DKK1

Dickkopf homolog 1 (Xenopus laevis)

Identifiers

DKK1; DKK-1; SK

External IDs

OMIM: 605189 MGI: 1329040 HomoloGene: 7689 GeneCards: DKK1 Gene

Gene Ontology
Molecular function	• signal transducer activity • protein binding • growth factor activity • receptor antagonist activity • low-density lipoprotein particle receptor binding
Cellular component	• extracellular region • extracellular space • plasma membrane
Biological process	• negative regulation of transcription from RNA polymerase II promoter • negative regulation of transcription from RNA polymerase II promoter • cell morphogenesis involved in differentiation • regulation of receptor internalization • signal transduction • multicellular organismal development • endoderm development • embryonic limb morphogenesis • negative regulation of BMP signaling pathway • forebrain development • negative regulation of protein complex assembly • response to retinoic acid • negative regulation of peptidyl-serine phosphorylation • face morphogenesis • positive regulation of heart induction by negative regulation of canonical Wnt receptor signaling pathway • negative regulation of canonical Wnt receptor signaling pathway • negative regulation of canonical Wnt receptor signaling pathway • Wnt receptor signaling pathway involved in somitogenesis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
54.07 – 54.08 Mb

Chr 19:
30.62 – 30.62 Mb

PubMed search

[1]

[2]

Dickkopf-related protein 1 is a protein that in humans is encoded by the DKK1 gene.^[1]

This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the WNT signaling pathway. Elevated levels of DKK1 in bone marrow plasma and peripheral blood is associated with the presence of osteolytic bone lesions in patients with multiple myeloma.^[1]

Interactions

DKK1 has been shown to interact with LRP6.^[2]

References

^ ^a ^b "Entrez Gene: DKK1 dickkopf homolog 1 (Xenopus laevis)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=22943.
^ Semënov, M V; Tamai K, Brott B K, Kühl M, Sokol S, He X (Jun. 2001). "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6". Curr. Biol. (England) 11 (12): 951–61. doi:10.1016/S0960-9822(01)00290-1. ISSN 0960-9822. PMID 11448771.

Fedi P, Bafico A, Nieto Soria A, et al. (1999). "Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling". J. Biol. Chem. 274 (27): 19465–72. doi:10.1074/jbc.274.27.19465. PMID 10383463.
Krupnik VE, Sharp JD, Jiang C, et al. (1999). "Functional and structural diversity of the human Dickkopf gene family". Gene 238 (2): 301–13. doi:10.1016/S0378-1119(99)00365-0. PMID 10570958.
Roessler E, Du Y, Glinka A, et al. (2000). "The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly". Cytogenet. Cell Genet. 89 (3–4): 220–4. doi:10.1159/000015618. PMID 10965128.
Mao B, Wu W, Li Y, et al. (2001). "LDL-receptor-related protein 6 is a receptor for Dickkopf proteins". Nature 411 (6835): 321–5. doi:10.1038/35077108. PMID 11357136.
Semënov MV, Tamai K, Brott BK, et al. (2001). "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6". Curr. Biol. 11 (12): 951–61. doi:10.1016/S0960-9822(01)00290-1. PMID 11448771.
Zorn AM (2001). "Wnt signalling: antagonistic Dickkopfs". Curr. Biol. 11 (15): R592–5. doi:10.1016/S0960-9822(01)00360-8. PMID 11516963.
Shou J, Ali-Osman F, Multani AS, et al. (2002). "Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA". Oncogene 21 (6): 878–89. doi:10.1038/sj.onc.1205138. PMID 11840333.
Mao B, Wu W, Davidson G, et al. (2002). "Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling". Nature 417 (6889): 664–7. doi:10.1038/nature756. PMID 12050670.
Aguilera O,Fraga MF, Ballestar E, et al. (2006). "Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer". Oncogene 25 (29): 4116–21. doi:10.1038/sj.onc.1209439. PMID 16491118.
Brott BK, Sokol SY (2002). "Regulation of Wnt/LRP Signaling by Distinct Domains of Dickkopf Proteins". Mol. Cell. Biol. 22 (17): 6100–10. doi:10.1128/MCB.22.17.6100-6110.2002. PMC 133995. PMID 12167704. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133995.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Gregory CA, Singh H, Perry AS, Prockop DJ (2003). "The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow". J. Biol. Chem. 278 (30): 28067–78. doi:10.1074/jbc.M300373200. PMID 12740383.
Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=403697.
Tian E, Zhan F, Walker R, et al. (2004). "The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma". N. Engl. J. Med. 349 (26): 2483–94. doi:10.1056/NEJMoa030847. PMID 14695408.
Yamaguchi Y, Itami S, Watabe H, et al. (2004). "Mesenchymal–epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation". J. Cell Biol. 165 (2): 275–85. doi:10.1083/jcb.200311122. PMC 2172049. PMID 15117970. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2172049.
Caricasole A, Copani A, Caraci F, et al. (2004). "Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain". J. Neurosci. 24 (26): 6021–7. doi:10.1523/JNEUROSCI.1381-04.2004. PMID 15229249.
Colland F, Jacq X, Trouplin V, et al. (2004). "Functional Proteomics Mapping of a Human Signaling Pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442148.
Zhang Z, Henzel WJ (2005). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Sci. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2286551.
Niida A, Hiroko T, Kasai M, et al. (2004). "DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway". Oncogene 23 (52): 8520–6. doi:10.1038/sj.onc.1207892. PMID 15378020.
Lee AY, He B, You L, et al. (2004). "Dickkopf-1 antagonizes Wnt signaling independent of beta-catenin in human mesothelioma". Biochem. Biophys. Res. Commun. 323 (4): 1246–50. doi:10.1016/j.bbrc.2004.09.001. PMID 15451431.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.

DKK1

Interactions

References

Further reading