TISIDB

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

[ TOP ]

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
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
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 [ TOP ]
There is no record.

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
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

[ TOP ]

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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
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

[ TOP ]

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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.704	0.0163
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.743	0.657
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.687	0.515
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.713	0.0798
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.898	0.676
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.476	0.857
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.001	0.998
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.374	0.811
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.432	0.807
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.249	0.699
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.276	0.739
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.088	0.393

> Mutation difference between responders and non-responders

[ TOP ]

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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	0	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	11.8	-11.8	0.193
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	15.4	-15.4	0.482
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	16.7	-16.7	1

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
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 [ TOP ]

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PHLPP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PHLPP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PHLPP1
Name	PH domain and leucine rich repeat protein phosphatase 1
Aliases	KIAA0606; SCOP; PLEKHE1; PHLPP; pleckstrin homology domain containing, family E (with leucine rich repeats) ......
Chromosomal Location	18q21.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PHLPP1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse PHLPP1