TISIDB

Summary
Symbol	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
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 Secreted 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-392499: Metabolism of proteins R-HSA-163125: Post-translational modification R-HSA-597592: Post-translational protein modification

Summary
Symbol	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ULBP2 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 ULBP2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25744717	Melanoma	Promote immunity (NK cell function)	Finally, we provide strong evidences that CEACAM1-3S triggers melanoma cells for NK cell-mediated cytolysis by upregulating cell surface expression of MICA and ULBP2, whereas CEACAM1-4L causes the contrary effect due to enhanced shedding of both NKG2D ligands (NKG2DLs).
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.
23820258	Acute Myeloid Leukemia; Adenocarcinoma	Promote immunity (NK cell function); essential for immunotherapy	NKG2D recognises several ligands, including polymorphic major histocompatibility complex class I chain-related chain-related proteins A and B (MICA/B) and unique long 16-binding proteins (ULBPs). These ligands are present on cancer cells and are recognised by NKG2D in a cell-structure-sensing manner, triggering natural killer (NK) cell cytotoxicity. Treatment with 1,25(OH)2D3 enhanced the susceptibility of both the haematological tumour cell line Kasumi-1 and solid tumour cell line MDA-MB-231 to NK92 cells. 1,25(OH)2D3 facilitates the immuno-attack of NK cells against malignant cells partly through downregulation of miR-302c and miR-520c and hence upregulation of the NKG2D ligands MICA/B and ULBP2.
21321117	Chronic myelogenous leukemia	Promote immunity (NK cell function)	Overexpression of IL-32alpha increases natural killer cell-mediated killing through up-regulation of Fas and UL16-binding protein 2 (ULBP2) expression in human chronic myeloid leukemia cells. Taken together, these data show that IL-32α stimulates Fas and ULBP2 expression via activation of p38 MAPK, which increases NK susceptibility of CML cells. Enhanced NK cell susceptibility of CML cells by IL-32α overexpression may improve the efficiency of NK cell-based immunotherapy.
24327582	Glioblastoma	Promote immunity	Here,we show that ADAM10 and ADAM17 are expressed on the cell surface of GIC and contribute to an immunosuppressive phenotype by cleavage of ULBP2. The cell surface expression of ULBP2 is enhanced upon blocking ADAM10 and ADAM17, and treatment with ADAM10 and ADAM17specific inhibitors leads to enhanced immunerecognition of GIC by natural killer cells.
24242212	Colon Carcinoma	Promote immunity	To this end we designed a fusion protein consisting of human ULBP2 and an antibody-derived single chain targeting the tumor carcinoembryonic antigen (CEA). The bispecific recombinant fusion protein re-directed NK cells towards malignant cells by binding to both, tumor cells and NK cells, and triggered NK cell-mediated target cell killing in vitro. Moreover, tumor growth was significantly delayed in a syngeneic colon carcinoma mouse model in response to immunoligand treatment.
22102694	Melanoma	Promote immunity	Accordingly, treatment of cancer cells with miRNA inhibitors led to upregulation of ULBP2, whereas miR-34 mimics led to downregulation of ULBP2, diminishing tumor cell recognition by NK cells.
25212604	Anaplastic thyroid carcinoma	Promote immunity（NK cell function)	We find that ATC cell lines are sensitive to lysis byNKcells correlating with their surface expression of ULBP2/5/6, indicating that ULBP2/5/6 could be used as a predictive marker for NK cell therapy
16891318	Glioblastoma	Promote immunity	We further delineate two independent mechanisms that can explain these expression patterns: (i) transforming growth factor-beta (TGF-beta) is upregulated during malignant progression and selectively downregulates MICA, ULBP2 and ULBP4 expression, while MICB, ULBP1 and ULBP3 are unaffected. (ii) Cleavage of MICA and ULBP2 is reduced by inhibition of metalloproteinases (MP), whereas no changes in the expression levels of other NKG2DL were detected. Consequently, NKG2DL-dependent NK cell-mediated lysis is enhanced by depletion of TGF-beta or inhibition of MP.

Summary
Symbol	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
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 ULBP2 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	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
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 ULBP2 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	-0.169	0.701
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.567	0.511
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.132	0.835
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.461	0.665
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	2.15	0.185
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.691	0.319
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.824	0.197
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.095	0.228
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.758	0.453
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.74	0.443
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	1.684	0.173
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.094	0.66

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ULBP2 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	0	3.7	0.27
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	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
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	0	0	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	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	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	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
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 ULBP2. 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	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
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 ULBP2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ULBP2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ULBP2. 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	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ULBP2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ULBP2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ULBP2
Name	UL16 binding protein 2
Aliases	RAET1H; ALCAN-alpha; N2DL2; NKG2DL2; retinoic acid early transcript 1H; UL16-binding protein 2; N2DL-2; NKG2 ......
Chromosomal Location	6q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ULBP2 collected from DrugBank database.

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

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