功能 |
Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero- posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (By similarity).
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總結(jié) |
DKK3, like DKK1, DKK2, and DKK4, possesses an N-terminal signal peptide and 2 conserved cysteine-rich domains, which are separated by a linker region and contain 10 cysteine residues each. The second cysteine region has a putative lipid-binding function that may facilitate WNT/DKK interactions at the plasma membrane. The linker region contains 50 to 55 amino acids in DKK1, DKK2, and DKK4, whereas in DKK3 it contains only 12 amino acids. All DKKs have several potential sites for cleavage by furin-type proteases. Northern blot analysis revealed wide expression of the DKK3 transcript, with highest expression in heart, brain, and spinal cord. In situ hybridization reveals highest expression in mouse brain, eye, and heart.
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