Browse ADAM10

Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
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
 
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
 
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
 
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
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
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
 
  Literatures describing the relation between ADAM10 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
23526433Breast Carcinoma; Pancreatic Carcinoma; Prostate CarcinomaInhibit 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.
24780758Pancreatic AdenocarcinomaInhibit immunityTumor 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.
29308299Metastatic Non-Squamous Non-Small Cell Lung CarcinomaInhibit 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.
24327582GlioblastomaInhibit 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.
22006996Prostate Carcinoma; Breast CarcinomaInhibit 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
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.080.81
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.0020.999
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.1340.938
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0190.957
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.2490.922
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.2760.929
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0640.89
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.1090.957
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2160.922
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.5660.705
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9480.678
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0020.988
> Mutation difference between responders and non-responders
 
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 Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.45.51.90.66
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.46.80.61
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.16.24.91
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
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
 
Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
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
 
> Receptor
 
Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ADAM10 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ADAM10 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolADAM10
NameADAM metallopeptidase domain 10
Aliases kuz; HsT18717; CD156c; a disintegrin and metalloproteinase domain 10; AD10; AD18; CDw156; a disintegrin and ......
Chromosomal Location15q2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ADAM10 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ADAM10.
ID Name Drug Type Targets #Targets
DB04991XL784Small MoleculeADAM101