KREMEN1

KREMEN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5FWS, 5FWT, 5FWV
Identifiers
Aliases	KREMEN1, KREMEN, KRM1, kringle containing transmembrane protein 1
External IDs	MGI: 1933988 HomoloGene: 12935 GeneCards: KREMEN1
Gene ontology Molecular function • protein binding Cellular component • integral component of membrane • membrane Biological process • regulation of canonical Wnt signaling pathway • cell communication • Wnt signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	83999	84035
Ensembl	ENSG00000183762	ENSMUSG00000020393
UniProt	Q96MU8	Q99N43
RefSeq (mRNA)	NM_001039570 NM_032045 NM_153379	NM_032396
RefSeq (protein)	NP_001034659.2 NP_114434.3	NP_115772.2
Location (UCSC)	Chr 22: 29.07 – 29.17 Mb	Chr 11: 5.19 – 5.26 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

Kremen protein 1 is a protein that in humans is encoded by the KREMEN1 gene.^[3][4] Kremen1 is non-conserved in invertebrates but at least two homologs are found in vertebrate species. The protein is a type I transmembrane receptor of ligands Dickkopf1,^[5] Dickkopf2, Dickkopf3, Dickkopf4, EpCAM^[6] 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.^[4]

Kremen1 also has a function in the induction of cell death by apoptosis.^[7] This proapototic activity is conditional and depends on the absence of ligand Dickkopf1.^[7] These observations led to the classification of this protein as a Dependence Receptor.

A mouse knock out of Kremen1 and its paralog Kremen2 has no obvious phenotype and is viable and fertile.^[8]

References

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. "Entrez Gene: KREMEN1 kringle containing transmembrane protein 1".
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. 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.
8. 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

• 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.
• Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• 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.
• 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.
• Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
• Dunham I, Shimizu N, Roe BA, et al. (1999). "The DNA sequence of human chromosome 22.". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.