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Reliable, easy-to-read patient information on common medical conditions — written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.

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KREMEN1

Introduction

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.[4] The protein is a type I transmembrane receptor of ligands Dickkopf1,[5] Dickkopf2, Dickkopf3, Dickkopf4, EpCAM[6] and Rspondin1.

Function

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.[2]

Kremen1 also has a function in the induction of cell death by apoptosis.[4] This proapototic activity is conditional and depends on the absence of ligand Dickkopf1.[4] 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]

References

References

  1. ↑ Nakamura T, Aoki S, Kitajima K, Takahashi T, Matsumoto K, Nakamura T (Mar 2001). “Molecular cloning and characterization of Kremen, a novel kringle-containing transmembrane protein”. Biochim Biophys Acta. 1518 (1–2): 63–72. doi:10.1016/s0167-4781(01)00168-3. PMID 11267660.
  2. ↑ 2.0 2.1 “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. doi:10.1016/S1673-8527(09)60082-5. ISSN 1673-8527. PMID 20933216.
  4. ↑ 4.0 4.1 4.2 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. doi:10.1038/cdd.2015.100. ISSN 1476-5403. PMC 4716294. PMID 26206087.
  5. ↑ 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. doi:10.1038/nature756. ISSN 0028-0836. PMID 12050670.
  6. ↑ 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. doi:10.1016/j.devcel.2013.01.021. ISSN 1878-1551. PMID 23484855.
  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. doi:10.1128/MCB.00222-08. ISSN 1098-5549. PMC 2493355. PMID 18505822.
Further reading

Further reading