KREMEN1 explained

Kremen protein 1 is a protein that in humans is encoded by the KREMEN1 gene.^{[1] [2]} Kremen1 is conserved in chordates including amphioxus^[3] and most vertebrate species. The protein is a type I transmembrane receptor of ligands Dickkopf1,^[4] Dickkopf2, Dickkopf3, Dickkopf4, EpCAM^[5] and Rspondin1.

Function

This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor that functionally cooperates with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein is a component of a membrane complex that modulates canonical WNT signaling through lipoprotein receptor-related protein 6 (LRP6). It contains extracellular Kringle, WSC, and CUB domains. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene.

Kremen1 also has a function in the induction of cell death by apoptosis.^[6] This proapototic activity is conditional and depends on the absence of ligand Dickkopf1. These observations led to the classification of this protein as a Dependence Receptor.

A mouse knock out of Kremen1 and its paralog Kremen2 is viable and fertile.^[7]

Further reading

• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Brandenberger R, Wei H, Zhang S, etal . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. . Nat. Biotechnol. . 22 . 6 . 707–16 . 2005 . 15146197 . 10.1038/nbt971 . 27764390 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Mao B, Wu W, Davidson G, etal . Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. . Nature . 417 . 6889 . 664–7 . 2002 . 12050670 . 10.1038/nature756 . 2002Natur.417..664M . 4418943 .
• Dias Neto E, Correa RG, Verjovski-Almeida S, etal . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. . Proc. Natl. Acad. Sci. U.S.A. . 97 . 7 . 3491–6 . 2000 . 10737800 . 10.1073/pnas.97.7.3491 . 16267 . 2000PNAS...97.3491D . free .
• Dunham I, Shimizu N, Roe BA, etal . The DNA sequence of human chromosome 22. . Nature . 402 . 6761 . 489–95 . 1999 . 10591208 . 10.1038/990031 . 1999Natur.402..489D . free .

Notes and References

1. Nakamura T, Aoki S, Kitajima K, Takahashi T, Matsumoto K, Nakamura T . Molecular cloning and characterization of Kremen, a novel kringle-containing transmembrane protein . Biochim Biophys Acta . 1518 . 1–2 . 63–72 . Mar 2001 . 11267660 . 10.1016/s0167-4781(01)00168-3.
2. Web site: Entrez Gene: KREMEN1 kringle containing transmembrane protein 1.
3. Zhang. Yujun. Mao. Bingyu. 2010-09-01. Embryonic expression and evolutionary analysis of the amphioxus Dickkopf and Kremen family genes. Journal of Genetics and Genomics = Yi Chuan Xue Bao. 37. 9. 637–645. 10.1016/S1673-8527(09)60082-5. 1673-8527. 20933216.
4. Mao. Bingyu. Wu. Wei. Davidson. Gary. Marhold. Joachim. Li. Mingfa. Mechler. Bernard M.. Delius. Hajo. Hoppe. Dana. Stannek. Peter. 2002-06-06. Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature. 417. 6889. 664–667. 10.1038/nature756. 0028-0836. 12050670. 2002Natur.417..664M. 4418943.
5. Lu. Huiqiang. Ma. Jun. Yang. Yun. Shi. Wenchao. Luo. Lingfei. 2013-03-11. EpCAM is an endoderm-specific Wnt derepressor that licenses hepatic development. Developmental Cell. 24. 5. 543–553. 10.1016/j.devcel.2013.01.021. 1878-1551. 23484855. free.
6. Causeret. F.. Sumia. I.. Pierani. A.. 2016-02-01. Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner. Cell Death and Differentiation. 23. 2. 323–332. 10.1038/cdd.2015.100. 1476-5403. 4716294. 26206087.
7. Ellwanger. Kristina. Saito. Hiroaki. Clément-Lacroix. Philippe. Maltry. Nicole. Niedermeyer. Joachim. Lee. Woon Kyu. Baron. Roland. Rawadi. Georges. Westphal. Heiner. 2008-08-01. Targeted disruption of the Wnt regulator Kremen induces limb defects and high bone density. Molecular and Cellular Biology. 28. 15. 4875–4882. 10.1128/MCB.00222-08. 1098-5549. 2493355. 18505822.