| + |
PP1 | down-regulates activity 
dephosphorylation
|
CAD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264653 |
Ser1406 |
GAGGRRLsSFVTKGY |
in vitro |
|
| pmid |
sentence |
| 4092695 |
Cyclic AMP-dependent protein kinase phosphorylates two serine residues on the protein termed sites 1 and 2| Site 1: Arg-Leu-Ser(P)-Ser-Phe-Val-Thr-Lys Site 2: Ile-His-Arg-Ala-Ser(P)-Asp-Pro-Gly-Leu-Pro-Ala-Glu-Glu-Pro-Lys | Both phosphorylation and activation can be reversed using purified preparations of the catalytic subunits of protein phosphatases 1- and -2A, and inactivation also correlates better with dephosphorylation of site 1 rather than site 2. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
PRKACA | down-regulates activity
phosphorylation
|
CAD |
0.31 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250344 |
Ser1406 |
GAGGRRLsSFVTKGY |
|
|
| pmid |
sentence |
| 11986331 |
CAD is down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. PKA phosphorylates Ser1406 and Ser1859, although only Ser1406 is involved in regulation. |
|
| Publications: |
1 |
| + |
PKA | down-regulates activity
phosphorylation
|
CAD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267442 |
Ser1406 |
GAGGRRLsSFVTKGY |
in vitro |
|
| pmid |
sentence |
| 17485345 |
The multifunctional protein CAD initiates de novo pyrimidine biosynthesis in mammalian cells. CAD is activated by MAP kinase (Erk1/2) just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. MAP kinase phosphorylates Thr456, while PKA phosphorylates Ser1406 and Ser1859, although only Ser1406 is involved in regulation. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Nucleotide Biosynthesis |
| + |
PRKACA | down-regulates
phosphorylation
|
CAD |
0.31 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151816 |
Ser1406 |
GAGGRRLsSFVTKGY |
Homo sapiens |
|
| pmid |
sentence |
| 17206380 |
Protein kinase a phosphorylation at thr456 of the multifunctional protein cad antagonizes activation by the map kinase cascade. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PPP1CA | down-regulates activity
dephosphorylation
|
CAD |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263741 |
Ser1406 |
CSGAGGRrLSSFVTK |
in vitro |
|
| pmid |
sentence |
| 4092695 |
Cyclic AMP-dependent protein kinase phosphorylates two serine residues on the protein termed sites 1 and 2| Site 1: Arg-Leu-Ser(P)-Ser-Phe-Val-Thr-Lys Site 2: Ile-His-Arg-Ala-Ser(P)-Asp-Pro-Gly-Leu-Pro-Ala-Glu-Glu-Pro-Lys | Both phosphorylation and activation can be reversed using purified preparations of the catalytic subunits of protein phosphatases 1- and -2A, and inactivation also correlates better with dephosphorylation of site 1 rather than site 2. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
RPS6KB1 | up-regulates 
phosphorylation
|
CAD |
0.386 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-201117 |
Ser1859 |
PPRIHRAsDPGLPAE |
Homo sapiens |
|
| pmid |
sentence |
| 23429703 |
Mtorc1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein s6 kinase 1 (s6k1), which directly phosphorylates s1859 on cad, the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. Growth signaling through mtorc1 thus stimulates the production of new nucleotides to accommodate an increase in rna and dna synthesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
PRKACA |
phosphorylation
|
CAD |
0.31 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250343 |
Ser1859 |
PPRIHRAsDPGLPAE |
|
|
| pmid |
sentence |
| 11986331 |
CAD is down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. PKA phosphorylates Ser1406 and Ser1859, although only Ser1406 is involved in regulation. |
|
| Publications: |
1 |
| + |
RPS6KB1 | up-regulates activity
phosphorylation
|
CAD |
0.386 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267443 |
Ser1859 |
PPRIHRAsDPGLPAE |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 23429703 |
CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
RPS6K | up-regulates activity
phosphorylation
|
CAD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267197 |
Ser1859 |
PPRIHRAsDPGLPAE |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23429703 |
Activation of mTORC1 led to the acute stimulation of metabolic flux through the de novo pyrimidine synthesis pathway. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glutamine metabolism |
| + |
CAD | up-regulates activity
phosphorylation
|
CAD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250610 |
Thr1037 |
QQCRVLGtSPEAIDS |
in vitro |
|
| pmid |
sentence |
| 11986331 |
Autophosphorylation resulted in a 2-fold increase in CPSase activity, an increased sensitivity to the feedback inhibitor UTP, and decreased allosteric activation by 5-phosphoribosyl-1-pyrophosphate |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Glutamine metabolism, Nucleotide Biosynthesis |
| + |
MAPK1 | up-regulates
phosphorylation
|
CAD |
0.392 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-137171 |
Thr456 |
KVYFLPItPHYVTQV |
Homo sapiens |
|
| pmid |
sentence |
| 15890648 |
Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
ERK1/2 | up-regulates activity
phosphorylation
|
CAD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267441 |
Thr456 |
KVYFLPItPHYVTQV |
in vitro |
|
| pmid |
sentence |
| 17485345 |
The multifunctional protein CAD initiates de novo pyrimidine biosynthesis in mammalian cells. CAD is activated by MAP kinase (Erk1/2) just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. MAP kinase phosphorylates Thr456, while PKA phosphorylates Ser1406 and Ser1859, although only Ser1406 is involved in regulation. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| Pathways: | Nucleotide Biosynthesis |
| + |
MAPK3 | up-regulates
phosphorylation
|
CAD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-137179 |
Thr456 |
KVYFLPItPHYVTQV |
Homo sapiens |
|
| pmid |
sentence |
| 15890648 |
Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CAD | up-regulates quantity
chemical modification
|
N-carbamoyl-L-aspartate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267425 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
CAD | down-regulates quantity
chemical modification
|
L-glutamine zwitterion |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267418 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glutamine metabolism, Nucleotide Biosynthesis |
| + |
Gbeta | up-regulates
phosphorylation
|
CAD |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269998 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15890648 |
Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CAD | down-regulates quantity
chemical modification
|
hydrogencarbonate |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267419 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
CAD | down-regulates quantity
chemical modification
|
N-carbamoyl-L-aspartate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267427 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
CAD | up-regulates quantity
chemical modification
|
(S)-dihydroorotate |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267420 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
| + |
CAD | down-regulates quantity
chemical modification
|
glutamine |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267199 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24332717 |
In animals, the first three reactions of the pathway are catalyzed by CAD, an 240 kDa multifunctional protein that combines glutamine-dependent carbamyl phosphate synthetase (GLNCPSase), aspartate transcarbamylase (ATCase), and dihydroorotase (DHOase) activities |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CAD | up-regulates activity 
|
Pyrimidine biosynthesis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267196 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15096496 |
The CPSase activity of CAD is the major locus of control of de novo pyrimidine biosynthesis |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glutamine metabolism |
| + |
CAD | up-regulates quantity
chemical modification
|
carbamoyl phosphate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267194 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24332717 |
In animals, the first three reactions of the pathway are catalyzed by CAD, an 240 kDa multifunctional protein that combines glutamine-dependent carbamyl phosphate synthetase (GLNCPSase), aspartate transcarbamylase (ATCase), and dihydroorotase (DHOase) activities |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glutamine metabolism, Nucleotide Biosynthesis |
| + |
CAD | up-regulates quantity
chemical modification
|
L-glutamate(1-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267421 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glutamine metabolism, Nucleotide Biosynthesis |
| + |
CAD | down-regulates quantity
chemical modification
|
carbamoyl phosphate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268092 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Glutamine metabolism, Nucleotide Biosynthesis |
| + |
CAD | down-regulates quantity
chemical modification
|
L-aspartate(1-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267424 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28552578 |
CAD is a 243 kDa polypeptide formed by the fusion of four enzymatic domains that initiate the de novo biosynthesis of pyrimidine nucleotides . The first two domains, glutaminase (GLN) and carbamoyl phosphate synthetase (CPS-II), initiate the pathway, catalyzing the formation of carbamoyl phosphate (CP) from bicarbonate, glutamine, and two ATP molecules. Next, the labile CP is partially channeled to the C-terminal aspartate transcarbamoylase (ATC) domain where it reacts with aspartate to form carbamoyl aspartate. Then, carbamoyl aspartate is condensated to dihydroorotate, the cyclic precursor of the pyrimidine ring, by the dihydroorotase (DHO), a Zn metalloenzyme fused between CPS and ATC domains. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Nucleotide Biosynthesis |
3.0
CAD
- 
- 