DKK1

This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

Full Name

Dickkopf WNT Signaling Pathway Inhibitor 1

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).

Biological Process

Learning or memory Source: ARUK-UCL
Limb development Source: UniProtKB
Modulation of age-related behavioral decline Source: ARUK-UCL
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
Negative regulation of canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment Source: BHF-UCL
Negative regulation of cardiac muscle cell differentiation Source: BHF-UCL
Negative regulation of mesodermal cell fate specification Source: BHF-UCL
Negative regulation of ossification Source: UniProtKB
Negative regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
Negative regulation of peptidyl-serine phosphorylation Source: BHF-UCL
Negative regulation of protein binding Source: ParkinsonsUK-UCL
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Negative regulation of Wnt-Frizzled-LRP5/6 complex assembly Source: ParkinsonsUK-UCL
Negative regulation of Wnt signaling pathway Source: UniProtKB
Positive regulation of cell death Source: ARUK-UCL
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
Positive regulation of JUN kinase activity Source: ARUK-UCL
Positive regulation of neuron death Source: ARUK-UCL
Positive regulation of tau-protein kinase activity Source: ARUK-UCL
Positive regulation of Wnt signaling pathway, calcium modulating pathway Source: ARUK-UCL
Positive regulation of Wnt signaling pathway, planar cell polarity pathway Source: ARUK-UCL
Regulation of dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
Regulation of endodermal cell fate specification Source: BHF-UCL
Regulation of receptor internalization Source: BHF-UCL
Synapse pruning Source: ParkinsonsUK-UCL
Wnt signaling pathway Source: UniProtKB-KW

Cellular Location

Secreted