Target General Infomation
Target ID
T31902 (Former ID: TTDI02327)
Target Name
Mammalian disintegrin-metalloprotease (ADAM10)
Synonyms
Mammalian disintegrinmetalloprotease; MADM; Kuzbanian protein homolog; KUZ; Disintegrin and metalloproteinase domaincontaining protein 10; Disintegrin and metalloproteinase domain-containing protein 10; CDw156; CD156c; ADAM 10
Gene Name
ADAM10
Target Type
Clinical trial target
[1]
Disease [+] 1 Target-related Diseases +
1 Breast cancer [ICD-11: 2C60-2C6Y]
Function
Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. 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). Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity. Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis. Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B. Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3. May regulate the EFNA5-EPHA3 signaling. Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' to its mature soluble form.
BioChemical Class
Peptidase
UniProt ID
ADA10_HUMAN
EC Number
EC 3.4.24.81
Sequence
MVLLRVLILLLSWAAGMGGQYGNPLNKYIRHYEGLSYNVDSLHQKHQRAKRAVSHEDQFL
RLDFHAHGRHFNLRMKRDTSLFSDEFKVETSNKVLDYDTSHIYTGHIYGEEGSFSHGSVI
DGRFEGFIQTRGGTFYVEPAERYIKDRTLPFHSVIYHEDDINYPHKYGPQGGCADHSVFE
RMRKYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTRE
AVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKF
LELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNT
GIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYAR
ATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCK
DECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFT
ALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMK
KMDPSTCASTGSVQWSRHFSGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKA
IFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTL
KRRRPPQPIQQPQRQRPRESYQMGHMRR
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 1 Clinical Trial Drugs +
1 Aderbasib Drug Info Phase 1/2 Breast cancer [2]
Mode of Action [+] 2 Modes of Action +
Modulator [+] 1 Modulator drugs +
1 Aderbasib Drug Info [1]
Inhibitor [+] 1 Inhibitor drugs +
1 IAI-100 Drug Info [3]
Target Regulators
Target-regulating microRNAs
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Affiliated Biological Pathways
KEGG Pathway [+] 2 KEGG Pathways +
1 Alzheimer's disease
2 Epithelial cell signaling in Helicobacter pylori infection
NetPath Pathway [+] 1 NetPath Pathways +
1 RANKL Signaling Pathway
Panther Pathway [+] 1 Panther Pathways +
1 Alzheimer disease-amyloid secretase pathway
PID Pathway [+] 3 PID Pathways +
1 Notch signaling pathway
2 Presenilin action in Notch and Wnt signaling
3 Posttranslational regulation of adherens junction stability and dissassembly
Reactome [+] 10 Reactome Pathways +
1 Collagen degradation
2 Degradation of the extracellular matrix
3 Activated NOTCH1 Transmits Signal to the Nucleus
4 Constitutive Signaling by NOTCH1 PEST Domain Mutants
5 Constitutive Signaling by NOTCH1 t(7
6 M1580_K2555) Translocation Mutant
7 Constitutive Signaling by NOTCH1 HD Domain Mutants
8 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
9 NOTCH2 Activation and Transmission of Signal to the Nucleus
10 EPH-ephrin mediated repulsion of cells
WikiPathways [+] 6 WikiPathways +
1 Hypertrophy Model
2 Copper homeostasis
3 Signaling by NOTCH3
4 Signaling by NOTCH4
5 Signaling by NOTCH2
6 Alzheimers Disease
References
REF 1 Company report (Incyte)
REF 2 ClinicalTrials.gov (NCT02141451) INCB7839 With Rituximab After Autologous Hematopoietic Cell Transplantation for Diffuse Large B Cell Non-Hodgkin Lymphoma. U.S. National Institutes of Health.
REF 3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8679).

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