TISIDB

Summary
Symbol	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
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. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome.
Domain	PF00149 Calcineurin-like phosphoesterase
Function	Protein phosphatase that is involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signaling, NF-kappa-B activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AFX phosphorylated on Ser-140 (gamma-H2AFX) generated during DNA replication and required for DNA double strand break repair. Dephosphorylates NDEL1 at CDK1 phosphorylation sites and negatively regulates CDK1 activity in interphase (By similarity). In response to DNA damage, catalyzes RPA2 dephosphorylation, an essential step for DNA repair since it allows the efficient RPA2-mediated recruitment of RAD51 to chromatin.

> Gene Ontology [ TOP ]
Biological Process	GO:0000018 regulation of DNA recombination GO:0000724 double-strand break repair via homologous recombination GO:0000725 recombinational repair GO:0006282 regulation of DNA repair GO:0006302 double-strand break repair GO:0006310 DNA recombination GO:0006470 protein dephosphorylation GO:0010569 regulation of double-strand break repair via homologous recombination GO:0016311 dephosphorylation GO:0038061 NIK/NF-kappaB signaling GO:0051052 regulation of DNA metabolic process GO:2000779 regulation of double-strand break repair GO:2001020 regulation of response to DNA damage stimulus
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0004702 receptor signaling protein serine/threonine kinase activity GO:0004704 NF-kappaB-inducing kinase activity GO:0004721 phosphoprotein phosphatase activity GO:0004722 protein serine/threonine phosphatase activity GO:0005057 receptor signaling protein activity GO:0016791 phosphatase activity GO:0042578 phosphoric ester hydrolase activity
Cellular Component	GO:0008287 protein serine/threonine phosphatase complex GO:0030289 protein phosphatase 4 complex GO:1903293 phosphatase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04922 Glucagon signaling pathway
Reactome	R-HSA-5693532: DNA Double-Strand Break Repair R-HSA-73894: DNA Repair R-HSA-5693567: HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693538: Homology Directed Repair R-HSA-5693607: Processing of DNA double-strand break ends

Summary
Symbol	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PPP4C 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	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
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 PPP4C 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	Second most enriched score: 0.55	Sensitive to T cell-mediated killing
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	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
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

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Points in the above scatter plot represent the expression difference of PPP4C 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	0.075	0.776
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.059	0.983
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.083	0.968
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.381	0.421
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.256	0.887
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.547	0.824
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.05	0.893
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.227	0.886
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.125	0.944
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.195	0.921
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	-0.169	0.955
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.164	0.0128

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PPP4C in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	20	20	0.294

Summary
Symbol	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PPP4C. 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	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PPP4C. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PPP4C. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PPP4C. 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	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PPP4C expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PPP4C and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PPP4C
Name	protein phosphatase 4, catalytic subunit
Aliases	PPX; protein phosphatase X, catalytic subunit; protein phosphatase 4 (formerly X), catalytic subunit; PP-X; ......
Chromosomal Location	16p11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PPP4C collected from DrugBank database.

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

Browse PPP4C