Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene: DKK2 - dickkopf homolog 2 (Xenopus laevis)

Homo sapiens

Synonyms: Dickkopf-2, Dickkopf-related protein 2 precursor, Dkk-2, hDkk-2, UNQ682/PRO1316

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Katoh, M., Katoh, Y., Mao, B., Morvan, F., Michl, P., et al.

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Disease relevance of DKK2

DKK2 mRNA was expressed in Ewing's sarcoma, and fetal heart [1].

High impact information on DKK2

Furthermore, the expression of several CUTL1 target genes involved in proliferation and migration, such as DNA polymerase A and DKK2, was modulated by PKA-induced phosphorylation [2].
We show that Dkk1, unlike Dkk2, negatively regulates osteoblast differentiation and bone formation [3].
The related Dkk2, however, can function either as LRP6 agonist or antagonist, depending on the cellular context, suggesting that its activity is modulated by unknown co-factors [4].
We have recently identified the transmembrane proteins Kremen1 and -2 as additional Dkk receptors, which bind to both Dkk1 and Dkk2 with high affinity [4].
The Notch-DKK2 signaling loop, created or potentiated in primates, was complementary to WNT-DKK1 and BMP-IHH-SFRP1 signaling loops for negative regulation of canonical WNT signaling pathway [5].

Biological context of DKK2

Double NREs were identified within human DKK2 promoter by bioinformatics and human intelligence (Humint) [5].
Because DKK2 is a key player in the stem cell signaling network, the DKK2 gene at human chromosome 4q25 is a candidate tumor suppressor gene inactivated due to epigenetic silencing and/or deletion [5].
Comparative genomics on DKK2 and DKK4 orthologs [1].
TATA-box was identified within Dkk2 and Dkk4 promoters [1].

Anatomical context of DKK2

The human DKK2 gene was characterized as Notch signaling target in intestinal stem cells [5].
Unexpectedly, the Wnt antagonist Dkk2 is required for terminal osteoblast differentiation and mineralized matrix formation [3].

Associations of DKK2 with chemical compounds

Asn-linked glycosylation site at codon 52 was conserved among mammalian Dkk2 orthologs; however, Asn-linked glycosylation site was not identified among mammalian Dkk4 orthologs [1].

Other interactions of DKK2

Dkk3 and Dkk2 expression was also concentrated at crypt bases [6].

References

Comparative genomics on DKK2 and DKK4 orthologs. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2005)
CUTL1 is phosphorylated by protein kinase A, modulating its effects on cell proliferation and motility. Michl, P., Knobel, B., Downward, J. J. Biol. Chem. (2006)
Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. Morvan, F., Boulukos, K., Clément-Lacroix, P., Roman Roman, S., Suc-Royer, I., Vayssière, B., Ammann, P., Martin, P., Pinho, S., Pognonec, P., Mollat, P., Niehrs, C., Baron, R., Rawadi, G. J. Bone Miner. Res. (2006)
Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling. Mao, B., Niehrs, C. Gene (2003)
WNT antagonist, DKK2, is a Notch signaling target in intestinal stem cells: Augmentation of a negative regulation system for canonical WNT signaling pathway by the Notch-DKK2 signaling loop in primates. Katoh, M., Katoh, M. Int. J. Mol. Med. (2007)
Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis. Byun, T., Karimi, M., Marsh, J.L., Milovanovic, T., Lin, F., Holcombe, R.F. J. Clin. Pathol. (2005)