Comparative genomics on Dkk1 orthologs.
WNT family proteins bind to transmembrane proteins FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, FZD10, LRP5, LRP6, ROR1, ROR2, RYK, and also secreted proteins SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, and DAND4 (CER1). DKK family members antagonize WNT binding to LRPs, while SFRP family members antagonize WNT binding to FZDs. Here, we identified and characterized rat Dkk1 gene and cow Dkk1 gene by using bioinformatics. Rat and cow Dkk1 genes, consisting of four exons, were located within AC095296.4 and AC157142.1 genome sequences, respectively. Dkk1 gene at rat chromosome 1q52 was found to encode a 270-aa protein, showing 94.1, 81.5, 78.9, 53.7 and 48.1% total-amino-acid identity with mouse Dkk1, human DKK1, cow Dkk1, Xenopus dkk1 and zebrafish dkk1, respectively. Vertebrate Dkk1 orthologs were secreted proteins with two Cys rich regions, each containing ten conserved Cys residues. The C-terminal Cys rich region was well conserved among vertebrate Dkk1 orthologs. Nucleotide position 148898-147860 of AC009986.10 human genome sequence was identified as evolutionarily conserved human DKK1 promoter, and nucleotide position 55266-56301 of AC095296.4 rat genome sequence as evolutionarily conserved rat Dkk1 promoter. Human DKK1 promoter and rat Dkk1 promoter, showing 66.2% total nucleotide identity, were well conserved. TCF/LEF, CP2, POU2F1 (OCT1), HNF1 and FOXJ2-binding sites and TATA-box were conserved among human DKK1, rat Dkk1, mouse Dkk1, and cow Dkk1 promoters. Double TCF/LEF-binding sites within the proximal promoter region of mammalian Dkk1 orthologs are implicated in the negative feed back mechanism of WNT/beta-catenin signaling pathway.
Katoh
Yuriko
Y
M&M Medical BioInformatics, Hongo, Japan.
Katoh
Masaru
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016678:Genome; D023281:Genomics / Q000379:methods*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D040901:Proteomics / Q000379:methods; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D013045:Species Specificity; D015534:Trans-Activators / Q000378:metabolism; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; C501126:DKK1 protein, human; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D015534:Trans-Activators; D029961:Zebrafish Proteins; D051176:beta Catenin; C501128:dkk1b protein, zebrafish