Selenoprotein K (SELENOK)

Selenoprotein K (SELENOK) is a small, intrinsically disordered, single-pass transmembrane protein localized to the endoplasmic reticulum (ER) membrane, containing the rare amino acid selenocysteine. Unlike many other selenoproteins, SELENOK does not possess intrinsic enzymatic activity but serves as a cofactor that partners with the ER-resident acyltransferase DHHC6 to promote protein palmitoylation, notably of the inositol 1,4,5-trisphosphate receptor (IP3R) and transferrin receptor 1 (TfR-1)[1][3]. These modifications are critical for stabilizing target proteins, maintaining calcium flux in immune cells, and preserving iron homeostasis in neurons, respectively. SELENOK functions in ER-associated degradation (ERAD), facilitates immune cell activation, protects against ER stress-induced apoptosis, and plays a neuroprotective role via its effect on cellular and mitochondrial iron content[1][2][3]. Deficiency impairs immune, neurological, and metabolic functions, and altered SELENOK function has been linked to cancer progression, immune deficiencies, iron-related neurodegeneration, and ER stress-associated diseases[1][2][3]. SELENOK is considered a therapeutic target in cancer and immune modulation, although no direct drug modulators are currently described in the literature[1]. Loss or dysfunction leads to impaired immune cell activation, defective calcium signaling, decreased palmitoylation of protein targets (IP3R, TfR-1, CD36), and mitochondrial dysfunction due to iron mismanagement[1][3].

Other names

SELKHSPC030HSPC297SelKselenoprotein K

Enhanced or stabilized palmitoylation of protein targets (e.g., IP3R, TfR-1) through interaction with the acyltransferase DHHC6; Regulation of store-operated calcium entry (SOCE) in immune cells; Modulation of cellular response to ER stress and protein folding burden