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, ECTD13
External IDs	OMIM: 609898; MGI: 1933988; HomoloGene: 12935; GeneCards: KREMEN1; OMA:KREMEN1 - orthologs
Gene location (Human) Chr. Chromosome 22 (human) [1] Band 22q12.1 Start 29,073,035 bp [1] End 29,168,333 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11|11 A1 Start 5,141,552 bp [2] End 5,211,558 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of arm decidua parotid gland cardiac muscle tissue of right atrium vena cava tibialis anterior muscle myocardium of left ventricle gingival epithelium Skeletal muscle tissue of rectus abdominis body of tongue Top expressed in interventricular septum lip muscle layer of urethra thymus vestibular membrane of cochlear duct muscle of thigh soleus muscle ascending aorta aortic valve esophagus More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding Cellular component integral component of membrane membrane plasma membrane soma 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: 5.14 – 5.21 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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. Bibcode:2002Natur.417..664M. doi:10.1038/nature756. ISSN   0028-0836. PMID   12050670. S2CID   4418943.
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. S2CID   27764390.
• 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. Bibcode:2002PNAS...9916899M. 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. Bibcode:2002Natur.417..664M. doi:10.1038/nature756. PMID   12050670. S2CID   4418943.
• 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. Bibcode:2000PNAS...97.3491D. 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. Bibcode:1999Natur.402..489D. doi: 10.1038/990031 . PMID   10591208.