TISIDB

Summary
Symbol	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
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	Lysosome Melanosome. Secreted, extracellular space Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Domain	PF00112 Papain family cysteine protease PF08127 Peptidase family C1 propeptide
Function	Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.

> Gene Ontology [ TOP ]
Biological Process	GO:0001890 placenta development GO:0001893 maternal placenta development GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0007565 female pregnancy GO:0019058 viral life cycle GO:0030260 entry into host cell GO:0030574 collagen catabolic process GO:0031349 positive regulation of defense response GO:0032963 collagen metabolic process GO:0044236 multicellular organism metabolic process GO:0044243 multicellular organism catabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0044409 entry into host GO:0044706 multi-multicellular organism process GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0046697 decidualization GO:0046718 viral entry into host cell GO:0048608 reproductive structure development 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:0060135 maternal process involved in female pregnancy GO:0061458 reproductive system development GO:0097066 response to thyroid hormone GO:0097067 cellular response to thyroid hormone stimulus
Molecular Function	GO:0001948 glycoprotein binding GO:0004175 endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0005518 collagen binding GO:0008234 cysteine-type peptidase activity GO:0008236 serine-type peptidase activity GO:0017171 serine hydrolase activity GO:0043394 proteoglycan binding
Cellular Component	GO:0005775 vacuolar lumen GO:0031904 endosome lumen GO:0036019 endolysosome GO:0036021 endolysosome lumen GO:0042470 melanosome GO:0043202 lysosomal lumen GO:0044440 endosomal part GO:0048770 pigment granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04140 Regulation of autophagy hsa04142 Lysosome hsa04210 Apoptosis hsa04612 Antigen processing and presentation hsa04621 NOD-like receptor signaling pathway
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-2022090: Assembly of collagen fibrils and other multimeric structures R-HSA-1442490: Collagen degradation R-HSA-1474290: Collagen formation R-HSA-1474228: Degradation of the extracellular matrix R-HSA-1474244: Extracellular matrix organization R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-2132295: MHC class II antigen presentation R-HSA-6798695: Neutrophil degranulation R-HSA-168898: Toll-Like Receptors Cascades R-HSA-1679131: Trafficking and processing of endosomal TLR

> KEGG and Reactome Pathway

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KEGG

hsa04140 Regulation of autophagy
hsa04142 Lysosome
hsa04210 Apoptosis
hsa04612 Antigen processing and presentation
hsa04621 NOD-like receptor signaling pathway

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-2022090: Assembly of collagen fibrils and other multimeric structures
R-HSA-1442490: Collagen degradation
R-HSA-1474290: Collagen formation
R-HSA-1474228: Degradation of the extracellular matrix
R-HSA-1474244: Extracellular matrix organization
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-2132295: MHC class II antigen presentation
R-HSA-6798695: Neutrophil degranulation
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-1679131: Trafficking and processing of endosomal TLR

Summary
Symbol	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CTSB 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 CTSB and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
15894359	Cervical Carcinoma	Inhibit immunity	Immunosuppressive activity of proteases in cervical carcinoma. We found that purified enzymes such as trypsin, cathepsin B, uPA and type IV collagenase suppressed the proliferative response in a dose-dependent fashion.

Summary
Symbol	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
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 CTSB 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	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
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 CTSB 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	-0.327	0.387
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.101	0.982
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.473	0.872
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.121	0.831
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.57	0.835
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.999	0.782
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.154	0.839
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.358	0.906
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.012	0.997
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.224	0.939
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	0.73	0.874
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.07	0.585

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CTSB 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	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	16.7	-16.7	0.429
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	6.2	-6.2	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	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
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	0	0	1
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	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CTSB. 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	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CTSB. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CTSB. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CTSB. 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	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CTSB expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CTSB and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CTSB
Name	cathepsin B
Aliases	APPS; APP secretase; amyloid precursor protein secretase; cathepsin B1; cysteine protease
Chromosomal Location	8p23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CTSB collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CTSB.

ID	Name	Drug Type	Targets	#Targets
DB02108	2-Aminoethanimidic Acid	Small Molecule	CTSB	1
DB02148	3-Amino-4-Oxybenzyl-2-Butanone	Small Molecule	CTSB	1
DB02685	3-Methylphenylalanine	Small Molecule	CTSB	1
DB02855	N-(3-Propylcarbamoyloxirane-2-Carbonyl)-Isoleucyl-Proline	Small Molecule	CTSB	1
DB03329	2-Pyridinethiol	Small Molecule	CTSB	1
DB03588	Diphenylacetic Acid	Small Molecule	CTSB	1
DB04126	N-[1-Hydroxycarboxyethyl-Carbonyl]Leucylamino-2-Methyl-Butane	Small Molecule	CTSB, CTSH	2
DB04579	N-{[(2S,3S)-3-(ETHOXYCARBONYL)OXIRAN-2-YL]CARBONYL}-	Small Molecule	CTSB	1
DB07160	N-{[(2S,3S)-3-(ETHOXYCARBONYL)OXIRAN-2-YL]CARBONYL}-L-ISOLEUCINE	Small Molecule	CTSB	1
DB07219	BENZYL N-({(2S,3S)-3-[(PROPYLAMINO)CARBONYL]OXIRAN-2-YL}CARBONYL)-L-ISOLEUCYL-L-PROLINATE	Small Molecule	CTSB	1
DB07223	METHYL N-({(2S,3S)-3-[(PROPYLAMINO)CARBONYL]OXIRAN-2-YL}CARBONYL)-L-ISOLEUCYL-L-PROLINATE	Small Molecule	CTSB	1
DB07224	N-{[(2S,3S)-3-(ETHOXYCARBONYL)OXIRAN-2-YL]CARBONYL}-L-ISOLEUCYL-L-ALANINE	Small Molecule	CTSB	1
DB07225	N-{[(2S,3S)-3-(ETHOXYCARBONYL)OXIRAN-2-YL]CARBONYL}-L-ISOLEUCYL-L-ISOLEUCINE	Small Molecule	CTSB	1
DB07231	N-({(2S,3S)-3-[(BENZYLAMINO)CARBONYL]OXIRAN-2-YL}CARBONYL)-L-ISOLEUCYL-L-PROLINE	Small Molecule	CTSB	1

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