Biomedical subjects

Masaru Katoh

Publications and source records attributed to Masaru Katoh.

At least 127 records · Page 7Linked to original sources

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

Characterization of human FOXN4 gene in silico.

Forkhead-box (FOX) superfamily genes are implicated in carcinogenesis through gene amplification, retroviral integration and chromosomal translocation. FOX superfamily genes within the human genome are classified into 17 or 18 families, designated FOX# (# is alphabet A-Q or R). FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1) and FOXN6 (FOXR2) genes constitute the FOXN gene family. Here, we characterized human FOXN4 gene by using bioinformatics. FOXN4 gene at human chromosome 12q24.12 was found to encode three isoforms. FOXN4 isoform 1 (representative transcript), encoding a 518-aa protein, consists of exons 1-10. FOXN4 isoform 2 (NM_ 213596.1), encoding a 337-aa protein, consists of exons 1, 2, 7v, 8-10. FOXN4 isoform 3, encoding a 314-aa protein, consists of exons 1-5, 7-10. Codon 205-518 of isoform 1 was conserved in isoforms 2 and 3. FOXN4 mRNA was expressed in testis, embryonic stem (ES) cells, uterus tumors, and leiomyosarcoma. FOXN4 was most homologous to FOXN1 among human FOXN family members. FOXN4 and FOXN1 showed 41.3% total-amino-acid identity. FOX domain (codon 192-305 of FOXN4) was well conserved among mammalian FOXN family members. FN14 domain (codon 367-456 of FOXN4) was identified as the novel domain conserved among FOXN4 and FOXN1 orthologs. FOXN4 and FOXN1 orthologs were found to share the common domain structure, consisting of FOX and FN14 domains. This is the first report on comprehensive characterization of the human FOXN4 gene as well as on identification of the FN14 domain.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of FBXL19 gene in silico.

CXXC1, CXXC2 (FBXL10), CXXC3 (MBD1), CXXC4 (IDAX), CXXC5, CXXC6, CXXC7 (MLL), CXXC8 (FBXL11), CXXC9 (DNMT1) and CXXC10 are CXXC family genes within the human genome. Recently, we identified and characterized CXXC5 and CXXC10 genes as the homologs of CXXC4, which is implicated in the WNT signaling pathway. Here, we identified human FBXL19 (CXXC11) gene by using bioinformatics. Complete coding sequence of FBXL19 cDNA was determined by assembling 10 exons within AC135048.2 genome sequence. NM_019085.1 cDNA was a 5'-truncated partial cDNA corresponding to nucleotide position 138-2025 of FBXL19 complete coding sequence. FBXL19-BCL7C locus at chromosome 16p11.2, FBXL10-RHOF-BCL7A locus at chromosome 12q24.31, and FBXL11-RHOD locus at chromosome 11q13.2 were paralogous regions within the human genome. FBXL19 gene was found to encode a 674-amino-acid FBXL19 protein. Human FBXL19 showed 97.5% total-amino-acid identity with mouse Fbxl19. FBXHA domain (codon 11-128 of FBXL19) and FBXHB domain (codon 404-674 of FBXL19) were identified as novel domains conserved among FBXL19, FBXL10 and FBXL11. CXXC domain was located within the FBXHA domain, and F-box domain was located within the FBXHB domain. FBXL19 consists of FBXHA and FBXHB domains, while FBXL10 and FBXL11 consist of Jumonji C (JmjC), FBXHA and FBXHB domains. This is the first report on human FBXL19 gene as well as FBXHA and FBXHB domains.

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↗

PubMed2004

Characterization of KIF7 gene in silico.

Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog (DHH) are Hedgehog family ligands, which play key roles in embryogenesis and carcinogenesis, especially in pancreatic cancer and gastric cancer. Drosophila Costal-2 (Cos2) is a Hedgehog signaling regulator, interacting with Smoothened (Smo), Cubitus interruptus (Ci), Fused (Fu) and microtubule. KIF27 is one of the mammalian orthologs for Drosophila Cos2. KIF7 gene is the paralog of KIF27 gene; however, complete coding sequence (CDS) of KIF7 remains elusive. Here we characterized human KIF7 gene by using bioinformatics. Human LOC374654 cDNA (NM_198525.1) was a 5'-truncated partial KIF7 cDNA, corresponding to the nucleotide position 1418-4538 of KIF7 complete CDS. KIF7 gene, consisting of 19 exons, was found to encode a 1343-amino-acid KIF7 protein. Human KIF7 showed 43.6% total-amino-acid identity with human KIF27. Kinesin motor catalytic (KISc) domain (codon 15-347 of KIF7) and novel KIF7-KIF27 homologous (KIF727H) domain (codon 699-1196 of KIF7) were well conserved between KIF7 and KIF27. Three coiled-coil regions were located within the KIF727H domain. KIF7 and KIF27 were N-type Kinesins with the KIF727H domain. KIF7 mRNA was expressed in embryonic stem (ES) cells, melanotic melanoma and Jurkat T cells, while KIF27 mRNA was expressed in testis, pancreatic islet, germ cell tumors and Jurkat T cells. This is the first report on the characterization of the KIF7 gene as well as on the identification of KIF727H domain.

Amino Acid Sequence↗

PubMed2004

[Chymotrypsin].

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Chymotrypsin↗

PubMed2003

Expression of Wnt, Frizzled, sFRP, and DKK genes in adult human pancreas.

Wnts are important signaling molecules involved in many normal developmental processes in the human body as well as some forms of cancer. Nineteen Wnt genes are found in the human genome, as well as 10 Wnt receptor genes called Frizzled. Two coreceptors called LRP 5 and 6 are critical for Wnt signal transduction. The interaction of the Wnts with the receptors is regulated by two classes of extracellular Wnt or LRP binding proteins called sFRP and Dickkopf (DKK), which modulate Wnt signaling. We have examined the expression of all Wnt family members both in the exocrine portion and in isolated islets of adult human pancreas. RT-PCR analysis of the 1-day cultured exocrine pellet fraction from the islet isolation procedure showed that Wnt 2, 2b, 3, 4, 5a, 5b, 7a, 7b, 14, and 15 were detectable. All 10 Frizzled (Frz) receptors were expressed but only Frizzled 1, 2, 4, 5, and 6 strongly. RT-PCR performed on purified human islets revealed that Wnt 2b, 3, 4, 5a, 7b, 10a, and 14 and Frz 4, 5, and 6 were the most highly expressed. DKK 1, 3, and 4 as well as sFRP 1, 4, and 5 were expressed in the exocrine fraction. sFRP 2 and 3 were detectable but only at low levels. In situ hybridization for Frz 1-7 showed that expression colocalized with the islets of Langerhans. Together the data suggest that active Wnt signaling occurs in adult pancreas and is probably important for physiological functions.

Adolescent↗

PubMed2003

Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells.

WNT family of secreted-type glycoproteins play key roles in carcinogenesis and embryogenesis. We have cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14 and WNT14B/WNT15 using bioinformatics and cDNA-PCR, and also reported frequent up-regulation of WNT2 in primary gastric cancer. Here, expression and regulation of WNT1 in human cancer were investigated using cDNA-PCR. WNT1 mRNA was relatively highly expressed in OKAJIMA cells (gastric cancer) and BxPC-3 cells (pancreatic cancer). Expression of WNT1 mRNA was up-regulated in 5 out of 10 cases of primary gastric cancer. Effects of beta-estradiol on expression of human WNT1 in MCF-7 cells (breast cancer) was next investigated, because mouse Wnt-1 induces mammary carcinogenesis even in estrogen receptor alpha (ERalpha) knockout mice. Expression of WNT1 mRNA was significantly up-regulated by beta-estradiol in MCF-7 cells. WNT1 was found to be one of estrogen target genes in human MCF-7 cells, which in part explains Wnt1-induced mammary carcinogenesis in ERalpha knockout mice.

Actins↗

PubMed2003

Identification and characterization of human Inscuteable gene in silico.

Neuroblast undergoes asymmetrical cell division to produce the neuroblast itself and ganglion mother cell along the apical-basal axis. Inscuteable (Insc) and Partner of Inscuteable (Pins) are translocated to the apical cell cortex during asymmetrical cell division of Drosophila neuroblast. Insc is implicated in the apical-basal orientation of mitotic spindle and the basal localization of Prospero (Pros) and Numb. Here, we identified and characterized human Inscuteable (INSC) gene using bioinformatics. Human INSC gene, consisting of at least 13 exons, was located within human genome draft sequence AC090744.5 (around nucleotide position 150581-16936 in reverse orientation). Human INSC gene, closely linked to CALCB gene with an interval of about 30 kb, was assigned to human chromosome 11p15.2-p15.1. Amino-acid sequence of human INSC polypeptide (579 aa) was determined based on exon sequences of human INSC gene. C. elegans hypothetical protein F43E2.3 (NP_495539), homologous to human INSC, was designated C. elegans Insc. Central INSC homologous (ISH) domain and C-terminal PDZ-binding motif were evolutionary conserved among INSC proteins. The former part of ISH domain is implicated in Pros localization, while function of the latter part of ISH domain and C-terminal PDZ-binding motif remain to be elucidated. Human INSC mRNA was expressed in eye, kidney, fetal cochlea, parathyroid tumor, chondrosarcoma, epidermoid carcinoma, and skin tumor. Because LGN/Pins, PARD3/Par-3Bazooka, PARD6A/Par-6 and PRKCZ/aPKC genes implicated in asymmetrical cell division are evolutionarily and functionally conserved, human INSC protein might be implicated in asymmetrical cell division of human neural stem cells and other stem cells.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle.

Drosophila prickle is implicated in tissue polarity or planar polarity. Here, human PRICKLE1 gene corresponding to FLJ31937 cDNA and human PRICKLE2 gene corresponding to DKFZp686D143 cDNA were identified to be homologous to Drosophila prickle gene by using bioinformatics. PRICKLE1 gene was mapped to human chromosome 12p11-q12, and PRICKLE2 gene was mapped to human chromosome 3p14. Mouse Prickle1 and Prickle2 genes were next identified in mouse genome draft sequences NW_000106.1 and NW_000262.1, respectively. Human PRICKLE1, PRICKLE2, Xenopus Prickle, and Drosophila prickle were homologous in the PET domain, three LIM domains, and the C-terminal Prickle homologous (PKH) domain. LMO6 and TESTIN, containing the PET domain and three LIM domains, were found to lack the PKH domain. Therefore, PRICKLE1 and PRICKLE2 rather than LMO6 and TESTIN were found to be human homologs of Drosophila prickle. PRICKLE1 and PRICKLE2 mRNAs were expressed together in brain, eye and testis. PRICKLE1 mRNA was expressed in fetal heart and hematological malignancies, while PRICKLE2 mRNA in fetal brain, adult cartilage, pancreatic islet, gastric cancer with signet-ring cell features, and uterus tumors. Because tissue polarity genes frizzled, dishevelled, flamingo, and Vang are evolutionary and functionary conserved from Drosophila to human, PRICKLE1 and PRICKLE2 might be implicated in the localization of Frizzled and Dishevelled proteins, just like Drosophila prickle. This is the first report on identification and characterization of human PRICKLE1, PRICKLE2, mouse Prickle1, and Prickle2 genes.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Identification and characterization of human SNAIL3 (SNAI3) gene in silico.

Human SNAIL1 (SNAI1) protein encoded by SNAI1/SNA gene represses transcription of E-cadherin/CDH1 gene. Human SNAIL2 (SNAI2) protein encoded by SNAI2/SLUG gene induces the first phase of epithelial-mesenchymal transition (EMT), including desmosome dissociation, cell spreading, and initiation of cell separation. Here, we have identified human SNAIL3 (SNAI3) gene using bioinformatics. Human SNAI3 gene, consisting of at least three exons, spans around the nucleotide position 320214-328221 of human reference genomic contig NT_010404.8 in the reverse orientation. SNAI3 gene, was located between KIAA0233 gene and CBFA2T3 gene in human chromosome 16q24.3, a region affected in breast cancer, gastric cancer, hepatocellular carcinoma, ovarian cancer, and therapy-related myeloid leukemia with t(16;21)(q24;q22) translocation. Human SNAI3 gene was found to encode 292-amino-acid polypeptide with the N-terminal SNAG domain and five zinc finger domains. N-terminal SNAG domain was identified in zinc finger proteins SNAI1, SNAI2, SNAI3, SCRATCH (SCRT1), GFI1, and GFI1B. ATP/GTP binding site was identified in SCRT1, GFI1 and GFI1B, but not in SNAI1, SNAI2 and SNAI3. Phylogenetic analysis of human zinc finger proteins with SNAG domain revealed that SNAI1, SNAI2 and SNAI3 were more closely related. These results clearly indicate that SNAI1, SNAI2 and SNAI3 constitute a subfamily among SNAG zinc-finger proteins. Human SNAI3 mRNA was expressed in skin melanotic melanoma, lung epidermoid carcinoma, and germ cell tumor. Because SNAG zinc-finger proteins are transcriptional repressors implicated in carcinogenesis and embryogenesis, SNAI3 gene might be a potent target of pharmacogenomics in the field of oncology and regenerative medicine.

Amino Acid Sequence↗

PubMed2003

Identification and characterization of human DAPPER1 and DAPPER2 genes in silico.

WNT signals play key roles in carcinogenesis and embryogenesis through the specification of cell fate and polarity. Dishevelled (DVL) proteins are WNT signaling molecules implicated in beta-catenin pathway and PCP pathway. Xenopus Dapper and Frodo are Dvl-binding proteins, showing 89.8% total-amino-acid identity. Here, we identified and characterized human homologs of Xenopus Dapper and Frodo using bioinformatics. Human DAPPER1 gene was located within human genome draft sequence NT_025892.9 (nucleotide position 39378960-39387891 in the forward orientation), and human DAPPER2 gene within NT_007302.10 (nucleotide position 660279-672480 in the reverse orientation). DAPPER1 (799-amino-acids) and DAPPER2 (774-amino-acids) showed 28.8% total-amino-acid identity. Seven DAPPER homologous (DAPH) domains, including DAPH2 (leucine zipper), DAPH3 (serine rich) and DAPH7 (PDZ binding), were conserved between DAPPER1 and DAPPER2. Phylogenetic analysis of vertebrate Dapper proteins revealed that Xenopus Dapper and Frodo are orthologs of human DAPPER1. DAPPER1 mRNA was expressed in amnion, fetal brain, eye, heart, adult brain medulla, gastric cancer (signet ring cell features), RER+ colon tumor, acute lymphoblastic leukemia, germ cell tumor, chondrosarcoma, and parathyroid tumor. DAPPER2 mRNA was expressed in placenta, genitourinary tract tumor, and endometrial adenocarcinoma. DAPPER1 and DAPPER2 genes were mapped to human chromosome 14q22.3 and 6q27, respectively. Human chromosome 14q22.3 is deleted in astrocytoma, while human chromosome 6q27 is deleted in breast, ovarian, and gastric cancer. Based on evolutionary and functional conservation of WNT signaling molecules as well as human chromosomal localization, DAPPER1 and DAPPER2 genes are predicted to be potent cancer-associated genes.

Adaptor Proteins, Signal Transducing↗

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↗