogenesis (PubMed:10421573, PubMed:12834865, PubMed:9160754). Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795). 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). Involved in the regulation of neurite outgrowth (By similarity). 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 (PubMed:30429473). {ECO:0000250|UniProtKB:P49768, ECO:0000269|PubMed:10421573, ECO:0000269|PubMed:11226248, ECO:0000269|PubMed:11517342, ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12834865, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:19834068, ECO:0000269|PubMed:30429473, ECO:0000269|PubMed:9160754}.
uniprot
proteins
mass_dalton
52640
uniprot
proteins
post_translational_modification
PTM: Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by caspase-3 to produce the fragment, PS1-CTF12. {ECO:0000250|UniProtKB:P49768}.; PTM: After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-346 inhibits endoproteolysis. {ECO:0000250|UniProtKB:P49768}.
uniprot
proteins
protein_family
Peptidase A22A family
uniprot
proteins
pubmed
10421573
uniprot
proteins
pubmed
11226248
uniprot
proteins
pubmed
11517342
uniprot
proteins
pubmed
11953314
uniprot
proteins
pubmed
12834865
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16959576
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17428795
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19834068
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
30429473
uniprot
proteins
pubmed
7596406
uniprot
proteins
pubmed
9160754
uniprot
proteins
pubmed
9295283
uniprot
proteins
sequence_length
467
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000250|UniProtKB:P49768}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P49768}. Golgi apparatus membrane {ECO:0000269|PubMed:19834068}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P49768}. Cytoplasmic granule {ECO:0000250|UniProtKB:P49768}. Cell membrane {ECO:0000269|PubMed:10421573, ECO:0000269|PubMed:11517342, ECO:0000269|PubMed:19834068}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P49768}. Cytoplasmic vesicle {ECO:0000269|PubMed:10421573, ECO:0000305|PubMed:11517342}. Cell projection, growth cone {ECO:0000250|UniProtKB:P49768}. Cell projection, neuron projection {ECO:0000250|UniProtKB:P49768}. Early endosome {ECO:0000250|UniProtKB:P49768}. Early endosome membrane {ECO:0000250|UniProtKB:P49768}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P49768}. Cell projection, axon {ECO:0000250|UniProtKB:Q4JIM4}. Synapse {ECO:0000250|UniProtKB:Q4JIM4}. Note=Translocates with bound NOTCH1 from the endoplasmic reticulum and/or Golgi to the cell surface. Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane. Also present in azurophil granules of neutrophils. Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes. Also highly enriched in mitochondria-associated endoplasmic reticulum membrane contact site (PubMed:19834068). {ECO:0000250|UniProtKB:P49768, ECO:0000269|PubMed:19834068}.
uniprot
proteins
transmembrane_region
TRANSMEM 83..103; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 133..153; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 167..189; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 195..216; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 221..241; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 249..272; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 381..401; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 408..428; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768"; TRANSMEM 433..453; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P49768
uniprot
proteins