DKK1: 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. Interacts with LRP6. Interacts (via the C-termianl Cys- rich domain) with LRP5 (via beta-propeller regions 3 and 4); the interaction, enhanced by MESD and or KREMEN, antagonizes Wnt- mediated signaling. Placenta. Belongs to the dickkopf family.
Protein type: Inhibitor; Secreted, signal peptide; Secreted
Chromosomal Location of Human Ortholog: 10q11.2
Cellular Component: early endosome membrane; extracellular region; extracellular space; plasma membrane
Molecular Function: growth factor activity; low-density lipoprotein receptor binding; protein binding; receptor antagonist activity; signal transducer activity
Biological Process: cellular morphogenesis during differentiation; embryonic limb morphogenesis; endoderm formation; forebrain development; hair follicle development; mesoderm formation; negative regulation of BMP signaling pathway; negative regulation of mesodermal cell fate specification; negative regulation of peptidyl-serine phosphorylation; negative regulation of protein binding; negative regulation of skeletal muscle development; negative regulation of synaptogenesis; negative regulation of transcription from RNA polymerase II promoter; negative regulation of Wnt receptor signaling pathway; regulation of endodermal cell fate specification; regulation of receptor internalization; response to retinoic acid
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