TISIDB

Summary
Symbol	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
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	Endoplasmic reticulum Endoplasmic reticulum lumen Melanosome Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:12643545).
Domain	PF00085 Thioredoxin
Function	-

> Gene Ontology [ TOP ]
Biological Process	GO:0002474 antigen processing and presentation of peptide antigen via MHC class I GO:0006457 protein folding GO:0006606 protein import into nucleus GO:0006621 protein retention in ER lumen GO:0006913 nucleocytoplasmic transport GO:0017038 protein import GO:0019882 antigen processing and presentation GO:0032507 maintenance of protein location in cell GO:0034504 protein localization to nucleus GO:0034975 protein folding in endoplasmic reticulum GO:0034976 response to endoplasmic reticulum stress GO:0035437 maintenance of protein localization in endoplasmic reticulum GO:0044744 protein targeting to nucleus GO:0045185 maintenance of protein location GO:0045454 cell redox homeostasis GO:0048002 antigen processing and presentation of peptide antigen GO:0051169 nuclear transport GO:0051170 nuclear import GO:0051220 cytoplasmic sequestering of protein GO:0051235 maintenance of location GO:0051651 maintenance of location in cell GO:0070972 protein localization to endoplasmic reticulum GO:0072595 maintenance of protein localization in organelle GO:0097191 extrinsic apoptotic signaling pathway GO:1902593 single-organism nuclear import GO:2001233 regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
Molecular Function	GO:0003756 protein disulfide isomerase activity GO:0004175 endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0004620 phospholipase activity GO:0004629 phospholipase C activity GO:0008081 phosphoric diester hydrolase activity GO:0008234 cysteine-type peptidase activity GO:0015036 disulfide oxidoreductase activity GO:0016298 lipase activity GO:0016667 oxidoreductase activity, acting on a sulfur group of donors GO:0016853 isomerase activity GO:0016860 intramolecular oxidoreductase activity GO:0016864 intramolecular oxidoreductase activity, transposing S-S bonds GO:0042578 phosphoric ester hydrolase activity
Cellular Component	GO:0005788 endoplasmic reticulum lumen GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction GO:0042470 melanosome GO:0043209 myelin sheath GO:0048770 pigment granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04141 Protein processing in endoplasmic reticulum hsa04612 Antigen processing and presentation
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983170: Antigen Presentation R-HSA-1236975: Antigen processing-Cross presentation R-HSA-446203: Asparagine N-linked glycosylation R-HSA-901042: Calnexin/calreticulin cycle R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-1236974: ER-Phagosome pathway R-HSA-168256: Immune System R-HSA-392499: Metabolism of proteins R-HSA-532668: N-glycan trimming in the ER and Calnexin/Calreticulin cycle R-HSA-597592: Post-translational protein modification

> KEGG and Reactome Pathway

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KEGG

hsa04141 Protein processing in endoplasmic reticulum
hsa04612 Antigen processing and presentation

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-983170: Antigen Presentation
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-446203: Asparagine N-linked glycosylation
R-HSA-901042: Calnexin/calreticulin cycle
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1236974: ER-Phagosome pathway
R-HSA-168256: Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-532668: N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-597592: Post-translational protein modification

Summary
Symbol	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PDIA3 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	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
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 PDIA3 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	STARS Score: 7.56; FDR: 0.000	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 4.96; FDR: 0.004	Resistant to T cell-mediated killing
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	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
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 PDIA3 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	0.12	0.66
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.116	0.972
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.116	0.964
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.146	0.704
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.029	0.991
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.365	0.913
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.016	0.979
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.015	0.995
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.003	0.999
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.653	0.812
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	1.058	0.802
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.158	0.0424

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PDIA3 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	3.7	4.1	-0.4	1
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	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	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	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PDIA3. 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	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PDIA3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PDIA3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PDIA3. 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	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PDIA3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PDIA3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PDIA3
Name	protein disulfide isomerase family A, member 3
Aliases	ERp61; ERp57; GRP57; HsT17083; GRP58; glucose regulated protein, 58kDa; protein disulfide isomerase-associat ......
Chromosomal Location	15q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PDIA3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PDIA3.

ID	Name	Drug Type	Targets	#Targets
DB01593	Zinc	Small Molecule	A1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......	119
DB09130	Copper	Small Molecule	A1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......	141

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