Homo sapiens Protein: ADAM10
InnateDB Protein IDBP-14157.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol ADAM10
Protein Name ADAM metallopeptidase domain 10
Synonyms AD10; AD18; CD156c; HsT18717; kuz; MADM; RAK;
Species Homo sapiens
Ensembl Protein ENSP00000260408
InnateDB Gene IDBG-14155 (ADAM10)
Protein Structure
UniProt Annotation
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. Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth- like factor, ephrin-A2 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. May regulate the EFNA5-EPHA3 signaling. {ECO:0000269PubMed:11477090, ECO:0000269PubMed:11786905, ECO:0000269PubMed:12475894, ECO:0000269PubMed:16239146, ECO:0000269PubMed:17557115, ECO:0000269PubMed:19114711, ECO:0000269PubMed:20592283, ECO:0000269PubMed:21288900}.
Subcellular Localization Cell membrane; Single-pass type I membrane protein. Endomembrane system; 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.
Disease Associations Reticulate acropigmentation of Kitamura (RAK) [MIM:615537]: A rare cutaneous pigmentation disorder characterized by reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet and appearing in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities. The manifestations tend to progress until middle age, after which progression of the eruptions stops. The pigmentary augmentation is found on the flexor aspects of the wrists, neck, patella and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, occasionally plantar keratoderma, and partial alopecia. {ECO:0000269PubMed:23666529}. Note=The disease is caused by mutations affecting the gene represented in this entry.Alzheimer disease 18 (AD18) [MIM:615590]: A late-onset form of Alzheimer disease, a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C- terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. {ECO:0000269PubMed:19608551}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Tissue Specificity Expressed in spleen, lymph node, thymus, peripheral blood leukocyte, bone marrow, cartilage, chondrocytes and fetal liver. {ECO:0000269PubMed:11511685, ECO:0000269PubMed:9016778}.
Number of Interactions This gene and/or its encoded proteins are associated with 17 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.
Experimentally validated
Total 17 [view]
Protein-Protein 16 [view]
Protein-DNA 0
Protein-RNA 0
RNA-RNA 1 [view]
Predicted by orthology
Total 3 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004175 endopeptidase activity
GO:0004222 metalloendopeptidase activity
GO:0005102 receptor binding
GO:0005178 integrin binding
GO:0005515 protein binding
GO:0008237 metallopeptidase activity
GO:0008270 zinc ion binding
GO:0017124 SH3 domain binding
GO:0019901 protein kinase binding
GO:0042803 protein homodimerization activity
Biological Process
GO:0001701 in utero embryonic development
GO:0006468 protein phosphorylation
GO:0006508 proteolysis
GO:0006509 membrane protein ectodomain proteolysis
GO:0007162 negative regulation of cell adhesion
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007219 Notch signaling pathway
GO:0007220 Notch receptor processing
GO:0007229 integrin-mediated signaling pathway
GO:0007267 cell-cell signaling
GO:0008219 cell death
GO:0008284 positive regulation of cell proliferation
GO:0010820 positive regulation of T cell chemotaxis
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:0030574 collagen catabolic process
GO:0034612 response to tumor necrosis factor
GO:0042117 monocyte activation
GO:0045087 innate immune response (InnateDB)
GO:0051088 PMA-inducible membrane protein ectodomain proteolysis
GO:0051089 constitutive protein ectodomain proteolysis
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005798 Golgi-associated vesicle
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0014069 postsynaptic density
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0070062 extracellular vesicular exosome
GO:0097038 perinuclear endoplasmic reticulum
GO:0097197 tetraspanin-enriched microdomain
Protein Structure and Domains
InterPro IPR001590 Peptidase M12B, ADAM/reprolysin
IPR001762 Blood coagulation inhibitor, Disintegrin
IPR002870 Peptidase M12B, propeptide
PFAM PF01421
Post-translational Modifications
SwissProt O14672
PhosphoSite PhosphoSite-O14672
UniProt Splice Variant
Entrez Gene 102
UniGene Hs.594928
RefSeq NP_001101
OMIM 602192
HPRD 03723
EMBL AF009615 CH471082 Z48579
GenPept AAC51766 CAA88463 EAW77540 EAW77541