TISIDB

Summary
Symbol	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
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	Isoform 1: Cytoplasmic vesicle, secretory vesicle membrane Peripheral membrane protein Secreted Note=Associated with the secretory granule membrane through direct binding to lipid rafts in intragranular conditions. ; SUBCELLULAR LOCATION: Isoform 2: Nucleus
Domain	PF00246 Zinc carboxypeptidase
Function	Removes residual C-terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing. Processes proinsulin.

> Gene Ontology [ TOP ]
Biological Process	GO:0003007 heart morphogenesis GO:0003205 cardiac chamber development GO:0003206 cardiac chamber morphogenesis GO:0003208 cardiac ventricle morphogenesis GO:0003214 cardiac left ventricle morphogenesis GO:0003231 cardiac ventricle development GO:0007218 neuropeptide signaling pathway GO:0007507 heart development GO:0010817 regulation of hormone levels GO:0016055 Wnt signaling pathway GO:0016485 protein processing GO:0016486 peptide hormone processing GO:0030070 insulin processing GO:0042445 hormone metabolic process GO:0051604 protein maturation GO:0072657 protein localization to membrane GO:0198738 cell-cell signaling by wnt GO:1901142 insulin metabolic process
Molecular Function	GO:0004180 carboxypeptidase activity GO:0004181 metallocarboxypeptidase activity GO:0004185 serine-type carboxypeptidase activity GO:0008235 metalloexopeptidase activity GO:0008236 serine-type peptidase activity GO:0008237 metallopeptidase activity GO:0008238 exopeptidase activity GO:0017171 serine hydrolase activity GO:0042043 neurexin family protein binding GO:0050839 cell adhesion molecule binding GO:0070008 serine-type exopeptidase activity
Cellular Component	GO:0030133 transport vesicle GO:0030141 secretory granule GO:0030658 transport vesicle membrane GO:0030659 cytoplasmic vesicle membrane GO:0030667 secretory granule membrane GO:0043025 neuronal cell body GO:0044297 cell body GO:0097060 synaptic membrane GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-264876: Insulin processing R-HSA-392499: Metabolism of proteins R-HSA-2980736: Peptide hormone metabolism

Summary
Symbol	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CPE 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	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
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 CPE 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	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
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 CPE 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	-1.647	0.00206
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.363	0.208
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.124	0.434
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.019	0.97
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.196	0.918
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.197	0.929
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.109	0.852
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.042	0.978
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.24	0.889
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.809	0.702
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	1.788	0.581
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.3	0.0929

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CPE 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	0	2.7	-2.7	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	0	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
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	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
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	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	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	6.2	0	6.2	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	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CPE. 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	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CPE. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CPE. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CPE. 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	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CPE expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CPE and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CPE
Name	carboxypeptidase E
Aliases	carboxypeptidase H; enkephalin convertase; insulin granule-associated carboxypeptidase; cobalt-stimulated ch ......
Chromosomal Location	4q32.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CPE collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CPE.

ID	Name	Drug Type	Targets	#Targets
DB00030	Insulin Human	Biotech	CPE, CTSD, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV, PCSK1, PCSK2, RB1, ......	12
DB00071	Insulin Pork	Biotech	CPE, CTSD, HLA-DQA2, HLA-DQB1, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV ......	14

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