PSEN1
entrez
5663
canonical
uniprot
P49768
canonical
ensembl
ENSG00000080815
resolver
ensp
ENSP00000326366
resolver
ensp
ENSP00000350342
resolver
ensp
ENSP00000377719
resolver
ensp
ENSP00000450551
resolver
ensp
ENSP00000514901
resolver
ensp
ENSP00000514903
resolver
ensp
ENSP00000514904
resolver
ensp
ENSP00000514968
resolver
ensp
ENSP00000564220
resolver
ensp
ENSP00000564230
resolver
genesymbol
PSEN1
resolver
genesymbol_syn
AD3
resolver
genesymbol_syn
PS1
resolver
genesymbol_syn
PSNL1
resolver
hgnc
HGNC:9508
resolver
uniprot
A0A024R6A3
resolver
uniprot
A0A0S2Z4D2
resolver
uniprot
B2R6D3
resolver
uniprot
O95465
resolver
uniprot
Q14762
resolver
uniprot
Q15719
resolver
uniprot
Q15720
resolver
uniprot
Q96P33
resolver
uniprot
Q9UIF0
resolver
uniprot_entry
A0A024R6A3_HUMAN
resolver
uniprot_entry
A0A0S2Z4D2_HUMAN
resolver
uniprot_entry
PSN1_HUMAN
resolver
uniprot_sec
B2R6D3
resolver
uniprot_sec
O95465
resolver
uniprot_sec
Q14762
resolver
uniprot_sec
Q15719
resolver
uniprot_sec
Q15720
resolver
uniprot_sec
Q96P33
resolver
uniprot_sec
Q9UIF0
resolver
amino_acid_sequence
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
uniprot
proteins
disease_involvement
DISEASE: Alzheimer disease 3 (AD3) [MIM:607822]: 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:10025789, ECO:0000269|PubMed:10090481, ECO:0000269|PubMed:10200054, ECO:0000269|PubMed:10208579, ECO:0000269|PubMed:10439444, ECO:0000269|PubMed:10441572, ECO:0000269|PubMed:10447269, ECO:0000269|PubMed:10533070, ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10644793, ECO:0000269|PubMed:11027672, ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:11561050, ECO:0000269|PubMed:11568920, ECO:0000269|PubMed:11701593, ECO:0000269|PubMed:11710891, ECO:0000269|PubMed:11796781, ECO:0000269|PubMed:11920851, ECO:0000269|PubMed:12048239, ECO:0000269|PubMed:12058025, ECO:0000269|PubMed:12370477, ECO:0000269|PubMed:12484344, ECO:0000269|PubMed:12493737, ECO:0000269|PubMed:12552037, ECO:0000269|PubMed:15004326, ECO:0000269|PubMed:15122701, ECO:0000269|PubMed:15364419, ECO:0000269|PubMed:15534188, ECO:0000269|PubMed:15534260, ECO:0000269|PubMed:15851849, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16344340, ECO:0000269|PubMed:16628450, ECO:0000269|PubMed:16752394, ECO:0000269|PubMed:16897084, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17366635, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:17502474, ECO:0000269|PubMed:18430735, ECO:0000269|PubMed:19667325, ECO:0000269|PubMed:19797784, ECO:0000269|PubMed:20164095, ECO:0000269|PubMed:20460383, ECO:0000269|PubMed:21335660, ECO:0000269|PubMed:21501661, ECO:0000269|PubMed:22461631, ECO:0000269|PubMed:22503161, ECO:0000269|PubMed:22529981, ECO:0000269|PubMed:23123781, ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:24121961, ECO:0000269|PubMed:24495933, ECO:0000269|PubMed:24582897, ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:26145164, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26549787, ECO:0000269|PubMed:27073747, ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:29175279, ECO:0000269|PubMed:29404783, ECO:0000269|PubMed:29466804, ECO:0000269|PubMed:30180983, ECO:0000269|PubMed:30200536, ECO:0000269|PubMed:7550356, ECO:0000269|PubMed:7596406, ECO:0000269|PubMed:7651536, ECO:0000269|PubMed:8634711, ECO:0000269|PubMed:8634712, ECO:0000269|PubMed:8733303, ECO:0000269|PubMed:8837617, ECO:0000269|PubMed:8875251, ECO:0000269|PubMed:9172170, ECO:0000269|PubMed:9225696, ECO:0000269|PubMed:9298817, ECO:0000269|PubMed:9384602, ECO:0000269|PubMed:9507958, ECO:0000269|PubMed:9521423, ECO:0000269|PubMed:9719376, ECO:0000269|PubMed:9831473, ECO:0000269|PubMed:9833068, ECO:0000269|Ref.95}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Frontotemporal dementia 1 (FTD1) [MIM:600274]: A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons. {ECO:0000269|PubMed:11094121}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated, 1U (CMD1U) [MIM:613694]: 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, ECO:0000269|PubMed:27930341}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Acne inversa, familial, 3 (ACNINV3) [MIM:613737]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. {ECO:0000269|PubMed:20929727}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pick disease of the brain (PIDB) [MIM:172700]: A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration. {ECO:0000269|PubMed:15122701}. Note=The gene represented in this entry may be involved in disease pathogenesis.
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:10206644, PubMed:10545183, PubMed:10593990, PubMed:10811883, PubMed:10899933, PubMed:12679784, PubMed:12740439, PubMed:15274632, PubMed:20460383, PubMed:25043039, PubMed:26280335, PubMed:28269784, PubMed:30598546, PubMed:30630874). 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:10593990, PubMed:10811883, PubMed:10899933, PubMed:9738936). 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:11953314, PubMed:9738936). 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:16959576, PubMed:25394380). 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). {ECO:0000250|UniProtKB:P49769, ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10545183, ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:10811883, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:15004326, ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:20460383, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:28269784, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874, ECO:0000269|PubMed:9738936}.
uniprot
proteins
mass_dalton
52668
uniprot
proteins
mutagenesis
MUTAGEN 66..72; /note="Missing: No effect on interaction with GFAP."; /evidence="ECO:0000269|PubMed:12058025"; MUTAGEN 76..77; /note="KY->AA: No effect on interaction with GFAP."; /evidence="ECO:0000269|PubMed:12058025"; MUTAGEN 82..83; /note="VI->EE: Loss of interaction with GFAP."; /evidence="ECO:0000269|PubMed:12058025"; MUTAGEN 82; /note="V->K,E: Loss of interaction with GFAP."; /evidence="ECO:0000269|PubMed:12058025"; MUTAGEN 84..85; /note="ML->EE: Loss of interaction with GFAP."; /evidence="ECO:0000269|PubMed:12058025"; MUTAGEN 99; /note="T->A: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 105; /note="F->I: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 108; /note="R->Q: Nearly abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 112; /note="Q->C: Formation of an artifactual disulfide bond with a substrate protein."; /evidence="ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874"; MUTAGEN 113; /note="L->Q: Severe decrease of protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 117; /note="P->A: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 123; /note="E->K: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 131; /note="H->R: Severe decrease of protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 136; /note="A->G: Decreased protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 143; /note="I->V: Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 150; /note="L->P: Nearly abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 165; /note="W->G: Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 168; /note="I->T: Nearly abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 176; /note="F->L: Nearly abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 184; /note="E->G: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 202; /note="I->F: Nearly abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:27930341"; MUTAGEN 212; /note="S->Y: Nearly abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 214; /note="H->D: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 219; /note="L->F: Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 223; /note="Q->R: Abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 226; /note="L->F: Increases protease activity with APP."; /evidence="ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:27930341"; MUTAGEN 230; /note="S->I: Abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 238; /note="I->M: Abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 239; /note="K->N: Abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 245; /note="T->P: Abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 248; /note="L->R: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:27930341"; MUTAGEN 256; /note="Y->F: Alters gamma-secretase cleavage specificity. Increased production of amyloid-beta protein 42. No effect on enzymatic activity."; /evidence="ECO:0000269|PubMed:15341515"; MUTAGEN 256; /note="Y->S: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 257; /note="D->A: Loss of endoproteolytic cleavage. Severe decrease of protease activity with APP. Reduces production of amyloid-beta. Reduces production of NICD in NOTCH1 processing. Impaired ability to cleave Ephb2/CTF1."; /evidence="ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:22529981"; MUTAGEN 257; /note="D->E: Abolishes gamma-secretase activity. Reduces production of amyloid-beta in APP processing. Accumulation of full-length PS1. Loss of binding of transition state analog gamma-secretase inhibitor."; /evidence="ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:15341515"; MUTAGEN 272; /note="V->A: Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 273; /note="E->A: Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 278; /note="R->K: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 284; /note="P->S: No significant change of protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 286; /note="L->A,E,P,Q,R,W: Increases production of amyloid-beta in APP processing."; /evidence="ECO:0000269|PubMed:10811883"; MUTAGEN 286; /note="L->E,R: Reduces production of NICD in NOTCH1 processing."; /evidence="ECO:0000269|PubMed:10811883"; MUTAGEN 288..290; /note="Missing: Loss of NOTCH1 and APPC83 cleavage."; /evidence="ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874"; MUTAGEN 291; /note="T->P: Abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 292; /note="M->D: Loss of endoproteolytic cleavage."; /evidence="ECO:0000269|PubMed:10545183"; MUTAGEN 310; /note="S->A: Abolishes PKA-mediated phosphorylation; no effect on caspase-mediated cleavage."; /evidence="ECO:0000269|PubMed:14576165"; MUTAGEN 345; /note="D->N: Abolishes caspase cleavage."; /evidence="ECO:0000269|PubMed:9485372"; MUTAGEN 346; /note="S->A: Abolishes PKC-mediated phosphorylation; no effect on PKA-mediated phosphorylation."; /evidence="ECO:0000269|PubMed:14576165"; MUTAGEN 346; /note="S->E: Inhibits caspase-mediated cleavage. Modulates progression of apoptosis."; /evidence="ECO:0000269|PubMed:14576165"; MUTAGEN 352; /note="R->C: Decreased protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 365; /note="S->A: Slightly increased protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 373; /note="D->N: No effect on caspase cleavage."; /evidence="ECO:0000269|PubMed:9485372"; MUTAGEN 377..381; /note="Missing: Loss of NOTCH1 and APPC83 cleavage."; /evidence="ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874"; MUTAGEN 377; /note="R->W: Nearly abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 385; /note="D->A: Loss of endoproteolytic cleavage. Severe decrease of protease activity with APP. Reduces production of amyloid-beta. Loss of NOTCH1 cleavage. Disassembly of the N-cadherin/PS1 complex at the cell surface. Impairs CDH2 processing."; /evidence="ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:14515347, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:22529981, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874, ECO:0000269|PubMed:9485372"; MUTAGEN 385; /note="D->E: Abolishes gamma-secretase activity. Reduces production of amyloid-beta in APP processing. Accumulation of full-length PS1. Loss of binding of transition state analog gamma-secretase inhibitor."; /evidence="ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:14515347, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:9485372"; MUTAGEN 385; /note="D->N: No effect on caspase cleavage."; /evidence="ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:14515347, ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:9485372"; MUTAGEN 386; /note="F->S: Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 389; /note="Y->F: Alters gamma-secretase cleavage specificity. Increased production of amyloid-beta protein 42. No effect on enzymatic activity."; /evidence="ECO:0000269|PubMed:15341515"; MUTAGEN 391; /note="V->F: Decreased protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 412; /note="V->I: Abolishes protease activity with APP."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 420; /note="L->R: Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341"; MUTAGEN 424; /note="L->V: Increases protease activity with APP."; /evidence="ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:27930341"; MUTAGEN 432..434; /note="Missing: Loss of NOTCH1 and APPC83 cleavage."; /evidence="ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874"; MUTAGEN 432; /note="L->P: Loss of NOTCH1 and APPC83 cleavage."; /evidence="ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874"; MUTAGEN 433; /note="P->A: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Slightly increased amyloid-beta protein 42/40 ratio."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 433; /note="P->D,F,L,N,V: No endoproteolytic cleavage; no APP, nor NOTCH1 processing. No detectable amyloid-beta."; /evidence="ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:20460383"; MUTAGEN 433; /note="P->G: Very little endoproteolysis. Little APP processing. No NOTCH1 processing. Very low levels amyloid-beta protein 40 and no detectable amyloid-beta protein 42."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 434; /note="A->C: Some loss of endoproteolytic cleavage. Some loss of APP and NOTCH1 processing. 6 to 13-fold increase in amyloid-beta protein 42/40 ratio."; /evidence="ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:27930341"; MUTAGEN 434; /note="A->D,I,L,V: No endoproteolytic cleavage. No APP nor NOTCH1 processing. No detectable amyloid-beta."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 434; /note="A->G: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Reduced amyloid-beta protein 42/40 ratio."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 435; /note="L->A: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Greatly reduced amyloid-beta protein 42/40 ratio."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 435; /note="L->G: Greatly reduced endoproteolytic cleavage. Very little APP and NOTCH1 processing. Very low levels of amyloid-beta protein 40 and no detectable amyloid-beta protein 42."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 435; /note="L->I: No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 435; /note="L->R: No endoproteolytic cleavage; no APP, nor NOTCH1 processing. No detectable amyloid-beta."; /evidence="ECO:0000269|PubMed:20460383"; MUTAGEN 435; /note="L->V: No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Some increase in amyloid-beta protein 42/40 ratio."; /evidence="ECO:0000269|PubMed:16305624"; MUTAGEN 437; /note="I->V: Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro."; /evidence="ECO:0000269|PubMed:27930341
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:0000269|PubMed:10545183, ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:9173929, ECO:0000269|PubMed:9485372}.; 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:0000269|PubMed:14576165, ECO:0000269|PubMed:9144240}.
uniprot
proteins
protein_family
Peptidase A22A family
uniprot
proteins
pubmed
10025789
uniprot
proteins
pubmed
10037471
uniprot
proteins
pubmed
10090481
uniprot
proteins
pubmed
10200054
uniprot
proteins
pubmed
10206644
uniprot
proteins
pubmed
10208579
uniprot
proteins
pubmed
10439444
uniprot
proteins
pubmed
10441572
uniprot
proteins
pubmed
10447269
uniprot
proteins
pubmed
10533070
uniprot
proteins
pubmed
10545183
uniprot
proteins
pubmed
10551805
uniprot
proteins
pubmed
10593990
uniprot
proteins
pubmed
10631141
uniprot
proteins
pubmed
10644793
uniprot
proteins
pubmed
10811883
uniprot
proteins
pubmed
10854253
uniprot
proteins
pubmed
10899933
uniprot
proteins
pubmed
11027672
uniprot
proteins
pubmed
11094121
uniprot
proteins
pubmed
11524469
uniprot
proteins
pubmed
11561050
uniprot
proteins
pubmed
11568920
uniprot
proteins
pubmed
11701593
uniprot
proteins
pubmed
11710891
uniprot
proteins
pubmed
11796781
uniprot
proteins
pubmed
11799129
uniprot
proteins
pubmed
11920851
uniprot
proteins
pubmed
11953314
uniprot
proteins
pubmed
11987239
uniprot
proteins
pubmed
12048239
uniprot
proteins
pubmed
12058025
uniprot
proteins
pubmed
12214059
uniprot
proteins
pubmed
12370477
uniprot
proteins
pubmed
12484344
uniprot
proteins
pubmed
12493737
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
12552037
uniprot
proteins
pubmed
12679784
uniprot
proteins
pubmed
12740439
uniprot
proteins
pubmed
14515347
uniprot
proteins
pubmed
14576165
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14759258
uniprot
proteins
pubmed
15004326
uniprot
proteins
pubmed
15122701
uniprot
proteins
pubmed
15274632
uniprot
proteins
pubmed
15341515
uniprot
proteins
pubmed
15364419
uniprot
proteins
pubmed
15385547
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15534188
uniprot
proteins
pubmed
15534260
uniprot
proteins
pubmed
15851849
uniprot
proteins
pubmed
16126725
uniprot
proteins
pubmed
16305624
uniprot
proteins
pubmed
16344340
uniprot
proteins
pubmed
16628450
uniprot
proteins
pubmed
16752394
uniprot
proteins
pubmed
16897084
uniprot
proteins
pubmed
16959576
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17186461
uniprot
proteins
pubmed
17366635
uniprot
proteins
pubmed
17428795
uniprot
proteins
pubmed
17502474
uniprot
proteins
pubmed
18430735
uniprot
proteins
pubmed
18485326
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19667325
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19797784
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20164095
uniprot
proteins
pubmed
20299451
uniprot
proteins
pubmed
20460383
uniprot
proteins
pubmed
20929727
uniprot
proteins
pubmed
21143716
uniprot
proteins
pubmed
21248752
uniprot
proteins
pubmed
21335660
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21501661
uniprot
proteins
pubmed
22461631
uniprot
proteins
pubmed
22503161
uniprot
proteins
pubmed
22529981
uniprot
proteins
pubmed
23123781
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23843529
uniprot
proteins
pubmed
24121961
uniprot
proteins
pubmed
24495933
uniprot
proteins
pubmed
24582897
uniprot
proteins
pubmed
25043039
uniprot
proteins
pubmed
25394380
uniprot
proteins
pubmed
25918421
uniprot
proteins
pubmed
26145164
uniprot
proteins
pubmed
26280335
uniprot
proteins
pubmed
26549787
uniprot
proteins
pubmed
26623517
uniprot
proteins
pubmed
27073747
uniprot
proteins
pubmed
27930341
uniprot
proteins
pubmed
28269784
uniprot
proteins
pubmed
29175279
uniprot
proteins
pubmed
29404783
uniprot
proteins
pubmed
29466804
uniprot
proteins
pubmed
30180983
uniprot
proteins
pubmed
30200536
uniprot
proteins
pubmed
30598546
uniprot
proteins
pubmed
30630874
uniprot
proteins
pubmed
7550356
uniprot
proteins
pubmed
7596406
uniprot
proteins
pubmed
7651536
uniprot
proteins
pubmed
8574969
uniprot
proteins
pubmed
8634711
uniprot
proteins
pubmed
8634712
uniprot
proteins
pubmed
8641442
uniprot
proteins
pubmed
8733303
uniprot
proteins
pubmed
8804415
uniprot
proteins
pubmed
8837617
uniprot
proteins
pubmed
8875251
uniprot
proteins
pubmed
9070286
uniprot
proteins
pubmed
9144240
uniprot
proteins
pubmed
9172170
uniprot
proteins
pubmed
9173929
uniprot
proteins
pubmed
9225696
uniprot
proteins
pubmed
9298817
uniprot
proteins
pubmed
9384602
uniprot
proteins
pubmed
9437013
uniprot
proteins
pubmed
9485372
uniprot
proteins
pubmed
9507958
uniprot
proteins
pubmed
9521418
uniprot
proteins
pubmed
9521423
uniprot
proteins
pubmed
9719376
uniprot
proteins
pubmed
9738936
uniprot
proteins
pubmed
9831473
uniprot
proteins
pubmed
9833068
uniprot
proteins
pubmed
9851443
uniprot
proteins
pubmed
9851450
uniprot
proteins
pubmed
9915968
uniprot
proteins
sequence_length
467
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000269|PubMed:25394380}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:8574969, ECO:0000269|PubMed:9738936, ECO:0000305|PubMed:10037471, ECO:0000305|PubMed:15274632}; Multi-pass membrane protein {ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25918421, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Golgi apparatus membrane {ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:8574969, ECO:0000305|PubMed:10037471, ECO:0000305|PubMed:15274632}; Multi-pass membrane protein {ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25918421, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Cytoplasmic granule {ECO:0000269|PubMed:11987239}. Cell membrane {ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:11987239, ECO:0000269|PubMed:21143716}; Multi-pass membrane protein {ECO:0000269|PubMed:25918421, ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Cell projection, growth cone {ECO:0000269|PubMed:15004326}. Early endosome {ECO:0000269|PubMed:25394380}. Early endosome membrane {ECO:0000305|PubMed:25394380}; Multi-pass membrane protein {ECO:0000269|PubMed:25918421, ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Cell projection, neuron projection {ECO:0000269|PubMed:15004326}. 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 (PubMed:10593990). Colocalizes with CDH1/2 at sites of cell-cell contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the proximity of the plasma membrane (PubMed:9738936). Also present in azurophil granules of neutrophils (PubMed:11987239). Colocalizes with UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures called aggresomes (PubMed:21143716). Also highly enriched in mitochondria-associated endoplasmic reticulum membrane contact site (By similarity). {ECO:0000250|UniProtKB:P49769, ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:11987239, ECO:0000269|PubMed:21143716, ECO:0000269|PubMed:9738936}.
uniprot
proteins
transmembrane_region
TRANSMEM 83..103; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 133..153; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 167..189; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 195..216; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 221..241; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 249..272; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 381..401; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 408..428; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335"; TRANSMEM 433..453; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335
uniprot
proteins