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. Note: This description may include information from UniProtKB.
Protein type: Secreted; Secreted, signal peptide; Inhibitor protein
Chromosomal Location of Human Ortholog: 10q11.2
Cellular Component: extracellular space; early endosome membrane; plasma membrane; extracellular region
Molecular Function: signal transducer activity; protein binding; receptor antagonist activity; growth factor activity; low-density lipoprotein receptor binding
Biological Process: cellular morphogenesis during differentiation; negative regulation of skeletal muscle development; negative regulation of Wnt receptor signaling pathway; response to retinoic acid; regulation of receptor internalization; negative regulation of peptidyl-serine phosphorylation; negative regulation of transcription from RNA polymerase II promoter; negative regulation of BMP signaling pathway; mesoderm formation; hair follicle development; negative regulation of mesodermal cell fate specification; endoderm formation; forebrain development; regulation of endodermal cell fate specification; negative regulation of protein complex assembly; embryonic limb morphogenesis
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.