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Identification and characterization of human CKTSF1B2 and CKTSF1B3 genes in silico
1M&M Medical BioInformatics, Narashino 275-0022, Japan.
Abstract:
Bone morphogenetic proteins (BMPs) are implicated in the regulation of morphogenesis and proliferation during embryogenesis and carcinogenesis. We have previously reported over-expression of BMP4 in diffuse-type gastric cancer cells. BMP signaling is regulated by tissue-specific expression of ligands and receptors as well as by secreted-type antagonists, such as CKTSF1B1 (Gremlin), CER1 (Cerberus 1), Noggin, SOSTDC1 (Ectodin), and Chordin. Here, we identified two novel genes related to CKTSF1B1 and CER1 by using bioinformatics. Two novel members of human CKTSF1B gene family were designated CKTSF1B2 (GREM2 or PRDC) and CKTSF1B3 (GREM3 or DANTE). FLJ21195 (BC046632.1) was the representative human CKTSF1B2 cDNA, and CKTSF1B2 gene was mapped to human chromosome 1q43. Human CKTSF1B2 showed 94.0% total amino-acid identity with mouse Cktsf1b2 (Prdc). FLJ38607 (AK095926.1) was the representative human CKTSF1B3 cDNA, and CKTSF1B3 gene was mapped to human chromosome 19p13.2. Human CKTSF1B3 showed 61.9% total amino-acid identity with mouse Cktsf1b2 (Dante). N-terminal signal peptide and DAN domain with nine cysteine residues were conserved among CKTSF1B1, CKTSF1B2, CKTSF1B3 and CER1. Phylogenetic analyses revealed that CKTSF1B2 was more related to CKTSF1B1, and that CKTSF1B3 was more related to CER1. CKTSF1B1, CKTSF1B2, CKTSF1B3 and CER1 constitute the CKTSF1B family among secreted-type cysteine knot superfamily proteins. This is the first report on identification and characterization of the human CKTSF1B2 and CKTSF1B3 genes.
Insights
Researchers identified two novel human genes, CKTSF1B2 and CKTSF1B3, related to bone morphogenetic protein (BMP) signaling antagonists. These findings expand the known CKTSF1B gene family, crucial for embryonic development and cancer research.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Bone morphogenetic proteins (BMPs) regulate key cellular processes including embryogenesis and carcinogenesis.
- BMP signaling is modulated by secreted antagonists, with CKTSF1B1 (Gremlin) and CER1 (Cerberus 1) previously identified.
- Over-expression of BMP4 has been observed in diffuse-type gastric cancer.
Purpose of the Study:
- To identify novel genes associated with BMP signaling antagonists.
- To characterize the newly identified human CKTSF1B2 and CKTSF1B3 genes.
- To analyze the evolutionary relationships within the CKTSF1B gene family.
Main Methods:
- Bioinformatic analysis was employed to identify novel genes related to CKTSF1B1 and CER1.
- Gene mapping and sequence identity analysis were performed for the novel human genes.
- Phylogenetic analysis was used to determine evolutionary relationships among family members.
Main Results:
- Two novel human genes, CKTSF1B2 (GREM2/PRDC) and CKTSF1B3 (GREM3/DANTE), were identified.
- CKTSF1B2 maps to chromosome 1q43 and shares 94.0% amino-acid identity with mouse Cktsf1b2.
- CKTSF1B3 maps to chromosome 19p13.2 and shares 61.9% amino-acid identity with mouse Cktsf1b2 (Dante).
- Conserved N-terminal signal peptide and DAN domain with nine cysteine residues were found across CKTSF1B1, CKTSF1B2, CKTSF1B3, and CER1.
- Phylogenetic analysis indicated CKTSF1B2 is closely related to CKTSF1B1, and CKTSF1B3 is related to CER1.
- CKTSF1B1, CKTSF1B2, CKTSF1B3, and CER1 form the CKTSF1B family within secreted-type cysteine knot superfamily proteins.
Conclusions:
- This study reports the first identification and characterization of human CKTSF1B2 and CKTSF1B3 genes.
- These novel genes expand the known human CKTSF1B gene family, contributing to understanding BMP signaling regulation.
- The findings provide a foundation for further research into the roles of these genes in development and disease.

