TISIDB

Summary
Symbol	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
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 III membrane protein
Domain	PF01582 TIR domain
Function	Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP.

> Gene Ontology [ TOP ]
Biological Process	GO:0001818 negative regulation of cytokine production GO:0001959 regulation of cytokine-mediated signaling pathway GO:0001960 negative regulation of cytokine-mediated signaling pathway GO:0002237 response to molecule of bacterial origin GO:0002526 acute inflammatory response GO:0002831 regulation of response to biotic stimulus GO:0002832 negative regulation of response to biotic stimulus GO:0006953 acute-phase response GO:0031663 lipopolysaccharide-mediated signaling pathway GO:0031664 regulation of lipopolysaccharide-mediated signaling pathway GO:0031665 negative regulation of lipopolysaccharide-mediated signaling pathway GO:0032102 negative regulation of response to external stimulus GO:0032496 response to lipopolysaccharide GO:0032602 chemokine production GO:0032642 regulation of chemokine production GO:0032682 negative regulation of chemokine production GO:0042033 chemokine biosynthetic process GO:0042035 regulation of cytokine biosynthetic process GO:0042036 negative regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0043900 regulation of multi-organism process GO:0043901 negative regulation of multi-organism process GO:0045073 regulation of chemokine biosynthetic process GO:0045079 negative regulation of chemokine biosynthetic process GO:0050755 chemokine metabolic process GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0060759 regulation of response to cytokine stimulus GO:0060761 negative regulation of response to cytokine stimulus GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071396 cellular response to lipid
Molecular Function	-
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-166058: MyD88 R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179: Toll Like Receptor TLR1 R-HSA-168188: Toll Like Receptor TLR6 R-HSA-168898: Toll-Like Receptors Cascades

Summary
Symbol	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SIGIRR 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 ]

Literatures describing the relation between SIGIRR and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21652674	Chronic Lymphocytic Leukemia	Promote immunity	Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened.

Summary
Symbol	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
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 SIGIRR 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	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
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 SIGIRR 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	0.001	0.999
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.055	0.98
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.047	0.975
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.664	0.134
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.547	0.79
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.812	0.755
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.063	0.873
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.037	0.974
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.011	0.994
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.285	0.868
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	0.309	0.906
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.035	0.763

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SIGIRR 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	0	0	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	0	0	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	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	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	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SIGIRR. 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	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SIGIRR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SIGIRR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SIGIRR. 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	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SIGIRR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SIGIRR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SIGIRR
Name	single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
Aliases	TIR8; single immunoglobulin domain IL1R1 related; single Ig IL-1R-related molecule; single immunoglobulin do ......
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SIGIRR collected from DrugBank database.

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

Browse SIGIRR