Metalloprotease TIKI1 (TRABD2A)

Metalloprotease TIKI1 (TRABD2A) is a membrane-associated metalloprotease that functions primarily as a negative regulator of the Wnt signaling pathway by cleaving the N-terminal residues of select Wnt proteins, specifically WNT3A and WNT5, leading to their inactivation via oxidation and disulfide-bonded oligomer formation[1][3][4][5]. This activity modulates embryonic development, particularly head formation, and regulates tissue homeostasis and stem cell proliferation in adults. TIKI1 is classified as a member of a new superfamily of enzymes termed the TIKI/TraB superfamily, sharing structural and mechanistic features with DUF399 and bacterial erythromycin esterases[2]. Aberrant Wnt regulation is implicated in cancers, neurodegenerative, and inflammatory diseases, placing TIKI1 at a critical node for these conditions, though no direct drugs, mechanisms of pharmacological modulation, or clinical biomarkers are currently established for TRABD2A[3][2].

Other names

TraB domain containing 2ATIKI1C2orf89TRAB domain-containing protein 2AUPF0632 protein C2orf89LOC105374836