ADAM10

Target id: 1658

Nomenclature: ADAM10

Family: M12: Astacin/Adamalysin

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     ADAM10 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 748 15q2 ADAM10 ADAM metallopeptidase domain 10
Mouse - 749 9 D Adam10 a disintegrin and metallopeptidase domain 10
Rat - 544 8q24 Adam10 ADAM metallopeptidase domain 10
Previous and Unofficial Names
Kuzbanian protein homolog | Mammalian disintegrin-metalloprotease | CD156c | kuz | MADM | a disintegrin and metallopeptidase domain 10 | ADAM metallopeptidase domain 10 | HER-2 sheddase
Database Links
Specialist databases
MEROPS M12.210 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.24.81

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
ilomastat Hs Inhibition 8.1 pIC50 5
pIC50 8.1 (IC50 8.1x10-9 M) [5]
Description: Measured in an in vitro assay.
compound 25 [PMID: 18068976] Hs Inhibition 7.8 pIC50 1
pIC50 7.8 (IC50 1.6x10-8 M) [1]
GI254023X Hs Inhibition 5.3 pIC50 3
pIC50 5.3 (IC50 5.3x10-6 M) [3]
Immunopharmacology Comments
ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of ICOS ligand, and regulation of ICOS/ICOSL-dependent immune responses [4]. B cell ADAM10 inhibition represents a novel mechanism to modulate the ICOS/ICOSL pathway and alter the humoral immune response. Experimental evidence using patient-derived cells has identified ADAM10 as important for the shedding of soluble semaphorin 4D (Sema4D) from CD15+ granulocytes, a pathway implicated in the promotion of autoreactive antibody secretion by B cells that leads to the development of the autoimmune skin condition bullous pemphigoid [6].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of T cell chemotaxis (GO:0010820) IMP
monocyte activation (GO:0042117) IMP
neutrophil degranulation (GO:0043312) TAS
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of T cell chemotaxis (GO:0010820) IMP
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  response to tumor necrosis factor (GO:0034612) IDA
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of T cell chemotaxis (GO:0010820) IMP
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  monocyte activation (GO:0042117) IMP
neutrophil degranulation (GO:0043312) TAS
References: 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Reticulate acropigmentation of Kitamura; RAK
OMIM: 615537
Orphanet: ORPHA178307
General Comments
The proteolytic domains of ADAM10 and ADAM17 exhibit a high degree of homology, which explains their ability to cleave overlapping substrates. ADAM10 is responsible for cleaving a variety of substrates, including Notch receptors, delta-like 1, IL-6R, CXCL16, CD23 and ICOS ligand [2,4,7].

References

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1. Burns DM, He C, Li Y, Scherle P, Liu X, Marando CA, Covington MB, Yang G, Pan M, Turner S et al.. (2008) Conversion of an MMP-potent scaffold to an MMP-selective HER-2 sheddase inhibitor via scaffold hybridization and subtle P1' permutations. Bioorg. Med. Chem. Lett.18 (2): 560-4. [PMID:18068976]

2. Gibb DR, El Shikh M, Kang DJ, Rowe WJ, El Sayed R, Cichy J, Yagita H, Tew JG, Dempsey PJ, Crawford HC et al.. (2010) ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo. J. Exp. Med.207 (3): 623-35. [PMID:20156974]

3. Hoettecke N, Ludwig A, Foro S, Schmidt B. (2010) Improved synthesis of ADAM10 inhibitor GI254023X. Neurodegener Dis7 (4): 232-8. [PMID:20197648]

4. Lownik JC, Luker AJ, Damle SR, Cooley LF, El Sayed R, Hutloff A, Pitzalis C, Martin RK, El Shikh MEM, Conrad DH. (2017) ADAM10-Mediated ICOS Ligand Shedding on B Cells Is Necessary for Proper T Cell ICOS Regulation and T Follicular Helper Responses. J. Immunol.,  [Epub ahead of print]. [PMID:28814605]

5. Oh M, Im I, Lee YJ, Kim YH, Yoon JH, Park HG, Higashiyama S, Kim YC, Park WJ. (2004) Structure-based virtual screening and biological evaluation of potent and selective ADAM12 inhibitors. Bioorg. Med. Chem. Lett.14 (24): 6071-4. [PMID:15546732]

6. Shen S, Ke Y, Dang E, Fang H, Chang Y, Zhang J, Zhu Z, Shao S, Qiao P, Zhang T et al.. (2017) Semaphorin 4D from CD15(+) Granulocytes via ADAM10-induced Cleavage Contributes to Antibody Production in Bullous Pemphigoid. J. Invest. Dermatol.,  [Epub ahead of print]. [PMID:29054606]

7. Weskamp G, Ford JW, Sturgill J, Martin S, Docherty AJ, Swendeman S, Broadway N, Hartmann D, Saftig P, Umland S et al.. (2006) ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23. Nat. Immunol.7 (12): 1293-8. [PMID:17072319]

How to cite this page

M12: Astacin/Adamalysin: ADAM10. Last modified on 25/10/2017. Accessed on 22/01/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1658.