ADAM10:Zn2+ binds TSPANs

Stable Identifier
R-HSA-9010113
Type
Reaction [binding]
Species
Homo sapiens
Compartment
endoplasmic reticulum lumen
ReviewStatus
5/5
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ADAM10:Zn2+ binds TSPANs
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The ADAM (A disintegrin and metalloprotease domain) family are membrane-anchored metalloproteases that mediate the proteolytic cleavage of many transmembrane proteins within their extracellular regions. This so-called ectodomain shedding plays an important role in many cell and developmental processes. ADAM10 (A Disintegrin and Metalloproteinase 10) has been identified as the major physiological alpha-secretase in neurons (Lammich et al. 1999, Kuhn et al. 2010), responsible for cleaving amyloid precursor protein (APP) in a non-amyloidogenic manner and producing APPs-alpha, a neuroprotective APP-derived peptide.

The trafficking of ADAM10 is regulated by a subgroup of the tetraspanin superfamily which have eight cysteines in the largest of the two extracellular domains and are referred to as TspanC8 tetraspanins. Tetraspanins associate specifically and directly with a limited number of proteins, and also with other tetraspanins, thereby generating a "tetraspanin web". Through these interactions, tetraspanins are believed to have a role in cell and membrane compartmentalisation (Charrin et al. 2014). TSPAN4, 14, 15 and 33 are thought to mediate ADAM10 exit from the ER and transport to the plasma membrane in a variety of ways (Noy et al. 2016, Jouannet et al. 2016).

Literature References
PubMed ID Title Journal Year
26668317 TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions: EVIDENCE FOR DISTINCT BINDING MECHANISMS FOR DIFFERENT TspanC8 PROTEINS

Yang, J, Matthews, AL, Tomlinson, MG, Noy, PJ, Furmston, J, Charlton, AE, Reyat, JS, Rainger, GE, Rogers, DA

J. Biol. Chem. 2016
26686862 TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization

Milhiet, PE, Nguyen, V, Brou, C, Boucheix, C, Jouannet, S, Saint-Pol, J, Charrin, S, Fernandez, L, Rubinstein, E

Cell. Mol. Life Sci. 2016
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Authored
Jassal, B  (2017-06-26)
Reviewed
Meras-Rios, A  (2018-08-10)
Created
Jassal, B  (2017-06-26)
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