Biomedical subjects

Masaru Katoh

Publications and source records attributed to Masaru Katoh.

At least 55 records · Page 3Linked to original sources

PubMed2005

Comparative genomics on Wnt3-Wnt9b gene cluster.

WNT signals, transduced through Frizzled (FZD) receptors with extracellular WNT-binding domain and cytoplasmic Dishevelled-binding domain, are implicated in carcinogenesis and embryogenesis. WNT3-WNT9B (WNT14B) locus (17q21.31) and WNT3A-WNT9A (WNT14) locus (1q42.13) are paralogous regions within the human genome. Here, the rat Wnt3 and Wnt9b genes were identified and characterized by using bioinformatics. Wnt3 and Wnt9b genes at rat chromosome 10q32.1 were clustered in head-to-head manner with an interval of about 24 kb within AC105632.3 genome sequence. The rat Wnt3 gene, consisting of five exons, encoded a 355-aa protein with N-terminal signal peptide, 24 conserved Cys residues and two Asn-linked glycosylation sites. The rat Wnt9b gene, consisting of four exons, encoded a 359-aa protein with N-terminal signal peptide, 24 conserved Cys residues and one Asn-linked glycosylation site. The rat Wnt3 core promoter showed 80.5% nucleotide identity with human WNT3 core promoter, while rat Wnt9b core promoter showed 45.6% nucleotide identity with human WNT9B core promoter. MYB (c-Myb), ELK1, POU2F1 (OCT1), HNF4A (HNF-4), COMP1, NFYA (NF-Y) and NKX2-5 binding sites were conserved between rat Wnt3 and human WNT3 core promoters. The Wnt3-Wnt9b intergenic conserved region (IGCR), corresponding to nucleotide position 124747-125252 of AC105632.3 genome sequence, showed 85.6% nucleotide identity with human WNT3-WNT9B IGCR. GC content of rat Wnt3-Wnt9b IGCR was 59.5%. Wnt3-Wnt9b IGCR was predicted as regulatory element rather than gene because cDNA or EST derived from Wnt3-Wnt9b IGCR was not identified. This is the first report on the rat Wnt3 and Wnt9b genes as well as on comparative genomics on the Wnt3-Wnt9b gene cluster.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Wnt5a and Wnt5b genes.

Canonical WNTs (WNT2, WNT2B, etc) activate the beta-catenin-TCF pathway to induce carcinogenesis, while non-canonical WNTs (WNT5A, WNT11, etc) activate the planar cell polarity (PCP) pathway to induce cell motility and metastasis. WNT5A gene at chromosome 3p14.3 and WNT5B gene at chromosome 12p13.33 are paralogs within the human genome. Here, we identified and characterized rat Wnt5a and Wnt5b genes by using bioinformatics. Rat Wnt5a and Wnt5b genes, consisting of five exons, were identified within AC095764.5 and AC112027.3 genome sequences, respectively. Rat Wnt5a (380 aa) and Wnt5b (359 aa) were secreted proteins with 24 conserved Cys residues and four Asn-linked glycosylation sites, which showed 75.8% total-amino-acid identity. Nucleotide position 182586-183836 of AC095764.5 genome sequence and nucleotide position 161044-159886 of AC121764.2 genome sequence were identified as evolutionarily conserved rat Wnt5a and human WNT5A promoters, respectively. Nucleotide identity between rat Wnt5a and human WNT5A promoters was 72.5%. E47 and NKX2-5-binding sites were evolutionarily conserved among rat Wnt5a, mouse Wnt5a, and human WNT5A promoters. On the other hand, rodent Wnt5b promoters and human WNT5B promoter were significantly divergent. Up-regulation of Wnt5b during rodent adipocytic differentiation does not simply indicate the implication of WNT5B in human adipogenesis. Real susceptibility gene for type 2 diabetes, associated with SNP within intron 3 of human WNT5B gene (IMS-JST024404), remains to be identified. This is the first report on rat Wnt5a and Wnt5b genes as well as on comparative genomics for Wnt5a and Wnt5b orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Wnt16 orthologs.

The WNT16 gene at human chromosome 7q31.31 encodes two isoforms due to alternative splicing of an alternative promoter type. Here, we identified and characterized the rat Wnt16 and zebrafish wnt16 genes using bioinformatics. The rat Wnt16 and zebrafish wnt16 genes, consisting of four exons, were located within the AC117014.4 and CR925699.1 genome sequences, respectively. Exons 1b, 2, 3 and 4 of the human WNT16 gene were conserved in the rodent Wnt16 and zebrafish wnt16 genes; however, exon 1a of the human WNT16 gene was not conserved. Human WNT16 isoform 1 (NM_057168.1), consisting of exons 1b, 2, 3 and 4, was identified as the evolutionarily conserved representative isoform. Because zebrafish NM_207096.1 was an aberrant wnt16 cDNA with a retained 3'-part intron 1, complete CDS of representative zebrafish wnt16 was determined by deleting nucleotide position 183-239 from NM_207096.1 aberrant cDNA. Rat Wnt16 (364 aa) with an N-terminal signal peptide, 24 Cys residues and 3 Asn-linked glycosylation sites showed 97.3, 90.4 and 65.9% total-amino-acid identity with mouse Wnt16, human WNT16, and zebrafish wnt16, respectively. Phylogenetic analyses on WNT family members revealed that WNT16 was most closely related to WNT7A and WNT7B paralogs. Promoters of human WNT16, rat Wnt16 and mouse Wnt16 genes were well conserved. Double CCAAT motifs were conserved among mammalian Wnt16 promoters. This is the first report on the rat Wnt16 and zebrafish wnt16 genes, as well as the double CCAAT motifs within the core promoter regions of mammalian Wnt16 orthologs.

Amino Acid Motifs↗

PubMed2005

Comparative genomics on Wnt7a orthologs.

WNT and Hedgehog signaling pathways network together during carcinogenesis and embryogenesis. WNT7A mRNA is expressed in human gastric and pancreatic cancer cells. WNT7A mRNA expression is relatively high in the temporal, occipital and parietal lobes, paracentral gyrus of the cerebral cortex, caudate nucleus, hippocampus, medulla oblongata and putamen within the adult human brain. Here, we identified and characterized the rat Wnt7a gene using bioinformatics. The rat Wnt7a gene, consisting of four exons, was located within the AC106100.7 genome sequence. Rat Wnt7a (349 aa) with 24 Cys residues and 3 Asn-linked glycosylation sites showed 99.7, 99.1 and 93.7% total-amino- acid identity with mouse Wnt7a, human WNT7A and chicken wnt7a, respectively. The N-terminal signal peptide was not identified within the Wnt7a orthologs. Exonic regions, except the 3'-UTR, were conserved between the rat Wnt7a and human WNT7A genes; however, the 5'-flanking region was significantly divergent between the rat Wnt7a and human WNT7A genes. Although the COMP1- and ELK1-binding sites within exon 1 were conserved among mammalian Wnt7a promoters, transcriptional regulation of the rodent Wnt7a orthologs was predicted to be distinct from that of human WNT7A based on the divergence within the 5'-flanking promoter region. Therefore, biological functions of rodent Wnt7a are not always consistent with those of human WNT7A due to promoter evolution. This is the first report on the rat Wnt7a gene and comparative genomics for Wnt7a orthologs.

Animals↗

PubMed2005

Comparative genomics on Wnt11 gene.

Non-canonical WNTs activate the planar cell polarity (PCP) pathway to induce cell motility and metastasis, while canonical WNTs activate the beta-catenin-TCF pathway to induce carcinogenesis. WNT11 gene at human chromosome 11q13.5 encodes non-canonical WNT11 protein, which is applicable for regenerative medicine of heart diseases. Here, we identified and characterized rat Wnt11 gene by using bioinformatics. Rat Wnt11 gene, consisting of five exons, was identified within AC120107.3 genome sequence. Rat Wnt11 (354 aa) was a secreted protein with 24 conserved Cys residues and five Asn-linked glycosylation sites. Rat Wnt11 showed 99.4%, 97.5%, 84.5% and 76.0% total-amino-acid identity with mouse Wnt11, human WNT11, chicken wnt11 and zebrafish wnt11, respectively. Comparative proteomics revealed that the number of Asn-linked glycosylation sites increased during molecular evolution of Wnt11 orthologs. Comparative genomics revealed that exon 1, but not 5'-flanking region, was well conserved between rat Wnt11 and human WNT11 genes. Although conserved transcription-factor-binding site was not identified within 5'-flanking region of rat Wnt11 and human WNT11 genes, Nkx2-5-binding site within exon 1 was evolutionarily conserved among mammalian Wnt11 orthologs. Because Nkx2-5 and Wnt11 are key regulators of heart development, Wnt11 was predicted as a target gene of Nkx2-5 transcription factor during cardiac myocyte differentiation. This is the first report on rat Wnt11 gene as well as on comparative genomics for Wnt11 orthologs.

5' Flanking Region↗

PubMed2005

Comparative genomics on Norrie disease gene.

DAND1 (NBL1), DAND2 (CKTSF1B1 or GREM1 or GREMLIN), DAND3 (CKTSF1B2 or GREM2 or PRDC), DAND4 (CER1), DAND5 (CKTSF1B3 or GREM3 or DANTE), MUC2, MUC5AC, MUC5B, MUC6, MUC19, WISP1, WISP2, WISP3, VWF, NOV and Norrie disease (NDP or NORRIN) genes encode proteins with cysteine knot domain. Cysteine-knot superfamily proteins regulate ligand-receptor interactions for a variety of signaling pathways implicated in embryogenesis, homeostasis, and carcinogenesis. Although Ndp is unrelated to Wnt family members, Ndp is claimed to function as a ligand for Fzd4. Here, we identified and characterized rat Ndp, cow Ndp, chicken ndp and zebrafish ndp genes by using bioinformatics. Rat Ndp gene, consisting of three exons, was located within AC105563.4 genome sequence. Cow Ndp and chicken ndp complete CDS were derived from CB467544.1 EST and BX932859.2 cDNA, respectively. Zebrafish ndp gene was located within BX572627.5 genome sequence. Rat Ndp (131 aa) was a secreted protein with C-terminal cysteine knot-like (CTCK) domain. Rat Ndp showed 100, 96.9, 95.4, 87.8 and 66.4 total-amino-acid identity with mouse Ndp, cow Ndp, human NDP, chicken ndp and zebrafish ndp, respectively. Exon-intron structure of mammalian Ndp orthologs was well conserved. FOXA2, CUTL1 (CCAAT displacement protein), LMO2, CEBPA (C/EBPalpha)-binding sites and triple POU2F1 (OCT1)-binding sites were conserved among promoters of mammalian Ndp orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Vangl1 and Vangl2 genes.

WNT signals are transduced to the beta-catenin pathway or the planar cell polarity (PCP) pathway. WNT - beta-catenin pathway is implicated in carcinogenesis, while WNT-PCP pathway is implicated in cell motility and metastasis. Drosophila Van Gogh (Vang), Frizzled (Fz), Starry night (Stan), Prickle (Pk) and Diego (Dgo) are PCP signaling molecules. Vangl1 (Strabismus 2) and Vangl2 (Strabismus 1 or Ltap) are mammalian homologs of Drosophila Vang interacting with PRICKLE1, PRICKLE2, ANKRD6, DVL1, DVL2, DVL3, KAI1 and MAGI3. Here we identified and characterized rat Vangl1 and Vangl2 genes by using bioinformatics. Rat Vangl1 gene, consisting of eight exons, was located within AC098913.7 and AC108524.6 genome sequences. Rat Vangl2 gene, consisting of eight exons, was located within AC118856.3 and AC115243.5 genome sequences. Exon-intron structure of mammalian Vangl1 and Vangl2 orthologs was well conserved. E47 and double ELK1-binding sites were conserved among promoters of mammalian Vangl1 orthologs. PAX4, NFkappaB, HNF4, SOX9, RFX1, and POU2F1 (OCT1)-binding sites were conserved among promoters of mammalian Vangl2 orthologs. Rat Vangl1 (526 aa) and Vangl2 (521 aa) were four-transmembrane proteins with 71.5% total-amino-acid identity. Ser cluster motif (SxxSxxSxxSxxSxxS) in the N-terminal cytoplasmic region and PDZ-binding motif in the C-terminal cytoplasmic tail were evolutionarily conserved among vertebrate Vangl1 and Vangl2 orthologs. This is the first report on rat Vangl1 and Vangl2 genes as well as on comparative genomics for Vangl1 and Vangl2 orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Wnt9a orthologs.

WNT, Hedgehog and Notch signaling pathways network together during carcinogenesis and embryogenesis. WNT3A-WNT9A (WNT14) locus at chromosome 1q42.13 and WNT3-WNT9B (WNT14B) locus at chromosome 17q21.31 are paralogous regions within the human genome. WNT9A mRNA is expressed in various types of human cancer, such as gastric cancer, pancreatic cancer, and breast cancer. In addition, Wnt9a gene is implicated in chondrogenesis and joint formation during embryogenesis. Here we identified and characterized rat Wnt9a gene by using bioinformatics. Rat Wnt9a gene, consisting of four exons, was located within AC121055.4 and AC133374.2 genome sequences. Rat Wnt9a protein (365 aa) with N-terminal signal peptide, 24 Cys residues and one Asn-linked glycosylation site showed 100%, 98.1% and 82.5% total amino-acid identity with mouse Wnt9a, human WNT9A and chicken wnt9a, respectively. Exonic regions except 3'-UTR were well conserved between human WNT9A and rodent Wnt9a genes; however, 5'-flanking promoter region was not well conserved. Transcription-factor-binding sites conserved between human WNT9A and rodent Wnt9a 5'-flanking promoter regions were not identified by using the Match program. Although the amino-acid sequence was highly conserved among mammalian Wnt9a orthologs, the 5'-flanking promoter region was significantly divergent between human WNT9A and rodent Wnt9a genes. This is the first report on rat Wnt9a gene as well as on comparative genomics for Wnt9a orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Fzd8 orthologs.

WNT signaling pathway networks with Hedgehog, Notch and FGF signaling pathways during carcinogenesis and embryogenesis. FZD8 is up-regulated in HeLa S3 and A549 cells. Here we identified and characterized rat Fzd8 gene by using bioinformatics. Rat Fzd8 gene was identified within AC131883.2 genome sequence. Rat Fzd8 (684 aa) showed 99.1, 96.8, 71.8 and 71.6% total amino-acid identity with mouse Fzd8, human FZD8, zebrafish fzd8 and Xenopus fzd8, respectively. Vertebrate Fzd8 orthologs were seven-transmembrane receptors with Frizzled (Fz) domain within the N-terminal extracellular region, leucine zipper motif around the fifth transmembrane domain, and Dishevelled (Dvl)-binding motif within the C-terminal cytoplasmic region. Two Asn-linked glycosylation sites within the N-terminal extracellular region were conserved among vertebrate Fzd8 orhologs. One Asn-linked glycosylation site within the second extracellular loop was conserved among mammalian Fzd8 orthologs, but not in Xenopus and zebrafish fzd8 orthologs. These facts indicate the molecular evolution of Fzd8 orthologs. The 5'-flanking region and exonic region were well conserved among mammalian Fzd8 orthologs. Nucleotide position 92950-94221 of AC131883.2 genome sequence was identified as the evolutionarily conserved promoter region of rat Fzd8 gene, and nucleotide position 133421-132134 of AL121749.14 genome sequence as the evolutionarily conserved promoter region of human FZD8 gene. Match program revealed that ELK1- and PAX4-binding sites were conserved between rat Fzd8 and human FZD8 promoters. This is the first report on the rat Fzd8 gene as well as on comparative genomics for Fzd8 orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on nemo-like kinase gene.

WNT signals are transduced to the planar cell polarity (PCP) pathway or the beta-catenin pathway. Drosophila Frizzled (Fz), Starry night (Stan), Van Gogh (Vang), Dishevelled (Dsh), Prickle (Pk), Diego (Dgo) and Nemo (Nmo) are implicated in the PCP signaling pathway. Choi and Benzer identified Drosophila Nmo in 1994, and Brott et al identified mouse Nemo-like kinase (Nlk) in 1998. Nlk positively regulates the PCP pathway, and negatively regulates the beta-catenin pathway. Here, we identified and characterized rat Nlk gene, Nlk2 gene and Nlkp pseudogene by using bioinformatics. Nlk gene, consisting of 11 exons, was mapped to rat chromosome 10q25. Rat Nlk gene encoded 515-aa Nlk protein with the serine/threonine kinase domain, poly(His) tracts and poly(Ala) tract, which showed 100, 99.8, 97.1 and 89.5% total-amino-acid identity with mouse Nlk, human NLK, Xenopus nlk and zebrafish nlk, respectively. Rat Nlk2 gene and Nlkp pseudogene were mapped to rat chromosome 13p13 and 2q44, respectively. Nlk2 gene and Nlkp pseudogene, consisting of a single exon, were not evolutionarily conserved. Nlk2 gene and Nlkp pseudogene were predicted as retrotransposed Nlk homologs within the rat genome. Nlk2 gene encoded a 480-aa Nlk2 protein with partial deletion within the kinase domain, which was predicted as the dominant negative Nlk homolog. This is the first report on the Nlk gene and retrotransposed Nlk homologs within the rat genome.

Amino Acid Sequence↗

PubMed2005

Identification and characterization of rat Dact1 and Dact2 genes in silico.

DACT1 (DAPPER1), Frizzled receptors, MUSK receptor, VANGL1, VANGL2, PRICKLE1, PRICKLE2, DAAM1, Casein kinases, MARK3 (PAR1), PP2C, AXIN1, AXIN2, NKD1, NKD2, FRAT1, FRAT2 and CXXC4 are WNT signaling molecules associating with Dishevelled family proteins. Human DACT1 is the ortholog of Xenopus Dapper and Frodo, and human DACT2 (DAPPER2) is the paralog of human DACT1. Here, we identified and characterized rat Dact1 (Dapper1) and Dact2 (Dapper2) genes by using bioinformatics. Rat Dact1 gene, consisting of four exons, was located within AC136677.3 genome sequence. Rat Dact2 gene, consisting of four exons, was located within AC139434.3 genome sequence. Dact1 was mapped to rat chromosome 6q24, and Dact2 gene to rat chromosome 1q12. Rat Dact1 (778 aa) showed 93.7, 82.9, 60.3, 58.7 and 48.6% total-amino-acid identity with mouse Dact1, human DACT1, Xenopus Dapper, Xenopus Frodo and zebrafish dact1, respectively. Rat Dact2 (768 aa) showed 86.6, 59.6 and 38.3% total-amino-acid identity with mouse Dact2, human DACT2 and zebrafish dact2, respectively. Dact1 orthologs were more evolutionarily conserved than Dact2 orthologs. Seven DAPH domains (DAPH1-DAPH7), originally identified as the regions conserved between human DACT1 and DACT2, were conserved among mammalian Dact1 orthologs and Dact2 orthologs. DAPH2 domain, corresponding to the Leucine zipper motif, was located within the coiled-coil region. DAPH3 domain was the Serine rich region. DAPH7 domain was the C-terminal PDZ binding region. This is the first report on the rat Dact1 and Dact2 genes.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Comparative genomics on Fzd7 orthologs.

WNT signaling pathway networks with Hedgehog and Notch signaling pathways during carcinogenesis and embryogenesis. FZD7 is up-regulated in gastric cancer, esophageal cancer, and hepatocellular carcinoma (HCC). Here we identified and characterized rat Fzd7 gene by using bioinformatics. Rat Fzd7 gene was identified within AC136379.2 genome sequence. The 5'-flanking region and exonic region were well conserved among mammalian Fzd7 orthologs. Nucleotide position 153000-152216 of AC136379.2 genome sequence was identified as the evolutionarily conserved promoter region of rat Fzd7 gene, and nucleotide position 2273-3046 of AC069148.6 genome sequence as the evolutionarily conserved promoter region of human FZD7 gene. Match program revealed that PAX4-binding site was conserved among rat Fzd7, mouse Fzd7 and human FZD7 promoters. Rat Fzd7 (572 aa) was a seven-transmembrane-type Wnt receptor, which showed 99.3, 96.9, 87.4, 85.5, 79.5 and 79.0% total-amino-acid identity with mouse Fzd7, human FZD7, chicken fzd7, Xenopus fzd7, zebrafish fzd7a and fzd7b, respectively. Frizzled (Fz) domain within the N-terminal extracellular region, Leucine zipper motif around the fifth transmembrane (TM5) region, Dishevelled (Dvl)- and Magi3-binding motifs within the C-terminal cytoplasmic region were conserved among vertebrate Fzd7 orthologs. Leucine zipper motif around the TM5 region of Fzd7 orthologs was disrupted in FzE3 aberrant cDNA due to multiple cloning artifacts or sequencing errors. These facts indicate that experimental data obtained by using FzE3 cDNA do not always reflect the functions of Fzd7 orthologs.

Amino Acid Motifs↗

PubMed2005

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.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on mammalian Fgf3-Fgf4 locus.

The CCND1-ORAOV1-FGF19-FGF4-FGF3-TMEM16A-FADD-PPFIA1-CTTN (EMS1) locus at human chromosome 11q13.3 is amplified in head and neck tumors, esophageal cancer, Kaposi's sarcoma, bladder tumors, breast cancer, and liver cancer. Fgf4 mRNA is expressed in embryonic stem (ES) cells depending on Sox2 and Pou5f1 (Oct3/Oct4) transcription factors, and in myotomes and limb bud AER depending on MyoD (or Myf5) and GATA transcription factors. Here, rat Fgf3 and Fgf4 complete coding sequences were determined by using bioinformatics. Multiple errors, including one-base insertion and 22-base deletion, were identified within the coding region of rat Fgf4 RefSeq (NM_053809.1 or AB079673.1). Rat Fgf3 and Fgf4 genes, consisting of three exons, were clustered in tail-to-head manner with an interval of about 16 kb. CUTL1 (CCAAT-displacement protein, CDP) and NKX2-5 binding sites and TATA box within 5'-flanking promoter region were conserved among human, rat and mouse Fgf3 orthologs. MYOD and MYOG (Myogenin) binding sites and TATA box within 5'-flanking promoter region as well as GATA, MYOD, SOX2 and POU5F1 binding sites within exon 3 were conserved among mammalian Fgf4 orthologs. Human FGF3 and FGF4 genes were clustered in tail-to-head manner with an interval of about 35 kb. Major repetitive sequence (FGF34Rep1) and minor repetitive sequence (FGF34Rep2) were identified within human FGF3-FGF4 gene cluster. FGF34Rep1 were clustered within the FGF3-FGF4 locus as well as around the IL28RA locus (1p36.11) and the NFAM1 locus (22q13.2). FGF34Rep2 was characterized by the CCA(T/C) repeats. This is the first report on comparative genomics analyses on the Fgf3-Fgf4 locus within human, rat and mouse genomes.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Shisa orthologs.

WNT signaling molecules are implicated in a variety of human tumors, such as gastric cancer and colorectal cancer. FGFR2 gene, encoding FGF receptor 2, is amplified in human gastric and breast cancer. WNT and FGF signaling pathways network together during carcinogenesis and embryogenesis. Xenopus shisa is claimed to inhibit the post-translational maturation of wnt and fgf receptors. Here, we identified and characterized the rat Shisa (Tmem46) gene by using bioinformatics for comparative proteomics and comparative genomics analyses. Rat Shisa gene, consisting of two exons, was located within AC126002.4 genome sequence. Shisa gene at rat chromosome 15p12 was found to encode a type I transmembrane protein (295 aa), showing 99.3, 92.5, 81.7, 40.3 and 38.6% total-amino-acid identity with mouse Shisa, human SHISA, chicken shisa, Xenopus shisa and zebrafish shisa, respectively. The extracellular Cys-rich domain with eight Cys residues was conserved among vertebrate Shisa orthologs. The C-terminal cytoplasmic region was conserved among mammalian and chicken Shisa orthologs, but not in Xenopus and zebrafish Shisa orthologs. Human SHISA promoter and rat Shisa promoter were not conserved well. Function of human SHISA is predicted to be divergent from that of Xenopus shisa due to the protein evolution and the promoter evolution. This is the first report on the rat Shisa gene and on molecular evolution of Shisa orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Fgf11 orthologs.

Human FGF19 is the ortholog of rodent Fgf15, and 22 FGF family genes exist within the human genome as well as within the rodent genome. Mouse Fgf11 refSeq NM_010198.1 and rat Fgf11 RefSeq NM_130816.1 correspond only to the coding region. Here, complete coding sequences of mouse, rat and dog Fgf11 orthologs were determined by using bioinformatics. Mouse Fgf11, rat Fgf11 and dog Fgf11 genes, consisting of five exons, were located within AL603707.5, AC098923.8 and AC126237.5 genome sequences, respectively. Human FGF11 showed 97.8%, 96.9%, 96.9% and 68.9% total-amino-acid identity with dog, mouse, rat and zebrafish Fgf11 orthologs, respectively. Rat Fgf11 showed Val205Met amino-acid substitution compared with rat Fgf11 RefSeq NP_570829.1. Met 205 of rat Fgf11 determined in this study was conserved among vertebrate Fgf11 orthologs. N-terminal signal peptide was not identified within vertebrate Fgf11 orthologs. Two Asn-linked glycosylation sites were identified within zebrafish fgf11, but not within mammalian Fgf11 orthologs. The 5'-flanking region, exonic regions, and intronic regions except intron 3 were well conserved between human FGF11 and mouse Fgf11 genes. Match program revealed that EVI1, ELK1, AP1 and E47-binding sites were conserved between human FGF11 and mouse Fgf11 promoter regions. Human FGF11 mRNA was expressed in embryonic stem (ES) cells, neuroblastoma, retinoblastoma, and brain tumors. This is the first report on the dog Fgf11 gene as well as on comparative genomics analyses of Fgf11 orthologs.

Animals↗

PubMed2005

Comparative genomics on FGF20 orthologs.

We cloned and characterized human FGF20 in August, 2000. Ohmachi et al claimed the same gene as a novel FGF family member in October, 2000, and Jeffers et al in April, 2001. FGF20 is up-regulated in colorectal cancer due to the activation of WNT/beta-catenin pathway. FGF20 is applicable as the mucosal protective agent for inflammatory bowel disease and chemotherapy/radiation-induced oral mucositis, and also as the inducer of dopaminergic neurons for Parkinson's disease. FGF20 is a target of pharmacogenomics in the field of oncology and regenerative medicine. Here, comparative genomics analyses on FGF20 orthologs were performed. Zebrafish fgf20 gene, consisting of three exons, was located within BX323810.8 genome sequence. Zebrafish fgf20 (208 aa) showed 76.9%, 76.4%, 76.0% and 75.5% total-amino-acid identity with human FGF20, Xenopus fgf20, rat Fgf20 and mouse Fgf20, respectively. Fgf20 orthologs were well conserved among vertebrates. Human FGF20 gene was linked to EFHA2 gene in head-to-head manner with an interval of about 25 kb. FGF20-EFHA2 locus at human chromosome 8p22 and FGF9-EFHA1 locus at human chromosome 13q12.11 were paralogous regions (paralogons) within the human genome. The 5'-flanking promoter region, exonic regions except 3'-UTR, and middle regions within intron 1 were conserved between human FGF20 and mouse Fgf20 genes. Double TCF/LEF binding sites, double EVI1-binding sites, TGIF, PAX4, E47 and AREB6-binding sites were conserved between human FGF20 promoter and mouse Fgf20 promoter.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on BMP4 orthologs.

Bone morphogenetic proteins (BMPs) are implicated in cell-fate determination of embryonic stem (ES) cells and cancer cells. GREM1 (CKTSF1B1 or DAND2) and CER1 (Cerberus 1 or DAND4) are cysteine knot superfamily proteins, functioning as secreted-type BMP antagonists. BMP4 is preferentially expressed in diffuse-type gastric cancer cells. Here, vertebrate BMP4 orthologs were identified and characterized by using bioinformatics for comparative proteomics and comparative genomics analyses. Baboon BMP4 gene within AC153751.2 genome sequence encoded a 408-aa protein, showing A152V and S298P amino-acid substitutions compared with human BMP4. Cow Bmp4, bat Bmp4 and zebrafish bmp4 genes were located within AC149774.2, AC156788.2 and CR391996.2 genome sequences, respectively. Human BMP4 showed 99.5%, 98.0%, 97.8%, 97.1%, 96.3%, 83.3% and 71.1% total-amino-acid identity with baboon BMP4, cow Bmp4, bat Bmp4, mouse Bmp4, rat Bmp4, chicken bmp4 and zebrafish bmp4, respectively. Human BMP4 gene was found consisting of six exons, including novel exon 1C, and known exons 1 (1A or I), 1B (II), 2 (III), 3 (IV) and 4 (V). Forty human BMP4 ESTs started from exon 1, seven from intron 1 (5'-flanking region of exon 2), and two from exon 1C. Fourteen mouse Bmp4 ESTs started from exon 1, and one from intron 1. The 5'-flanking region of exon 1 and exon 1 itself, but not exons 1C and 1B, were well conserved between human BMP4 and rodent Bmp4 genes. The major promoter region of human BMP4 and rodent Bmp4 genes were located within the 5'-flanking region of exon 1. FOXA2, OLF1, and MYC-binding sites were conserved among the major promoter region of human, baboon, cow, bat, mouse and rat BMP4 orthologs.

Amino Acid Sequence↗