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Available structures
PDB Ortholog search: PDBe RCSB
Aliases KREMEN1, KREMEN, KRM1, kringle containing transmembrane protein 1
External IDs MGI: 1933988 HomoloGene: 12935 GeneCards: KREMEN1
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 22: 29.07 – 29.17 Mb Chr 11: 5.19 – 5.26 Mb
PubMed search [1] [2]
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Kremen protein 1 is a protein that in humans is encoded by the KREMEN1 gene.[3][4] Kremen1 is conserved in chordates including amphioxus[5] and most vertebrate species.[6] The protein is a type I transmembrane receptor of ligands Dickkopf1,[7] Dickkopf2, Dickkopf3, Dickkopf4, EpCAM[8] and Rspondin1.


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.[4]

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.[6] 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.[9]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. 
  4. ^ a b "Entrez Gene: KREMEN1 kringle containing transmembrane protein 1". 
  5. ^ 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. 
  6. ^ a b c 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 4716294Freely accessible. PMID 26206087. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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 2493355Freely accessible. PMID 18505822. 

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