Kringle-containing transmembrane protein 2 (KREMEN2)

Kringle-containing transmembrane protein 2 (KREMEN2) is a type-I transmembrane protein and high-affinity receptor for Dickkopf (DKK) family proteins, especially DKK1. By forming a ternary complex with DKK1 and the Wnt co-receptor LRP5/6, KREMEN2 induces endocytosis and removal of Wnt receptors from the cell membrane, thereby inhibiting Wnt/beta-catenin signaling. This regulatory action is critical for appropriate embryonic development, tissue patterning, bone formation, and stem cell differentiation. KREMEN2 is upregulated in several types of cancer and may influence tumor proliferation, migration, and apoptosis, serving both as a potential therapeutic target and disease biomarker. It contains characteristic kringle, WSC, and CUB extracellular domains, and is distinct from other receptor families. Mutations or altered expression of KREMEN2 are associated with genetic syndromes and limb defects, underscoring its developmental importance

Other names

KREMEN2Kremen protein 2KRM2Dickkopf receptor 2MGC10791Kringle domain-containing transmembrane protein 2Kringle-containing protein marking the eye and the nose

Inhibition of Wnt/beta-catenin signaling via promoting endocytosis and removal of LRP5/LRP6 in cooperation with Dickkopf proteins (primarily DKK1 and DKK2) Induction of apoptosis and cell cycle arrest by KREMEN2 knockdown (e.g. via modulation of PI3K/Akt pathway in cancer models)