Recombinant Human Dickkopf-related protein 1 (DKK1) (Active)

Function

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 (PubMed:22000856). 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 (PubMed:17143291). Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti-apoptotic activity (By similarity)

Subcellular Location

Secreted

Tissue Specificity

Placenta

Subunit

Interacts with LRP6 (PubMed:11448771, PubMed:17804805, PubMed:20093360, PubMed:22000856). Interacts (via the C-terminal Cys-rich domain) with LRP5 (via beta-propeller regions 3 and 4); the interaction, enhanced by MESD and or KREMEN, antagonizes Wnt-mediated signaling (PubMed:19746449). Forms a ternary complex with LRP6 and KREM1 (PubMed:27524201). Interacts with KREM1 (PubMed:17804805)

• Fedi P. et al. Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling. — J. Biol. Chem. (1999)
• Krupnik V.E. et al. Functional and structural diversity of the human Dickkopf gene family. — Gene (1999)
• Tate G. et al. PubMed: CI-8G7JMR5JB5FSI (NOV-)
• Roessler E. et al. The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly. — Cytogenet. Cell Genet. (2000)
• Clark H.F. et al. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. — Genome Res. (2003)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)