DKK4, like DKK1, DKK2, and DKK3, 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 detected no expression of DKK4, but RT-PCR analysis detected DKK4 expression in cerebellum, T-cell, esophagus, and lung cDNA libraries. DKK4 blocks Xenopus Wnt8, Wnt3a, and Wnt2b, but not Dsh or Fz8, induction of a secondary axis in frog embryos, indicating that DKKs antagonize WNT function upstream of WNT receptors.
Alternate names: Dickkopf-related protein 4, Dkk-4