TISIDB

Summary
Symbol	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
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	Cell membrane; Single-pass type I membrane protein Endoplasmic reticulum membrane; Single-pass type I membrane protein Cytoplasm, cytoskeleton Sarcoplasmic reticulum Note=Translocates from the endoplasmic reticulum to the cell membrane in response to a depletion of intracellular calcium and is detected at punctae corresponding to junctions between the endoplasmic reticulum and the cell membrane (PubMed:19249086, PubMed:16005298, PubMed:16208375, PubMed:18854159). Associated with the microtubule network at the growing distal tip of microtubules (PubMed:19632184). Colocalizes with ORAI1 at the cell membrane (PubMed:27185316). Colocalizes preferentially with CASQ1 at endoplasmic reticulum in response to a depletion of intracellular calcium (PubMed:27185316).
Domain	PF07647 SAM domain (Sterile alpha motif) PF16533 STIM1 Orai1-activating region
Function	Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores (PubMed:15866891, PubMed:16005298, PubMed:16208375, PubMed:16537481, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:18854159, PubMed:19249086, PubMed:22464749, PubMed:24069340, PubMed:24351972, PubMed:24591628, PubMed:26322679, PubMed:25326555, PubMed:28219928). Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit ORAI1 (PubMed:16208375, PubMed:16537481). Involved in enamel formation (PubMed:24621671). Activated following interaction with STIMATE, leading to promote STIM1 conformational switch (PubMed:26322679).

> Gene Ontology [ TOP ]
Biological Process	GO:0002115 store-operated calcium entry GO:0003013 circulatory system process GO:0003015 heart process GO:0005513 detection of calcium ion GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0008015 blood circulation GO:0008016 regulation of heart contraction GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010959 regulation of metal ion transport GO:0022898 regulation of transmembrane transporter activity GO:0031214 biomineral tissue development GO:0032237 activation of store-operated calcium channel activity GO:0032409 regulation of transporter activity GO:0032411 positive regulation of transporter activity GO:0032412 regulation of ion transmembrane transporter activity GO:0032414 positive regulation of ion transmembrane transporter activity GO:0034505 tooth mineralization GO:0034762 regulation of transmembrane transport GO:0034764 positive regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0034767 positive regulation of ion transmembrane transport GO:0035637 multicellular organismal signaling GO:0042475 odontogenesis of dentin-containing tooth GO:0042476 odontogenesis GO:0043270 positive regulation of ion transport GO:0044057 regulation of system process GO:0051592 response to calcium ion GO:0051924 regulation of calcium ion transport GO:0051928 positive regulation of calcium ion transport GO:0055074 calcium ion homeostasis GO:0060047 heart contraction GO:0061337 cardiac conduction GO:0070166 enamel mineralization GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:0097186 amelogenesis GO:1901019 regulation of calcium ion transmembrane transporter activity GO:1901021 positive regulation of calcium ion transmembrane transporter activity GO:1901339 regulation of store-operated calcium channel activity GO:1901341 positive regulation of store-operated calcium channel activity GO:1903169 regulation of calcium ion transmembrane transport GO:1903522 regulation of blood circulation GO:1903779 regulation of cardiac conduction GO:1904062 regulation of cation transmembrane transport GO:1904064 positive regulation of cation transmembrane transport GO:1904427 positive regulation of calcium ion transmembrane transport GO:2001257 regulation of cation channel activity GO:2001259 positive regulation of cation channel activity
Molecular Function	GO:0002020 protease binding GO:0005246 calcium channel regulator activity GO:0008017 microtubule binding GO:0015631 tubulin binding GO:0016247 channel regulator activity GO:0051010 microtubule plus-end binding
Cellular Component	GO:0005874 microtubule GO:0005938 cell cortex GO:0016528 sarcoplasm GO:0016529 sarcoplasmic reticulum GO:0030176 integral component of endoplasmic reticulum membrane GO:0031227 intrinsic component of endoplasmic reticulum membrane GO:0031984 organelle subcompartment GO:0032541 cortical endoplasmic reticulum GO:0033017 sarcoplasmic reticulum membrane GO:0044448 cell cortex part GO:0071782 endoplasmic reticulum tubular network GO:0098827 endoplasmic reticulum subcompartment GO:0099568 cytoplasmic region

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04020 Calcium signaling pathway hsa04611 Platelet activation
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983695: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers R-HSA-5576891: Cardiac conduction R-HSA-139853: Elevation of cytosolic Ca2+ levels R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-5578775: Ion homeostasis R-HSA-397014: Muscle contraction R-HSA-418360: Platelet calcium homeostasis R-HSA-418346: Platelet homeostasis R-HSA-983705: Signaling by the B Cell Receptor (BCR)

> KEGG and Reactome Pathway

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KEGG

hsa04020 Calcium signaling pathway
hsa04611 Platelet activation

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-983695: Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-5576891: Cardiac conduction
R-HSA-139853: Elevation of cytosolic Ca2+ levels
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-5578775: Ion homeostasis
R-HSA-397014: Muscle contraction
R-HSA-418360: Platelet calcium homeostasis
R-HSA-418346: Platelet homeostasis
R-HSA-983705: Signaling by the B Cell Receptor (BCR)

Summary
Symbol	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between STIM1 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 STIM1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23922331	Melanoma; Colon Carcinoma	Promote immunity	Patients with loss-of-function mutations in the CRAC channel genes ORAI1 or STIM1 are immunodeficient and are prone to develop virus-associated tumours. Using conditional knock out mice lacking STIM1 and its homologue STIM2, we find that SOCE in CD8(+) T cells is required to prevent the engraftment of melanoma and colon carcinoma cells and to control tumour growth.

Summary
Symbol	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
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

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Statistical results of STIM1 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	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
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

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Points in the above scatter plot represent the expression difference of STIM1 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	0.201	0.377
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.35	0.846
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.096	0.94
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.34	0.349
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.096	0.966
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.892	0.757
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.24	0.513
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.162	0.915
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.256	0.886
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.805	0.597
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	1.359	0.543
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.066	0.336

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of STIM1 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	3.7	4.1	-0.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.4	0.3	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	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
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	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
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 STIM1. 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	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
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 STIM1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by STIM1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
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 STIM1. 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	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of STIM1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between STIM1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	STIM1
Name	stromal interaction molecule 1
Aliases	GOK; D11S4896E; IMD10; STRMK; TAM; TAM1
Chromosomal Location	11p15.5
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting STIM1 collected from DrugBank database.

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

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