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 O14672	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 >= 0.40

Basic 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

Ensembl

ENSG00000137845

Entrez Gene Symbol

ADAM10

Gene Synonym (4)

CD156CHsT18717kuzMADM

Gene Description

ADAM metallopeptidase domain 10

Chromosome

Position

58588809-58749791

Supporting publications (n)

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)

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Molecular Function (12)

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Biological Process (3)

KEGG (4)

Reactome (26)

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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

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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	NOTC2	Q04721	Yes	Yes	No	WangCellTalkDBSignaLink3ACSN	ACSN:19601831 ACSN:19726682 SignaLink3:10423016 SignaLink3:23331499 ACSN:19704010 CellTalkDB:24842903
ADA10	O14672	NOTC3	Q9UM47	Yes	Yes	No	WangSignaLink3ACSN	SignaLink3:12651094 ACSN:19601831 ACSN:19726682 SignaLink3:23331499 ACSN:19704010
TSN33	Q86UF1	ADA10	O14672	Yes	Yes	No	SIGNORIntAct	IntAct:23091066 SIGNOR:30463011 IntAct:26686862
ADA10	O14672	CADH1	P12830	Yes	Yes	No	WangSIGNOR	SIGNOR:26284334
ADA10	O14672	BTC	P35070	Yes	Yes	Yes	WangSIGNOR	SIGNOR:26284334
ELAV4	P26378	ADA10	O14672	Yes	Yes	No	SIGNOR	SIGNOR:19221430
ELAV2	Q12926	ADA10	O14672	Yes	Yes	No	SIGNOR	SIGNOR:19221430
ADA10	O14672	CD44	P16070	Yes	Yes	No	CellTalkDBSIGNOR	CellTalkDB:18971959 SIGNOR:26284334
ELAV1	Q15717	ADA10	O14672	Yes	Yes	No	SIGNOR	SIGNOR:19221430
ELAV3	Q14576	ADA10	O14672	Yes	Yes	No	SIGNOR	SIGNOR:19221430

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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)

Breast cancer Solid tumour/cancer

Biomarker

Phase 1/2; Investigative

Drugs (16)

ADERBASIB INCB7839 ILOMASTAT CXCL17 FUROSEMIDE MARIMASTAT COMPOUND 25 [PMID: 18068976]GI254023X KYNURENIC ACID BUMETANIDE ZAPRINAST CID2745687 2-OLEOYL-LPA PAMOIC ACID COMPOUND 83 [PMID: 23888932]LODOXAMIDE TROMETHAMINE

Antibody (2)

CAB001709 HPA050670

Interaction Protein (2)

ENSG00000099282ENSG00000168785

Interaction Count

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.