Biomedical subjects

Masuko Katoh

Publications and source records attributed to Masuko Katoh.

At least 91 records · Page 5Linked to original sources

PubMed2003

Identification and characterization of human DAAM2 gene in silico.

WNT signals play key roles in carcinogenesis and embryogenesis through the specification of cell fate and polarity. Dishevelled proteins are implicated in the WNT - beta-catenin pathway and the WNT-PCP pathway. DAAM1/KIAA0666 is a Dishevelled-binding protein transducing WNT signals to the PCP pathway. Here, we identified and characterized DAAM2 gene by using bioinformatics. Uncharacterized FLJ34430 and KIAA0381 cDNAs were homologous to DAAM1. FLJ34430 was recombined with URB (XM_087331) in the 3'-region, and KIAA0381 was truncated in the 5'-region. Nucleotide sequence of DAAM2 cDNA was determined in silico by adding nucleotide position 1-793 of FLJ34430 onto the 5'-end of KIAA0381. DAAM2 gene consists of 27 exons, and gives rise to four splicing variants due to alternative splicing of alternative promoter type as well as of cassette exon type. DAAM2 gene was linked to the MOCS1 gene on human chromosome 6p21.3 with an interval less than 1 kb. DAAM2 mRNA was expressed in fetal heart, adult hypothalamus, eye, spinal cord, lung, prostate, kidney, and also in glioblastoma, oligodendroglioma, melanoma, mammary adenocarcinoma and chondrosarcoma. DAAM2 was a 1077-amino-acid protein with Formin-homology FH1 and FH2 domains, which showed 68.9% total-amino-acid identity with DAAM1. Among Formin-homology proteins, FDD (Formin-like, Diaphanous, Daam) domain was conserved in FMNL1/FMNL/KW-13, FMNL2/KIAA1902/FHOD2, DIAPH1, DIAPH2, DAAM1 and DAAM2, but not in Fmn1, Fmn2, FHOD1 and Grid2ip. Therefore, it was concluded that FMNL1, FMNL2, DIAPH1, DIAPH2, DAAM1 and DAAM2 proteins constitute the Formin-homology FDD subfamily.

Alternative Splicing↗

PubMed2003

FGFR2 and WDR11 are neighboring oncogene and tumor suppressor gene on human chromosome 10q26.

Oncogenes and tumor suppressor genes are clustered around recombination hot spots or fragile sites in the genome, because double-strand break is the common initial step in translocation, deletion and gene amplification. FGFR2 gene on human chromosome 10q26 is amplified in diffuse-type gastric cancer, while WDR11 gene on human chromosome 10q26 is disrupted in glial tumors. Here, we investigated genomic structure around FGFR2 and WDR11 loci. The FGFR2 gene, consisting of 21 exons, was located within nucleotide position 485637-605687 of NT_030764.5 (reverse orientation), and WDR11 gene was located within nucleotide position 6515786-6574126 of NT_008902.12 (forward orientation). Because nucleotide position 1-91397 of NT_030764.5 corresponded to nucleotide position 6639437-6748623 of NT_008902.12, FGFR2 and WDR11 genes were found to be closely linked in tail-to-tail manner with an interval of ca. 570 kb. Due to the deletion of exon 21 within FGFR2 amplicons, exon 21 is substituted by exon 20 or other aberrant exons in aberrant FGFR2 transcripts previously isolated from KATO-III, OCUM-2M and HSC43 cells. Mapping of aberrant exons and deletion junctions around the WDR11-FGFR2 locus in KATO-III and OCUM-2M cells revealed that inverted-type recombination occurred through end joining of the FGFR2 locus on one allele and that on the other allele. Amplification of FGFR2 gene with such recombination around exon 21 results in exclusion of WDR11 gene from the FGFR2 amplicon. Tumor suppressor genes closely linked to oncogenes might be excluded from amplicon through a breakage-fusion-bridge process during oncogene amplification.

Brain Neoplasms↗

PubMed2003

Identification and characterization of human FMNL1, FMNL2 and FMNL3 genes in silico.

FMNL (NM_005892.2) is a 5'-truncated partial cDNA encoding a Formin-homology protein related to DAAM1, DAAM2, DIAPH1 and DIAPH2. Here, we identified three members of FMNL gene family in the human genome by using bioinformatics. FMNL1 gene, corresponding to 5'-truncated KW-13 and FMNL cDNAs, was located within reference genomic contig NT_010748.9 (nucleotide position 100576-125849, forward orientation). FMNL2 gene, corresponding to KIAA1902 and FHOD2 cDNAs, was located within NT_005151.10 (nucleotide position 122465-436828, forward orientation). FMNL3 gene, corresponding to 5'-truncated DKFZp762B245 and KIAA2014 cDNAs, was located within NT_026397.10 (nucleotide position 209769-279037, reverse orientation). FMNL1, FMNL2 and FMNL3 genes encode A and B isoforms with the C-terminal divergence due to alternative splicing (cassette splicing of exon 26). FMNL1A (1100 aa), FMNL1B (1114 aa), FMNL2A (1087 aa), FMNL2B (1093 aa), FMNL3A (1028 aa) and FMNL3B (1027 aa) consist of FDD, FH1 and FH2 domains. Total amino-acid identity were as follows: FMNL1A vs. FMNL2A, 59.3%; FMNL1A vs. FMNL3A, 56.1%; FMNL2A vs. FMNL3A, 68.6%. FMNL1 gene was mapped to human chromosome 17q21. FMNL2 gene was linked to FNBP3/HYPA gene on chromosome 2q23.3, while FMNL3 gene was linked to FNBP3L/HYPC gene on chromosome 12q13. FMNL1 mRNA was expressed in natural killer cells, Burkitt lymphoma, pancreatic cancer, prostate cancer, and lung large cell carcinoma, FMNL2 mRNA in several normal tissues, diffuse-type gastric cancer, breast cancer, chondrosarcoma, melanoma, and glioblastoma, and FMNL3 mRNA in gastric cancer. FMNL1, FMNL2 and FMNL3 might be implicated in polarity control, invasion, migration, or metastasis through regulation of the Rho-related signaling pathway.

Alternative Splicing↗

PubMed2003

Recombination cluster around FGFR2-WDR11-HTPAPL locus on human chromosome 10q26.

FGFR2 is an oncogene amplified in diffuse-type gastric cancer, and WDR11 is a tumor suppressor gene disrupted in glial tumor. WDR11-FGFR2 locus on human chromosome 10q26 is one of cancer-related recombination hot spots. In this study, we investigated recombination and nucleotide substitution around the WDR11-FGFR2 locus during evolution by using bioinformatics. Inter-chromosomal comparison revealed that the human BAG3-FGFR2-TACC2 region was paralogous to the human BAG4-FGFR1-TACC1 region. Inter-specific comparison on the BAG3-FGFR2-TACC2 region revealed that HTPAPL-WDR11-FGFR2 locus containing species-specific insertion or deletion was one of evolutionary recombination hot spots. Between human and mouse, coding-region nucleotide substitution rate and amino-acid substitution rate were significantly lower in the HTPAPL-WDR11-FGFR2 locus than in the surrounding locus (P<0.0001). The HTPAPL-WDR11-FGFR2 locus was more susceptible to recombination than to nucleotide substitution. Detailed comparison of human and mouse genomes could identify evolutionary recombination hot spots overlooked during gross comparison of human and mouse genomes. Because DNA double-strand break is the initial step in various types of recombination including chromosomal translocation, rearrangement, deletion, gene amplification, retroviral integration and retrotransposition, it is reasonable that the HTPAPL-WDR11-FGFR2 locus is the recombination hot spot during evolution as well as during carcinogenesis. Therefore, comparative genomics might be applicable to identification of recombination hot spots and genes related to cancer.

Amino Acid Substitution↗

PubMed2003

CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family.

Microarray analyses combined with laser-capture microdissection have been applied for risk assessments of gastric cancer as well as for identification of novel genes associated with gastric cancer. EST AA393089 derived from an unknown gene has been reported to be frequently down-regulated in intestinal-type gastric cancer. Here, we identified and characterized the gene corresponding to EST AA393089 by using bioinformatics. EST AA393089 overlapped with BC016047 cDNA, and BC016047 overlapped with EST BM821052. Because the mRNA determined by assembling BM821052 and BC016047 was derived from a novel Claudin (CLDN) family gene, the gene corresponding to EST AA393089 was designated CLDN23. Human CLDN23 mRNA was expressed in germinal center B cells, placenta, stomach as well as in colon tumor. Mouse AK009330 and AK037108 cDNAs were derived from mouse Cldn23 gene. Human CLDN23 (292 aa) and mouse Cldn23 (296 aa) were four-transmembrane proteins, showing 79.5% total-amino-acid identity. WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C, was conserved among four-transmembrane proteins of CLDN family. CLDN23 gene, linked to MFHAS1 and PPP1R3B genes, was mapped to human chromosome 8p23.1. CLDN21, CLDN22, and CLDN24 genes were also identified in this study. CLDN21 and CLDN22 genes were located within human genomic contig NT_022792.13. CLDN24 gene on human chromosome 11q23 was located within human genomic contig NT_033899.3. Among 23 CLDN family genes within the human genome, CLDN1 and CLDN16 genes were clustered on human chromosome 3q28, CLDN3 and CLDN4 on 7q11, CLDN6 and CLDN9 on 16p13.3, CLDN8 and CLDN17 on 21q22.11, CLDN21 and CLDN22 on 4q35.1. This is the first report on comprehensive characterization of CLDN23 gene, a candidate tumor suppressor gene implicated in intestinal-type gastric cancer.

Amino Acid Sequence↗

PubMed2003

FNBP2 gene on human chromosome 1q32.1 encodes ARHGAP family protein with FCH, FBH, RhoGAP and SH3 domains.

Parallel analyses of DNA copy number and mRNA expression level by using microarray measurements have been successfully applied for genome-wide screening of proto-oncogenes and tumor suppressor genes. The uncharacterized KIAA0456 cDNA was reported amplified and overexpressed in human breast cancer cell lines UACC812 and ZR-75-1. Here, we characterized the gene corresponding to KIAA0456 cDNA by using bioinformatics. KIAA0456 cDNA was found derived from the FNBP2 gene, consisting of 22 exons. FNBP2 gene was linked to IKBKE and NORE1 genes on human chromosome 1q32.1. FNBP2 mRNA was expressed in melanoma, germ cell tumors, chondrosarcoma and retinoblastoma. ARHGAP13/SRGAP1, ARHGAP14/SRGAP2 and ARHGAP4 cDNAs were homologous to FNBP2/KIAA0456 cDNA. KIAA1304 cDNA was a splicing variant derived from the ARHGAP13 gene, and the nucleotide sequence of representative ARHGAP13 cDNA was determined by assembling EST BU520980 and KIAA1304 cDNA. FNBP2 (1071 aa), ARHGAP13 (1062 aa), ARHGAP14 (1099 aa) and ARHGAP4 (946 aa) constitute the FNBP2 family characterized by FCH, RhoGAP and SH3 domains. The region corresponding to codon 227-345 of FNBP2 was conserved among FNBP2 family proteins as well as FNBP1 and TRIP10 proteins. Because FNBP2 and FNBP1 are formin-binding proteins, the region corresponding to codon 227-345 of FNBP2 was designated FNBP2-FNBP1 homologous (FBH) domain. FNBP2 family proteins consist of FCH, FBH, RhoGAP and SH3 domains, while FNBP1 family proteins (FNBP1 and TRIP10) consist of FCH, FBH and SH3 domains. This is the first report on comprehensive characterization of FNBP2 gene as well as on identification of the FBH domain.

Adaptor Proteins, Signal Transducing↗

PubMed2003

MGC9753 gene, located within PPP1R1B-STARD3-ERBB2-GRB7 amplicon on human chromosome 17q12, encodes the seven-transmembrane receptor with extracellular six-cystein domain.

MYC, ERBB2, MET, FGFR2, CCNE1, MYCN, WNT2, CD44, MDM2, NCOA3, IQGAP1 and STK6 loci are amplified in human gastric cancer. It has been reported that the gene corresponding to EST H16094 is co-amplified with ERBB2 gene in human gastric cancer. Here, we identified and characterized the gene corresponding to EST H16094 by using bioinformatics. BLAST programs revealed that EST H16094 was derived from the uncharacterized MGC9753 gene. Two ORFs were predicted within human MGC9753 mRNA, and ORF1 (nucleotide position 18-980 of NM_033419.1) was predicted as the coding region of human MGC9753 mRNA based on comparative genomics. Nucleotide sequence of mouse Mgc9753 mRNA was next determined in silico by modification of AK052486 cDNA (deleting C at the nucleotide position 37). Human MGC9753 and mouse Mgc9753 proteins were 320-amino-acid seven-transmembrane receptors with the N-terminal six-cysteine domain and an N-glycosylation site (85.0% total-amino-acid identity). Human MGC9753 protein showed 90.6% total-amino-acid identity with human CAB2 aberrant protein, which lacked the third-transmembrane domain of MGC9753 due to frame shifts within ORF. Human MGC9753 gene, consisting of eight exons, were clustered with PPP1R1B, STARD3, TCAP, PNMT, ERBB2, MGC14832 and GRB7 genes within the 120-kb region. PPP1R1B, STARD3, MGC9753, ERBB2 and GRB7 genes are co-amplified in several cases of gastric cancer. This is the first report on comprehensive characterization of the amplicon around the PPP1R1B-STARD3-TCAP-PNMT-MGC9753-ERBB2-MGC14832-GRB7 locus on human chromosome 17q12.

Amino Acid Sequence↗

PubMed2003

FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products.

The CCND1-EMS1 locus on human chromosome 11q13 is amplified in esophageal cancer, bladder tumors, and breast cancer. During analyses of FGF gene cluster within the CCND1-EMS1 locus, we identified a 5'-truncated partial cDNA (NM_018043.1) derived from the uncharacterized FLJ10261 gene. Here, we characterized the FLJ10261 gene by using bioinformatics. NM_018043.1 cDNA corresponded to the nucleotide position 1129-4258 of 4558-bp DKFZp686O1156 cDNA, and the nucleotide position 50-3010 of DKFZ-p686O1156 was the coding region of the FLJ10261 gene. FLJ10261 gene, consisting of 26 exons, was located between FGF3 and FADD genes within the CCND1-EMS1 locus. Two FLJ10261 isoforms with or without exon 15 were transcribed due to alternative splicing. FLJ10261 mRNA was expressed in head and neck tumors, parathyroid tumors, breast, pancreatic, and gastric cancer. Mouse Flj10261 gene (AK052589) was located between Fgf3 and Fadd genes on mouse chromosome 7. Human FLJ10261 gene was homologous to C12orf3 gene on human chromosome 12p13, C11orf25 gene on 11p14, and FLJ34272 gene on 12q23. Human FLJ10261 protein showed 89.8% total-amino-acid identity with mouse Flj10261 protein, and also 58.4%, 38.3%, and 38.6% identity with human C12orf3, C11orf25, and FLJ34272/BAC03704 proteins, respectively. FLJ10261, C12orf3, C11orf25 and FLJ34272 proteins were eight-transmembrane proteins with N- and C-terminal tails facing the cytoplasm, which might function as transporters for unidentified substrates. This is the first report on comprehensive characterization of the FLJ10261 gene located within the CCND1-ORAOV1-FGF19-FGF4-FGF3-FLJ10261-FADD-PPFIA1-EMS1 locus on human chromosome 11q13.

Amino Acid Sequence↗

PubMed2003

KIAA1735 gene on human chromosome 11q23.1 encodes a novel protein with myosine-tail homologous domain and C-terminal DIX domain.

Dishevelled 1 (DVL1), DVL2 and DVL3 are DIX-domain proteins implicated in the WNT signaling pathway. Here, we searched for a novel DIX-domain protein by using bioinformatics. Uncharacterized human KIAA1735 gene was found encoding a novel DIX-domain protein. Mouse ortholog of human KIAA1735 gene was next identified, and the nucleotide sequence of mouse Kiaa1735 cDNA was determined in silico by assembling nucleotide sequences of ESTs BY753211, BQ931084, CA750490, BQ960056 and a 5'-truncated partial cDNA AK082960. Human KIAA1735 protein (472 aa) and mouse Kiaa1735 protein (474 aa) showed 90.9% total-amino-acid identity. Myosine-tail homologous (MTH) domain and C-terminal DIX domain were conserved between human KIAA1735 and mouse Kiaa1735 proteins. A tyrosine phosphorylation site (Tyr 242) within the MTH domain was conserved between human KIAA1735 and mouse Kiaa1735 proteins. Leucine zipper motif (codon 202-237) and another tyrosine phosphorylation site (Tyr 272) were identified within the MTH domain of human KIAA1735, but not within that of mouse Kiaa1735. Human KIAA1735 mRNA was expressed in brain, subchondral bone, and also in lung cancer. KIAA1735 gene, consisting of 16 exons, was about 45 kb in size. KIAA1735 gene was linked to DLAT gene in tail-to-head manner with an interval less than 4.0 kb. KIAA1735 gene on human chromosome 11q23.1 was located between D11S1391 and D11S1347 loci, the region deleted in sporadic breast cancer. This is the first report on comprehensive characterization of the KIAA1735 gene.

Amino Acid Motifs↗

PubMed2003

MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer, encodes secreted-type protein with conserved cysteine residues.

Microarray analyses is applied for prognosis of gastric cancer, including risk assessments of lymph-node metastasis and peritoneal dissemination. EST AA769445 derived from an unknown gene is reported to be frequently down-regulated in intestinal-type gastric cancer based on microarray analyses. Here, we identified and characterized the gene corresponding to EST AA769445 by using bioinformatics. EST AA769445 overlapped with MGC29506 cDNA (BC021275) and PACAP cDNA (AF338109). MGC29506 protein (189 aa) and PACAP protein (123 aa) were identical in codon 1-59, but were divergent in the C-terminal region due to a frame shift caused by sixteen-base insertion in PACAP cDNA. MGC29506 and PACAP were derived from the same gene, consisting of four exons, due to alternative splicing of alternative splice-acceptor-site type. Fourteen human ESTs were the MGC29506 type, while one human EST was the PACAP type. MGC29506 was the major isoform of the MGC29506/PACAP gene on human chromosome 5q31.2. MGC29506 orthologs in other species were next searched for. AK088094 and AK008016 cDNAs with nucleotide substitutions resulting in four-amino-acid substitutions were derived from mouse Mgc29506 gene. Rat Mgc29506 gene was identified in the rat genome draft sequence AC135285. ESTs AJ396310 and AJ441435 were derived from chicken Mgc29506 gene, while ESTs BW315632 and BW251767 from ciona mgc29506 gene. N-terminal signal peptide, six cysteine residues and other amino acids were conserved among human, mouse, rat, chicken, and ciona MGC29506 proteins. MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer, was found to encode secreted-type protein with six conserved cysteine residues.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Evolutionary conservation of CCND1-ORAOV1-FGF19-FGF4 locus from zebrafish to human.

The CCND1-ORAOV1-FGF19-FGF4-FGF3-FLJ10261-FADD-PPFIA1-EMS1 locus on human chromosome 11q13 is frequently amplified in esophageal cancer, breast cancer, and bladder tumors. FGF19, FGF4 and FGF3 genes are implicated in embryogenesis and carcinogenesis. We proposed in 2002 the hypothesis that mouse Fgf15 might be the ortholog of human FGF19 based on comparative genomics. Here, we identified zebrafish fgf19 and oraov1 genes by using bioinformatics to demonstrate the hypothesis. Zebrafish fgf19 gene, consisting of three exons, was located around nucleotide position 121802-124963 of zebrafish genome draft sequence AL929586.12 in the reverse orientation. Zebrafish fgf19 (209 aa) was more homologous to chicken fgf19 and human FGF19 than to rodent Fgf15. Zebrafish oraov1 gene, consisting of five exons, was located around nucleotide position 112172-115838 of AL929586.12 in the reverse orientation. Zebrafish oraov1 protein (141 aa) was more homologous to human ORAOV1 than to rodent Oraov1. The CCND1-ORAOV1-FGF19-FGF4 locus was well conserved between human and zebrafish genomes in the order of genes, in the direction of genes, and in the exon-intron structure. Rat Ccnd1-Oraov1-Fgf15-Fgf4 locus was synthenic to mouse Ccnd1-Oraov1 (also known as 2210010N10Rik)-Fgf15-Fgf4 locus. Fgf15, homologous to human FGF19 and zebrafish fgf19, was located on the synthenic locus of human FGF19 and zebrafish fgf19 within rodent genomes. Based on the evolutionary conservation of the CCND1-ORAOV1-FGF19-FGF4 locus from zebrafish to human, it was concluded that Fgf15 gene is the rodent ortholog of human FGF19 gene.

Amino Acid Sequence↗

PubMed2003

IGSF11 gene, frequently up-regulated in intestinal-type gastric cancer, encodes adhesion molecule homologous to CXADR, FLJ22415 and ESAM.

EST H04796 is reported frequently up-regulated in intestinal-type gastric cancer based on microarray analysis combined with laser-capture microdissection. Here, we identified and characterized the gene corresponding to EST H04796 by using bioinformatics. H04796 overlapped with DKFZp586B0620, and DKFZp586B0620 overlapped with IGSF11 cDNA (NM_152538). IGSF11-1 isoform without the N-terminal signal peptide corresponded to IGSF11 cDNA, while IGSF11-2 isoform with the N-terminal signal peptide to EST BI549168. IGSF11-1 isoform, consisting of exons 1a, 2a, 3a, and 4-9, was expressed in brain medulla and testis. IGSF11-2 isoform, consisting of exons 1b, and 4-9, was expressed in brain hippocampus and testis. IGSF11 gene consisting of 10 exons, was found to encode two isoforms due to alternative splicing. IGSF11 gene on human chromosome 3q13.3 was homologous to CXADR gene on 21q21.1, FLJ22415 gene on 11q24.1, and ESAM gene on 11q24.2. CXADR is a receptor for coxsackievirus and adenovirus. FLJ22415 is the human ortholog of mouse Asp5 and rat OL-16 specifically expressed in adipose tissue. ESAM is a tight junction protein selectively expressed on endothelial cells and platelets. IGSF11-2, CXADR, FLJ22415 and ESAM are type I transmembrane proteins with extracellular immunoglobulin (Ig)-like domain(s), cytoplasmic juxtamembrane domain and C-terminal PZD-binding domain. IGSF11-2 is predicted to be an adhesion molecule based on structural similarity with CXADR, FLJ22415 and ESAM. Because IGSF11 gene is frequently up-regulated in intestinal-type gastric cancer, IGSF11 protein might be clinically applied as targets for early diagnosis of gastric cancer as well as for drug delivery to gastric cancer.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of human TIPARP gene within the CCNL amplicon at human chromosome 3q25.31.

Array CGH combined with mRNA microarray analyses was successfully applied for genome-wide screening of proto-oncogenes as well as tumor suppressor genes in 2002. It has been reported that an uncharacterized gene, corresponding to a 5'-truncated partial cDNA DKFZp434J214, is amplified and up-regulated together with CCNL in head-and-neck squamous cell carcinoma (HNSCC). Here, we identified that the novel gene, corresponding to the 5'-truncated DKFZp434J214 cDNA, is the human ortholog of mouse Tiparp gene, by using bioinformatics. Complete coding sequence of human TIPARP mRNA was determined in silico by assembling nucleotide sequences of BC034397 and DKFZp434J214 cDNAs. Human TIPARP gene, consisting of six exons, was located between SSR3 and CCNL genes at human chromosome 3q25.31. Fugu tiparp gene was located around nucleotide position 14280-23355 of fugu genome draft sequence CAAB01003597.1. Human TIPARP showed 91.8% and 52.7% total amino-acid identity with mouse Tiparp and fugu tiparp, respectively. TPH domain (codon 242-296 of human TIPARP), WWE domain (codon 329-378) and PARP-like domain (codon 465-648) were evolutionarily conserved among TIPARP proteins. CCCH-type zinc finger was located within the N-terminal part of the TPH domain. Human TIPARP showed 27.5% and 26.0% total-amino-acid identity with human FLJ22693 and ZAP, respectively. TIPARP, FLJ22693 and ZAP, sharing the common structure with the TPH, WWE and PARP-like domains, were found to constitute the TIPARP family. This is the first report on human TIPARP and fugu tiparp genes as well as on the TIPARP family.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of mouse Ppfia1 gene in silico.

Array CGH combined with mRNA microarray analyses was successfully applied for genome-wide screening of proto-oncogenes and tumor suppressor genes in 2002. The CCND1-ORAOV1-FGF19-FGF4-FGF3-FLJ10261-FADD-PPFIA1-EMS1 locus on human chromosome 11q13 is one of the most frequently amplified regions within the human genome. Here, we identified and characterized mouse Ppfia1 gene by using bioinformatics. Nucleotide sequence of mouse Ppfia1 cDNA was determined in silico by assembling nucleotide sequences of ESTs BY727670, CA327608, BU708520, BQ886535, and a 5'-truncated partial cDNA BC038349. Mouse Ppfia1 gene, consisting of 28 exons, was located between Fadd and Ems1 (also known as Cttn) genes on mouse chromosome 7. Mouse Ppfia1 (1201 aa) and human PPFIA1 (1202 aa), showing 95.8% total-amino-acid identity, were found to consist of MAH (myosin heavy chain tail and ATPase homologous) domain and three SAM (sterile alpha motif) domains. MAH domain is implicated in the homo- or hetero-oligomer formation through the coiled-coil interaction, while SAM domain is implicated in the interaction with other proteins. Mouse Ccnd1-Ems1 locus and human CCND1-EMS1 locus were evolutionarily conserved in the order and the orientation of genes therein. Nucleotide and amino-acid substitution rates of Ccnd1, Ppfia1 and Ems1 genes located near both ends of the Ccnd1-Ems1 locus were relatively lower than those in the middle part of the locus. This is the first report on mouse Ppfia1 gene as well as comprehensive comparison of CCND1-EMS1 locus within the human and mouse genomes.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Identification and characterization of human ZPBP-like gene in silico.

PP1R1B-ERBB2-GRB7 locus on human chromo-some 17q12 is frequently amplified in gastric and breast cancer. Because recombination hot spot or fragile site is located around the terminus of amplified region (amplicon), we searched for a novel gene closely linked to the teromeric end of the ERBB2 amplicon. Here, we identified and characterized the ZPBP-like (ZPBPL) gene by using bioinformatics. ZPBPL gene, corresponding to BC043152 cDNA, was found to consist of seven exons. ZPBPL (316 aa) and ZPBP (351 aa) proteins, showing 34.8% total amino-acid identity, shared the zona pellucida binding protein homologous (ZPBH) domain with conserved 15 cysteine residues. ZPBPL was a secreted-type glycoprotein with the ZPBH domain, while ZPBP was a type 2 transmembrane protein with the extracellular ZPBH domain. ZPBPL mRNA was co-expressed with ZPBP mRNA in testis, germ cell tumor, and brain medulla. ZPBPL might be implicated in the gamete interaction during fertilization just like ZPBP. The MGC9753-ERBB2-MGC14832-GRB7-ZNFN1A3-ZPBPL-PRO2521-ORMDL3-GSDM locus on human chromosome 17q12-q21 and the ZPBP-ZNFN1A1-FIGNL1-DDC-GRB10-COBL-SEC61G-EGFR-LANCL2 locus on human chromosome 7p12-p11 were next compared. Comparative genomics revealed that ZPBPL-ZNFN1A3-GRB7-ERBB2 and ZPBP-ZNFN1A1-GRB10-EGFR loci were paralogous regions within the human genome. This is the first report on identification and characterization of the ZPBPL gene.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of LASP2 gene in silico.

LASP1 (also known as MLN50) gene, located centromeric to the PPP1R1B-ERBB2-GRB7 locus on human chromosome 17q12, is amplified and over-expressed in breast cancer. Here, we identified and characterized a novel LASP1-related gene, LASP2, by using bioinformatics. Nucleotide sequence of human LASP2 cDNA was determined in silico by assembling EST BF699808 and 5'-truncated FLJ39221 cDNA. Nucleotide sequence of mouse Lasp2 cDNA was derived from 1200007O21Rik cDNA. Human LASP2 (270 aa) showed 97.4% and 63.7% total-amino-acid identity with mouse Lasp2 and human LASP1, respectively. LASP2 and LASP1 were the LASP family proteins consisting of LIM domain, Nebulin repeat, and SH3 domain. LASP2 and NEBL mRNAs were transcribed from the LASP2/NEBL gene on human chromosome 10p12 due to alternative splicing. LASP2 mRNA consists of exons 1a-4a, 24, 27, and 28 of the LASP2/NEBL gene, while NEBL mRNA consists of exons 1-28. Exon 1a-4a of the LASP2/NEBL gene were more homologous to exon 1-4 of the LASP1 gene on human chromosome 17q12, while exon 1-28 of the LASP2/NEBL gene were more homologous to exons of NEB gene on human chromosome 2q23. Some part of the LASP2/ NEBL-TEM7L-ARL8-CACNB2 locus on 10p12 was paralogous to the LASP1-TEM7-CACNB1 locus on 17q12, while the other part of the LASP2/NEBL-TEM7L-ARL8-CACNB2 locus was paralogous to the NEB-ARL5-CACNB4 locus on 2q23. These facts indicate that the LASP2/NEBL-TEM7L-ARL8-CACNB2 is a chimeric locus, which might be generated through the homologous recombination between the ancestral lasp2-tem7l-cacnb2 locus and the ancestral nebl-arl8 locus. Therefore, gene fusion during evolution is one of the mechanisms to generate alternative splicing.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Identification and characterization of mouse Erbb2 gene in silico.

The PPP1R1B-STARD3-TCAP-PNMT-MGC9753-ERBB2-MGC14832-GRB7 locus on human chromosome 17q12 is frequently amplified in human gastric and breast cancer. We have recently identified and characterized human MGC9753 (also known as wild-type CAB2) and mouse Mgc9753. Here, we identified and characterized mouse Erbb2 gene by using bioinformatics. BLAST programs revealed that mouse AK031099 cDNA was derived from mouse Erbb2 gene. Because AK031099 cDNA showed 806 C-->A nucleotide substitution compared with mouse genome draft sequences and mouse Erbb2 ESTs, the nucleotide sequence of mouse Erbb2 cDNA was determined in silico by correcting 806 A of AK031099 cDNA to C. Nucleotide position 48-3818 of mouse Erbb2 cDNA was the coding region. Mouse Erbb2 gene, consisting of 27 exons, was located within the Ppp1r1b-Grb7 locus on the mouse chromosome 11. Mouse Erbb2 protein (1256 aa) showed 87.5% total-amino-acid identity with human ERBB2 protein, and 95.2% total-amino-acid identity with rat Erbb2 protein. Mouse Ppp1r1b-Grb7 locus and human Ppp1r1b-Grb7 locus were evolutionarily conserved in the order and the orientation of genes therein. Nucleotide and amino-acid substitution rates of Neurod2 located centromeric to the Ppp1r1b-Grb7 locus were significantly lower than others within the Ppp1r1b-Grb7 locus. This is the first report on the complete coding sequence of mouse Erbb2 gene as well as on the comprehensive comparison of Ppp1r1b-Grb7 locus within the human and mouse genomes.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of ASXL2 gene in silico.

Drosophila Asx is a Polycomb group gene. Because Drosophila Asx mutations exhibit anterior and posterior transformations, Drosophila Asx is one of the ETP (Enhancers of trithorax and Polycomb) genes with dual functions in transcriptional activation and silencing. ASXL1 is one of human homologs of Drosophila Asx. Here, we searched for ASXL1-related gene within the human genome by using bioinformatics, and identified the ASXL2 gene. Nucleotide sequence of human ASXL2 cDNA was determined by assembling the nucleotide sequences of human EST AI797346, and partial cDNAs MGC44431 (BC042999) and KIAA1685 (AB051472). Nucleotide sequence of mouse Asxl2 was derived from uncharacterized mouse cDNA 9930017F14 (AK036839). Human ASXL2 (1435 aa) showed 79.4% total-amino-acid identity with mouse Asxl2 (1370 aa), and 29.8% total-amino-acid identity with human ASXL1. ASXN domain (codon 1-86 of ASXL2), ASXM domain (codon 269-380 of ASXL2), and PHD domain (codon 1400-1431 of ASXL2) were conserved between human ASXL2 and ASXL1. Human ASXL2 gene, consisting of at least 13 exons, was mapped to human chromosome 2p23.3, one of recombination hot spots or fragile sites associated with carcinogenesis. The DNMT3A-ASXL2-KIF3C locus on human chromosome 2p23.3 and the DNMT3B-ASXL1-KIF3B locus on human chromosome 20q11.21 were paralogous regions within the human genome. Polycomb group and trithorax group proteins are implicated in embryogenesis and carcinogenesis due to transcriptional regulation of target genes through histone modification and chromatin remodeling. Based on functional conservation and human chromosomal localization, ASXL2 and ASXL1 genes were predicted cancer-associated genes.

Amino Acid Sequence↗