TISIDB

Summary
Symbol	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
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	Isoform 1: Cytoplasm, perinuclear region.; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm, perinuclear region. Cell projection, ruffle membrane.; SUBCELLULAR LOCATION: Isoform 4: Membrane; Peripheral membrane protein. Note=Isoform 4 has propensity for association with membranes.; SUBCELLULAR LOCATION: Isoform 6: Cytoplasm, perinuclear region.; SUBCELLULAR LOCATION: Isoform 7: Cytoplasm. Membrane. Note=Predominantly cytoplasmic.
Domain	PF00233 3'5'-cyclic nucleotide phosphodiesterase
Function	Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

> Gene Ontology [ TOP ]
Biological Process	GO:0006195 purine nucleotide catabolic process GO:0006198 cAMP catabolic process GO:0007608 sensory perception of smell GO:0009150 purine ribonucleotide metabolic process GO:0009154 purine ribonucleotide catabolic process GO:0009166 nucleotide catabolic process GO:0009187 cyclic nucleotide metabolic process GO:0009214 cyclic nucleotide catabolic process GO:0009261 ribonucleotide catabolic process GO:0010737 protein kinase A signaling GO:0010738 regulation of protein kinase A signaling GO:0019439 aromatic compound catabolic process GO:0019932 second-messenger-mediated signaling GO:0019933 cAMP-mediated signaling GO:0019935 cyclic-nucleotide-mediated signaling GO:0034655 nucleobase-containing compound catabolic process GO:0035690 cellular response to drug GO:0042493 response to drug GO:0043949 regulation of cAMP-mediated signaling GO:0044270 cellular nitrogen compound catabolic process GO:0046058 cAMP metabolic process GO:0046434 organophosphate catabolic process GO:0046700 heterocycle catabolic process GO:0072523 purine-containing compound catabolic process GO:1901136 carbohydrate derivative catabolic process GO:1901292 nucleoside phosphate catabolic process GO:1901361 organic cyclic compound catabolic process GO:1901565 organonitrogen compound catabolic process
Molecular Function	GO:0004112 cyclic-nucleotide phosphodiesterase activity GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity GO:0008081 phosphoric diester hydrolase activity GO:0030551 cyclic nucleotide binding GO:0030552 cAMP binding GO:0042578 phosphoric ester hydrolase activity
Cellular Component	GO:0001726 ruffle GO:0031252 cell leading edge GO:0031253 cell projection membrane GO:0031256 leading edge membrane GO:0032587 ruffle membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04024 cAMP signaling pathway hsa00230 Purine metabolism
Reactome	R-HSA-180024: DARPP-32 events R-HSA-418555: G alpha (s) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-111885: Opioid Signalling R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PDE4A 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	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
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

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Statistical results of PDE4A 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	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
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 PDE4A 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	-0.506	0.188
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.034	0.322
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.116	0.882
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.428	0.181
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.702	0.721
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.085	0.971
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.221	0.601
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.057	0.96
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.353	0.787
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.019	0.306
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	1.563	0.271
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.351	0.00198

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PDE4A 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	22.2	5.5	16.7	0.0222
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	22.2	6.8	15.4	0.0651
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
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	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	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	0	0	1
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	0	0	1

Summary
Symbol	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PDE4A. 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	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PDE4A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PDE4A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PDE4A. 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	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PDE4A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PDE4A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PDE4A
Name	phosphodiesterase 4A, cAMP-specific
Aliases	phosphodiesterase E2 dunce homolog (Drosophila); DPDE2; phosphodiesterase 4A, cAMP-specific (dunce (Drosophi ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PDE4A collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PDE4A.

ID	Name	Drug Type	Targets	#Targets
DB00201	Caffeine	Small Molecule	ADORA1, ADORA2A, ATM, ITPR1, ITPR2, ITPR3, PDE10A, PDE11A, PDE1A, ......	33
DB00277	Theophylline	Small Molecule	ADORA1, ADORA2A, ADORA2B, CPNE1, HDAC2, HM13, NOMO1, PARP1, PDE3A, ......	14
DB00651	Dyphylline	Small Molecule	ADORA1, ADORA2A, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B	8
DB00806	Pentoxifylline	Small Molecule	ADORA1, ADORA2A, NT5E, PDE4A, PDE4B, PDE5A	6
DB00824	Enprofylline	Small Molecule	ADORA1, ADORA2A, ADORA2B, ADORA3, PDE4A, PDE4B	6
DB00975	Dipyridamole	Small Molecule	ADA, ORM1, PDE10A, PDE4A, PDE5A, RCAN1	6
DB01088	Iloprost	Small Molecule	PDE4A, PDE4B, PDE4C, PDE4D, PLAT, PTGDR2, PTGER1, PTGIR	8
DB01303	Oxtriphylline	Small Molecule	ADORA1, ADORA2A, HDAC2, PDE3A, PDE4A	5
DB01656	Roflumilast	Small Molecule	PDE4A, PDE4B, PDE4C, PDE4D	4
DB01791	Piclamilast	Small Molecule	PDE4A, PDE4B, PDE4C, PDE4D	4
DB05219	Crisaborole	Small Molecule	PDE4A, PDE4B, PDE4C, PDE4D	4
DB05266	Ibudilast	Small Molecule	PDE3A, PDE4A, PDE4B, PDE4C, PDE4D	5
DB05676	Apremilast	Small Molecule	IFNG, IL2, NOS3, PDE4A, PDE4B, PDE4D, TNF	7
DB05876	PDE4	Small Molecule	PDE4A	1
DB06479	Propentofylline	Small Molecule	PDE4A	1
DB06751	Drotaverine	Small Molecule	CACNA1C, PDE4A	2
DB06842	(4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one	Small Molecule	PDE4A, PDE4D	2
DB08299	4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid	Small Molecule	PDE4A, PDE4B, PDE4D	3
DB08811	Tofisopam	Small Molecule	PDE10A, PDE2A, PDE3A, PDE4A	4
DB09283	Trapidil	Small Molecule	PDE10A, PDE11A, PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE3B, PDE4A, P ......	21

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