TISIDB

Summary
Symbol	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
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 Golgi apparatus membrane Single-pass type I membrane protein Note=Is localized in the plasma membrane but is predominantly expressed in the Golgi apparatus and in released membrane vesicles derived likely from the Golgi.
Domain	PF00200 Disintegrin PF01562 Reprolysin family propeptide
Function	Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-\|-Val-77' to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:26686862, PubMed:11786905). Contributes to the normal cleavage of the cellular prion protein (PubMed:11477090). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (PubMed:12475894). Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (PubMed:17557115). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (PubMed:19114711, PubMed:21288900). May regulate the EFNA5-EPHA3 signaling (PubMed:16239146).

> Gene Ontology [ TOP ]
Biological Process	GO:0001558 regulation of cell growth GO:0001701 in utero embryonic development GO:0002274 myeloid leukocyte activation GO:0002685 regulation of leukocyte migration GO:0002687 positive regulation of leukocyte migration GO:0002688 regulation of leukocyte chemotaxis GO:0002690 positive regulation of leukocyte chemotaxis GO:0006509 membrane protein ectodomain proteolysis GO:0007162 negative regulation of cell adhesion GO:0007219 Notch signaling pathway GO:0007220 Notch receptor processing GO:0007229 integrin-mediated signaling pathway GO:0010818 T cell chemotaxis GO:0010819 regulation of T cell chemotaxis GO:0010820 positive regulation of T cell chemotaxis GO:0016049 cell growth GO:0016485 protein processing GO:0022617 extracellular matrix disassembly GO:0030198 extracellular matrix organization GO:0030307 positive regulation of cell growth GO:0030335 positive regulation of cell migration GO:0030595 leukocyte chemotaxis GO:0032103 positive regulation of response to external stimulus GO:0033619 membrane protein proteolysis GO:0034612 response to tumor necrosis factor GO:0040017 positive regulation of locomotion GO:0042117 monocyte activation GO:0043062 extracellular structure organization GO:0045927 positive regulation of growth GO:0048013 ephrin receptor signaling pathway GO:0048247 lymphocyte chemotaxis GO:0050900 leukocyte migration GO:0050920 regulation of chemotaxis GO:0050921 positive regulation of chemotaxis GO:0051088 PMA-inducible membrane protein ectodomain proteolysis GO:0051089 constitutive protein ectodomain proteolysis GO:0051272 positive regulation of cellular component movement GO:0051604 protein maturation GO:0060326 cell chemotaxis GO:0072676 lymphocyte migration GO:0072678 T cell migration GO:1901623 regulation of lymphocyte chemotaxis GO:2000147 positive regulation of cell motility GO:2000401 regulation of lymphocyte migration GO:2000403 positive regulation of lymphocyte migration GO:2000404 regulation of T cell migration GO:2000406 positive regulation of T cell migration
Molecular Function	GO:0004175 endopeptidase activity GO:0004222 metalloendopeptidase activity GO:0005178 integrin binding GO:0008237 metallopeptidase activity GO:0017124 SH3 domain binding GO:0050839 cell adhesion molecule binding
Cellular Component	GO:0005798 Golgi-associated vesicle GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0014069 postsynaptic density GO:0030055 cell-substrate junction GO:0060076 excitatory synapse GO:0097038 perinuclear endoplasmic reticulum GO:0097197 tetraspanin-enriched microdomain GO:0098794 postsynapse GO:0099572 postsynaptic specialization

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-422475: Axon guidance R-HSA-1442490: Collagen degradation R-HSA-2691232: Constitutive Signaling by NOTCH1 HD Domain Mutants R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2660826: Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1 R-HSA-1474228: Degradation of the extracellular matrix R-HSA-1266738: Developmental Biology R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-2682334: EPH-Ephrin signaling R-HSA-3928665: EPH-ephrin mediated repulsion of cells R-HSA-1474244: Extracellular matrix organization R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-2979096: NOTCH2 Activation and Transmission of Signal to the Nucleus R-HSA-6798695: Neutrophil degranulation R-HSA-156988: Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-157118: Signaling by NOTCH R-HSA-1980143: Signaling by NOTCH1 R-HSA-2691230: Signaling by NOTCH1 HD Domain Mutants in Cancer R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2644603: Signaling by NOTCH1 in Cancer R-HSA-2660825: Signaling by NOTCH1 t(7;9)(NOTCH1 R-HSA-1980145: Signaling by NOTCH2 R-HSA-1980148: Signaling by NOTCH3 R-HSA-1980150: Signaling by NOTCH4

> KEGG and Reactome Pathway

[ TOP ]

KEGG

Reactome

R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-422475: Axon guidance
R-HSA-1442490: Collagen degradation
R-HSA-2691232: Constitutive Signaling by NOTCH1 HD Domain Mutants
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2660826: Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1
R-HSA-1474228: Degradation of the extracellular matrix
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2682334: EPH-Ephrin signaling
R-HSA-3928665: EPH-ephrin mediated repulsion of cells
R-HSA-1474244: Extracellular matrix organization
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-2979096: NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-6798695: Neutrophil degranulation
R-HSA-156988: Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2691230: Signaling by NOTCH1 HD Domain Mutants in Cancer
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer
R-HSA-2660825: Signaling by NOTCH1 t(7;9)(NOTCH1
R-HSA-1980145: Signaling by NOTCH2
R-HSA-1980148: Signaling by NOTCH3
R-HSA-1980150: Signaling by NOTCH4

Summary
Symbol	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ADAM10 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 ADAM10 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23526433	Breast Carcinoma; Pancreatic Carcinoma; Prostate Carcinoma	Inhibit immunity (NK cell function)	The interaction of the MHC class I-related chain molecules A and B (MICA and MICB) with the corresponding natural killer group 2, member D (NKG2D) receptor triggers cytotoxic effector activity of natural killer cells and certain T-cell subsets and provides a costimulatory signal for cytokine production. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) revealed that all tested tumor cells constitutively expressed MICA and MICB on the cell surface and also released NKG2D ligands into the supernatant. Studies using RNA interference not only revealed a prominent role of ADAM10 and ADAM17 in NKG2D ligand shedding but also a tumor cell-specific role of ADAM10 and/or ADAM17 in shedding of MICA or MICB. These data indicate that the release of NKG2D ligands from individual tumor entities is by far more complex than suggested in previously reported MICA/B transfection systems.
24780758	Pancreatic Adenocarcinoma	Inhibit immunity	Tumor cells from different cancer entities released B7-H6 by ectodomain shedding mediated by the cell surface proteases "a disintegrin and metalloproteases" (ADAM)-10 and ADAM-17, as demonstrated through the use of pharmacologic inhibitors or siRNA-mediated gene attenuation. Inhibiting this proteolytic shedding process increased the levels of B7-H6 expressed on the surface of tumor cells, enhancing NKp30-mediated activation of NK cells.
29308299	Metastatic Non-Squamous Non-Small Cell Lung Carcinoma	Inhibit immunity (NK cell function)	Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells. Similar results were obtained upon exposure of tumor cells to platelet-releasate and can be attributed to the sheddases ADAM10 and ADAM17 that are detectable on the platelet surface and in releasate following activation and at higher levels on platelets of patients with metastasized lung cancer compared with healthy controls.
24327582	Glioblastoma	Inhibit immunity (NK cell function)	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. And treatment with ADAM10 and ADAM17 specific inhibitors leads to enhanced immunerecognition of GIC by natural killer cells. Therefore, ADAM10 and ADAM17 constitute suitable targets to boost an immune response against GIC.
22006996	Prostate Carcinoma; Breast Carcinoma	Inhibit immunity (NK cell function)	Indeed, our findings show a mechanistic link between hypoxia-induced accumulation of the α-subunit of HIF-1 (HIF-1α), increased expression of ADAM10, and decreased surface MICA levels leading to tumor cell resistance to lysis mediated by innate immune effectors.

Summary
Symbol	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
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 ADAM10 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	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
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 ADAM10 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	0.08	0.81
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.002	0.999
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.134	0.938
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.019	0.957
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.249	0.922
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.276	0.929
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.064	0.89
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.109	0.957
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.216	0.922
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.566	0.705
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	0.948	0.678
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.002	0.988

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ADAM10 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	7.4	5.5	1.9	0.66
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	7.4	6.8	0.6	1
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	20	0	20	0.357
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	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	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ADAM10. 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	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ADAM10. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ADAM10. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ADAM10. 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	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ADAM10 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ADAM10 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ADAM10
Name	ADAM metallopeptidase domain 10
Aliases	kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location	15q2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ADAM10 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting ADAM10.

ID	Name	Drug Type	Targets	#Targets
DB04991	XL784	Small Molecule	ADAM10	1

Browse ADAM10