TISIDB

Summary
Symbol	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
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 Nucleus speckle Note=Colocalizes with MITF in the nucleus. Colocalizes with GFI1 in nuclear dots. Colocalizes with SUMO1 in nuclear granules.
Domain	PF14324 PINIT domain PF02891 MIZ/SP-RING zinc finger
Function	Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (PubMed:21965678, PubMed:9388184). Sumoylates CCAR2 which promotes its interaction with SIRT1 (PubMed:25406032). Diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus (PubMed:24651376).

> Gene Ontology [ TOP ]
Biological Process	GO:0016925 protein sumoylation GO:0018205 peptidyl-lysine modification GO:0033233 regulation of protein sumoylation GO:0033234 negative regulation of protein sumoylation GO:0033235 positive regulation of protein sumoylation GO:0042391 regulation of membrane potential GO:0045838 positive regulation of membrane potential GO:1903320 regulation of protein modification by small protein conjugation or removal GO:1903321 negative regulation of protein modification by small protein conjugation or removal GO:1903322 positive regulation of protein modification by small protein conjugation or removal
Molecular Function	GO:0008022 protein C-terminus binding GO:0015459 potassium channel regulator activity GO:0016247 channel regulator activity GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0019789 SUMO transferase activity GO:0047485 protein N-terminus binding
Cellular Component	GO:0016604 nuclear body GO:0016607 nuclear speck GO:0030425 dendrite

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04120 Ubiquitin mediated proteolysis hsa04630 Jak-STAT signaling pathway
Reactome	R-HSA-73894: DNA Repair R-HSA-5696395: Formation of Incision Complex in GG-NER R-HSA-5696399: Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-392499: Metabolism of proteins R-HSA-5696398: Nucleotide Excision Repair R-HSA-597592: Post-translational protein modification R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins R-HSA-2990846: SUMOylation R-HSA-4615885: SUMOylation of DNA replication proteins R-HSA-3232118: SUMOylation of transcription factors

> KEGG and Reactome Pathway

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KEGG

hsa04120 Ubiquitin mediated proteolysis
hsa04630 Jak-STAT signaling pathway

Reactome

R-HSA-73894: DNA Repair
R-HSA-5696395: Formation of Incision Complex in GG-NER
R-HSA-5696399: Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-392499: Metabolism of proteins
R-HSA-5696398: Nucleotide Excision Repair
R-HSA-597592: Post-translational protein modification
R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins
R-HSA-2990846: SUMOylation
R-HSA-4615885: SUMOylation of DNA replication proteins
R-HSA-3232118: SUMOylation of transcription factors

Summary
Symbol	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PIAS3 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

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Literatures describing the relation between PIAS3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18676737	Glioblastoma	Promote immunity	Inhibition of PIAS3 resulted in enhanced glioblastoma cellular proliferation. Conversely, PIAS3 overexpression inhibited STAT-3 transcriptional activity, expression of STAT-3-regulated genes, and cell proliferation. We propose that the loss of PIAS3 in GBM contributes to enhanced STAT-3 transcriptional activity and subsequent cell proliferation.

Summary
Symbol	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
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 PIAS3 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	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
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 PIAS3 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	-0.38	0.0817
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.481	0.793
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.302	0.814
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.335	0.294
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.576	0.792
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.036	0.99
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.254	0.479
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.093	0.949
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.688	0.655
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.005	0.501
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	2.095	0.303
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.024	0.773

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PIAS3 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% 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	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	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	0	0	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	3.7	-3.7	0.415
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	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
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	0	0	1

Summary
Symbol	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PIAS3. 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	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PIAS3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PIAS3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PIAS3. 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	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PIAS3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PIAS3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PIAS3
Name	protein inhibitor of activated STAT, 3
Aliases	FLJ14651; ZMIZ5; zinc finger, MIZ-type containing 5; protein inhibitor of activated STAT protein 3; E3 SUMO- ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PIAS3 collected from DrugBank database.

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

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