Biomedical subjects

Masaru Katoh

Publications and source records attributed to Masaru Katoh.

At least 145 records · Page 8Linked to original sources

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

Trefoil factors and human gastric cancer (review).

TFF1/pS2, TFF2/SP and TFF3/ITF are soluble peptides with trefoil domain(s) and C-terminal dimerization domain, which are conserved among human, cow, mouse and rat. TFF1 mRNA is expressed in stomach (mucous cells in fundus and antrum), TFF2 mRNA in stomach (mucous neck cells in fundus and basal cells in antral and pyloric glands) and duodenum (Brunner's gland), TFF3 mRNA in small intestine and large intestine (goblet cells). Expression of TFF1, TFF2 and TFF3 mRNAs are differentially regulated by FGF2/bFGF, FGF7/KGF, estrogen, aspirin, arachidonic acid, X-ray irradiation, and hydrogen peroxide. Gastric cancer is classified into the intestinal type and the diffuse type. TFF mRNAs are preferentially expressed in diffuse-type gastric cancer cells. Custom-made microarray (TFF mRNAs) and ELISA (TFF proteins) might be applicable for screening methods of peritoneal and bone marrow dissemination from diffuse-type gastric cancer. TFF1 and TFF2 mRNAs are frequently down-regulated in intestinal-type gastric cancer. TFF1 gene, inactivated by deletion, missense mutation and promoter hypermethylation, is a tumor suppressor gene implicated in gastric cancer. TFF2 is a candidate tumor suppressor gene; however, genetic and epigenetic alterations of TFF2 gene in human gastric cancer remain unclear. TFF1, TFF2 and TFF3 play key roles in mucosal protection through mucous-barrier formation, and also in mucosal repair through promotion of restitution after injury. Patients with chronic atrophic gastritis and those with ulcerative colitis are at risk of gastric cancer and colorectal cancer, respectively. TFF1, TFF2 and TFF3 proteins might be applicable for chemoprevention of gastrointestinal cancer associated with chronic persistent inflammation.

Amino Acid Sequence↗

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↗

PubMed2003

Identification and characterization of TPARM gene in silico.

Several tumor suppressor genes are located within human chromosome 11q23 region. We have cloned and characterized MFRP and RNF26 genes at 11q23.3. We also identified and characterized KIAA1735/MTHDIX gene at 11q23.1 and CLDN24 gene at 11q23.2 by using bioinformatics. Here, a novel human gene corresponding to a 5'-truncated FLJ20535 cDNA was identified. FLJ20535 corresponded to nucleotide position 55-2255 of FLJ13859, and nucleotide position 52-2169 of FLJ13859 was the coding region. Because of tetratricopeptide repeat (TPR) and armadillo repeat (ARM) domains within its gene product, the novel human gene was designated TPARM. Mouse E330017O07Rik cDNA was derived from mouse Tparm gene. Human TPARM (705 aa) and mouse Tparm (704 aa), showing 75.4% total-amino-acid identity, consist of TPR domain and three ARM domains. TPR domain of TPARM was most homologous to that of SMAP1, while ARM1-ARM3 domains of TPARM were most homologous to ARM7-ARM9 domains of CTNNB1 (also known as beta-catenin). TPARM might be implicated in the WNT-beta-catenin signaling pathway. TPARM mRNA was expressed in testis, prostate, lung, germinal center B-cells, and also in neuroblastoma, teratocarcinoma, colon cancer, and gastric cancer. Human TPARM gene was found to consist of 22 exons. TPARM gene, located between NCAM1 and DRD2 genes, was mapped to human chromosome 11q23.2. TPARM as well as NCAM1 and DRD2 were predicted to be candidate tumor suppressor genes within the commonly deleted region of malignant melanoma on 11q23.1-q23.2 (between microsatellite markers D11S1347 and D11S4122).

Amino Acid Sequence↗

PubMed2003

Identification and characterization of FLJ10737 and CAMTA1 genes on the commonly deleted region of neuroblastoma at human chromosome 1p36.31-p36.23.

Tumor suppressor genes of neuroblastoma are located at human chromosome 1p36, 4p16, 11q23.3, and 14q32. We have previously cloned and characterized MFRP and RNF26 genes at 11q23.3. Here, we searched for genes within the 1p36.31-p36.23 commonly deleted region between microsatellite markers D1S2731 and D1S2666 by using bioinformatics. D1S2731 was located within FLJ10737 gene, consisting of 16 exons. D1S2666 was located within CAMTA1 gene, consisting of 23 exons. FLJ10737 and CAMTA1 genes were located in the head-to-head manner with an interval of about 83 kb. Exons 1-10 of FLJ10737 gene as well as exons 1-5 of CAMTA1 gene were located within the 1p36.31-p36.23 commonly deleted region. FLJ10737 (559 aa) was found to consist of the DnaJ domain, bipartite nuclear localization signal (NLS), FADH domain, and FEMCA domain. Mouse E030019A03, zebrafish MGC55845, Drosophila CG8531 and Arabidopsis At2g35720 were homologs of human FLJ10737. FADH domain was conserved among vertebrate FLJ10737 orthologs as well as human AD-015, mouse Histocompatibility 47, and rat Ratsg2. KIAA0833 was the representative human CAMTA1 cDNA. Nucleotide sequence of mouse Camta1 cDNA was determined in silico by assembling nucleotide sequences of BY733411, BU610694 ESTs and AK122383 cDNA. Human CAMTA1 (1673 aa) and mouse Camta1 (1682 aa) showed 94.1% total-amino-acid identity. CAMTA1 was a Calmodulin-binding transcription activator (CAMTA) family protein, consisting of CG-1 domain, TIG domain, ankyrin repeats, and IQ motifs. FLJ10737 and CAMTA1 genes on 1p36.31-p36.23 are candidate tumor suppressor genes of neuroblastoma.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of human BCL9L gene and mouse Bcl9l gene in silico.

Human BCL9 gene is over-expressed in some cases of acute lymphoblastic leukemia (ALL) with t(1;14)(q21;q32). Drosophila segment polarity gene legless (lgs), encoding wingless-armadillo (WNT - beta-catenin) signaling molecule, is the homolog of human BCL9. Here, we identified and characterized human BCL9-like (BCL9L) gene as well as mouse Bcl9-like (Bcl9l) gene by using bioinformatics. Uncharacterized DLNB11 cDNA (AB094091.1) was derived from human BCL9L gene. Nucleotide sequence of mouse Bcl9l cDNA was determined in silico by assembling mouse ESTs BF464707, BQ258167, 5'-truncated BC003321 cDNA, and mouse genome clone RP24-308H8 (AC125129.5). Human BCL9L and mouse Bcl9l genes were found to consist of eight exons. Exon-intron structure was well conserved between human BCL9L and mouse Bcl9l genes. Human BCL9L (1499 aa) showed 94.0% and 34.8% total-amino-acid identity with mouse Bcl9l (1494 aa) and human BCL9, respectively. Six domains (B9H1-B9H6) were conserved among mammalian BCL9 family proteins. B9H1 and B9H2 domains, and N-terminal part of B9H3 domain were identical to HD1, HD2, and HD3 domains conserved between human BCL9 and Drosophila lgs. B9H4, B9H5 and B9H6 were novel domains. B9H4 domain was characterized by multiple Ser-Pro repeats. Human BCL9L mRNA was expressed in fetal brain, adult lung, amygdala, eye, prostate, and also in several types of tumors including pancreatic cancer, prostate cancer, head and neck tumor and embryonal tumor. BCL9L gene was located between BLR1 and UPK2 genes within the commonly deleted region of neuroblastoma at human chromosome 11q23.3. This is the first report on human BCL9L and mouse Bcl9l.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of human FNBP3 gene in silico.

FMNL1, FMNL2, FMNL3, DAAM1, DAAM2, DIAPH1 and DIAPH2 constitute the Formin-homology subfamily with FDD, FH1 and FH2 domains. FMNL2 gene is linked to FNBP3 (also known as HYPA) gene on human chromosome 2q23.3, while FMNL3 gene to FNBP3L (also known as HYPC) gene on 12q13. Because human FNBP3 cDNA (NM_017892.2) was a 5'-truncated partial clone, we identified and characterized human FNBP3 gene by using bioinformatics. Human FNBP3 gene, consisting of 26 exons, was located within human genome sequences AC079344.5, AC012443.8, and human chromosome 2 genomic contig NT_005403.13. Nucleotide sequence of human FNBP3 cDNA was determined in silico by assembling nucleotide sequences of 26 exons of FNBP3 gene. HYPA cDNA and IMAGE cDNA clones 3356968, 4026200, 4733897 were 3'-truncated partial FNBP3 cDNAs, while FNBP3 (NM_017892.2), FLJ11559, NY-REN-6, and FLJ20585 were 5'-truncated partial FNBP3 cDNAs. Two FNBP3 isoforms with or without 126-bp region in the 3'-part of exon 1 were transcribed due to alternative splicing. FNBP3 isoform 2 without the 126-bp region was the major FNBP3 transcript. Two WW domains, two FF domains, two bipartite nuclear localization signals, FB3HM and FB3HC domains were conserved among vertebrate FNBP3 homologs, including human FNBP3, FNBP3L, mouse Fnbp3, Fnbp3l, chicken fnbp3 and zebrafish fnbp3. FNBP3, binding to TNFSF6 (Fas ligand), Huntingtin and Formin proteins, might transduce extracellular signals to the Rho-related signaling pathway. On the other hand, FNBP3 with nuclear localization signals and two tyrosine phosphorylation sites might transduce extracellular signals to the nucleus. This is the first report on comprehensive characterization of human FNBP3 gene.

Alternative Splicing↗

PubMed2003

Identification and characterization of human KIAA1391 and mouse Kiaa1391 genes encoding novel RhoGAP family proteins with RA domain and ANXL repeats.

The commonly deleted region of breast cancer at human chromosome 11q23.1 is located between microsatellite markers D11S927 and D11S1347. We have previously identified and characterized the KIAA1735 gene, encoding MTH and DIX domain protein, within the 11q23.1 commonly deleted region. The BTG4 gene, encoding BTG/TOB family protein, as well as the SIK2 gene, encoding salt-inducible serine/threonine kinase 2, were also located within the 11q23.1 region. We identified and characterized the KIAA1391 gene within the 11q23.1 commonly deleted region by using bioinformatics. The nucleotide position 11-3586 of human KIAA1391 cDNA was predicted as the coding region of human KIAA1391 gene. Mouse Kiaa1391 gene was located within mouse genome sequences RP23-95E13 (AC102770.4), RP23-212M11 (AC140363.1), and mouse chromosome 9 genomic contig NT_039473.1. Exon-intron structure was well conserved between human KIAA1391 gene and mouse Kiaa1391 gene. Nucleotide sequence of mouse Kiaa1391 cDNA was determined in silico by assembling nucleotide sequences of exon 1-15 of mouse Kiaa1391 gene. Human KIAA1391 protein (1191 aa) and mouse Kiaa1391 protein (1182 aa) showed 79.1% total-amino-acid identity. RA domain (codon 198-274), RhoGAP domain (codon 363-546), and two Annexin-like (ANXL) repeats (codon 657-767 and 796-909) of human KIAA1391 protein were conserved in mouse Kiaa1391 protein. This is the first report on the comprehensive characterization of human KIAA1391 gene and mouse Kiaa1391 gene, encoding RhoGAP proteins with RA domain and two ANXL repeats.

Amino Acid Sequence↗