TISIDB

Summary
Symbol	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
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 Lipid-anchor, GPI-anchor Endoplasmic reticulum Note=In CMV-infected fibroblasts, detected in the endoplasmic reticulum/cis-Golgi.
Domain	PF00129 Class I Histocompatibility antigen
Function	Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.

> Gene Ontology [ TOP ]
Biological Process	GO:0001906 cell killing GO:0001909 leukocyte mediated cytotoxicity GO:0002228 natural killer cell mediated immunity GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0019882 antigen processing and presentation GO:0030101 natural killer cell activation GO:0042267 natural killer cell mediated cytotoxicity
Molecular Function	GO:0003823 antigen binding GO:0046703 natural killer cell lectin-like receptor binding
Cellular Component	GO:0031225 anchored component of membrane GO:0046658 anchored component of plasma membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04650 Natural killer cell mediated cytotoxicity
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Summary
Symbol	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ULBP1 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 ULBP1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27116977	Glioma	Promote immunity (NK cell function)	IDH mutant glioma cells acquire resistance to NK cells through epigenetic silencing of NKG2D ligands ULBP1 and ULBP3.
25745066	Lymphoma; Acute Myeloid Leukemia	Promote immunity (NK cell function)	In contrast, we show that in mice, a shed form of MULT1, a high-affinity NKG2D ligand, causes NK cell activation and tumor rejection.
23509364	Breast Carcinoma; Hepatocellular Carcinoma; Colorectal Carcinoma	Promote immunity	NK group 2, member D (NKG2D) is an NK cell-activating receptor crucially involved in cancer immunosurveillance. In this study, we show that induction of EMT by TGF-β stimulation of human keratinocytes, by glycogen synthase kinase-3β inhibition in several epithelial tumor cell lines, and by Snail1 overexpression in colorectal cancer cells strongly upregulated the expression of NKG2D ligands (NKG2DLs), MHC class I chain-related molecules A and B (MICA/B) and ULBP1-3.
16621962	Lymphoma	Promote immunity (T and NK cell function)	ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15. ULBPs are human ligands for NKG2D, an activating receptor expressed on natural killer (NK) cells, NK1.1(+) T cells, and T cells. We report that ectopic expression of ULBP1 or ULBP2 on murine EL4 or RMA tumor cells elicits potent antitumor responses in syngeneic C57BL/6 and SCID mice. Although binding of ULBP3 to murine NKG2D could not be demonstrated in vitro, ULBP3 can also stimulate antitumor responses, suggesting that ULBP3 binds to murine NKG2D or possibly another receptor in vivo. IL-15 was found to strongly enhance the immune response directed against ULBP-expressing tumors.
21756848	Hepatocellular Carcinoma	Promote immunity	Remarkably, recurrence-free survival of patients with ULBP1-negative HCC was significantly shorter than that of patients with ULBP1-positive HCC (p=0.006). ULBP1 is prevalently expressed in DN to mod-HCC, but loss of its expression correlates with tumor progression and early recurrence.

Summary
Symbol	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
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 ULBP1 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	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
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 ULBP1 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	-0.177	0.395
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.299	0.523
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.085	0.833
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.293	0.628
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.25	0.802
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.344	0.759
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.296	0.607
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.959	0.323
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.294	0.8
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.315	0.574
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	0.771	0.311
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.564	0.0336

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ULBP1 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	1.4	2.3	0.469
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	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	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	25	14.3	10.7	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	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ULBP1. 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	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ULBP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ULBP1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ULBP1. 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	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ULBP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ULBP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ULBP1
Name	UL16 binding protein 1
Aliases	RAET1I; N2DL-1; NKG2DL1; UL16-binding protein 1; alcan-beta; retinoic acid early transcript 1I; NKG2D ligand ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ULBP1 collected from DrugBank database.

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

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