TISIDB

Summary
Symbol	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
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 Note=Seems to also be secreted in plasma by cancerous cells but at a low level.
Domain	PF00079 Serpin (serine protease inhibitor)
Function	May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of c-Jun NH(2)-terminal kinase (JNK1).

> Gene Ontology [ TOP ]
Biological Process	GO:0001837 epithelial to mesenchymal transition GO:0001933 negative regulation of protein phosphorylation GO:0006469 negative regulation of protein kinase activity GO:0007254 JNK cascade GO:0010466 negative regulation of peptidase activity GO:0010717 regulation of epithelial to mesenchymal transition GO:0010718 positive regulation of epithelial to mesenchymal transition GO:0010950 positive regulation of endopeptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0010952 positive regulation of peptidase activity GO:0019058 viral life cycle GO:0030260 entry into host cell GO:0030335 positive regulation of cell migration GO:0031098 stress-activated protein kinase signaling cascade GO:0032872 regulation of stress-activated MAPK cascade GO:0032873 negative regulation of stress-activated MAPK cascade GO:0033673 negative regulation of kinase activity GO:0035425 autocrine signaling GO:0038001 paracrine signaling GO:0040017 positive regulation of locomotion GO:0042326 negative regulation of phosphorylation GO:0043405 regulation of MAP kinase activity GO:0043407 negative regulation of MAP kinase activity GO:0043409 negative regulation of MAPK cascade GO:0043506 regulation of JUN kinase activity GO:0043508 negative regulation of JUN kinase activity GO:0044409 entry into host GO:0045861 negative regulation of proteolysis GO:0045862 positive regulation of proteolysis GO:0046328 regulation of JNK cascade GO:0046329 negative regulation of JNK cascade GO:0046718 viral entry into host cell GO:0048762 mesenchymal cell differentiation GO:0051272 positive regulation of cellular component movement GO:0051346 negative regulation of hydrolase activity GO:0051348 negative regulation of transferase activity GO:0051403 stress-activated MAPK cascade GO:0051701 interaction with host GO:0051806 entry into cell of other organism involved in symbiotic interaction GO:0051828 entry into other organism involved in symbiotic interaction GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0060485 mesenchyme development GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070303 negative regulation of stress-activated protein kinase signaling cascade GO:0071900 regulation of protein serine/threonine kinase activity GO:0071901 negative regulation of protein serine/threonine kinase activity GO:1902532 negative regulation of intracellular signal transduction GO:2000147 positive regulation of cell motility
Molecular Function	GO:0001618 virus receptor activity GO:0002020 protease binding GO:0004857 enzyme inhibitor activity GO:0004866 endopeptidase inhibitor activity GO:0004867 serine-type endopeptidase inhibitor activity GO:0004869 cysteine-type endopeptidase inhibitor activity GO:0030414 peptidase inhibitor activity GO:0061134 peptidase regulator activity GO:0061135 endopeptidase regulator activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation

Summary
Symbol	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SERPINB3 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 SERPINB3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27668655	Melanoma	Promote immunity (T cell function); essential for immunotherapy	Here we show that somatic mutations in SERPINB3 and SERPINB4 are associated with survival after anti-CTLA4 immunotherapy in two independent cohorts of patients with melanoma. Interestingly, serpins are homologs of the well-known ovalbumin antigen and are associated with autoimmunity.

Summary
Symbol	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
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 SERPINB3 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	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
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 SERPINB3 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	0.862	0.333
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.111	0.937
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.592	0.192
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.845	0.392
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.863	0.561
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.82	0.635
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.98	0.311
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.92	0.625
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.146	0.56
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.561	0.47
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	-0.561	0.594
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.757	0.213

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SERPINB3 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	25.9	5.5	20.4	0.00789
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	25.9	6.8	19.1	0.0313
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
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	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	10.5	3.7	6.8	0.393
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	7.7	1.4	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	12.5	0	12.5	0.485
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	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SERPINB3. 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	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SERPINB3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SERPINB3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SERPINB3. 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	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SERPINB3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SERPINB3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SERPINB3
Name	serpin peptidase inhibitor, clade B (ovalbumin), member 3
Aliases	T4-A; HsT1196; SCC; serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3; SCCA-1; SCCA-P ......
Chromosomal Location	18q21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SERPINB3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting SERPINB3.

ID	Name	Drug Type	Targets	#Targets
DB03929	D-Serine	Small Molecule	GLRA1, GRIN1, SERPINB3	3
DB04522	Dexfosfoserine	Small Molecule	CFTR, KCNC4, PDPK1, PIM1, PRKACA, PRKCQ, PYGL, PYGM, REG1A, RHO, S ......	13

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