TISIDB

Summary
Symbol	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
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	Secreted, extracellular space, extracellular matrix
Domain	PF06468 Spondin_N PF00090 Thrombospondin type 1 domain
Function	Cell adhesion protein that promotes adhesion and outgrowth of hippocampal embryonic neurons. Binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of bacteria. Essential in the initiation of the innate immune response and represents a unique pattern-recognition molecule in the ECM for microbial pathogens (By similarity). Binds bacterial lipopolysaccharide (LPS).

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0002237 response to molecule of bacterial origin GO:0002367 cytokine production involved in immune response GO:0002440 production of molecular mediator of immune response GO:0002443 leukocyte mediated immunity GO:0002444 myeloid leukocyte mediated immunity GO:0002448 mast cell mediated immunity GO:0002697 regulation of immune effector process GO:0002699 positive regulation of immune effector process GO:0002700 regulation of production of molecular mediator of immune response GO:0002702 positive regulation of production of molecular mediator of immune response GO:0002718 regulation of cytokine production involved in immune response GO:0002720 positive regulation of cytokine production involved in immune response GO:0006909 phagocytosis GO:0006959 humoral immune response GO:0007409 axonogenesis GO:0007411 axon guidance GO:0008228 opsonization GO:0009615 response to virus GO:0009620 response to fungus GO:0010934 macrophage cytokine production GO:0010935 regulation of macrophage cytokine production GO:0019730 antimicrobial humoral response GO:0019731 antibacterial humoral response GO:0032496 response to lipopolysaccharide GO:0032635 interleukin-6 production GO:0032640 tumor necrosis factor production GO:0032675 regulation of interleukin-6 production GO:0032680 regulation of tumor necrosis factor production GO:0032755 positive regulation of interleukin-6 production GO:0032760 positive regulation of tumor necrosis factor production GO:0042742 defense response to bacterium GO:0043152 induction of bacterial agglutination GO:0048667 cell morphogenesis involved in neuron differentiation GO:0050832 defense response to fungus GO:0051607 defense response to virus GO:0060907 positive regulation of macrophage cytokine production GO:0061081 positive regulation of myeloid leukocyte cytokine production involved in immune response GO:0061082 myeloid leukocyte cytokine production GO:0061564 axon development 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 GO:0071706 tumor necrosis factor superfamily cytokine production GO:0097485 neuron projection guidance GO:0098542 defense response to other organism GO:1903555 regulation of tumor necrosis factor superfamily cytokine production GO:1903557 positive regulation of tumor necrosis factor superfamily cytokine production
Molecular Function	GO:0001530 lipopolysaccharide binding GO:0003823 antigen binding
Cellular Component	GO:0005578 proteinaceous extracellular matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5083635: Defective B3GALTL causes Peters-plus syndrome (PpS) R-HSA-1643685: Disease R-HSA-3906995: Diseases associated with O-glycosylation of proteins R-HSA-3781865: Diseases of glycosylation R-HSA-392499: Metabolism of proteins R-HSA-5173214: O-glycosylation of TSR domain-containing proteins R-HSA-5173105: O-linked glycosylation R-HSA-597592: Post-translational protein modification

Summary
Symbol	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SPON2 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 SPON2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29440144	Hepatocellular Carcinoma	Promote immunity (infiltration)	Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signalling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.

Summary
Symbol	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
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

[ TOP ]

Statistical results of SPON2 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	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
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

[ TOP ]

Points in the above scatter plot represent the expression difference of SPON2 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	-0.731	0.253
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.061	0.495
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.274	0.875
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.449	0.358
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.625	0.783
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.222	0.941
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.038	0.955
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.054	0.969
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.102	0.954
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.538	0.759
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	1.687	0.494
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.318	0.0736

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SPON2 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	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	22.2	-22.2	0.505
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	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	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SPON2. 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	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SPON2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SPON2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SPON2. 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	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SPON2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SPON2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SPON2
Name	spondin 2, extracellular matrix protein
Aliases	DIL1; Mindin; M-spondin; DIL-1; differentially expressed in cancerous and non-cancerous lung cells 1; Spondi ......
Chromosomal Location	4p16.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SPON2 collected from DrugBank database.

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

Browse SPON2