| + |
CASP8 | up-regulates activity 
cleavage
|
PSEN1 |
0.377 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261754 |
Asp333 |
DTVAENDdGGFSEEW |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261760 |
Asp345 |
EEWEAQRdSHLGPHR |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | Alzheimer |
| + |
CASP6 | up-regulates activity
cleavage
|
PSEN1 |
0.381 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261753 |
Asp333 |
DTVAENDdGGFSEEW |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261759 |
Asp345 |
EEWEAQRdSHLGPHR |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
SCAF11 | up-regulates activity
cleavage
|
PSEN1 |
0.297 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261742 |
Asp333 |
DTVAENDdGGFSEEW |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261758 |
Asp345 |
EEWEAQRdSHLGPHR |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| + |
CASP1 | up-regulates activity
cleavage
|
PSEN1 |
0.395 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261755 |
Asp345 |
EEWEAQRdSHLGPHR |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
CASP3 | up-regulates activity
cleavage
|
PSEN1 |
0.47 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261756 |
Asp345 |
EEWEAQRdSHLGPHR |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Alzheimer |
| + |
CASP7 | up-regulates activity
cleavage
|
PSEN1 |
0.349 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261757 |
Asp345 |
EEWEAQRdSHLGPHR |
in vitro |
|
| pmid |
sentence |
| 10069390 |
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PRKACA |
phosphorylation
|
PSEN1 |
0.467 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250036 |
Ser310 |
PEAQRRVsKNSKYNA |
in vitro |
|
| pmid |
sentence |
| 14576165 |
PKA-mediated phosphorylation of PS1 is completely inhibited by mutation of Ser310.phosphorylation of Ser310 does not inhibit the caspase-mediated cleavage of PS1, and the biological function of this phosphorylation event remains to be determined in further experiments. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
MAPK9 | up-regulates
phosphorylation
|
PSEN1 |
0.385 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179676 |
Ser319 |
NSKYNAEsTERESQD |
Homo sapiens |
|
| pmid |
sentence |
| 18667537 |
This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-179680 |
Thr320 |
SKYNAEStERESQDT |
Homo sapiens |
|
| pmid |
sentence |
| 18667537 |
This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
PRKCA | up-regulates activity
phosphorylation
|
PSEN1 |
0.269 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249236 |
Ser346 |
EWEAQRDsHLGPHRS |
Homo sapiens |
|
| pmid |
sentence |
| 14576165 |
A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCG | up-regulates activity
phosphorylation
|
PSEN1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249238 |
Ser346 |
EWEAQRDsHLGPHRS |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 14576165 |
A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCZ | up-regulates activity
phosphorylation
|
PSEN1 |
0.342 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249239 |
Ser346 |
EWEAQRDsHLGPHRS |
Homo sapiens |
|
| pmid |
sentence |
| 14576165 |
A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKCB | up-regulates activity
phosphorylation
|
PSEN1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249237 |
Ser346 |
EWEAQRDsHLGPHRS |
Homo sapiens |
|
| pmid |
sentence |
| 14576165 |
A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B/Axin/APC | down-regulates activity 
phosphorylation
|
PSEN1 |
0.407 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228018 |
Ser353 |
SHLGPHRsTPESRAA |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17360711 |
We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-228022 |
Ser357 |
PHRSTPEsRAAVQEL |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17360711 |
We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GSK3B | down-regulates activity
phosphorylation
|
PSEN1 |
0.61 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-153627 |
Ser353 |
SHLGPHRsTPESRAA |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17360711 |
We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-153631 |
Ser357 |
PHRSTPEsRAAVQEL |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 17360711 |
We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Alzheimer |
| + |
CDK5 | up-regulates
phosphorylation
|
PSEN1 |
0.53 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-89145 |
Thr354 |
HLGPHRStPESRAAV |
Homo sapiens |
|
| pmid |
sentence |
| 12056836 |
Cyclin-dependent kinase-5/p35 phosphorylates presenilin 1 to regulate carboxy-terminal fragment stabilityhere we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates ps1 on threonine(354) within c-ps1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize c-ps1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TMED10 | up-regulates
binding
|
PSEN1 |
0.637 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-146364 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16641999 |
Here we report that tmp21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NCSTN | up-regulates
binding
|
PSEN1 |
0.964 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-118852 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14572442 |
Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-98724 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12603837 |
Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-96253 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12471034 |
Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Tissue: |
Ovary |
| Pathways: | Alzheimer |
| + |
PSEN1 | down-regulates
binding
|
CTNNB1 |
0.802 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-22837 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 2195779 |
Importantly, our data show that binding of ps1 to cadherin mediates the effects of ps1 on the phosphorylation, ubiquitination, and destabilization of beta-catenin. Thus, cadherins mediate both the association of ps1 and beta-catenin and the effects of ps1 on the cellular levels of beta-catenin |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PSEN1 | up-regulates
cleavage
|
gamma-secretase |
0.956 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217746 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10497236 |
Presenilin-1 (ps1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both notch and beta-amyloid precursor protein (app) within their trans- membrane domains. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-217743 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10593990 |
Presenilin-1 (ps1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both notch and beta-amyloid precursor protein (app) within their trans- membrane domains. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Alzheimer |
| + |
APH1A | up-regulates
binding
|
PSEN1 |
0.945 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-93262 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12297508 |
By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97068 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12522139 |
Biochemical and genetic studies have recently identified nicastrin, aph-1, and pen-2 as essential cofactors that physically interact with ps1 and are necessary for the gamma-secretase activity. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
4-[2-[(1R)-1-(N-(4-chlorophenyl)sulfonyl-2,5-difluoroanilino)ethyl]-5-fluorophenyl]butanoic acid | down-regulates
chemical inhibition
|
PSEN1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-159344 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18032377 |
We employed a combination of chimeric constructs and point mutants to identify structural determinants for ps1-selective inhibition by eln318463. Our studies identified amino acid residues leu(172), thr(281), and leu(282) in ps1 as necessary for ps1-selective inhibition by eln318463. These residues also contributed in part to the ps1-selective inhibition by bms299897. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
PSEN1 | up-regulates
cleavage
|
NOTCH |
0.79 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254308 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10593990 |
Presenilin-1 (ps1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both notch and beta-amyloid precursor protein (app) within their trans- membrane domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DAPT | down-regulates
chemical inhibition
|
PSEN1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-145385 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16569643 |
The catalytic aspartates are necessary for binding of the transition state analogue inhibitor, l-685,458, to ps1. It is possible that these catalytic aspartates also contribute to the direct interaction of ps with dapt. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PSENEN | up-regulates
cleavage
|
PSEN1 |
0.958 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97113 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12522139 |
Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PSEN1 | up-regulates
cleavage
|
NOTCH1 |
0.79 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-72886 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10593990 |
Presenilin-1 (ps1), a polytopic membrane protein primarily localized to the endoplasmic reticulum, is required for efficient proteolysis of both notch and beta-amyloid precursor protein (app) within their trans- membrane domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
APH1B | up-regulates
binding
|
PSEN1 |
0.906 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-97107 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12522139 |
Biochemical and genetic studies have recently identified nicastrin, aph-1, and pen-2 as essential cofactors that physically interact with ps1 and are necessary for the gamma-secretase activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 1-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
PSEN1 |
0.273 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272601 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12354302 |
SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production SEL-10 protein is a homologue of yeast Cdc4, a member of the SCF (Skp1-Cdc53/CUL1-F-box protein) E2-E3 ubiquitin ligase family. In this study, we show that human SEL-10 interacts with PS1 and enhances PS1 ubiquitination, thus altering cellular levels of unprocessed PS1 and its N- and C-terminal fragments. These observations suggest that SEL-10 mediated ubiquitination of PS1-CTF and PS1-NTF leads to their degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PSEN1 | form complex 
binding
|
gamma-secretase |
0.956 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-209705 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25610395 |
-Secretase is a four subunit, 19-pass transmembrane enzymeBiochemical studies indicated that -secretase activity is catalyzed by the presenilin (PS)-containing macromolecular complex (Li et al., 2000a). The search for other components of the complex revealed three additional proteins: nicastrin (Nct), anterior pharynx-defective-1 (Aph-1), and presenilin enhancer-2 (Pen-2) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Alzheimer |
| + |
FBXW7 | down-regulates quantity by destabilization
binding
|
PSEN1 |
0.511 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272600 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 12354302 |
SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production SEL-10 protein is a homologue of yeast Cdc4, a member of the SCF (Skp1-Cdc53/CUL1-F-box protein) E2-E3 ubiquitin ligase family. In this study, we show that human SEL-10 interacts with PS1 and enhances PS1 ubiquitination, thus altering cellular levels of unprocessed PS1 and its N- and C-terminal fragments. These observations suggest that SEL-10 mediated ubiquitination of PS1-CTF and PS1-NTF leads to their degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
PSEN1
- 
- 