Thymocyte selection-associated family member 2 (THEMIS2)

Thymocyte selection-associated family member 2 (THEMIS2) is a signaling adaptor protein containing two tandem CABIT (Cysteine-containing, All-Beta-In-THEMIS) domains, expressed primarily in B lymphocytes, macrophages, and dendritic cells. Unlike its paralog THEMIS (involved in T cell development), THEMIS2 modulates B cell receptor signaling thresholds and regulates activation of B cells, particularly in response to weak antigens. In macrophages, THEMIS2 has been implicated in control of the inflammatory response, enhancing LPS-induced, TLR4-mediated TNF production. THEMIS2 interacts with key signaling molecules including GRB2, VAV, and LYN, and is phosphorylated upon B cell receptor engagement, linking it to BCR signal transduction. It localizes to both the cytoplasm and nucleus, though its nuclear roles remain undefined. Despite its central position in signaling networks, knockout studies in mice have shown that THEMIS2 is not essential for normal B cell development or humoral immune responses, indicating redundancy or compensation in immune signaling pathways. No drugs are currently known to target THEMIS2, and it is not recognized as a therapeutic or biomarker target in current clinical practice.

Other names

Protein THEMIS2C1orf38ICB-1Protein ICB-1Induced by contact to basement membrane 1 proteinThymocyte-expressed molecule involved in selection protein 2

No approved or experimental drugs directly targeting THEMIS2 with defined mechanisms of action