Browse PHLPP1

Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=In colorectal cancer tissue, expression is concentrated at the lateral membrane of epithelial cells.; SUBCELLULAR LOCATION: Isoform 2: Cell membrane
Domain PF13516 Leucine Rich repeat
PF13855 Leucine rich repeat
PF00169 PH domain
PF00481 Protein phosphatase 2C
Function

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).

> Gene Ontology
 
Biological Process GO:0002249 lymphocyte anergy
GO:0002507 tolerance induction
GO:0002517 T cell tolerance induction
GO:0002643 regulation of tolerance induction
GO:0002664 regulation of T cell tolerance induction
GO:0002667 regulation of T cell anergy
GO:0002870 T cell anergy
GO:0002911 regulation of lymphocyte anergy
GO:0006470 protein dephosphorylation
GO:0007254 JNK cascade
GO:0007623 circadian rhythm
GO:0009649 entrainment of circadian clock
GO:0016311 dephosphorylation
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032872 regulation of stress-activated MAPK cascade
GO:0038066 p38MAPK cascade
GO:0042752 regulation of circadian rhythm
GO:0043491 protein kinase B signaling
GO:0046328 regulation of JNK cascade
GO:0048511 rhythmic process
GO:0051403 stress-activated MAPK cascade
GO:0051896 regulation of protein kinase B signaling
GO:0051898 negative regulation of protein kinase B signaling
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:1900744 regulation of p38MAPK cascade
GO:1902532 negative regulation of intracellular signal transduction
Molecular Function GO:0004721 phosphoprotein phosphatase activity
GO:0016791 phosphatase activity
GO:0042578 phosphoric ester hydrolase activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04151 PI3K-Akt signaling pathway
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-180292: GAB1 signalosome
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-199418: Negative regulation of the PI3K/AKT network
R-HSA-198203: PI3K/AKT activation
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between PHLPP1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.

Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of PHLPP1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of PHLPP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.7040.0163
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.7430.657
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.6870.515
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.7130.0798
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.8980.676
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4760.857
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0010.998
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3740.811
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.4320.807
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.2490.699
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.2760.739
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0880.393
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of PHLPP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)2117011.8-11.80.193
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86016.7-16.70.429
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916012.5-12.50.52
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 1113015.4-15.40.482
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 512016.7-16.71
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PHLPP1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PHLPP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PHLPP1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PHLPP1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of PHLPP1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between PHLPP1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolPHLPP1
NamePH domain and leucine rich repeat protein phosphatase 1
Aliases KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location18q21.32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting PHLPP1 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.