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MGP000052

UniProt Annotations

Entry Information

Gene Name	ADAM metallopeptidase domain 10
Protein Entry	ADA10_HUMAN
UniProt ID	O14672
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O14672-1; Sequence=Displayed; Name=2; IsoId=O14672-2; Sequence=VSP_056401; Note=No experimental confirmation available.;
Catalytic Activity	Endopeptidase of broad specificity.
Cofactor	Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion. {ECO:0000250};
Disease	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:0000269\|PubMed:19608551}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease	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:0000269\|PubMed:23666529}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Domain	The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. 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. {ECO:0000250}.
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:0000269\|PubMed:11477090, ECO:0000269\|PubMed:11786905, ECO:0000269\|PubMed:12475894, ECO:0000269\|PubMed:16239146, ECO:0000269\|PubMed:17557115, ECO:0000269\|PubMed:19114711, ECO:0000269\|PubMed:20592283, ECO:0000269\|PubMed:21288900}.
Induction	In osteoarthritis affected-cartilage.
Ptm	The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
Similarity	Contains 1 disintegrin domain. {ECO:0000255\|PROSITE- ProRule:PRU00068}.
Similarity	Contains 1 peptidase M12B domain. {ECO:0000255\|PROSITE-ProRule:PRU00276}.
Subcellular Location	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.
Subunit	Interacts with EPHA2 (By similarity). Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells. {ECO:0000250, ECO:0000269\|PubMed:16239146}.
Tissue Specificity	Expressed in spleen, lymph node, thymus, peripheral blood leukocyte, bone marrow, cartilage, chondrocytes and fetal liver. {ECO:0000269\|PubMed:11511685, ECO:0000269\|PubMed:9016778}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ADAM10ID44397ch15q21.html";