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Details for messenger / hormone: Dkk1

EndoNet ID: ENH00498

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Synonyms

  • SK
  • dickkopf-related protein 1
  • Dkk1
  • dkk 1
  • Dkk-1
  • dickkopf 1
  • dickkopf1
  • hDkk-1
  • dickkopf related protein-1

General information

  • The human Dkk-1 gene, a transcriptional target of the p53 tumor suppressor, encodes a powerful inhibitor of the Wnt signaling pathway and regulates the spatial patterning/morphogenesis of the mammalian central nervous system. [1]
  • LRP inhibitor.
  • Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. [2]
  • Induction of Dickkopf-1 is associated with neuronal degeneration in Alzheimer's brain. [3]
  • Dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. [4]
  • Dkk proteins compete for the Lrp5/6 receptor to prevent activation of the canonical signaling pathway. [5]
  • Human Dkk-1 responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA. [1]
  • Dickkopf1 is a secreted protein that acts as a Wnt inhibitor. [6]
  • Secreted inhibitor of Wnt signaling.
  • Dkk-1 antagonizes Wnt signaling upstream of its effect on beta-catenin regulation. [7]
  • Dkks limit the availability of Lrp5/6 receptors to Wnts by sequestring Lrp5/6 into complexes with Kremens and possibly promoting their internalization to lysosomes. [5]
  • Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning. [6]

Classification

Hormone function

  • development and growth
    • embryogenesis

    Chemical classification

    Composition

    Dickkopf homolog 1 mature peptide

    Sequence
    TLNSVLNSN AIKNLPPPL GGAAGHPGS 
    AVSAAPGIL YPGGNKYQT IDNYQPYPC 
    AEDEECGTD EYCASPTRG GDAGVQICL 
    ACRKRRKRC MRHAMCCPG NYCKNGICV 
    SSDQNHFRG EIEETITES FGNDHSTLD 
    GYSRRTTLS SKMYHTKGQ EGSVCLRSS 
    DCASGLCCA RHFWSKICK PVLKEGQVC 
    TKHRRKGSH GLEIFQRCY CGEGLSCRI 
    QKDHHQASN SSRLHTCQR H

    Links to other resources

    UniProt O94907
    Ensembl ENST00000373970
    KEGG hsa:22943
    • Anatomical structure: hippocampus

      • Dkk-1 is specifically found in degenerating neurons of patients affected by mesial temporal lobe epilepsy associated with hippocampal sclerosis. [8]
      • All samples (bioptic or autoptic) with histological evidence of hippocampal sclerosis showed a robust expression of Dkk-1 in the hippocampus. [8]
    • Anatomical structure: pancreas

    • Anatomical structure: osteoblast

    • Anatomical structure: brain

    • Anatomical structure: placenta

    Targets

    Cellkremen 1kremen 2LRP5LRP6
    adrenal cortex Present
    beta cell of islet of Langerhans Present
    brain Present
    eye Present
    hepatocyte Present
    kidney Present
    Kupffer cell stellate cell of liver Present
    lipocyte of liver Present
    Phenotypes
    • positive regulation of cell-matrix adhesion
    macrophage Present
    osteoblast Present
    Present
    uterus Present
    Reference