TISIDB

Summary
Symbol	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
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
Domain	PF00403 Heavy-metal-associated domain PF00080 Copper/zinc superoxide dismutase (SODC)
Function	Delivers copper to copper zinc superoxide dismutase (SOD1).

> Gene Ontology [ TOP ]
Biological Process	GO:0000041 transition metal ion transport GO:0000302 response to reactive oxygen species GO:0000303 response to superoxide GO:0000305 response to oxygen radical GO:0006801 superoxide metabolic process GO:0006825 copper ion transport GO:0006979 response to oxidative stress GO:0009636 response to toxic substance GO:0010035 response to inorganic substance GO:0015680 intracellular copper ion transport GO:0019430 removal of superoxide radicals GO:0034599 cellular response to oxidative stress GO:0034614 cellular response to reactive oxygen species GO:0051341 regulation of oxidoreductase activity GO:0051353 positive regulation of oxidoreductase activity GO:0071450 cellular response to oxygen radical GO:0071451 cellular response to superoxide GO:0072593 reactive oxygen species metabolic process GO:0098754 detoxification GO:0098869 cellular oxidant detoxification GO:1990748 cellular detoxification
Molecular Function	GO:0004784 superoxide dismutase activity GO:0005507 copper ion binding GO:0008047 enzyme activator activity GO:0015035 protein disulfide oxidoreductase activity GO:0015036 disulfide oxidoreductase activity GO:0016209 antioxidant activity GO:0016530 metallochaperone activity GO:0016531 copper chaperone activity GO:0016532 superoxide dismutase copper chaperone activity GO:0016667 oxidoreductase activity, acting on a sulfur group of donors GO:0016721 oxidoreductase activity, acting on superoxide radicals as acceptor GO:0045296 cadherin binding GO:0050839 cell adhesion molecule binding GO:0098631 protein binding involved in cell adhesion GO:0098632 protein binding involved in cell-cell adhesion GO:0098641 cadherin binding involved in cell-cell adhesion
Cellular Component	GO:0005913 cell-cell adherens junction

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-2262752: Cellular responses to stress R-HSA-3299685: Detoxification of Reactive Oxygen Species

Summary
Symbol	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CCS 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	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
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 CCS 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	logFC: -2.70; FDR: 0.03680	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	logFC: -1.99; FDR: 0.04220	Resistant to T cell-mediated killing
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	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
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 CCS 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	0.125	0.675
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.131	0.954
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.309	0.856
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.033	0.914
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.042	0.982
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.019	0.994
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.133	0.688
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.308	0.797
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.673	0.628
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.02	0.991
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	0.586	0.822
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.022	0.725

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CCS 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	0	0	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	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
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	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	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	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCS. 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	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCS. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCS. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCS. 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	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CCS expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CCS and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CCS
Name	copper chaperone for superoxide dismutase
Aliases	superoxide dismutase copper chaperone
Chromosomal Location	11q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CCS collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CCS.

ID	Name	Drug Type	Targets	#Targets
DB01593	Zinc	Small Molecule	A1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......	119

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