TISIDB

Summary
Symbol	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
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	Membrane; Single-pass type I membrane protein.
Domain	PF02189 Immunoreceptor tyrosine-based activation motif PF11628 T-cell surface glycoprotein CD3 zeta chain
Function	Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002431 Fc receptor mediated stimulatory signaling pathway GO:0002433 immune response-regulating cell surface receptor signaling pathway involved in phagocytosis GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002831 regulation of response to biotic stimulus GO:0006909 phagocytosis GO:0007159 leukocyte cell-cell adhesion GO:0009615 response to virus GO:0022407 regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0031294 lymphocyte costimulation GO:0031295 T cell costimulation GO:0038093 Fc receptor signaling pathway GO:0038094 Fc-gamma receptor signaling pathway GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0042110 T cell activation GO:0043900 regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0045785 positive regulation of cell adhesion GO:0050688 regulation of defense response to virus GO:0050690 regulation of defense response to virus by virus GO:0050792 regulation of viral process GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050870 positive regulation of T cell activation GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0051607 defense response to virus GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071593 lymphocyte aggregation GO:0098542 defense response to other organism GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion
Molecular Function	-
Cellular Component	GO:0042101 T cell receptor complex GO:0042105 alpha-beta T cell receptor complex GO:0043235 receptor complex GO:0098802 plasma membrane receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04650 Natural killer cell mediated cytotoxicity hsa04660 T cell receptor signaling pathway
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-388841: Costimulation by the CD28 family R-HSA-1643685: Disease R-HSA-202424: Downstream TCR signaling R-HSA-2029481: FCGR activation R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-202433: Generation of second messenger molecules R-HSA-162906: HIV Infection R-HSA-162909: Host Interactions of HIV factors R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-5663205: Infectious disease R-HSA-168249: Innate Immune System R-HSA-164944: Nef and signal transduction R-HSA-389948: PD-1 signaling R-HSA-202427: Phosphorylation of CD3 and TCR zeta chains R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation R-HSA-2029485: Role of phospholipids in phagocytosis R-HSA-202403: TCR signaling R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis R-HSA-202430: Translocation of ZAP-70 to Immunological synapse

> KEGG and Reactome Pathway

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KEGG

hsa04650 Natural killer cell mediated cytotoxicity
hsa04660 T cell receptor signaling pathway

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-388841: Costimulation by the CD28 family
R-HSA-1643685: Disease
R-HSA-202424: Downstream TCR signaling
R-HSA-2029481: FCGR activation
R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-202433: Generation of second messenger molecules
R-HSA-162906: HIV Infection
R-HSA-162909: Host Interactions of HIV factors
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-164944: Nef and signal transduction
R-HSA-389948: PD-1 signaling
R-HSA-202427: Phosphorylation of CD3 and TCR zeta chains
R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation
R-HSA-2029485: Role of phospholipids in phagocytosis
R-HSA-202403: TCR signaling
R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-202430: Translocation of ZAP-70 to Immunological synapse

Summary
Symbol	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD247 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 CD247 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27549124	Sarcoma; Neuroblastoma	Promote immunity (T cell function); essential for immunotherapy	T cells engineered to express a third-generation GD2-CAR incorporating the 14g2a-scFv with the CD28, OX40, and CD3ζ signaling domains (14g2a.CD28.OX40.ζ) mediated efficient and comparable lysis of both GD2+ sarcoma and neuroblastoma cell lines in vitro
25049283	neuroblastoma	Promote immunity (T cell function); essential for immunotherapy	We compared CAR.GD2 constructs that encoded the CD3ζ chain alone, with CD28, 4-1BB, or CD28 and 4-1BB costimulatory endodomains. CAR.GD2 expression rendered NKT cells highly cytotoxic against NB cells without affecting their CD1d-dependent reactivity. We observed a striking T helper 1-like polarization of NKT cells by 4-1BB-containing CARs. Importantly, expression of both CD28 and 4-1BB endodomains in the CAR.GD2 enhanced in vivo persistence of NKT cells. These CAR.GD2 NKT cells effectively localized to the tumor site had potent antitumor activity, and repeat injections significantly improved the long-term survival of mice with metastatic NB.
24986688	melanoma	Promote immunity	Compared with CARs containing the CD3ζ chain alone, or in tandem with the CD28 or the 4-1BB intracellular domains, ICOS signaling increased IL-17A, IL-17F, and IL-22 following antigen recognition.
25209187	colorectal carcinoma	Promote immunity	Our initial studies with patients with stage IV colorectal cancer show that before treatment the patients displayed an immunosuppressive status indicated by elevated MDSC levels and the downregulated CD247 expression, which is critical for T-cell and NK cell activities.

Summary
Symbol	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
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 CD247 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	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
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 CD247 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	0.027	0.958
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.137	0.908
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.053	0.955
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.301	0.58
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.841	0.451
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.376	0.792
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.779	0.194
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.01	0.307
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.536	0.614
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.516	0.246
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	0.65	0.755
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.125	0.544

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD247 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	2.7	1	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	3.7	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
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	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD247. 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	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD247. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD247. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD247. 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	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD247 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD247 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD247
Name	CD247 molecule
Aliases	CD3H; CD3Q; CD3Z; CD3z antigen, zeta polypeptide (TiT3 complex); CD247 antigen; CD3-ZETA; IMD25; T3Z; TCRZ; ......
Chromosomal Location	1q24.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD247 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CD247.

ID	Name	Drug Type	Targets	#Targets
DB00075	Muromonab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, CD247, CD3D, CD3E, CD3G, FCGR1A, FCGR2 ......	15

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