InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ADAM10

Summary

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}.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	1 [view]
DNA-RNA	0

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