| + |
FYN | up-regulates activity 
phosphorylation
|
DCC |
0.554 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268175 |
Tyr1261 |
PTLESAQyPGILPSP |
Mus musculus |
N1E-115 Cell |
| pmid |
sentence |
| 15557120 |
Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268176 |
Tyr1420 |
TEDSANVyEQDDLSE |
Mus musculus |
N1E-115 Cell |
| pmid |
sentence |
| 15557120 |
Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
UNC5B | down-regulates activity 
binding
|
DCC |
0.645 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268166 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25881791 |
In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Nervous System |
| + |
UNC5C | down-regulates activity
binding
|
DCC |
0.657 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268165 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25881791 |
In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Nervous System |
| + |
DCC | up-regulates activity
|
CACNA1D |
0.302 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268292 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12827203 |
DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
UNC5A | down-regulates activity
binding
|
DCC |
0.648 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268164 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25881791 |
In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Nervous System |
| Pathways: | Axon guidance |
| + |
SOX9 | up-regulates quantity by expression 
transcriptional regulation
|
DCC |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255188 |
|
|
Homo sapiens |
Chondrocyte Cell Line |
| pmid |
sentence |
| 19745029 |
Promoter analysis and transfection studies showed that the up-regulation of DCC in OA chondrocytes may be mediated by the transcription factors Sox9 and AP-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DCC | up-regulates activity
|
CACNA1C |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268291 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12827203 |
DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DCC | up-regulates activity
binding
|
SRC |
0.516 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268372 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15494734 |
Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin. Mutation of the tyrosine phosphorylation residue in DCC abolished its function of mediating netrin-induced axon attraction. On the basis of our observations, we suggest a model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Axon guidance |
| + |
TRIO | up-regulates quantity
binding
|
DCC |
0.587 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-273856 |
|
|
Rattus norvegicus |
Cerebral Cortical Neuron |
| pmid |
sentence |
| 23230270 |
TrioY2622 is required for both netrin-1-induced activation of Rac1 and enhanced association with DCC. Phosphorylation of Trio at Tyr2622 participates in maintaining the level of surface DCC at the growth cone plasma membrane leading to axon outgrowth. Therefore, we propose that TrioY2622 is essential for the proper assembly and stability of the DCC/Trio signaling complex at the cell surface of growth cones in order to mediate netrin-1-induced cortical axon outgrowth. |
|
| Publications: |
1 |
Organism: |
Rattus Norvegicus |
| + |
DCC | up-regulates activity
|
CACNA1A |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268293 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12827203 |
DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Axon guidance |
| + |
MYO10 | up-regulates quantity
relocalization
|
DCC |
0.672 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268282 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 17237772 |
Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites. Moreover, expression of DCC, but not neogenin, stimulates Myo X-mediated formation and elongation of filopodia, suggesting that Myo X function may be differentially regulated by DCC and neogenin. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Axon guidance |
| + |
DCC | up-regulates activity
binding
|
PTK2 |
0.707 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268370 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29479476 |
The initial step of signaling inside the cell after netrin-1/DCC ligation is the binding of DCC cytoplasmic P3 motif to focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Here we report the crystal structure of P3/FAT complex. The helical P3 peptide interacts with a helix-swapped FAT dimer in a 2:2 ratio. Dimeric FAT binding is P3-specific and stabilized by a calcium ion. We propose that netrin-1/DCC engagement creates a small cluster of P3/FAT for FAK recruitment close to the cell membrane, which exerts a concerted effect with PIP2 for FAK signaling. Axon guidance assays confirm that this DCC/FAK complex is physiologically essential for netrin-1-induced chemoattraction. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268371 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15494734 |
Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin. Mutation of the tyrosine phosphorylation residue in DCC abolished its function of mediating netrin-induced axon attraction. On the basis of our observations, we suggest a model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Axon guidance |
| + |
DCC | up-regulates activity
binding
|
MYO10 |
0.672 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268281 |
|
|
Mus musculus |
Neuron |
| pmid |
sentence |
| 17237772 |
Here, we provide evidence for the involvement of the unconventional myosin X (Myo X) in netrin-1 function. We find that Myo X interacts with the netrin receptor deleted in colorectal cancer (DCC) and neogenin, a DCC-related protein. Expression of Myo X redistributes DCC to the cell periphery or to the tips of neurites, whereas its silencing prevents DCC distribution in neurites. Moreover, expression of DCC, but not neogenin, stimulates Myo X-mediated formation and elongation of filopodia, suggesting that Myo X function may be differentially regulated by DCC and neogenin. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Axon guidance |
| + |
UNC5D | down-regulates activity
binding
|
DCC |
0.567 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268167 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25881791 |
In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Nervous System |
| + |
UNC5 | down-regulates activity
binding
|
DCC |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268168 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25881791 |
In the presence of netrin-1, UNC5 co-immuno-precipitates with DCC, suggesting the formation of a ternary complex of netrin-1 with ecto-domains of DCC and UNC5. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. DCC binding to netrin-1 alone leads to axon attraction. Importantly, DCC has the ability to switch the netrin-1-mediated responses from attraction to repulsion when another receptor UNC5 co-exists. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Nervous System |
| Pathways: | Axon guidance |
| + |
TFAP2A | up-regulates quantity by expression
transcriptional regulation
|
DCC |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255189 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 19745029 |
Promoter analysis and transfection studies showed that the up-regulation of DCC in OA chondrocytes may be mediated by the transcription factors Sox9 and AP-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NTN1 | up-regulates activity
binding
|
DCC |
0.907 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268162 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25881791 |
DCC (Deleted in Colorectal Cancer) is a single-pass transmembrane protein that belongs to the immunoglobulin superfamily. It was originally identified as a prognostic tumor marker and then subsequently found to be a receptor for netrin-1. DCC plays a key role in axon guidance and also in a number of other important cellular processes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Nervous System |
| Pathways: | Axon guidance |
| + |
DCC | up-regulates
|
Chemoattraction_of_axon |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268163 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25881791 |
DCC constitutively expresses on the axonal surface. Netrin-1-binding to DCC induces chemoattraction |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Nervous System |
| Pathways: | Axon guidance |
3.0
DCC
- 
- 