KREMEN1

Kremen protein 1 is a protein that in humans is encoded by the KREMEN1 gene.[5][6] Kremen1 is conserved in chordates including amphioxus[7] and most vertebrate species.[8] The protein is a type I transmembrane receptor of ligands Dickkopf1,[9] Dickkopf2, Dickkopf3, Dickkopf4, EpCAM[10] and Rspondin1.

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, ECTD13
External IDs	OMIM: 609898 MGI: 1933988 HomoloGene: 12935 GeneCards: KREMEN1
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q12.1 Start 29,073,078 bp[1] End 29,168,333 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A1 Start 5,191,552 bp[2] End 5,261,558 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding Cellular component • integral component of membrane • membrane • cell membrane • neuronal cell body Biological process • regulation of canonical Wnt signaling pathway • cell communication • Wnt signaling pathway • apoptotic process • negative regulation of ossification • limb development • negative regulation of canonical Wnt signaling pathway • negative regulation of axon regeneration 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 NP_114434	NP_115772
Location (UCSC)	Chr 22: 29.07 – 29.17 Mb	Chr 11: 5.19 – 5.26 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

Kremen1 also has a function in the induction of cell death by apoptosis.[8] This proapototic activity is conditional and depends on the absence of ligand Dickkopf1.[8] 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.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000183762 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020393 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: KREMEN1 kringle containing transmembrane protein 1".
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.