| Tchem | PH domain leucine-rich repeat-containing protein phosphatase 1 |
Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity).
This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]
This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]
Comments
| Disease | Target Count |
|---|---|
| Neoplastic Cell Transformation | 81 |
| Disease | Target Count | P-value |
|---|---|---|
| Breast cancer | 3099 | 3.27713967959715E-6 |
| interstitial cystitis | 2299 | 7.00088961792521E-6 |
| osteosarcoma | 7933 | 7.20598692775255E-6 |
| lung cancer | 4473 | 1.27888331083555E-5 |
| psoriasis | 6685 | 1.46435133864805E-5 |
| tuberculosis | 1563 | 2.24443549971926E-5 |
| group 3 medulloblastoma | 2254 | 4.51693500177726E-5 |
| medulloblastoma, large-cell | 6234 | 5.48671429000309E-5 |
| pituitary cancer | 1972 | 3.51174914137318E-4 |
| Down syndrome | 548 | 9.19552002602119E-4 |
| invasive ductal carcinoma | 2950 | 0.00664325430196979 |
| atypical teratoid/rhabdoid tumor | 1095 | 0.0279032503870473 |
| subependymal giant cell astrocytoma | 2287 | 0.0399580235228344 |
| Disease | log2 FC | p |
|---|---|---|
| psoriasis | -2.900 | 0.000 |
| osteosarcoma | -2.973 | 0.000 |
| group 3 medulloblastoma | -1.600 | 0.000 |
| medulloblastoma, large-cell | -1.700 | 0.000 |
| tuberculosis | -1.100 | 0.000 |
| lung cancer | 1.900 | 0.000 |
| interstitial cystitis | -2.100 | 0.000 |
| atypical teratoid/rhabdoid tumor | -1.200 | 0.028 |
| subependymal giant cell astrocytoma | -1.974 | 0.040 |
| invasive ductal carcinoma | -1.182 | 0.007 |
| Breast cancer | -1.100 | 0.000 |
| pituitary cancer | -1.200 | 0.000 |
| Down syndrome | 1.400 | 0.001 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Horse | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Pig | OMA EggNOG Inparanoid |
| Opossum | OMA EggNOG Inparanoid |
| Chicken | OMA Inparanoid |
| Anole lizard | OMA Inparanoid |
| PMID | Text |
|---|---|
| 26823799 | our results suggest that PHLPP1 plays a crucial role in sacral chordoma |
| 26463718 | high levels of PHLPP might reflect a less aggressive lung adenocarcinoma phenotype and predict better survival in patients with lung adenocarcinoma. |
| 26427440 | Data show that both serine/threonine phosphatases PHLPP and dephosphorylated the physiological substrates of Akt1 and Akt3 with similar efficiencies. |
| 26245343 | Results showed that PHLPP1 and PHLPP2 gene expression are down-regulated in esophageal squamous cell carcinoma. Their promotor is a target for mir-224. |
| 25793736 | Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma |
| 25776496 | PHLPP1, along with miR-522, promoted tumor cell growth in glioblastoma cells. |
| 24945731 | miR-141 and its targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis |
| 24892992 | biochemical characterization of phosphatase domain of PHLPP1 and PHLPP2;PHLPP1 and PHLPP2 have similar in vitro activities and respond comparably to the presence of metallic ions; metallic ions affect structural stability of the domain;identified 3 residues likely involved in metal coordination and 2 that may be important for structural integrity |
| 24599953 | conclude that cross-talk between PTEN and PHLPPs is silenced in normal prostate cells but activated in TGF-beta1 transformed prostate stem and cancer cells and facilitates invasive growth |
| 24393845 | PHLPP1 is a binding protein for Mst1 and it modulates the Hippo pathway by dephosphorylating Mst1 at the inhibitory Thr(387) of Mst1. |
| More... |
MEPAAAATVQRLPELGREDRASAPAAAAAAAAAAAAAAAALAAAAGGGRSPEPALTPAAPSGGNGSGSGA 1 - 70 REEAPGEAPPGPLPGRAGGAGRRRRRGAPQPIAGGAAPVPGAGGGANSLLLRRGRLKRNLSAAAAAASSS 71 - 140 SSSSAAAASHSPGAAGLPASCSASASLCTRSLDRKTLLLKHRQTLQLQPSDRDWVRHQLQRGCVHVFDRH 141 - 210 MASTYLRPVLCTLDTTAGEVAARLLQLGHKGGGVVKVLGQGPGAAAAREPAEPPPEAGPRLAPPEPRDSE 211 - 280 VPPARSAPGAFGGPPRAPPADLPLPVGGPGGWSRRASPAPSDSSPGEPFVGGPVSSPRAPRPVVSDTESF 281 - 350 SLSPSAESVSDRLDPYSSGGGSSSSSEELEADAASAPTGVPGQPRRPGHPAQPLPLPQTASSPQPQQKAP 351 - 420 RAIDSPGGAVREGSCEEKAAAAVAPGGLQSTPGRSGVTAEKAPPPPPPPTLYVQLHGETTRRLEAEEKPL 421 - 490 QIQNDYLFQLGFGELWRVQEEGMDSEIGCLIRFYAGKPHSTGSSERIQLSGMYNVRKGKMQLPVNRWTRR 491 - 560 QVILCGTCLIVSSVKDSLTGKMHVLPLIGGKVEEVKKHQHCLAFSSSGPQSQTYYICFDTFTEYLRWLRQ 561 - 630 VSKVASQRISSVDLSCCSLEHLPANLFYSQDLTHLNLKQNFLRQNPSLPAARGLNELQRFTKLKSLNLSN 631 - 700 NHLGDFPLAVCSIPTLAELNVSCNALRSVPAAVGVMHNLQTFLLDGNFLQSLPAELENMKQLSYLGLSFN 701 - 770 EFTDIPEVLEKLTAVDKLCMSGNCVETLRLQALRKMPHIKHVDLRLNVIRKLIADEVDFLQHVTQLDLRD 771 - 840 NKLGDLDAMIFNNIEVLHCERNQLVTLDICGYFLKALYASSNELVQLDVYPVPNYLSYMDVSRNRLENVP 841 - 910 EWVCESRKLEVLDIGHNQICELPARLFCNSSLRKLLAGHNQLARLPERLERTSVEVLDVQHNQLLELPPN 911 - 980 LLMKADSLRFLNASANKLESLPPATLSEETNSILQELYLTNNSLTDKCVPLLTGHPHLKILHMAYNRLQS 981 - 1050 FPASKMAKLEELEEIDLSGNKLKAIPTTIMNCRRMHTVIAHSNCIEVFPEVMQLPEIKCVDLSCNELSEV 1051 - 1120 TLPENLPPKLQELDLTGNPRLVLDHKTLELLNNIRCFKIDQPSTGDASGAPAVWSHGYTEASGVKNKLCV 1121 - 1190 AALSVNNFCDNREALYGVFDGDRNVEVPYLLQCTMSDILAEELQKTKNEEEYMVNTFIVMQRKLGTAGQK 1191 - 1260 LGGAAVLCHIKHDPVDPGGSFTLTSANVGKCQTVLCRNGKPLPLSRSYIMSCEEELKRIKQHKAIITEDG 1261 - 1330 KVNGVTESTRILGYTFLHPSVVPRPHVQSVLLTPQDEFFILGSKGLWDSLSVEEAVEAVRNVPDALAAAK 1331 - 1400 KLCTLAQSYGCHDSISAVVVQLSVTEDSFCCCELSAGGAVPPPSPGIFPPSVNMVIKDRPSDGLGVPSSS 1401 - 1470 SGMASEISSELSTSEMSSEVGSTASDEPPPGALSENSPAYPSEQRCMLHPICLSNSFQRQLSSATFSSAF 1471 - 1540 SDNGLDSDDEEPIEGVFTNGSRVEVEVDIHCSRAKEKEKQQHLLQVPAEASDEGIVISANEDEPGLPRKA 1541 - 1610 DFSAVGTIGRRRANGSVAPQERSHNVIEVATDAPLRKPGGYFAAPAQPDPDDQFIIPPELEEEVKEIMKH 1611 - 1680 HQEQQQQQQPPPPPQLQPQLPRHYQLDQLPDYYDTPL 1681 - 1717 //
| PMID | Year | Title |
|---|---|---|
| 26823799 | 2015 | Low expression of PHLPP1 in sacral chordoma and its association with poor prognosis. |
| 26463718 | 2015 | High PHLPP expression is associated with better prognosis in patients with resected lung adenocarcinoma. |
| 26427440 | 2016 | Photoreceptor Neuroprotection: Regulation of Akt Activation Through Serine/Threonine Phosphatases, PHLPP and PHLPPL. |
| 26245343 | 2015 | Expression and role of oncogenic miRNA-224 in esophageal squamous cell carcinoma. |
| 25820252 | 2015 | Interactome of the negative regulator of nuclear import BRCA1-binding protein 2. |
| 25793736 | 2015 | Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma. |
| 25776496 | 2015 | MiR-522 contributes to cell proliferation of human glioblastoma cells by suppressing PHLPP1 expression. |
| 24945731 | 2014 | MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2. |
| 24892992 | 2014 | Biochemical characterization of the phosphatase domain of the tumor suppressor PH domain leucine-rich repeat protein phosphatase. |
| 24599953 | 2014 | Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and PH domain and leucine-rich repeat phosphatase cross-talk (PHLPP) in cancer cells and in transforming growth factor ?-activated stem cells. |
| More... |
