Protein detail
ADA10
Disintegrin and metalloproteinase domain-containing protein 10 (ADAM 10) (EC 3.4.24.81) (CDw156) (Kuzbanian protein homolog) (Mammalian disintegrin-metalloprotease) (CD antigen CD156c)
Entry name ADA10 | UniProt ID | EVMP confidence score 0.63 |
Supporting publications (n) 8 | Transmembrane count 1 | Protein classification Cancer-related genesCD markersDisease related genesEnzymesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information13
Protein Names
Disintegrin and metalloproteinase domain-containing protein 10 (ADAM 10) (EC 3.4.24.81) (CDw156) (Kuzbanian protein homolog) (Mammalian disintegrin-metalloprotease) (CD antigen CD156c)
Protein Class (10)
Cancer-related genesCD markersDisease related genesEnzymesHuman disease related genesPlasma proteinsPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters
Protein Function (9)
- Cancer-related genes:Mutational cancer driver genes
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Neurodegenerative diseases
- CD markers
- Potential drug targets
- Enzymes
- ENZYME proteins:Hydrolases
- Transporters:Accessory Factors Involved in Transport
- Disease related genes
Transmembrane
673..693; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym (4)
CD156CHsT18717kuzMADM
Gene Description
ADAM metallopeptidase domain 10
Chromosome
15
Position
58588809-58749791
Supporting publications (n)
8
EVMP confidence score
0.63
Function & Pathway8
Protein Function (9)
- Cancer-related genes:Mutational cancer driver genes
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Neurodegenerative diseases
- CD markers
- Potential drug targets
- Enzymes
- ENZYME proteins:Hydrolases
- Transporters:Accessory Factors Involved in Transport
- Disease related genes
Cellular Component (24)
- GO:0000139 Golgi membrane
- GO:0005634 nucleus
- GO:0005737 cytoplasm
- GO:0005788 endoplasmic reticulum lumen
- GO:0005794 Golgi apparatus
- GO:0005798 Golgi-associated vesicle
- GO:0005886 plasma membrane
- GO:0005912 adherens junction
- GO:0005925 focal adhesion
- GO:0009986 cell surface
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Molecular Function (12)
- GO:0004175 endopeptidase activity
- GO:0004222 metalloendopeptidase activity
- GO:0005102 signaling receptor binding
- GO:0005178 integrin binding
- GO:0005515 protein binding
- GO:0008237 metallopeptidase activity
- GO:0017124 SH3 domain binding
- GO:0019901 protein kinase binding
- GO:0042803 protein homodimerization activity
- GO:0046872 metal ion binding
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Biological Process (3)
KEGG (4)
Reactome (26)
- R-hsa-2122948 activated notch1 transmits signal to the nucleus
- R-hsa-977225 amyloid fiber formation
- R-hsa-1442490 collagen degradation
- R-hsa-1474228 degradation of the extracellular matrix
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-3928665 eph ephrin mediated repulsion of cells
- R-hsa-2682334 eph ephrin signaling
- R-hsa-1474244 extracellular matrix organization
- R-hsa-168249 innate immune system
- R-hsa-9675108 nervous system development
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Canonical Pathways
M204 Pid rhodopsin pathway
Mediation Categories (6)
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence49
Ligand-Receptor Signaling (35)
35 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| cell_adhesion | cell_adhesion | Cellinker | Yes | Yes | No | Yes | No |
| adhesion | adhesion | OmniPath | Yes | Yes | No | Yes | No |
| cell_adhesion | cell_adhesion | OmniPath | Yes | Yes | No | Yes | No |
| cell_surface_enzyme | cell_surface_enzyme | Surfaceome | Yes | No | No | Yes | No |
| cell_surface_enzyme | cell_surface_enzyme | OmniPath | Yes | No | No | Yes | No |
| transmembrane | transmembrane | UniProt_location | No | No | No | Yes | No |
| transmembrane | transmembrane | UniProt_topology | No | No | No | Yes | No |
| transmembrane | transmembrane | UniProt_keyword | No | No | No | Yes | No |
| transmembrane_predicted | transmembrane | OmniPath | No | No | No | Yes | No |
| transmembrane | transmembrane | LOCATE | No | No | No | Yes | No |
Regulatory Interaction Network (13)
13 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| ADA10 | O14672 | ERBB2 | P04626 | Yes | Yes | No | SIGNOR | SIGNOR:26284334 |
| ADA10 | O14672 | NOTC1 | P46531 | Yes | Yes | No | CellTalkDBSIGNORACSNCellinkerWangLRdb | ACSN:19601831SIGNOR:28624438ACSN:19726682CellTalkDB:22399336ACSN:19704010LRdb:22399336Cellinker:22399336 |
| ADA10 | O14672 | EGF | P01133 | Yes | Yes | No | SIGNOR | SIGNOR:26284334 |
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Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential Ultracentrifugation | Mass spectrometryWestern blottingFlow cytometry | 1 | 38602325 |
Sequence, Structure & Domains13
Sequences
Length
748
Mass
84,142
Sequence
MVLLRVLILLLSWAAGMGGQYGNPLNKYIRHYEGLSYNVDSLHQKHQRAKRAVSHEDQFLRLDFHAHGRHFNLRMKRDTSLFSDEFKVETSNKVLDYDTSHIYTGHIYGEEGSFSHGSVIDGRFEGFIQTRGGTFYVEPAERYIKDRTLPFHSVIYHEDDINYPHKYGPQGGCADHSVFERMRKYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESYQMGHMRR
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O14672-1; Sequence=Displayed; Name=2; IsoId=O14672-2; Sequence=VSP_056401
Alternative Sequence
19..319; Missing (in isoform 2)
3D Structural Models
Turn
397..399; 476..478; 491..495; 505..507; 556..559; 633..636
Helix
230..236; 239..258; 280..284; 289..291; 297..305; 324..326; 374..388; 401..403; 407..411; 428..430; 434..447; 448..450; 571..575; 591..593; 604..606; 614..617; 653..662; 665..669
Beta Strand
219..228; 269..277; 313..322; 329..331; 336..338; 348..350; 359..367; 462..464; 482..484; 509..511; 515..517; 523..525; 529..531; 553..555; 560..563; 566..569; 577..580; 597..600; 630..632; 637..639; 645..647
3D Structure
Electron microscopy (1); X-ray crystallography (2)
Domain & Motif Annotations
Motif
171..178; Cysteine switch; 708..715; SH3-binding; 722..728; SH3-binding
Domain (CC)
The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.; DOMAIN: The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 complex but not the individual proteins (By similarity). Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is sufficient for interaction with TSPAN15 (By similarity).
Domain (FT)
220..456; Peptidase M12B; 457..551; Disintegrin
Region
704..748; Disordered; 734..748; Interaction with AP2A1, AP2A2 and AP2M1
Clinical Relevance8
Disease Involvement (5)
Alzheimer diseaseAmyloidosisCancer-related genesDisease variantNeurodegeneration
Related Diseases (2)
Biomarker
Phase 1/2; Investigative
Drugs (16)
Interaction Protein (2)
ENSG00000099282ENSG00000168785
Interaction Count
2
Interaction Dataset (2)
intact_biogrid_bioplexintact_biogrid
Supporting Publications8
| PMID | Title | Abstract |
|---|---|---|
| 16229685 | A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. | By analysing L1 (CD171) and CD44 in ovarian carcinoma cells, we show in the present paper that the cleavage induced by ionomycin, APMA (4-aminophenylmercuric acetate) or MCD (methyl-beta-cyclodextrin) is initiated in an endosomal compartment that is subsequently released in the form of exosomes. Calcium influx augmented the release of exosomes containing functionally active forms of ADAM10 (a disintegrin and metalloprotease 10) and ADAM17 [TACE (tumour necrosis factor a-converting enzyme)] as well as CD44 and L1 cytoplasmic cleavage fragments. Cleavage could also proceed in released exosomes, but only depletion of ADAM10 by small interfering RNA blocked cleavage under constitutive and induced conditions. |
| 18381078 | Functional role of N-glycosylation from ADAM10 in processing, localization and activity of the enzyme. | ADAM10 is sorted into secretory vesicles, the exosomes. Here, a fraction of ADAM10 from exosomes was found to contain more processed N-linked glycans than the cellular enzyme. |
| 19188015 | Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. | We found that malignant ascites-derived exosomes cargo tumor progression related proteins such as L1CAM, CD24, ADAM10, and EMMPRIN. |
| 29484441 | A disintegrin and metalloprotease 10-containing exosomes derived from nasal polyps promote angiogenesis and vascular permeability. | A disintegrin and metalloprotease 10 (ADAM10), an important type of proteinase that is overexpressed in various diseases, can influence angiogenesis and vascular permeability and has been observed in healthy nasal exosomes. ADAM10 was highly expressed in NLF‑derived exosomes from NPs when compared with healthy volunteers. Thus, NLF‑derived exosomes from NPs promoted angiogenesis and vascular permeability, which may be associated with abundant ADAM10 in NP exosomes. To the best of our knowledge, the expression levels and the function of ADAM10 in NLF‑derived exosomes from NPs has not been demonstrated previously. |
| 30909692 | Relation between Tetraspanin- Associated and Tetraspanin- Non- Associated Exosomal Proteases and Metabolic Syndrome in Colorectal Cancer Patients. | Results: The ADAM10-/ ADAM17- population predominated in plasma exosomes of CRCPs and the level of ADAM10+ exosomes was significantly higher in exosomes of CSs compared with CRCPs. The aim of this study was to evaluate the level of ADAM10, ADAM17 and 20S proteasomes in exosomes isolated from colorectal cancer patients (CRCPs) in relation with clinical and histopathological parameters. |
| 36612172 | Extracellular Vesicle Membrane Protein Profiling and Targeted Mass Spectrometry Unveil CD59 and Tetraspanin 9 as Novel Plasma Biomarkers for Detection of Colorectal Cancer. | No abstract available |
| 37549991 | MiRNAs that target amyloid precursor protein processing machinery in extracellular vesicles and particles derived from oral squamous cells carcinoma. | Considering that microRNAs (miRNAs), extracellular vesicles and particles (EVPs) and the amyloid precursor protein (APP) processing have been shown to be altered in oral squamous cells carcinoma (OSCC), it is possible that miRNAs that target APP processing pathways in EVPs are impacted in tumor cells. |
| 39317350 | Extracellular Release of a Disintegrin and Metalloproteinase Correlates With Periodontal Disease Severity. | Infection and the resulting cytokine release orchestrated the release of soluble ADAM8 by oral keratinocytes and primary neutrophils as soluble ectodomain and on exosomes, respectively. |