TISIDB

Summary
Symbol	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
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	Cell membrane Single-pass type I membrane protein.
Domain	PF16680 T-cell surface glycoprotein CD3 delta chain PF02189 Immunoreceptor tyrosine-based activation motif
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). In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface (PubMed:8187769). Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G.

> 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:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006909 phagocytosis GO:0007159 leukocyte cell-cell adhesion GO:0007163 establishment or maintenance of cell polarity 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:0045785 positive regulation of cell adhesion 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:0070227 lymphocyte apoptotic process GO:0070228 regulation of lymphocyte apoptotic process GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071593 lymphocyte aggregation GO:0071887 leukocyte apoptotic process GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion GO:2000106 regulation of leukocyte apoptotic process
Molecular Function	GO:0030159 receptor signaling complex scaffold activity GO:0032947 protein complex scaffold GO:0042608 T cell receptor binding GO:0046982 protein heterodimerization activity
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	hsa04640 Hematopoietic cell lineage hsa04660 T cell receptor signaling pathway
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828: Clathrin-mediated endocytosis R-HSA-388841: Costimulation by the CD28 family 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-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-168249: Innate Immune System R-HSA-199991: Membrane Trafficking 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-202430: Translocation of ZAP-70 to Immunological synapse R-HSA-5653656: Vesicle-mediated transport

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04640 Hematopoietic cell lineage
hsa04660 T cell receptor signaling pathway

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828: Clathrin-mediated endocytosis
R-HSA-388841: Costimulation by the CD28 family
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-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-168249: Innate Immune System
R-HSA-199991: Membrane Trafficking
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-202430: Translocation of ZAP-70 to Immunological synapse
R-HSA-5653656: Vesicle-mediated transport

Summary
Symbol	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD3G 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 CD3G and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
16397041	Lung carcinoma; Pancreatic carcinoma; Prostate carcinoma; Malignant Brain Neoplasm; Melanoma	Promote immunity (T cell function); essential for immunotherapy	Anti-CD3 x anti-epidermal growth factor receptor (EGFR) bispecific antibody redirects T-cell cytolytic activity to EGFR-positive cancers in vitro and in an animal model. Specific cytolytic activity of ATC armed with anti-CD3 x anti-EGFR (EGFRBi) against EGFR-expressing cancer cells derived from lung, pancreas, colon, prostate, brain, skin, or EGFR-negative breast cancer cells was evaluated in (51)Cr release assays.
21232138	Breast Carcinoma	Promote immunity (T cell function)	This finding was correlated with an increased ability of tumor-draining lymph node cells and splenocytes from α-TEA-treated mice to secrete interferon (IFN)-γ in response to CD3 or to mediate a cytolytic response in a tumor-specific fashion, respectively.

Summary
Symbol	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
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 CD3G 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	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
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 CD3G 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	0.122	0.802
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.471	0.596
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.134	0.858
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.108	0.796
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.05	0.961
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.311	0.785
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.992	0.165
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.85	0.0747
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.06	0.957
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	2.192	0.0381
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	1.699	0.292
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.098	0.654

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD3G 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	1.4	-1.4	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	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
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	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	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD3G. 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	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD3G. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD3G. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD3G. 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	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD3G expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD3G and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD3G
Name	CD3g molecule, gamma (CD3-TCR complex)
Aliases	CD3g antigen, gamma polypeptide (TiT3 complex); CD3-GAMMA; IMD17; T3G; CD3g molecule, epsilon (CD3-TCR compl ......
Chromosomal Location	11q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD3G collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CD3G.

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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