| + |
CTSD | down-regulates quantity by destabilization 
cleavage
|
APP |
0.507 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261737 |
Ala617 |
ISEVKMDaEFRHDSG |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261761 |
Asp572 |
PWHSFGAdSVPANTE |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261764 |
Asp638 |
KLVFFAEdVGSNKGA |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261765 |
Asp683 |
HHGVVEVdAAVTPEE |
in vitro |
|
| pmid |
sentence |
| 8943232 |
The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261790 |
Gln711 |
PTYKFFEqMQN |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261766 |
Glu612 |
IKTEEISeVKMDAEF |
in vitro |
|
| pmid |
sentence |
| 8943232 |
The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261767 |
Glu618 |
SEVKMDAeFRHDSGY |
in vitro |
|
| pmid |
sentence |
| 8943232 |
The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261768 |
Glu637 |
QKLVFFAeDVGSNKG |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261784 |
Leu664 |
ATVIVITlVMLKKKQ |
in vitro |
|
| pmid |
sentence |
| 8943232 |
The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261789 |
Met666 |
VIVITLVmLKKKQYT |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261769 |
Phe619 |
EVKMDAEfRHDSGYE |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261776 |
Phe708 |
YENPTYKfFEQMQN |
in vitro |
|
| pmid |
sentence |
| 8943232 |
The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Publications: |
12 |
Organism: |
In Vitro |
| + |
CTSD | up-regulates activity 
cleavage
|
APP |
0.507 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261738 |
Ala657 |
MVGGVVIaTVIVITL |
in vitro |
|
| pmid |
sentence |
| 10605825 |
In this work, we used a sensitive in vitro method of detection to investigate the role of cathepasin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic γ-cleavage sites. This occurred preferentially at Thr43–Val44 and at Ala42–Thr43, generating full length βA4 43 and βA4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34–Met35, Thr48–Leu49 and Leu49–Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19–Phe20, Phe20–Ala21 and Phe93–Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261783 |
Leu649 |
NKGAIIGlMVGGVVI |
in vitro |
|
| pmid |
sentence |
| 10605825 |
In this work, we used a sensitive in vitro method of detection to investigate the role of cathepasin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic γ-cleavage sites. This occurred preferentially at Thr43–Val44 and at Ala42–Thr43, generating full length βA4 43 and βA4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34–Met35, Thr48–Leu49 and Leu49–Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19–Phe20, Phe20–Ala21 and Phe93–Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261770 |
Phe634 |
VHHQKLVfFAEDVGS |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261771 |
Phe634 |
VHHQKLVfFAEDVGS |
in vitro |
|
| pmid |
sentence |
| 10605825 |
In this work, we used a sensitive in vitro method of detection to investigate the role of cathepasin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic γ-cleavage sites. This occurred preferentially at Thr43–Val44 and at Ala42–Thr43, generating full length βA4 43 and βA4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34–Met35, Thr48–Leu49 and Leu49–Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19–Phe20, Phe20–Ala21 and Phe93–Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261774 |
Phe635 |
HHQKLVFfAEDVGSN |
in vitro |
|
| pmid |
sentence |
| 10605825 |
In this work, we used a sensitive in vitro method of detection to investigate the role of cathepasin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic γ-cleavage sites. This occurred preferentially at Thr43–Val44 and at Ala42–Thr43, generating full length βA4 43 and βA4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34–Met35, Thr48–Leu49 and Leu49–Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19–Phe20, Phe20–Ala21 and Phe93–Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261778 |
Phe709 |
ENPTYKFfEQMQN |
in vitro |
|
| pmid |
sentence |
| 10605825 |
In this work, we used a sensitive in vitro method of detection to investigate the role of cathepasin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic γ-cleavage sites. This occurred preferentially at Thr43–Val44 and at Ala42–Thr43, generating full length βA4 43 and βA4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34–Met35, Thr48–Leu49 and Leu49–Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19–Phe20, Phe20–Ala21 and Phe93–Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261777 |
Phe709 |
ENPTYKFfEQMQN |
in vitro |
|
| pmid |
sentence |
| 8943232 |
FIG. 4. Schematic representation of the major cathepsin D cleavage sites in FLAG-bAPP156-bFGF and in bAPP100-FLAG. The amino acid sequences for the FLAG-bAPP156-bFGF and bAPP100-FLAG substrates are shown. Large arrows denote major cleavage sites. Unique cathepsin D cleavage sites in urea-denatured FLAG-bAPP156-bFGF are labeled (U). Small arrowheads denote minor bAPP100-FLAG cleavage sites determined by mass spectral analysis.|Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261792 |
Thr658 |
VGGVVIAtVIVITLV |
in vitro |
|
| pmid |
sentence |
| 10605825 |
In this work, we used a sensitive in vitro method of detection to investigate the role of cathepasin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic γ-cleavage sites. This occurred preferentially at Thr43–Val44 and at Ala42–Thr43, generating full length βA4 43 and βA4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34–Met35, Thr48–Leu49 and Leu49–Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19–Phe20, Phe20–Ala21 and Phe93–Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261793 |
Thr663 |
IATVIVItLVMLKKK |
in vitro |
|
| pmid |
sentence |
| 10605825 |
In this work, we used a sensitive in vitro method of detection to investigate the role of cathepasin D in the proteolytic processing of a 100-amino acid C-terminal fragment (C100) inclusive of βA4 and cytoplasmic domain of APP. Digestion of C100 with cathepsin D resulted in cleavage at the amyloidogenic γ-cleavage sites. This occurred preferentially at Thr43–Val44 and at Ala42–Thr43, generating full length βA4 43 and βA4 42 amyloid peptides, respectively. Cathepsin D was also found to cleave the substrate at the following nonamyloidogenic sites; Leu34–Met35, Thr48–Leu49 and Leu49–Val50. A high concentration of cathepsin D resulted in cleavage also occurring at Phe19–Phe20, Phe20–Ala21 and Phe93–Phe94 of the C100, suggesting that these sites are somewhat less sensitive to the action of cathepsin D. |
|
| Publications: |
9 |
Organism: |
In Vitro |
| + |
CASP6 | up-regulates activity
cleavage
|
APP |
0.708 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261762 |
Asp616 |
EISEVKMdAEFRHDS |
in vitro |
|
| pmid |
sentence |
| 10438520 |
Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Ab. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Ab-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
BACE1 | up-regulates activity
cleavage
|
APP |
0.789 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261763 |
Asp616 |
EISEVKMdAEFRHDS |
Homo sapiens |
|
| pmid |
sentence |
| 10931940 |
Figure 6 Preferred BACE1 and BACE2 cleavage sites. (A) Sequence of APP indicating α- and β-cleavage sites, BACE1- and BACE2-cleavage sites, and the location of mutations analyzed here. APP numbering is that of the 770-aa isoform. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255480 |
|
|
|
|
| pmid |
sentence |
| 28923680 |
Beta-secretase 1 (BACE1) cleaves the type-I transmembrane protein APP to form the N-terminus of Aβ. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, |
| + |
BACE2 | up-regulates activity
cleavage
|
APP |
0.567 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261773 |
Phe634 |
VHHQKLVfFAEDVGS |
Homo sapiens |
|
| pmid |
sentence |
| 10931940 |
BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.|Figure 6 Preferred BACE1 and BACE2 cleavage sites. (A) Sequence of APP indicating α- and β-cleavage sites, BACE1- and BACE2-cleavage sites, and the location of mutations analyzed here. APP numbering is that of the 770-aa isoform. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261772 |
Phe634 |
VHHQKLVfFAEDVGS |
Homo sapiens |
|
| pmid |
sentence |
| 10931940 |
BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.|Aβ is produced from the Aβ precursor protein (APP) by two proteolytic events. A β-secretase activity cleaves APP at the N terminus of Aβ (β site) between amino acids Met-671 and Asp-672 |We show here that BACE2 cleaves APP at its β site and more efficiently at sites within the Aβ region of APP, after Phe-19 and Phe-20 of Aβ. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261775 |
Phe635 |
HHQKLVFfAEDVGSN |
Homo sapiens |
|
| pmid |
sentence |
| 10931940 |
BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.|Aβ is produced from the Aβ precursor protein (APP) by two proteolytic events. A β-secretase activity cleaves APP at the N terminus of Aβ (β site) between amino acids Met-671 and Asp-672 |We show here that BACE2 cleaves APP at its β site and more efficiently at sites within the Aβ region of APP, after Phe-19 and Phe-20 of Aβ. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261779 |
Phe709 |
ENPTYKFfEQMQN |
Homo sapiens |
|
| pmid |
sentence |
| 10931940 |
BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.|Figure 6 Preferred BACE1 and BACE2 cleavage sites. (A) Sequence of APP indicating α- and β-cleavage sites, BACE1- and BACE2-cleavage sites, and the location of mutations analyzed here. APP numbering is that of the 770-aa isoform. |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| + |
CDK5 |
phosphorylation
|
APP |
0.591 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250651 |
Thr743 |
VEVDAAVtPEERHLS |
Rattus norvegicus |
Neuron |
| pmid |
sentence |
| 10936190 |
In vitro, active cyclin-dependent kinase 5 (Cdk5) phosphorylated the cytoplasmic domain of APP at Thr(668). Treatment of mature neurons with an antisense oligonucleotide to Cdk5 suppressed Cdk5 expression and significantly diminished the level of phosphorylated APP. The expression of APP was unaffected in antisense-treated neurons. These results indicate that in neurons APP is phosphorylated by Cdk5, and that this may play a role in its localization. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
GSK3B |
phosphorylation
|
APP |
0.564 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251220 |
Thr743 |
VEVDAAVtPEERHLS |
in vitro |
|
| pmid |
sentence |
| 8764598 |
The sole site of phosphorylation in APPcyt by GSK-3beta was determined by phosphoamino acid analysis and phosphorylation of APPcyt mutant peptides to be Thr743 (numbering as for APP770). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Alzheimer |
| + |
MAPK8 | up-regulates
phosphorylation
|
APP |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-204679 |
Thr743 |
VEVDAAVtPEERHLS |
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 24610780 |
Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. We found that the threonine 668 within the abetapp intracellular domain (aid or elsewhere aicd) is indeed phosphorylated by jnk1 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117852 |
Thr743 |
VEVDAAVtPEERHLS |
Homo sapiens |
SH-SY5Y Cell |
| pmid |
sentence |
| 12917434 |
Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. We found that the threonine 668 within the abetapp intracellular domain (aid or elsewhere aicd) is indeed phosphorylated by jnk1 |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
CDK5RAP2 | up-regulates quantity by stabilization
phosphorylation
|
APP |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260818 |
Thr743 |
VEVDAAVtPEERHLS |
Homo sapiens |
|
| pmid |
sentence |
| 15178331 |
The APPcyt is phosphorylated at Thr668 in vivo specifically in the brain. Cyclin‐dependent kinase 5 (Cdk5), a unique member of the Cdk family that is implicated in central nervous system development, participates in this phosphorylation. | In the present study, we demonstrate that APP phosphorylated at Thr668 is less vulnerable to cytoplasmic cleavage by caspase-3 and caspase-8. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MAPK10 | up-regulates
phosphorylation
|
APP |
0.565 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-204671 |
Thr743 |
VEVDAAVtPEERHLS |
Homo sapiens |
|
| pmid |
sentence |
| 24610780 |
Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. is regulated by jnk3 via phosphorylation of app at thr668 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
APP | up-regulates activity
binding
|
NAE1 |
0.724 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251577 |
|
|
Homo sapiens |
Alzheimer Disease Specific Cell Type |
| pmid |
sentence |
| 25568892 |
Alzheimer's disease (AD) is the gradual loss of the cognitive function due to neuronal death. Currently no therapy is available to slow down, reverse or prevent the disease. Here we analyze the existing data in literature and hypothesize that the physiological function of the Amyloid Precursor Protein (APP) is activating the AppBp1 pathway and this function is gradually lost during the progression of AD pathogenesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Alzheimer |
| + |
DAPT | down-regulates
chemical inhibition
|
APP |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-191292 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
APP | up-regulates 
|
Amyloid_fibril_formation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251638 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11578751 |
Neurodegeneration in Alzheimer's disease is a pathologic condition of cells rather than an accelerated way of aging. The senile plaques are generated by a deposition in the human brain of fibrils of the β-amyloid peptide (Aβ), a fragment derived from the proteolytic processing of the amyloid precursor protein (APP). Tau protein is the major component of paired helical filaments (PHFs), which form a compact filamentous network described as neurofibrillary tangles (NFTs). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Alzheimer |
| + |
PLD3 | up-regulates quantity
binding
|
APP |
0.387 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261200 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 24336208 |
Furthermore, PLD3 can be co-immunoprecipitated with APP in cultured cells (Extended Data Figure 4). Together, these studies demonstrate that PLD3 plays a role in APP processing. Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
APP | up-regulates
|
GSK3A |
0.421 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-144057 |
|
|
Homo sapiens |
Neuron |
| pmid |
sentence |
| 16446437 |
These results suggest a direct relationship between app proteolytic processing, but not amyloid-_, in gsk-3_ activation and tau phosphorylation in human neurons. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Alzheimer |
| + |
471905-41-6 | down-regulates
chemical inhibition
|
APP |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-194358 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Avagacestat | down-regulates
chemical inhibition
|
APP |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-190479 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ADAM17 | up-regulates activity
cleavage
|
APP |
0.561 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262829 |
|
|
in vitro |
|
| pmid |
sentence |
| 9774383 |
By the use of gene disruption (knockout), we now demonstrate that TACE (tumor necrosis factor alpha converting enzyme), a member of the ADAM family (a disintegrin and metalloprotease-family) of proteases, plays a central role in regulated alpha-cleavage of APP. Our data suggest that TACE may be the alpha-secretase responsible for the majority of regulated alpha-cleavage in cultured cells. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
ABCA7 | down-regulates quantity 
relocalization
|
APP |
0.423 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265176 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27472885 |
Together these results indicate that ABCA7 mediates phagocytic clearance of amyloid-β in the brain, and reveal a mechanism by which loss of function of ABCA7 increases the susceptibility to AD. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
PITRM1 | down-regulates activity
cleavage
|
APP |
0.382 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260661 |
|
|
Homo sapiens |
Brain |
| pmid |
sentence |
| 16849325 |
In the present study we have identified and characterized the human PreP homologue, hPreP, in brain mitochondria, and we show its capacity to degrade the amyloid beta-protein (Abeta). PreP belongs to the pitrilysin oligopeptidase family M16C containing an inverted zinc-binding motif. We show that hPreP is localized to the mitochondrial matrix. In situ immuno-inactivation studies in human brain mitochondria using anti-hPreP antibodies showed complete inhibition of proteolytic activity against Abeta. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PAFAH1B2 | up-regulates
|
APP |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-200188 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23238734 |
We provide evidence that the loss of pafah1b2 potently reduces a_ by promoting the degradation of its immediate precursor, the _ctf. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
gamma-secretase | up-regulates activity
cleavage
|
APP |
0.604 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251576 |
|
|
Homo sapiens |
Alzheimer Disease Specific Cell Type |
| pmid |
sentence |
| 19958215 |
The production and accumulation of the beta amyloid protein (Abeta) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer's disease (AD). A multi-subunit enzyme complex, referred to as gamma (gamma) secretase, plays a pivotal role in the generation of Abeta from its parent molecule, the amyloid precursor protein (APP). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Alzheimer |
| + |
CTCF | up-regulates quantity by expression
transcriptional regulation
|
APP |
0.27 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253823 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11706010 |
Depleting HeLa cell nuclear extract of endogenous CTCF specifically reduced transcriptional activity from the APP promoter. CTCF activates transcription from the APP promoter and that the activation domain is located on the N-terminal side of the zinc finger domain. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
(2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide | down-regulates
chemical inhibition
|
APP |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-206850 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
APP
- 
- 