Property Summary

NCBI Gene PubMed Count 58
PubMed Score 96.23
PubTator Score 100.67

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (13)

Disease log2 FC p
psoriasis -2.900 1.5e-05
osteosarcoma -2.973 7.2e-06
group 3 medulloblastoma -1.600 4.5e-05
medulloblastoma, large-cell -1.700 5.5e-05
tuberculosis -1.100 2.2e-05
lung cancer 1.900 1.3e-05
interstitial cystitis -2.100 7.0e-06
atypical teratoid/rhabdoid tumor -1.200 2.8e-02
subependymal giant cell astrocytoma -1.974 4.0e-02
invasive ductal carcinoma -1.182 6.6e-03
Breast cancer -1.100 3.3e-06
pituitary cancer -1.200 3.5e-04
Down syndrome 1.400 9.2e-04

Gene RIF (45)

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.
24145035 our results reveal WDR48 and USP12 as novel PHLPP1 regulators and potential suppressors of tumor cell survival.
24121273 Suppression of PHLPP1 by DNA methylation contributes to melanoma development and progression.
24061475 A hypoxia-induced decrease of PHLPP expression is attenuated by knocking down HIF1alpha but not HIF2alpha.
24037758 The overall survival time and relapse-free survival time in PHLPP1-positive gastric cancer patients were significantly longer than in PHLPP1-negative patients.
23846336 This study reveals functional and mechanistic links between miRNA-224 and the tumor suppressors PHLPP1 and PHLPP2 in the pathogenesis of colorectal cancer
23512990 Data indicate that binding affinities for the PH domains of Akt and PHLPP1 were greater than for other PH domain-containing proteins, which may underlie the preferential recruitment of these proteins to membranes containing tocopherols.
23440515 we found that SGT1 was able to regulate the stability of PHLPP1, which is the direct phosphatase for Akt ser473 phosphorylation
22931649 AG490 time-dependently down-regulated the protein expression of PHLPP and induced apoptosis of K562 cells
22426999 a novel USP1-PHLPP1-Akt signaling axis, and decreased USP1 level in lung cancer cells may play an important role in lung cancer progress.
22391563 USP46-mediated stabilization of PHLPP and the subsequent inhibition of Akt.
22340730 Studies suggest that the effects of PHLPP1 deletion on prostate carcinogenesis may be explained by the strong dependence of prostate cancer on phosphoinositide 3-kinase (PI3K)/Akt signalling.
22237780 Loss of PHLPP1 is associated with chronic lymphocytic leukemia.
22183406 PHLPP1 and PHLPP2 have an effect on retinal rod CNG channel sensitivity.
22144674 PHLPP as a novel tumor suppressor.
22044669 PHLPP1 has tumor suppressive activity and might represent a therapeutic or diagnostic tool for pancreatic ductal adenocarcinoma.
21986499 Knockdown of PHLPP1 or PHLPP2 resulted in an increase in S6K1 phosphorylation.
21840483 codeletion of PTEN and PHLPP1 in patient samples is highly restricted to metastatic disease and tightly correlated to deletion of TP53 and PHLPP2
21804599 show for the first time a significant disruption of all three members of the PTEN-NHERF1-PHLPP1 tumor suppressor network in high-grade tumors, correlating with Akt activation and patient's abysmal survival
21701506 Knockdown of Scribble (Scrib) results in redistribution of PHLPP1 from the membrane to the cytoplasm and an increase in Akt phosphorylation.
21461637 Increased abundance of PHLPP-1, production of which is regulated by insulin, may represent a new molecular defect in insulin-resistant states such as obesity.
21454620 the cellular localization of beta-TrCP1 is altered in glioblastoma, resulting in dysregulation of PHLPP1 and other substrates such as beta-catenin.
21177869 a compensatory feedback regulation in which the activation of Akt is inhibited by up-regulation of PHLPP through mTOR, and this mTOR-dependent expression of PHLPP subsequently determines the rapamycin sensitivity of cancer cells.
20861921 Reduced expression of the tumor suppressor PHLPP1 enhances the antiapoptotic B-cell receptor signal in chronic lymphocytic leukemia B-cells.
20677014 Observational study of gene-disease association. (HuGE Navigator)
20574456 Aberrantly expressed UCH-L1 boosts signaling through the Akt pathway by downregulating the antagonistic phosphatase PHLPP1, an event that requires its de-ubiquitinase activity
20513427 The PHLPP1 dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19797085 demonstrate a key role for beta-TrCP in controlling the level of PHLPP1, and activation of Akt negatively regulates this degradation process.
19745829 In the striatum, reduced levels of PHLPP1 can contribute to maintain high levels of activated Akt that may delay cell death and allow the recovery of neuronal viability after mutant huntingtin silencing
19690890 Observational study of gene-disease association. (HuGE Navigator)
19261608 Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells
19079341 Loss of PHLPP expression is associated with colon cancer.
18511290 Study focuses on the function of PHLPP1 and PHLPP2 in modulating signaling by Akt and PKC.
18162466 PHLPP controls the cellular levels of PKC by specifically dephosphorylating the hydrophobic motif, thus destabilizing the enzyme and promoting its degradation.
17386267 Mechanism to selectively terminate Akt-signaling pathways through the differential inactivation of specific Akt isoforms by specific PHLPP isoforms.

AA Sequence

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
//

Text Mined References (63)

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.
24530606 2014 PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice.
24393845 2014 PHLPP1 regulates contact inhibition by dephosphorylating Mst1 at the inhibitory site.
24145035 2013 WD repeat protein WDR48 in complex with deubiquitinase USP12 suppresses Akt-dependent cell survival signaling by stabilizing PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1).
24121273 2014 Oncogenic suppression of PHLPP1 in human melanoma.
24061475 2013 Downregulation of PHLPP expression contributes to hypoxia-induced resistance to chemotherapy in colon cancer cells.
24037758 2013 Loss expression of PHLPP1 correlates with lymph node metastasis and exhibits a poor prognosis in patients with gastric cancer.
23846336 2013 microRNA-224 promotes cell proliferation and tumor growth in human colorectal cancer by repressing PHLPP1 and PHLPP2.
23512990 2013 Vitamin E facilitates the inactivation of the kinase Akt by the phosphatase PHLPP1.
23440515 2013 SGT1 regulates Akt signaling by promoting beta-TrCP-dependent PHLPP1 degradation in gastric cancer cells.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22931649 2012 [AG490 inhibits the proliferation of K562 and down-regulates protein phosphatase PHLPP expression].
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22426999 2012 USP1 regulates AKT phosphorylation by modulating the stability of PHLPP1 in lung cancer cells.
22391563 2013 The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer.
22340730 2013 Suppression of survival signalling pathways by the phosphatase PHLPP.
22237780 2012 Mechanisms and consequences of the loss of PHLPP1 phosphatase in chronic lymphocytic leukemia (CLL).
22183406 2012 Ras-associating domain proteins: a new class of cyclic nucleotide-gated channel modulators.
22144674 2012 Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): a new player in cell signaling.
22044669 2012 The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and inhibits tumor formation.
21986499 2011 PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth.
21840483 2011 Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression.
21804599 2012 PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma.
21701506 2011 Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt.
21461637 2011 Increased levels of the Akt-specific phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP)-1 in obese participants are associated with insulin resistance.
21454620 2011 Mislocalization of the E3 ligase, ?-transducin repeat-containing protein 1 (?-TrCP1), in glioblastoma uncouples negative feedback between the pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and Akt.
21177869 2011 mTOR-dependent regulation of PHLPP expression controls the rapamycin sensitivity in cancer cells.
20861921 2010 Reduced expression of the tumor suppressor PHLPP1 enhances the antiapoptotic B-cell receptor signal in chronic lymphocytic leukemia B-cells.
20819118 2010 PHLPP1 splice variants differentially regulate AKT and PKC? signaling in hippocampal neurons: characterization of PHLPP proteins in the adult hippocampus.
20677014 2010 An approach based on a genome-wide association study reveals candidate loci for narcolepsy.
20574456 2010 The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling.
20513427 2010 Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20089132 2010 Serine/threonine kinase akt activation regulates the activity of retinal serine/threonine phosphatases, PHLPP and PHLPPL.
19797085 2009 beta-TrCP-mediated ubiquitination and degradation of PHLPP1 are negatively regulated by Akt.
19745829 2010 PH domain leucine-rich repeat protein phosphatase 1 contributes to maintain the activation of the PI3K/Akt pro-survival pathway in Huntington's disease striatum.
19732725 2009 FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt.
19690890 2009 Genetic analysis of diabetic nephropathy on chromosome 18 in African Americans: linkage analysis and dense SNP mapping.
19615732 2009 Defining the human deubiquitinating enzyme interaction landscape.
19261608 2009 Depletion of Pleckstrin homology domain leucine-rich repeat protein phosphatases 1 and 2 by Bcr-Abl promotes chronic myelogenous leukemia cell proliferation through continuous phosphorylation of Akt isoforms.
19079341 2009 Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis.
18511290 2008 PHLiPPing the switch on Akt and protein kinase C signaling.
18162466 2008 The phosphatase PHLPP controls the cellular levels of protein kinase C.
17386267 2007 PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16177791 2005 DNA sequence and analysis of human chromosome 18.
15951569 2005 Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules.
15808505 2005 PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12168954 2002 Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.
10570941 1999 SCOP, a novel gene product expressed in a circadian manner in rat suprachiasmatic nucleus.
9628581 1998 Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.