Dickkopf-related protein 1; Dickkopf-1; Dkk-1; hDkk-1; SK (DKK1)

Function

• antagonizes canonical Wnt signaling by inhibiting LRP5 &/or LRP6
• blocks canonical Wnt-mediated activation of beta-catenin signaling & induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes
  • affects the anagen-to-catagen transition in the hair cycle
  • in male pattern baldness, high tissue levels of androgen- inducible DKK-1 may produce the same effects
• interaction with Wnt & by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5 &/or LRP6
• DKKs play a role in vertebrate development, where they locally inhibit Wnt regulated processes such as anteroposterior axial patterning, limb development, somitogenesis & eye formation
• in adults, Dkks are implicated in bone formation
• interacts with LRP6
• interacts (via the C-termianl Cys-rich domain) with LRP5 (via beta-propeller regions 3 & 4)
  • interaction is enhanced by MESD & or KREMEN
  • interaction antagonizes Wnt-mediated signaling

Structure

• the C-terminal cysteine-rich domain mediates interaction with LRP5 & LRP6 (putative)
• belongs to the dickkopf family

Compartment

secreted

Expression

• placenta
• induced by androgens

Pathology

• Dkks are implicated in bone disease, cancer & Alzheimer disease
• may play a role in male-pattern baldness

More general terms

• Dickkopf homolog

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=22943
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:22943
• OMIM: https://mirror.omim.org/entry/605189
• UniProt: http://www.uniprot.org/uniprot/O94907.html