TISIDB

Summary
Symbol	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
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 Endosome Mitochondrion. Note=Undergoes endocytosis together with TLR4 upon LPS signaling (By similarity). Associated with mitochondria in response to virus.
Domain	PF02176 TRAF-type zinc finger
Function	Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.

> Gene Ontology [ TOP ]
Biological Process	GO:0001818 negative regulation of cytokine production GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002697 regulation of immune effector process GO:0002756 MyD88-independent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002831 regulation of response to biotic stimulus GO:0008063 Toll signaling pathway GO:0009615 response to virus GO:0031349 positive regulation of defense response GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032479 regulation of type I interferon production GO:0032480 negative regulation of type I interferon production GO:0032606 type I interferon production GO:0032608 interferon-beta production GO:0032648 regulation of interferon-beta production GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034612 response to tumor necrosis factor GO:0035666 TRIF-dependent toll-like receptor signaling pathway GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0043900 regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0050688 regulation of defense response to virus GO:0050792 regulation of viral process GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051607 defense response to virus GO:0071356 cellular response to tumor necrosis factor GO:0098542 defense response to other organism
Molecular Function	GO:0004842 ubiquitin-protein transferase activity GO:0005126 cytokine receptor binding GO:0005164 tumor necrosis factor receptor binding GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0019902 phosphatase binding GO:0019903 protein phosphatase binding GO:0031625 ubiquitin protein ligase binding GO:0031996 thioesterase binding GO:0032813 tumor necrosis factor receptor superfamily binding GO:0044389 ubiquitin-like protein ligase binding
Cellular Component	GO:0009898 cytoplasmic side of plasma membrane GO:0035631 CD40 receptor complex GO:0043235 receptor complex GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane GO:0098802 plasma membrane receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04064 NF-kappa B signaling pathway hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-like receptor signaling pathway hsa04622 RIG-I-like receptor signaling pathway hsa04668 TNF signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-936964: Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-5688426: Deubiquitination R-HSA-1643685: Disease R-HSA-5602358: Diseases associated with the TLR signaling cascade R-HSA-5260271: Diseases of Immune System R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-392499: Metabolism of proteins R-HSA-166166: MyD88-independent TLR3/TLR4 cascade R-HSA-936440: Negative regulators of RIG-I/MDA5 signaling R-HSA-5689896: Ovarian tumor domain proteases R-HSA-597592: Post-translational protein modification R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways R-HSA-5676594: TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway R-HSA-5668541: TNFR2 non-canonical NF-kB pathway R-HSA-5602571: TRAF3 deficiency - HSE R-HSA-918233: TRAF3-dependent IRF activation pathway R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168898: Toll-Like Receptors Cascades

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04064 NF-kappa B signaling pathway
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04668 TNF signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-936964: Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-5688426: Deubiquitination
R-HSA-1643685: Disease
R-HSA-5602358: Diseases associated with the TLR signaling cascade
R-HSA-5260271: Diseases of Immune System
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-936440: Negative regulators of RIG-I/MDA5 signaling
R-HSA-5689896: Ovarian tumor domain proteases
R-HSA-597592: Post-translational protein modification
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-5676594: TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-5668541: TNFR2 non-canonical NF-kB pathway
R-HSA-5602571: TRAF3 deficiency - HSE
R-HSA-918233: TRAF3-dependent IRF activation pathway
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168898: Toll-Like Receptors Cascades

Summary
Symbol	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TRAF3 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	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
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

[ TOP ]

Statistical results of TRAF3 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	logFC: -2.94; FDR: 0.00722	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	STARS Score: 5.79; FDR: 0.000	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 6.38; FDR: 0.000	Resistant to T cell-mediated killing
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	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
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

[ TOP ]

Points in the above scatter plot represent the expression difference of TRAF3 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	0.123	0.559
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.292	0.809
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.003	0.998
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.255	0.315
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.209	0.911
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.318	0.898
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.106	0.768
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.162	0.914
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.042	0.98
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.531	0.617
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	0.595	0.708
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.025	0.705

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of TRAF3 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	7.1	0	7.1	0.452
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	25	0	25	0.222
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	4.8	0	4.8	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	0	0	0	1
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	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	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TRAF3. 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	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TRAF3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TRAF3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TRAF3. 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	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TRAF3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TRAF3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TRAF3
Name	TNF receptor-associated factor 3
Aliases	CAP-1; CD40bp; CRAF1; IIAE5; CD40 associated protein 1; CD40 binding protein; CD40 receptor associated facto ......
Chromosomal Location	14q32.32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TRAF3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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