Biomedical subjects

Yuriko Katoh

Publications and source records attributed to Yuriko Katoh.

At least 37 records · Page 2Linked to original sources

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 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 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 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↗

PubMed2005

Comparative genomics on mammalian Fgf6-Fgf23 locus.

CCND2-C12orf5-FGF23-FGF6 locus at human chromosome 12p13.32 and CCND1-ORAOV1-FGF19-FGF4 locus at human chromosome 11q13.3 are paralogous regions (paralogons) within the human genome. FGF23 is the causative factor for tumor-induced osteomalacia (TIO), a paraneoplastic disorder characterized by hypophosphatemia and skeletal undermineralization, and also for autosomal dominant hypophosphatemic rickets (ADHR). Here, rat Fgf6 and Fgf23 complete coding sequences were determined by using bioinformatics. Rat Fgf6 and Fgf23 genes, consisting of three exons, were located within AC103292.6 rat genome sequence. Rat Fgf6 and Fgf23 genes were clustered in tail-to-head manner with an interval of about 52 kb. Human FGF6 and FGF23 genes were clustered in tail-to-head manner with an interval of about 54 kb. Intergenic conserved region (IGCR) within the FGF6-FGF23 gene cluster was identified based on the evolutionary conservation. Human FGF6-FGF23 IGCR (nucleotide position 111648-112242 of AC008012.8 genome sequence) and rat Fgf6-Fgf23 IGCR (nucleotide position 156318-156894 of AC103292.6 genome sequence) showed 77.6% total nucleotide identity. CP2, E47, CREB and PAX4 binding sites were conserved among human FGF6, rat Fgf6, and mouse Fgf6 promoters. GATA and E47 binding sites were conserved among human FGF23, rat Fgf23, and mouse Fgf23 promoters. Because mouse Fgf23 mRNA was expressed in dendritic cells and activated spleen, tumor infiltrating dendritic cells are candidate sources of FGF23 secretion in TIO patients. This is the first report on comparative genomics analyses on human FGF6-FGF23 gene cluster and rodents Fgf6-Fgf23 gene cluster.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on SFRP1 orthologs.

SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, WIF1, DKK1, DKK2, DKK3, DKK4 are secreted-type WNT signaling modulators. SFRP1 tumor suppressor gene at human chromosome 8p11.21 is inactivated in colorectal cancer and other tumors by deletion and by epigenetic CpG hypermethylation. Here, we identified and characterized the rat Sfrp1 gene by using bioinformatics. Rat Sfrp1 gene, consisting of three exons, was located within AC112899.4 genome sequence. Complete coding sequence of rat Sfrp1 was determined by assembling AC112899.4 genome sequence, CK838748 EST, and BF417482 EST. Rat Sfrp1 (314 aa) consisted of a signal peptide (codon 1-31), Frizzled domain with ten conserved Cys residues (codon 49-168), and Netrin (NTR) domain with six conserved Cys residues (codon 186-314). Rat Sfrp1 showed 98.7%, 95.2%, 94.3%, 82.5% and 58.3% total-amino-acid identity with mouse Sfrp1, human SFRP1, cow Sfrp1, chicken sfrp1 and zebrafish sfrp1, respectively. SFRP1 mRNA was expressed in embryonic stem (ES) cells, neuroblastoma, liver adeno-carcinoma, and skin squamous cell carcinoma. Match program revealed that AP1, COMP1, and double ETS1-binding sites were conserved between human SFRP1 and rat Sfrp1 promoters. This is the first report on comparative integromics analyses on Sfrp1 orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on DKK2 and DKK4 orthologs.

WNT family proteins activate the beta-catenin - TCF pathway to induce carcinogenesis through cell fate determination, and also activate the planar cell polarity (PCP) pathway to induce cell motility and metastasis. DKK1, DKK2, DKK3 and DKK4 are secreted-type WNT signaling modulators belonging to the Dickkopf family. Here, we identified and characterized rat Dkk2 and Dkk4 genes by using bioinformatics. Rat Dkk2 and Dkk4 genes, consisting of four exons, were located within AC120263.4 and AC109661.6 genome sequences, respectively. Rat Dkk2 gene encoded a 259-aa protein, showing 95.8% total-amino-acid identity with human DKK2. Rat Dkk4 gene encoded a 221-aa protein, showing 75.4% total-amino-acid identity with human DKK4. Mammalian Dkk family members were secreted proteins with two Cys-rich regions, each containing ten conserved Cys residues. Asn-linked glycosylation site at codon 52 was conserved among mammalian Dkk2 orthologs; however, Asn-linked glycosylation site was not identified among mammalian Dkk4 orthologs. Dkk2 proteins were more conserved than Dkk4 proteins, while Dkk4 promoters were more conserved than Dkk2 promoters. TATA-box was identified within Dkk2 and Dkk4 promoters. MYOD and triple TCF/LEF binding sites were conserved between human DKK4 promoter and rodent Dkk4 promoter. DKK2 mRNA was expressed in Ewing's sarcoma, and fetal heart. DKK4 mRNA was expressed in human embryonic stem (ES) cells differentiated to an early endodermal cell type, breast cancer, and diffuse type gastric cancer. DKK4 orthologs are implicated in the negative feed back mechanism of the WNT/beta-catenin signaling pathway (the canonical WNT signaling pathway).

Amino Acid Sequence↗

PubMed2005

Comparative genomics on SOX2 orthologs.

SOX2 and POU5F1 (OCT3 or OCT4) transcription factors are implicated in FGF4 expression in embryonic stem (ES) cells. SOX2, POU5F1, and FGF4 are key molecules for the integrome network in oncology and stem cell biology. SOX2 gene at human chromosome 3q26.33, SOX1 gene at 13q34, and SOX3 gene at Xq27.1 constitute a subfamily among the SOX gene family. Here, rat Sox2 and Xenopus sox2 genes were identified and characterized by using bioinformatics for comparative genomics and comparative proteomics analyses. Rat Sox2 gene, encoding a 319-aa protein, was located around the nucleotide position 73213-75621 of rat genome sequence AC123231.4. Xenopus tropicalis sox2 complete coding sequence, encoding a 311-aa protein, was derived from CR760314.1 cDNA. Rat Sox2 showed 98.4%, 97.8%, 92.2%, 88.1% and 86.8% total amino-acid identity with mouse Sox2, human SOX2, chicken sox2, Xenopus sox2 and zebrafish sox2, respectively. SOX123C domain was identified as the novel domain corresponding to the C-terminal region conserved among SOX1, SOX2 and SOX3 orthologs. Vertebrate SOX1, SOX2 and SOX3 orthologs were found consisting of HMG box and SOX123C domain. SOX9, TCF/LEF, POU2F1 and COMP1 binding sites were conserved among human SOX2 promoter, rat Sox2 promoter, and mouse Sox2 promoter. SOX2 mRNA was expressed in ES cells, fetal brain, anaplastic oligodendroglioma, rhabdomyosarcoma, and small cell lung carcinoma. Due to the pivotal role of SOX2 in the early embryogenesis, SOX2 promoter and SOX2 protein were well conserved during vertebrate evolution. This is the first report on comparative integromics analyses on the SOX2 orthologs.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on Sonic hedgehog orthologs.

Sonic hedgehog (SHH), Indian hedgehog (IHH), and Desert hedgehog (DHH) are key molecules for the integrome network in oncology and regenerative medicine. Soluble Hedgehog ligands bind to Patched receptor to activate Smoothened seven-transmembrane receptor with Frizzled domain. KIF27 and KIF7 are human homologs of Drosophila Costal-2 (Cos2), associating with Smoothened, GLI homolog, Fused, and microtubule. Smoothened activation leads to GLI1, GLI2, or GLI3-dependent transcription of Hedgehog target genes. Here, comparative proteomics analyses and comparative genomics analyses on SHH orthologs were performed by using bioinformatics. Human SHH representative transcript was assembled by using BX461534 EST, NM_000193.2 RefSeq, AA503654 EST, and AC078834.5 genome sequence. Human SHH mRNA was expressed in fetal brain, infant brain, and also in colorectal cancer. Chimpanzee SHH gene, consisting of three exons, was located within AC147335.2 genome sequence. Human SHH and chimpanzee SHH (462 aa) showed E284G and T416P amino-acid substitutions. Vertebrate SHH orthologs shared the common domain architecture, consisting of N-terminal signal peptide, Hedgehog signaling domain, Hint domain, and C-terminal HPLGMxxxxS motif. Evolutionarily conserved SHH promoter region (nucleotide position 104429-104083 of human genome sequence AC078834.5) was identified. Double bHLH binding sites, CCAAT box, and TATA box were conserved among human SHH promoter, chimpanzee SHH promoter, rat Shh promoter, and mouse Shh promoter.

Amino Acid Motifs↗

PubMed2005

Comparative genomics on FGF7, FGF10, FGF22 orthologs, and identification of fgf25.

FGF family members are key molecules for the integrome network in the fields of oncology and regenerative medicine. Based on the comparative genomics on the CCND1-ORAOV1-FGF19-FGF4 locus, we demonstrated that rodent Fgf15 is the ortholog of human FGF19 in 2003. FGF7 (KGF), FGF10, and FGF22 constitute a subfamily among FGF family members. Here, comparative genomics analyses and comparative proteomics analyses on FGF7, FGF10, and FGF22 orthologs were performed. Chicken fgf22, zebrafish fgf22 and fgf25 genes, consisting of three exons, were identified within AC150066.1, BX927243.9 and CR854981.2 genome sequences, respectively. Zebrafish fgf22 (207 aa) showed 46.9%, 48.6% and 53.5% total amino-acid identity with human FGF7, FGF10 and FGF22, respectively. Zebrafish fgf25 (186 aa) showed 39.2%, 52.9% and 45.9% total amino-acid identity with human FGF7, FGF10 and FGF22, respectively. Phylogenetic analyses revealed that zebrafish fgf25 belongs to the FGF10 ortholog group. Zebrafish fgf25 was a novel FGF family member generated by the duplication of fgf10. FGF10-MRPS30-HCN1 locus at human chromosome 5p12 and FGF22-POLRMT-HCN2 locus at 19p13.3 were paralogous regions within the human genome. FGF7 mRNA was expressed in fetal heart, placenta, lung, kidney, and blood vessels. FGF10 mRNA was expressed in fetal lung, placenta, and uterus. FGF22 mRNA was expressed in hippocampus and ovarian fibrotheoma. FGF7 promoter with bHLH biding site and CCAAT box and FGF10 promoter with double bHLH biding sites were conserved well, while FGF22 promoter was significantly divergent. This is the first report on fgf25 gene and also on the comparative integromics analyses of FGF7, FGF10 and FGF22 orthologs.

5' Flanking Region↗

PubMed2005

Comparative genomics on FGF16 orthologs.

We have previously reported comparative genomics analyses on FGF3, FGF4, FGF6, FGF7, FGF8, FGF10, FGF11, FGF17, FGF18, FGF19, FGF20, FGF22 and FGF23 genes. Here, we performed comparative genomics analyses on FGF1, FGF2, FGF5, FGF9, FGF12, FGF13, FGF14, FGF16 and FGF21 genes, and further characterized the FGF16 gene. Chimpanzee FGF16, chicken fgf16, and zebrafish fgf16 genes were identified within NW_121938.1, NW_060344.1, and CR855117.3 genome sequences, respectively. Chimpanzee FGF16 (207 aa), chicken fgf16 (207 aa), and zebrafish fgf16 (203 aa) showed 100%, 89.9%, and 79.2% total amino-acid identity with human FGF16. Because FGF16, FGF9, and FGF20 constitute FGF subfamily without N-terminal signal peptide, we next searched for uncharacterized FGF9 or FGF20 orthologs. Zebrafish fgf9 gene was identified within BX927112.11 genome sequence, and chicken fgf20 gene within NW_060349.1 genome sequence. Although N-terminal part was divergent, middle and C-terminal parts were well conserved among vertebrate FGF16, FGF9 and FGF20 orthologs. Phylogenetic analyses revealed that zebrafish fgf9 and fgf20 were more related to each other than to their chicken or mammalian orthologs. TCF/LEF binding site and TATA box were well conserved among the human FGF16, rat Fgf16, and mouse Fgf16 promoters. Because nuclear complex consisting of TCF/LEF (TCF1, TCF3, TCF4 or LEF1), beta-catenin, PYGO (PYGO1 or PYGO2) and Legless (BCL9 or BCL9L) binds to the TCF/LEF-binding site to up-regulate WNT/beta-catenin target genes, FGF16 gene was characterized as the evolutionarily conserved target of the WNT/beta-catenin signaling pathway, just like FGF18 and FGF20 genes. These facts indicate that FGF16, FGF18 and FGF20 are pharmacogenomics targets in the field of oncology and regenerative medicine.

Amino Acid Sequence↗

PubMed2005

Comparative genomics on SLIT1, SLIT2, and SLIT3 orthologs.

SLIT1 gene at human chromosome 10q24.1, SLIT2 gene at 4p15.31, and SLIT3 gene at 5q34-q35.1 encode large secreted proteins functioning as ligands for Roundabout (Robo) receptors. SLIT-ROBO signaling pathway is implicated in neurogenesis, angiogenesis, and immune response through the regulation of axonal guidance, endothelial cell migration, and denderitic cell migration, respectively. GREMLIN (CKTSF1B1 or GREM1) and DANTE (CKTSF1B3 or GREM3) are secreted antagonists for BMPs and SLITs. Here, comparative integromics analyses on SLIT1, SLIT2, and SLIT3 orthologs were performed by using bioinformatics. Rat Slit2 gene, consisting of 36 exons, was located within rat genome sequences AC098362.4 and AC111627.6. Mouse Slit3 complete coding sequence was determined by assembling BB634238 EST, AF144629 cDNA, and AK129223 cDNA. Leucine-rich repeats with nine conserved cysteine (LRRCC) domains and SLIT C-terminal cysteine-rich (SLITCCR) domain were identified in this study. CPxxCxCxxxxVxCxxxxLxxxPxxxPx(10~58) Nx(19,20)LxxNx(9)Fx(8)LxLxxNxxxCxxxxxFxxLxxx xxLxLxxNx(9)Fx(13)NxxxCxCxxxWLx(15)CxxPx(17)C was the consensus sequence of LRRCC domain. Mammalian SLIT1, SLIT2 and SLIT3 orthologs were large secreted proteins with four LRRCC domains, nine EGF domains, Laminin G (LamG) domain, and SLITCCR domain. SLIT1 mRNA was expressed in fetal brain, infant brain, anaplastic oligodendroglioma, and Jurkat T cells. SLIT2 and SLIT3 mRNAs were co-expressed in embryonic stem (ES) cells with embryoid body formation, and diffuse type gastric cancer with signet ring cell features. Double TCF/LEF and bHLH-binding sites were conserved among mammalian SLIT1 promoters. FOXJ2, E47, ETS1, and FOXA2-binding sites and CCAAT box were conserved among mammalian SLIT3 promoters. Mammalian SLIT1 orthologs were identified as evolutionarily conserved targets of the WNT/beta-catenin signaling pathway.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of CDC50A, CDC50B and CDC50C genes in silico.

Bni1p, implicated in cell polarity control and microtubule regulation during yeast budding, is the Saccharomyces cerevisiae homolog of human Formin-homology proteins, such as FMN1, FMN2, FHOD1, FHOD3, FHDC1, GRID2IP, FMNL1, FMNL2, FMNL3, DIAPH1, DIAPH2, DIAPH3, DAAM1 and DAAM2. Cdc50p is necessary for subcellular localization of Bni1p and asymmetrical cell division. Lem3p and Ynr048wp are yeast homologs of Cdc50p; however, mammalian homologs of Cdc50p remained to be identified. Here, we identified and characterized CDC50A (TMEM30A), CDC50B (TMEM30B) and CDC50C (TMEM30C) genes by using bioinformatics. C6orf67 and FLJ33850 were representative human CDC50A and CDC50B cDNAs, respectively. Complete coding sequence of CDC50C cDNA was determined by assembling seven exons within AC129803.3 genome sequence. CDC50A, CDC50B and CDC50C genes were mapped to human chromosome 6q14.1, 14q23.1 and 3q12, respectively. Human CDC50A mRNA was expressed in embryonic stem (ES) cells, placenta, brain and chondrosarcoma, while CDC50B mRNA was expressed in pancreatic islet, kidney, prostate as well as in lung carcinoid, parathyroid tumor, bladder tumor, meningioma and pancreatic cancer. Mouse Cdc50a (2010200I23), Cdc50b (9130011B11) and Cdc50c (4933401B01) cDNAs were also identified. Mammalian CDC50 homologs, including human CDC50A (361 aa), CDC50B (351 aa), CDC50C (341 aa), mouse Cdc50a (364 aa), Cdc50b (353 aa) and Cdc50c (342 aa), were two-transmembrane-spanning proteins with one extracellular loop. Membrane topology and extracellular loop containing three Cys residues and one Asn-linked glycosylation site were evolutionarily conserved among mammalian CDC50 homologs and yeast Cdc50p homologs. Mammalian CDC50 homologs were predicted components of phospholipid-translocators just like yeast Cdc50p and Lem3p.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Identification and characterization of ARHGAP27 gene in silico.

ARHGAP1, ARHGAP2, ARHGAP3, ARHGAP4, ARHGAP5, ARHGAP6, ARHGAP7 (DLC1), ARHGAP8, ARHGAP9, ARHGAP10, ARHGAP12, ARHGAP13 (SRGAP1), ARHGAP14 (SRGAP2), ARHGAP15, ARHGAP17 (RICH1), ARHGAP18, ARHGAP19, ARHGAP20, ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP26, STARD13 (DLC2), HA-1, GMIP, PARG1, RACGAP1, PIK3R1, PIK3R2, and FNBP2 genes encode Rho/Rac/Cdc42-like GTPase activating (RhoGAP) proteins. Here, we characterized human ARHGAP27 gene by using bioinformatics. Complete coding sequence of ARHGAP27 isoform 1, encoding a full-length 889-aa protein, was determined by assembling exon 1 (nucleotide position 143440-144096 of AC091132.16) and most part of FLJ43547 cDNA (nucleotide position 69-3628 of AK125535.1). Complete coding sequence of ARHGAP27 isoform 2, encoding an N-terminally truncated 548-aa protein, was derived from FLJ43547 cDNA. ARHGAP27 isoform 1 consists of exons 1-17, while ARHGAP27 isoform 2 consists of exons 1B, and 2-17. ARHGAP27 gene encoded two isoforms due to alternative splicing of alternative promoter type. ARHGAP27 mRNA was expressed in germinal center B cell, spleen, chronic lymphocytic leukemia, pancreatic cancer, and lung cancer. LOC303583 (NM_ 198759.1) was the representative rat Arhgap27 cDNA. Human ARHGAP27 showed 84.3% total-amino-acid identity with rat Arhgap27, and 39.0% total-amino-acid identity with human ARHGAP12. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. ARHGAP27 gene was located at human chromosome 17q21, while ARHGAP12 gene was located at human chromosome 10p11. ARHGAP family genes are cancer-associated genes, because their genetic alterations lead to carcinogenesis through the dysregulation of Rho/Rac/ Cdc42-like GTPases. This is the first report on identification and characterization of the ARHGAP27 gene.

Amino Acid Sequence↗

PubMed2004

KIF27 is one of orthologs for Drosophila Costal-2.

Signals of Hedgehog family proteins (SHH, IHH and DHH) are transduced through Patched family receptors (PTCH1 and PTCH2) and Smoothened (SMO) to GLI family transcription factors (GLI1, GLI2 and GLI3). SHH plays a key role in development and progression of pancreatic cancer, gastric cancer, basal cell carcinoma, and brain tumors. Drosophila Costal-2 (Cos2) is implicated in the Hedgehog pathway through the interaction with Smoothened (Smo), Cubitus interruptus (Ci), Fused (Fu), and microtubule; however, mammalian ortholog of Drosophila Cos2 remained to be identified. Here we identified and characterized human ortholog of Drosophila Cos2 by using bioinformatics. Full-length Drosophila Cos2 was most homologous to human KIF27, followed by mouse Kif7, and other KIF family members. KIF27 gene at human chromosome 9q22.1 and KIF7 gene at human chromosome 15q26.1 were paralogs within the human genome. Phylogenetic analysis revealed that KIF27, Kif7, KIF4A, KIF4B and KIF21A constitute the KIF27 subfamily among mammalian Kinesin family. Drosophila Cos2 protein consists of Kinesin motor (KISc) domain, Ci-binding domain, and Smo-binding domain. KIF27 itself shared the common domain structure with Drosophila Cos2, while other members of KIF27 subfamily shared partial domain structure with Drosophila Cos2. These facts indicate that KIF27 is one of mammalian orthologs for Drosophila Cos2.

Amino Acid Sequence↗