TISIDB

Summary
Symbol	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
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	Isoform 1: Cytoplasm. Golgi apparatus. Cell membrane. Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Note=Localized to the plasma membrane as a result of myristoylation. Phosphorylation on Ser-16 leads to its depletion from the membrane. Upon LPS stimulation colcoalizes with isoform 2 in late endosomes.; SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum. Early endosome membrane. Late endosome membrane. Note=Translocates to late endosomes upon LPS stimulation where it colcoalizes with isoform 1.
Domain	PF13676 TIR domain
Function	Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.; FUNCTION: Isoform 2: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0001959 regulation of cytokine-mediated signaling pathway GO:0001961 positive regulation of cytokine-mediated signaling pathway GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002237 response to molecule of bacterial origin GO:0002683 negative regulation of immune system 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:0007249 I-kappaB kinase/NF-kappaB signaling GO:0031349 positive regulation of defense response GO:0032496 response to lipopolysaccharide GO:0032602 chemokine production GO:0032609 interferon-gamma production GO:0032635 interleukin-6 production GO:0032642 regulation of chemokine production GO:0032649 regulation of interferon-gamma production GO:0032675 regulation of interleukin-6 production GO:0032722 positive regulation of chemokine production GO:0032729 positive regulation of interferon-gamma production GO:0032755 positive regulation of interleukin-6 production GO:0034121 regulation of toll-like receptor signaling pathway GO:0034122 negative regulation of toll-like receptor signaling pathway GO:0034123 positive regulation of toll-like receptor signaling pathway GO:0034127 regulation of MyD88-independent toll-like receptor signaling pathway GO:0034128 negative regulation of MyD88-independent toll-like receptor signaling pathway GO:0034142 toll-like receptor 4 signaling pathway GO:0034143 regulation of toll-like receptor 4 signaling pathway GO:0034145 positive regulation of toll-like receptor 4 signaling pathway GO:0035655 interleukin-18-mediated signaling pathway GO:0035666 TRIF-dependent toll-like receptor signaling pathway GO:0035668 TRAM-dependent toll-like receptor signaling pathway GO:0035669 TRAM-dependent toll-like receptor 4 signaling pathway GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0060759 regulation of response to cytokine stimulus GO:0060760 positive regulation of response to cytokine stimulus GO:0070265 necrotic cell death GO:0070266 necroptotic process GO:0070671 response to interleukin-12 GO:0070673 response to interleukin-18 GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071351 cellular response to interleukin-18 GO:0071396 cellular response to lipid GO:0071609 chemokine (C-C motif) ligand 5 production GO:0071649 regulation of chemokine (C-C motif) ligand 5 production GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production GO:0097300 programmed necrotic cell death GO:2000492 regulation of interleukin-18-mediated signaling pathway GO:2000494 positive regulation of interleukin-18-mediated signaling pathway
Molecular Function	GO:0005543 phospholipid binding
Cellular Component	GO:0005769 early endosome GO:0005770 late endosome GO:0010008 endosome membrane GO:0031901 early endosome membrane GO:0031902 late endosome membrane GO:0044440 endosomal part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04064 NF-kappa B signaling pathway hsa04620 Toll-like receptor signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-936964: Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon R-HSA-109581: Apoptosis R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway R-HSA-937041: IKK complex recruitment mediated by RIP1 R-HSA-975163: IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-140534: Ligand-dependent caspase activation R-HSA-975155: MyD88 dependent cascade initiated on endosome R-HSA-166166: MyD88-independent TLR3/TLR4 cascade R-HSA-6798695: Neutrophil degranulation R-HSA-5357801: Programmed Cell Death R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-937072: TRAF6 mediated induction of TAK1 complex R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling R-HSA-2562578: TRIF-mediated programmed cell death R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-168138: Toll Like Receptor 9 (TLR9) 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

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-936964: Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-109581: Apoptosis
R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-937041: IKK complex recruitment mediated by RIP1
R-HSA-975163: IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-140534: Ligand-dependent caspase activation
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-6798695: Neutrophil degranulation
R-HSA-5357801: Programmed Cell Death
R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines
R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-937072: TRAF6 mediated induction of TAK1 complex
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-2562578: TRIF-mediated programmed cell death
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168898: Toll-Like Receptors Cascades

Summary
Symbol	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TICAM2 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 TICAM2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
22065720	Melanoma	Inhibit immunity (T cell function)	In tumors arising in the autochthonous TiRP transgenic model of melanoma associated with systemic chronic inflammation, endogenous CD8(+) TCs were nonfunctional.

Summary
Symbol	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
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 TICAM2 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	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
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 TICAM2 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	-0.503	0.199
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.84	0.326
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.248	0.684
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.989	0.204
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-2.148	0.0666
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.474	0.733
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.361	0.679
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	0.782	0.527
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.165	0.363

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of TICAM2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% 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	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	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	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	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	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TICAM2. 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	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TICAM2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TICAM2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TICAM2. 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	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TICAM2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TICAM2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TICAM2
Name	toll-like receptor adaptor molecule 2
Aliases	TICAM-2; TIRP; MyD88-4; TIRAP3; NF-kappa-B-activating protein 502; TRIF-related adaptor molecule; cytoplasmi ......
Chromosomal Location	5q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TICAM2 collected from DrugBank database.

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

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