TISIDB

Summary
Symbol	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
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	Nucleus envelope. Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side.
Domain	PF01023 S-100/ICaBP type calcium binding domain
Function	May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes such as the reorganization of the actin cytoskeleton and in cell motility. Binds 2 calcium ions. Calcium binding is cooperative.

> Gene Ontology [ TOP ]
Biological Process	GO:0007409 axonogenesis GO:0048144 fibroblast proliferation GO:0048145 regulation of fibroblast proliferation GO:0048146 positive regulation of fibroblast proliferation GO:0048667 cell morphogenesis involved in neuron differentiation GO:0061564 axon development
Molecular Function	GO:0005523 tropomyosin binding GO:0044548 S100 protein binding GO:0048306 calcium-dependent protein binding
Cellular Component	GO:0001726 ruffle GO:0005635 nuclear envelope GO:0009898 cytoplasmic side of plasma membrane GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0031234 extrinsic component of cytoplasmic side of plasma membrane GO:0031252 cell leading edge GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between S100A6 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 S100A6 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28646023	Acute Lymphoblastic Leukemia	Inhibit immunity; Resistant to immunotherapy	Amlexanox Downregulates S100A6 to SensitizeKMT2A/AFF1-Positive Acute Lymphoblastic Leukemia to TNFα Treatment. In KMT2A/AFF1-positive transgenic (Tg) mice, amlexanox enhanced tumor immunity and lowered the penetrance of leukemia development. Similarly, in a NOD/SCID mouse model of humanKMT2A/AFF1-positive ALL, amlexanox broadened GVL responses and extended survival.

Summary
Symbol	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
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 S100A6 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	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
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 S100A6 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	-1.447	0.0481
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.729	0.733
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.212	0.711
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1.057	0.166
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1.064	0.695
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.053	0.767
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.085	0.902
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.708	0.763
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.496	0.856
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.92	0.776
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	1.269	0.799
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.046	0.784

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of S100A6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% 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	1.4	-1.4	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	1.7	-1.7	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	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	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	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of S100A6. 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	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of S100A6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by S100A6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of S100A6. 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	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of S100A6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between S100A6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	S100A6
Name	S100 calcium binding protein A6
Aliases	2A9; PRA; CACY; S100 calcium-binding protein A6 (calcyclin); S100 calcium binding protein A6 (calcyclin); 5B ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting S100A6 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting S100A6.

ID	Name	Drug Type	Targets	#Targets
DB11093	Calcium Citrate	Small Molecule	CADPS, CADPS2, CALB2, CALR, CALR3, CANX, CAPS, CASQ1, CASQ2, CASR, ......	29
DB11348	Calcium Phosphate	Small Molecule	CADPS, CADPS2, CALB2, CALR, CALR3, CANX, CAPS, CASQ1, CASQ2, CASR, ......	29

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