ADAM22 Recombinant Rabbit mAb (S-3201-8)

ADAM22 (a disintegrin and metalloproteinase domain-containing protein 22) is a unique non-proteolytic member of the ADAM family; because key zinc-binding motifs in its metalloproteinase catalytic domain are mutated, it has lost proteolytic activity and functions primarily as a cell surface adhesion molecule or receptor. The protein is highly expressed in the nervous system and is a key regulator of synaptic transmission: as the principal receptor for the secreted neuronal protein LGI1, the two form a 2:2 heterotetrameric complex through binding of the integrin-like domain of ADAM22 to the EPTP domain of LGI1, which then anchors to the postsynaptic density and regulates AMPA receptor-mediated synaptic transmission. Dysfunction of the LGI1-ADAM22 complex is directly linked to multiple neurological disorders: LGI1 gene mutations cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), while LGI1 autoantibodies trigger limbic encephalitis characterized by memory loss and seizures. ADAM22-deficient mice exhibit severe ataxia, insufficient peripheral nerve myelination, and lethal seizures, further confirming its central role in both the central and peripheral nervous systems. Beyond the nervous system, ADAM22 shows tumor-promoting effects in various cancers: in head and neck squamous cell carcinoma, it promotes epithelial-mesenchymal transition (EMT) and lymphatic metastasis through integrin signaling; in nasopharyngeal carcinoma, it drives metastasis via RAC2-mediated activation of the PI3K/Akt pathway; in pituitary adenomas, it promotes tumor progression by activating integrin β1 and FAK/PI3K and FAK/ERK signaling through its disintegrin domain; and in breast cancer, it acts as a direct target gene of SRC-1 to mediate endocrine therapy resistance and is an independent predictor of disease-free survival that is independent of estrogen receptor status. Notably, ADAM22 is expressed in normal brain tissue but lost in high-grade gliomas, and its disintegrin domain can inhibit cell proliferation through integrin-dependent pathways, suggesting that its functions are highly tissue- and context-dependent.