TISIDB

Summary
Symbol	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
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 Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Domain	PF09286 Pro-kumamolisin
Function	Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires substrates with an unsubstituted N-terminus (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001894 tissue homeostasis GO:0006986 response to unfolded protein GO:0007033 vacuole organization GO:0007040 lysosome organization GO:0030968 endoplasmic reticulum unfolded protein response GO:0034620 cellular response to unfolded protein GO:0034976 response to endoplasmic reticulum stress GO:0035966 response to topologically incorrect protein GO:0035967 cellular response to topologically incorrect protein GO:0036498 IRE1-mediated unfolded protein response GO:0043171 peptide catabolic process GO:0045453 bone resorption GO:0046849 bone remodeling GO:0048771 tissue remodeling GO:0048871 multicellular organismal homeostasis GO:0050885 neuromuscular process controlling balance GO:0050905 neuromuscular process GO:0060249 anatomical structure homeostasis GO:0080171 lytic vacuole organization GO:1901565 organonitrogen compound catabolic process
Molecular Function	GO:0004175 endopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0008236 serine-type peptidase activity GO:0008238 exopeptidase activity GO:0008240 tripeptidyl-peptidase activity GO:0017171 serine hydrolase activity GO:0033218 amide binding GO:0042277 peptide binding
Cellular Component	GO:0005775 vacuolar lumen GO:0042470 melanosome GO:0043202 lysosomal lumen GO:0048770 pigment granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04142 Lysosome
Reactome	R-HSA-381070: IRE1alpha activates chaperones R-HSA-392499: Metabolism of proteins R-HSA-381119: Unfolded Protein Response (UPR) R-HSA-381038: XBP1(S) activates chaperone genes

Summary
Symbol	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TPP1 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 TPP1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29217732	Lung Carcinoma	Promote immunity	Using a T-cell activation assay and mixed lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD-1/PD-L1. The growth rate of tumor masses in TPP-1 or PD-L1 antibody-treated mice was 56% or 71% lower than that in control peptide-treated mice, respectively, indicating that TPP-1 inhibits, or at least retards, tumor growth. IHC of the tumors showed that IFNγ and granzyme B expression increased in the TPP-1 or PD-L1 antibody-treated groups, indicating that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells may get reactivated.

Summary
Symbol	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
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 TPP1 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	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
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 TPP1 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	0.673	0.0865
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.402	0.668
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.137	0.955
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.287	0.34
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.095	0.967
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.772	0.794
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.048	0.926
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.094	0.968
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.247	0.927
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.236	0.583
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	1.738	0.607
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.073	0.387

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TPP1 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	3.7	1.4	2.3	0.469
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	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
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	0	9.1	-9.1	0.458
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	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TPP1. 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	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TPP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TPP1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TPP1. 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	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TPP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TPP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TPP1
Name	tripeptidyl peptidase I
Aliases	TPP I; CLN2; SCAR7; ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease); spinoce ......
Chromosomal Location	11p15.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TPP1 collected from DrugBank database.

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

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