TISIDB

Summary
Symbol	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
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	Secreted. Note=Colocalizes with GCP1 in secretory intracellular compartments.
Domain	PF00394 Multicopper oxidase PF07731 Multicopper oxidase PF07732 Multicopper oxidase
Function	Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000041 transition metal ion transport GO:0006825 copper ion transport GO:0006875 cellular metal ion homeostasis GO:0006879 cellular iron ion homeostasis GO:0046916 cellular transition metal ion homeostasis GO:0055072 iron ion homeostasis GO:0055076 transition metal ion homeostasis
Molecular Function	GO:0004322 ferroxidase activity GO:0005507 copper ion binding GO:0016722 oxidoreductase activity, oxidizing metal ions GO:0016724 oxidoreductase activity, oxidizing metal ions, oxygen as acceptor GO:0051087 chaperone binding
Cellular Component	GO:0005765 lysosomal membrane GO:0072562 blood microparticle GO:0098852 lytic vacuole membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00860 Porphyrin and chlorophyll metabolism
Reactome	R-HSA-917937: Iron uptake and transport R-HSA-425410: Metal ion SLC transporters R-HSA-425407: SLC-mediated transmembrane transport R-HSA-382551: Transmembrane transport of small molecules R-HSA-425366: Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds

Summary
Symbol	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CP 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	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
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 CP 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	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
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 CP 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	0.095	0.895
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.016	0.441
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.905	0.408
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.417	0.342
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.59	0.724
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.205	0.917
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.701	0.439
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.253	0.361
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.066	0.965
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-1.169	0.577
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	-1.281	0.676
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-1.096	0.00425

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CP 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	7.4	2.7	4.7	0.294
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	1.7	5.7	0.231
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	5.9	3.6	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	7.7	9.1	-1.4	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	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	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	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CP. 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	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CP. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CP. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CP. 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	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CP expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CP and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CP
Name	ceruloplasmin (ferroxidase)
Aliases	CP-2; Ferroxidase; Ceruloplasmin
Chromosomal Location	3q23-q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CP collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CP.

ID	Name	Drug Type	Targets	#Targets
DB00055	Drotrecogin alfa	Biotech	CP, F2, F5, F8, GGCX, PF4, PROCR, PROS1, SERPINA5, SERPINB6, SERPI ......	12
DB01373	Calcium	Small Molecule	ALPP, AOC1, ATP2C1, BMP4, CACNA1C, CAST, COMP, CP, MGP, PCDH19, PD ......	19
DB01592	Iron	Small Molecule	AHSP, CP, EGLN1, FEN1, FTH1, FXN, HBA1, HDAC8, NEIL1, NEIL2, POLB, ......	13
DB01593	Zinc	Small Molecule	A1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......	119

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