TISIDB

Summary
Symbol	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
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. Cytoplasmic granule. Note=Cytoplasmic granules of eosinophils and neutrophils.
Domain	PF03068 Protein-arginine deiminase (PAD) PF08527 Protein-arginine deiminase (PAD) middle domain PF08526 Protein-arginine deiminase (PAD) N-terminal domain
Function	Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.

> Gene Ontology [ TOP ]
Biological Process	GO:0000052 citrulline metabolic process GO:0006323 DNA packaging GO:0006333 chromatin assembly or disassembly GO:0006334 nucleosome assembly GO:0006338 chromatin remodeling GO:0016053 organic acid biosynthetic process GO:0016570 histone modification GO:0018101 protein citrullination GO:0018195 peptidyl-arginine modification GO:0019240 citrulline biosynthetic process GO:0019827 stem cell population maintenance GO:0031497 chromatin assembly GO:0034728 nucleosome organization GO:0036413 histone H3-R26 citrullination GO:0036414 histone citrullination GO:0044283 small molecule biosynthetic process GO:0065004 protein-DNA complex assembly GO:0071103 DNA conformation change GO:0071824 protein-DNA complex subunit organization GO:0098727 maintenance of cell number GO:1901605 alpha-amino acid metabolic process GO:1901607 alpha-amino acid biosynthetic process
Molecular Function	GO:0004668 protein-arginine deiminase activity GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds GO:0016813 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines GO:0016990 arginine deiminase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization

Summary
Symbol	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PADI4 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	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
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 PADI4 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	logFC: -2.38; FDR: 0.04180	Resistant to T cell-mediated killing
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	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
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 PADI4 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.247	0.0945
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-2.85	0.0165
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.769	0.57
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.03	0.971
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.131	0.922
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.073	0.963
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.234	0.748
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	-0.199	0.834
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.18	0.481

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PADI4 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	7.4	5.5	1.9	0.66
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	5.1	2.3	0.647
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	5.9	8.4	0.613
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	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	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	7.4	0.5	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	15.4	-6.3	0.618
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PADI4. 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	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PADI4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PADI4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PADI4. 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	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PADI4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PADI4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PADI4
Name	peptidyl arginine deiminase, type IV
Aliases	PDI5; PDI4; PADI5; peptidyl arginine deiminase, type V; PAD4; HL-60 PAD; PADI-H protein; protein-arginine de ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PADI4 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PADI4.

ID	Name	Drug Type	Targets	#Targets
DB00155	L-Citrulline	Small Molecule	ASS1, DDAH1, DDAH2, NOS1, NOS2, NOS3, OTC, PADI1, PADI2, PADI3, PA ......	12
DB00207	Azithromycin	Small Molecule	PADI4	1
DB00254	Doxycycline	Small Molecule	B2M, PADI4	2
DB00759	Tetracycline	Small Molecule	PADI4	1
DB01082	Streptomycin	Small Molecule	PADI4	1
DB07449	N-[(1S)-1-(AMINOCARBONYL)-4-(ETHANIMIDOYLAMINO)BUTYL]BENZAMIDE	Small Molecule	PADI4	1

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