The TOX gene encodes a protein that belongs to a large superfamily of chromatin associated proteins that share an approximately 75 amino acid DNA binding motif, the HMG (high mobility group)-box (named after that found in the canonical member of the family, high mobility group protein 1). Some high mobility group (HMG) box proteins (e.g., LEF1) contain a single HMG box motif and bind DNA in a sequence-specific manner, while other members of this family (e.g., HMGB1) have multiple HMG boxes and bind DNA in a sequence-independent but structure-dependent manner. While TOX has a single HMG-box motif, it is predicted to bind DNA in a sequence-independent manner. TOX is also a member of a small subfamily of proteins (TOX2, TOX3, and TOX4) that share almost identical HMG-box sequences. TOX3 has been identified as a breast cancer susceptibility locus. TOX is highly expressed in the thymus, the site of development of T lymphocytes. Knockout mice that lack TOX have a severe defect in development of certain subsets of T lymphocytes.
In cancer or during chronic viral infection, TOX is necessary for T cell persistence but also drives T-cell "exhaustion" thus contributing to diminished anti-tumor or anti-viral function in these cells.
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^Wilkinson B, Chen JY, Han P, Rufner KM, Goularte OD, Kaye J (Mar 2002). "TOX: an HMG box protein implicated in the regulation of thymocyte selection". Nat Immunol. 3 (3): 272–80. doi:10.1038/ni767. PMID11850626.