| Tchem | Protein phosphatase 1D |
Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins. Mediates MAPK14 dephosphorylation and inactivation (PubMed:21283629).
The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. [provided by RefSeq, Jul 2008]
The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. [provided by RefSeq, Jul 2008]
Comments
Property Summary
| Ligand Count | 5 |
| NCBI Gene PubMed Count | 115 |
| PubMed Score | 181.77 |
| PubTator Score | 127.67 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Brain Stem Neoplasms | 4 | 0.0 | 0.0 |
| Breast Neoplasms | 445 | 0.0 | 0.0 |
| Glioma | 74 | 0.0 | 0.0 |
| INTELLECTUAL DEVELOPMENTAL DISORDER WITH GASTROINTESTINAL DIFFICULTIES AND HIGH PAIN THRESHOLD | 1 | 0.0 | 0.0 |
| Neurodevelopmental Disorders | 70 | 0.0 | 0.0 |
| Disease | Target Count | P-value |
|---|---|---|
| osteosarcoma | 7950 | 4.5e-12 |
| ovarian cancer | 8520 | 2.9e-04 |
| invasive ductal carcinoma | 2951 | 7.8e-04 |
| lung cancer | 4740 | 1.9e-03 |
| group 3 medulloblastoma | 4104 | 3.3e-03 |
| subependymal giant cell astrocytoma | 2287 | 1.3e-02 |
| spina bifida | 1074 | 4.7e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Intellectual disability | 1016 | 0.0 | 4.0 |
| Disease | Target Count |
|---|---|
| Familial cancer of breast | 12 |
| brain stem cancer | 1 |
| Disease | log2 FC | p |
|---|---|---|
| group 3 medulloblastoma | 2.100 | 3.3e-03 |
| invasive ductal carcinoma | -1.360 | 7.8e-04 |
| lung cancer | -1.600 | 1.9e-03 |
| osteosarcoma | -3.033 | 4.5e-12 |
| ovarian cancer | -1.700 | 2.9e-04 |
| spina bifida | -1.387 | 4.7e-02 |
| subependymal giant cell astrocytoma | -2.105 | 1.3e-02 |
| Species | Source | Disease |
|---|---|---|
| Inparanoid OMA | ||
| OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid OMA EggNOG | ||
| Inparanoid EggNOG |
CHEMBL1939361
pIC50 6.32
CHEMBL3613748
pKi 6.64
CHEMBL3613747
pIC50 6.67
CHEMBL3109288
pKi 6.82
CHEMBL3613749
pIC50 7.06
MAGLYSLGVSVFSDQGGRKYMEDVTQIVVEPEPTAEEKPSPRRSLSQPLPPRPSPAALPGGEVSGKGPAV 1 - 70 AAREARDPLPDAGASPAPSRCCRRRSSVAFFAVCDGHGGREAAQFAREHLWGFIKKQKGFTSSEPAKVCA 71 - 140 AIRKGFLACHLAMWKKLAEWPKTMTGLPSTSGTTASVVIIRGMKMYVAHVGDSGVVLGIQDDPKDDFVRA 141 - 210 VEVTQDHKPELPKERERIEGLGGSVMNKSGVNRVVWKRPRLTHNGPVRRSTVIDQIPFLAVARALGDLWS 211 - 280 YDFFSGEFVVSPEPDTSVHTLDPQKHKYIILGSDGLWNMIPPQDAISMCQDQEEKKYLMGEHGQSCAKML 281 - 350 VNRALGRWRQRMLRADNTSAIVICISPEVDNQGNFTNEDELYLNLTDSPSYNSQETCVMTPSPCSTPPVK 351 - 420 SLEEDPWPRVNSKDHIPALVRSNAFSENFLEVSAEIARENVQGVVIPSKDPEPLEENCAKALTLRIHDSL 421 - 490 NNSLPIGLVPTNSTNTVMDQKNLKMSTPGQMKAQEIERTPPTNFKRTLEESNSGPLMKKHRRNGLSRSSG 491 - 560 AQPASLPTTSQRKNSVKLTMRRRLRGQKKIGNPLLHQHRKTVCVC 561 - 605 //
