Biomedical subjects

Masaru Katoh

Publications and source records attributed to Masaru Katoh.

At least 91 records · Page 5Linked to original sources

PubMed2004

Identification and characterization of human MPP7 gene and mouse Mpp7 gene in silico.

Drosophila Crumbs (Crb), Stardust (Sdt), Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl) are involved in the establishment and the maintenance of apicobasal polarity in epithelial tissues. Because epithelial polarity is disrupted in tumors, human homologs of Drosophila crb, sdt, dlg, scrib, and lgl are potential cancer-associated genes. MPP1/EMP55, MPP2, MPP3, MPP4, MPP5/PALS1 and MPP6/PALS2 genes are human homologs of Drosoplila sdt. Here, we identified and characterized a novel member of MPP gene family, MPP7, by using bioinformatics. Uncharacterized FLJ32798 cDNAs (BC038105 and AK057360) were derived from human MPP7 gene. BC038105 was a representative MPP7 cDNA, while AK057360 was an aberrant MPP7 cDNA with a frame shift. Human MPP7 mRNA was expressed in placenta, brain, testis as well as in uterus tumor, bladder tumor, and lymphoma. Microsatellite marker D10S588, linked to IDDM and hereditary thrombocytopenia, was located within the MPP7 gene at human chromosome 10p12.1. Nucleotide sequence of mouse Mpp7 cDNA was determined in silico by assembling 3'-truncated cDNA AK078849, genome clone RP24-255J24, and EST AV260217. Human MPP7 showed 92.9% total-amino-acid identity with mouse Mpp7, and 75.7% total-amino-acid identity with zebrafish humpback. MPP7 orthologs were MAGUK proteins with two L27 domains, PDZ domain, SH3 domain, and GuKc domain. MPP7 was most related to MPP3 among MPP family members, functioning as adopter molecules assembling Crb homologs (CRB1, CRB3), Dlt homologs (INADL/PATJ, MPDZ/MUPP1), and Lin-7 homologs (LIN7A, LIN7B, LIN7C). This is the first report on identification and characterization of human MPP7 and mouse Mpp7 genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human LLGL4 gene and mouse Llgl4 gene in silico.

Drosophila Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl) act in concert as regulators of epithelial polarity, and human homologs of Drosophila dlg, scrib, and lgl are cancer-associated genes. LLGL1, LLGL2, and LLGL3/STXBP5 genes, encoding LGL1, LGL2, and LGL3/Tomosyn, respectively, are human homologs of Drosophila lgl gene. Here, we identified and characterized LLGL4 (also known as STXBP5L) gene encoding LGL4 protein, by using bioinformatics. Uncharacterized human KIAA1006 cDNA (AB023223) was derived from human LLGL4 gene. LLGL4 mRNA was expressed in kidney, brain hippocampus, and also in lung carcinoid, and germ cell tumors. LLGL4 gene, consisting of 28 exons, was mapped to human chromosome 3q13.33. Mouse A830015P08Rik cDNA (NM_172440.1) was a 3'-truncated partial Llgl4 cDNA. Nucleotide sequence of full-length mouse Llgl4 cDNA was determined in silico by assembling A830015P08Rik cDNA, BU609516 EST and last two exons of Llgl4 gene within mouse genome clone RP24-174G4 (AC118742.3). Human LGL4 showed 95.8% total-amino-acid identity with mouse Lgl4, and 68.4% total-amino-acid identity with human LGL3. LGLH1 domain (codon 1-11 of LGL4), LGLH2 domain (codon 52-98) and LGLH3 domain (codon 994-1054) were identified as novel conserved regions among LGL family members. LGL1 and LGL2 consist of LGLH1, LGLH2, LGLH3 domains and five WD40 repeats, while LGL3 and LGL4 consist of LGLH1, LGLH2, LGLH3 domains, five WD40 repeats and the C-terminal Syntaxin-binding SNARE domain. This is the first report on identification and characterization of human LLGL4 and mouse Llgl4 genes.

Adaptor Proteins, Vesicular Transport↗

PubMed2004

Identification and characterization of Crumbs homolog 2 gene at human chromosome 9q33.3.

Drosophila Crumbs (Crb)--Stardust (Sdt)--Discs lost (Dlt) complex plays a pivotal role in the establishment and the maintenance of epithelial polarity. CRB1 and CRB3 are human homologs of Drosophila Crb, MPP1-MPP7 are human homologs of Drosophila Sdt, INADL/PATJ and MPDZ/MUPP1 are human homologs of Drosophila Dlt. Here, we identified and characterized a novel Crumbs family gene, Crumbs homolog 2 (CRB2), by using bioinformatics. CRB2 isoform 1 was assembled by adding nucleotide position 1-3353 of FLJ16786 cDNA (AK123000) to the 5'-end of 5'-truncated FLJ38464 cDNA (NM_173689.1), while that of CRB2 isoform 2 was derived from FLJ16786 cDNA. CRB2 isoform 1, consisting of exon 1-13, encoded a 1285-aa transmembrane protein. CRB2 isoform 2, consisting of exon 1-10 and intron 10, encoded a 1176-aa secreted protein. CRB2 gene was found to encode transmembrane protein as well as secreted protein due to alternative splicing. CRB2 isoform 1, showing 24.4% total amino-acid identity with CRB1, was type I transmembrane protein with 14 extracellular EGF-like domains, 3 extracellular Laminin G-like domains and the Crb cytoplasmic tail (CCT) domain. CCT domain, functioning as the binding site for PDZ domain of Sdt homologs, was conserved among human CRB1, CRB2, CRB3, mouse Crb1, Crb3, Drosophila Crb, and C. elegans crb. Comparative genomics revealed that CRB2-KIAA1608-LHX2-NEK6 locus at human chromosome 9q33.3 and CRB1-MGC27044-LHX9-NEK7 locus at human chromosome 1q31.3 were paralogous regions within the human genome. This is the first report on identification and characterization of the CRB2 gene.

Alternative Splicing↗

PubMed2004

Identification and characterization of human DIAPH3 gene in silico.

Formin homology proteins with FH1 and FH2 domains are signaling effectors for assembly and polarization of actin filaments. FH1 is the binding domain for Profilin, SRC, EMS1/Cortactin, FNBP1, FNBP2, FNBP3, FNBP4 and WBP4/Fbp21, while FH2 is the actin-filament modification domain. Here, we identified and characterized a novel member of Formin-homology gene family, Diaphanous homology 3 (DIAPH3), by using bioinformatics. DIAPH3 isoform 1, corresponding to 3'-truncated FLJ34705 cDNA and 5'-divergent IMAGE5265490 cDNA, encodes full-length DIAPH3 protein (1112 aa), while DIAPH3 isoform 2, identical to NM_030932.2 cDNA, encodes N-terminally truncated DIAPH3 protein (849 aa). DIAPH3 isoform 1, consisting of exons 1-27, was expressed in lymph node, erythroid progenitor cells as well as in pancreatic cancer. DIAPH3 isoform 2, consisting of exons 1b and 8-27, was expressed in testis. DIAPH3 gene at human chromosome 13q21.2 was found to encode two isoforms due to alternative splicing of the alternative promoter type. Full-length human DIAPH3 protein, consisting of FDD, FH1 and FH2 domains, showed 51.3% total-amino-acid identity with DIAPH1, and 57.3% total-amino-acid identity with DIAPH2. FMNL1/FMNL, FMNL2/FHOD2, FMNL3/WBP3, DAAM1, DAAM2, DIAPH1, DIAPH2 and DIAPH3 were classified as the FDD-type Formin homology proteins, while GRID2IP/Delphilin, FHOD1, Fmn1 and Fmn2 were classified as the non-FDD-type Formin homology proteins. This is the first report on identification and characterization of human DIAPH3 gene.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Evolutionary recombination hotspot around GSDML-GSDM locus is closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon.

PPP1R1B-STARD3-TCAP-PNMT-PERLD1-ERBB2-MGC14832-GRB7 locus at human chromosome 17q12 is frequently amplified in human gastric cancer and breast cancer. Here, we compared human GSDML-GSDM locus with rodent genomes by using bioinformatics. Rodent ortholog of human GSDML was not identified. Rat Gsdm gene was identified within rat genome clone CH230-28N16 (AC119462.4), and was mapped to rat chromosome 10q31. Rat Gsdm gene, consisting of 12 exons, encoded a 446-amino-acid protein, which showed 86.3% and 32.3% total-amino-acid identities with human GSDM and GSDML, respectively. Mouse Gsdm-like 1 (Gsdml1) and Gsdml2 genes were identified within mouse genome clone RP23-438D7 (AL591125.20). Gsdml1 and Gsdml2 genes were found to encode 456- and 443-amino-acid proteins, respectively. Mouse 2200001G21Rik cDNA (AK008613.1) was a partial cDNA derived from mouse Gsdml2 gene. Mouse Gsdml1 and Gsdml2 were also more homologous to human GSDM than to human GSDML. Mouse Gsdml1, Gsdml2 and Gsdm genes, existing in the tandem homologous gene cluster, was mapped to mouse chromosome 11D. Mouse Gsdml1-Gsdml2-Gsdm gene cluster was predicted to be generated due to triplication of mouse Gsdm gene, while GSDML gene was predicted to be generated due to duplication of GSDM gene. Evolutionary recombination hotspot around the GSDML-GSDM locus was closely linked to the oncogenomic recombination hotspot around the PPP1R1B-ERBB2-GRB7 amplicon. The evolutionary recombination hotspot and oncogenomic recombination hotspot might be clustered around the fragile sites within the human genome.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human GUKH2 gene in silico.

Drosophila Guanylate-kinase holder (Gukh) is an adaptor molecule bridging Discs large (Dlg) and Scribble (Scrib), which are implicated in the establishment and maintenance of epithelial polarity. Here, we searched for human homologs of Drosophila gukh by using bioinformatics, and identified GUKH1 and GUKH2 genes. GUKH1 was identical to Nance-Horan syndrome (NHS) gene, while GUKH2 was a novel gene. FLJ35425 (AK092744.1), DKFZp686P1949 (BX647246.1) and KIAA1357 (AB037778.1) cDNAs were derived from human GUKH2 gene. Nucleotide sequence of GUKH2 cDNA was determined by assembling 5'-part of FLJ35425 cDNA and entire region of DKFZp686P1949 cDNA. Human GUKH2 gene consists of 8 exons. Exon 5 (132 bp) of GUKH2 gene was spliced out in GUKH2 cDNA due to alternative splicing. GUKH2-REPS1 locus at human chromosome 6q24.1 and GUKH1-REPS2 locus at human chromosome Xp22.22-p22.13 are paralogous regions within the human genome. Mouse Gukh2 and zebrafish gukh2 genes were also identified. N-terminal part of human GUKH2, mouse Gukh2 and zebrafish gukh2 proteins were completely divergent from human GUKH1 protein. Human GUKH2 and GUKH1, consisting of eight GUKH homology (GKH1-GKH8) domains and Proline-rich domain, showed 28.5% total-amino-acid identity. GKH1, GKH4, GKH5, GKH7 and GKH8 domains were conserved among human GUKH1, human GUKH2 and Drosophila Gukh. Because human homologs of Drosophila dlg (DLG1-DLG7) as well as human homologs of Drosophila scrib (SCRIB, ERBB2IP and Densin-180) are cancer-associated genes, human homologs of Drosophila gukh (GUKH1 and GUKH2) are predicted cancer-associated genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of PDZRN3 and PDZRN4 genes in silico.

NUMB and NUMBL are implicated in cell fate determination through the inhibition of Notch signaling. LNX, binding to NUMB and CXADR (CAR), functions as E3 ubiquitin ligase at least for NUMB. LNX is the paralog of PDZRN1 (PDZ domain containing RING finger 1). Here, we identified two novel homologs of LNX and PDZRN1 by using bioinformatics, which were designated PDZRN3 (LNX3 or SEMCAP3) and PDZRN4 (LNX4 or SAMCAP3L), respectively. KIAA1095 cDNA (AB029018) was the representative PDZRN3 cDNA. Complete coding sequence of PDZRN4 cDNA was determined by assembling nucleotide sequences of ESTs (BF059062 and AW297403), FLJ33777 cDNA (AK091096) and IMAGE5767589 cDNA (BC040922). PDZRN4 gene, consisting of 11 exons, was found to encode two isoforms with N-terminal divergence (PDZRN4 and PDZRN4S) due to an alternative promoter. PDZRN3-CNTN3 locus at human chromosome 3p13-p12.3 and PDZRN4-CNTN1 locus at human chromosome 12q12 were paralogous regions within the human genome. PDZRN3 (1066 aa) and PDZRN4 (1036 aa) showed 59.9% total-amino-acid identity. Two bipartite nuclear localization signals (NLS) were located within the C-terminal region of PDZRN3 and PDZRN4. PR34H1 and PR34H2 domains were identified as the regions conserved among PDZRN3, PDZRN4 and Drosophila CG1783. PDZRN3 and PDZRN4 consist of RING, two PDZ, PR34H1, PR34H2 domains and two NLS, while PDZRN1 and LNX consist of RING and four PDZ domains. PDZRN family proteins were classified into the LNX-PDZRN1 subfamily and the PDZRN3-PDZRN4 subfamily. This is the first report on the PDZRN3 and PDZRN4 genes.

Alternative Splicing↗

PubMed2004

Identification and characterization of human FHOD3 gene in silico.

Formin homology proteins are actin regulators with scaffold function, which are implicated in organogenesis, normal tissue homeostasis, and cancer-cell invasion. FHOD1/FHOS, GRID2IP, Fmn1 and Fmn2 are non-FDD-type Formin homology proteins, while FMNL1, FMNL2/FHOD2, FMNL3, DAAM1, DAAM2, DIAPH1, DIAPH2 and DIAPH3 are FDD-type Formin homology proteins. Here, we identified and characterized FHOD3 (also known as FHOS2), a novel gene homologous to FHOD1, by using bioinformatics. Because FLJ46173, FLJ22297, KIAA1695 and FLJ34580 were partial FHOD3 cDNAs, complete coding sequence of FHOD3 cDNA was determined by assembling nucleotide sequences of FLJ46173 and FLJ22297. FHOD3 gene at human chromosome 18q12.2 was found consisting of at least 25 exons. Exon 11 of FHOD3 gene was spliced out in KIAA1695 cDNA and BF116064 EST, while exon 13 of FHOD3 gene was spliced out in FLJ46173 cDNA. FHOD3 gene encodes at least three isoforms due to alternative splicing of the exon skipping type. FHOD3 and FHOD1 showed 52.1% total-amino-acid identity. Drosophila CG32030 showed 43.9% total-amino-acid identity with human FHOD3, and 39.1% total-amino-acid identity with human FHOD1. FHDHN domain (codon 1-327 of FHOD3) and FHDHC domain (codon 1377-1421 of FHOD3) were identified as the N-terminal conserved region and the juxta C-terminal conserved region, respectively. Human FHOD3, FHOD1 and Drosophila CG32030 were found to share the conserved domain structure consisting of FHDHN, FH1, FH2, and FHDHC domains. This is the first report on the FHOD3 gene as well as on the novel FHDHN and FHDHC domains.

Alternative Splicing↗

PubMed2004

Identification and characterization of human FOXN5 and rat Foxn5 genes in silico.

Forkhead-box (FOX) genes are implicated in embryogenesis through transcriptional regulation depending on SHH-GLI pathway, TGF-beta pathway etc., and also in carcinogenesis through gene amplification, retroviral integration and chromosomal translocation. FOXN1, FOXN2 (HTLF), FOXN3 (CHES1) and FOXN4 constitute the FOXN family. Here, we identified and characterized the FOXN5 gene, a novel member of FOXN gene family, by using bioinformatics. IMAGE5167039 (BC028191.1) was the representative cDNA derived from human FOXN5 gene. Rat Foxn5 gene, consisting of six exons, was identified within rat genome sequence CH230-26K11 (AC107575.5). Complete coding sequence of rat Foxn5 cDNA was determined by assembling nucleotide sequences of rat Foxn5 exons. Human FOXN5 (292 aa) and rat Foxn5 (296 aa) showed 77.4% total-amino-acid identity. Codon 173-254 of FOXN5 was the Forkhead domain. FOXN5 gene, consisting of six exons, was linked to BCL9L gene at human chromosome 11q23.3. FOXN5 is a candidate tumor suppressor gene (TSG), just like ARHGAP20 (KIAA1391), BTG4, SNF1LK2 (SIK2), DIXDC1 (KIAA1735) genes at 11q23.1, TTC12 (TPARM) gene at 11q23.2, IGSF4, DSCAML1, LL5A (PHLDB1), BCL9L, RNF26, and MFRP genes at 11q23.3. This is the first report on the human FOXN5 and rat Foxn5 genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of TMEM16E and TMEM16F genes in silico.

TMEM16A (FLJ10261 or ORAOV2) gene within the CCND1-FGF4-EMS1 amplicon at human chromosome 11q13.3 encodes transmembrane protein homologous to TMEM16B (C12orf3), TMEM16C (C11orf25), and TMEM16D (FLJ34272). Here, we identified novel TMEM16 family genes by using bioinformatics. Novel genes corresponding to DKFZp451A148 cDNA (AL833271.1) and 9330162L24 cDNA (AK034197.1) were designated human TMEM16E gene and mouse Tmem16e gene, respectively. Novel genes corresponding to DKFZp451M105 cDNA (AL832340.1) and F730003B03 cDNA (BC060732.1) were designated human TMEM16F gene and mouse Tmem16f gene, respectively. NELL1-TMEM16E locus at human chromosome 11p15.1-p14.3 and NELL2-TMEM16F locus at human chromosome 12q12 were paralogous regions within the human genome. TMEM16E mRNA was expressed in testis and pancreatic islet, while TMEM16F mRNA was expressed in embryonic stem cell, fetal liver, retina, chronic myelogenous leukemia, and intestinal cancer. TMEM16E (913 aa) and TMEM16F (892 aa) showed 50.3% total-amino-acid identity. Eight-transmembrane domains were identified within TMEM16E and TMEM16F proteins by using the TMHMM2 program. Phylogenetic analysis revealed that TMEM16E and TMEM16F constitute a subfamily among TMEM16 family proteins. TM16H1 domain around transmembrane domain 1 (TM1)-TM2, TM16H2 domain around TM5, and TM16H3 domain around TM6-TM7 were identified as conserved regions among TMEM16 family proteins. TMEM16 family members were eight-transmenbrane proteins with TM16H1-TM16H3 domains and a conserved Asn glycosylation site. This is the first report on TMEM16E and TMEM16F genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human FCHSD1 and FCHSD2 genes in silico.

FNBP1 and FNBP2 are SH3-type Formin-binding proteins. FNBP1 consists of FCH, FBH, HR1 and SH3 domains, while FNBP2 consists of FCH, FBH, RhoGAP and SH3 domains. Here, we identified novel genes FCHSD1 and FCHSD2, which were distantly related to FNBP1 and FNBP2. FCHSD1 and FCHSD2 genes with conserved exon-intron structure were located at human chromosome 5q31.3 and 11q13.4, respectively. Complete coding sequence of human FCHSD1 was derived from FLJ00007 (NM_033449.1) cDNA. KIAA0769 (NM_014824.1), encoding N-terminally truncated 684-aa protein, was an aberrant human FCHSD2 cDNA with a frame shift due to skipping of 98-bp exon 2. Complete coding sequence of human FCHSD2 cDNA was determined by assembling CF995054 EST and KIAA0769 cDNA. A030002D08Rik (NM_175684.3) was the representative mouse Fchsd1 cDNA, while BC034086 (NM_199012.1) was a variant mouse Fchsd2 cDNA with an insertion of 72-bp additional exon. CG4684 was the Drosophila homolog of mammalian FCHSD family genes. Human FCHSD1 (690 aa) showed 41.7% total-amino-acid identity with human FCHSD2 (740 aa), and 91.0% total-amino-acid identity with mouse Fchsd1. Human FCHSD2 showed 96.5% total-amino-acid identity with mouse Fchsd2. Mammalian FCHSD family proteins shared the common domain structure consisting of FCH, FBH, two SH3 and C-terminal Proline-rich domains. FCHSD family proteins (FCHSD1 and FCHSD2), FNBP1 family proteins (FNBP1, FNBP1L and TRIP10/CIP4) and FNBP2 family proteins (FNBP2, ARHGAP13/SRGAP1, ARHGAP14/SRGAP2 and ARHGAP4) were found constituting the FCFBS superfamily characterized by FCH, FBH and SH3 domains. This is the first report on identification and characterization of the FCHSD family genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of ASXL3 gene in silico.

Polycomb group proteins are implicated in embryogenesis and carcinogenesis through transcriptional regulation of target genes. ASXL1 and ASXL2 genes, encoding Polycomb group protein with ASXN and ASXM domains, are human homologs of Drosophila additional sex combs (asx) gene. Exons 2-13 of the ASXL2 gene are fused to exons 1-14 of the MYST3 gene in a case of therapy-related myelodysplastic syndrome due to t(2;8)(p23.3;p11.2). Here, we identified the ASXL3 gene, a novel human homolog of Drosophila asx, by using bioinformatics. ASXL3 gene, consisting of 12 exons, was located within human genome sequences RP11-562H1 (AC023192.8), RP11-265C19 (AC090989.8), and RP11-470B24 (AC010798.9). Complete coding sequence of human ASXL3 cDNA was determined by assembling EST BE145544, exons 4-11, and 5'-truncated KIAA1713 cDNA (AB051500.2). Partial coding sequence of mouse Asxl3 cDNA was derived from 3'-truncated C230079D11 cDNA (AK082659.1). Human ASXL3 mRNA was expressed in pancreatic islet, testis as well as in neuroblastoma, head and neck tumor. Human ASXL3 protein (2248 aa) with ASXN, ASXM and PHD domains was the third member of the human ASXL family. The region between ASXM and PHD domains was divergent among ASXL family members. Proline-rich domain was located within the divergent region of ASXL3, but not within that of ASXL1 and ASXL2. ASXL3-DTNA locus at chromosome 18q12.1 and ASXL2-DTNB locus at 2p23.3 were paralogous regions within the human genome. ASXL3 was a predicted cancer-associated gene, just like ASXL1 and ASXL2. This is the first report on identification and characterization of the ASXL3 gene.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of JMJD2 family genes in silico.

JMJD1 family genes, including JMJD1 (TSGA), TRIP8, and C5orf7 (5qNCA), encode nuclear proteins with Jumonji C (JmjC), TRI8H1 and TRI8H2 domains. Here, we identified JMJD2 family genes. Human genes corresponding to KIAA0677, KIAA0876, KIAA0780 and FLJ10251 cDNAs were designated JMJD2A, JMJD2B, JMJD2C, and JMJD2D, respectively. In addition, JMJD2D homologous genes within human genome sequences AP002383.3 and AP001264.4 were designated JMJD2E and JMJD2F, respectively. JMJD2A gene was mapped to human chromosome 1p34.1, JMJD2B gene to 19p13.3, and JMJD2C gene to 9p24.1. JMJD2D, JMJD2E and JMJD2F genes were clustered at human chromosome 11q21. Coding region of JMJD2A, JMJD2B, JMJD2C genes was located on multiple exons, while that of JMJD2D, JMJD2E and JMJD2F genes was located on a single exon. These facts strongly indicate that JMJD2D, JMJD2E and JMJD2F genes are locally triplicated retrotransposed elements derived from JMJD2 family gene. JD2H domain with C2HC2HC2- and C5HC2-type Cys (His) clusters was identified as the region conserved among JMJD2A (1064 aa), JMJD2B (1096 aa), and JMJD2C (1056 aa) proteins. JMJD2A, JMJD2B and JMJD2C consist of JmjN, JmjC, JD2H, and two TUDOR domains, while JMJD2D (523 aa), JMJD2E (506 aa) and JMJD2F (638 aa) consist of JmjN and JmjC domains. JMJD2 family proteins were classified into one group with JD2H and TUDOR domains and another group without JD2H or TUDOR domains. Because JMJD2C gene (also known as GASC1 gene) is amplified in esophageal squamous cell carcinoma (ESCC), JMJD2 family genes are cancer-associated genes. This is the first report on identification and characterization of human JMJD2 gene family.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human PDZRN4L gene and mouse Pdzrn4l gene in silico.

LNX, functioning as E3 ubiquitin ligase for NUMB, is implicated in the cell fate determination through the inhibition of Notch signaling. LNX, PDZRN1 (LNX2), PDZRN3 (LNX3 or SEMCAP3) and PDZRN4 (LNX4 or SEMCAP3L) constitute the LNX (PDZRN) family. PDZRN4 gene encodes 2 isoforms due to alternative splicing. PDZRN4 consists of RING, 2 PDZ, PR34H1 and PR34H2 domains, and PDZRN4S consists of PDZ, PR34H1 and PR34H2 domains. Here, we identified novel PDZRN4-related genes by using bioinformatics. FLJ45072 (AK127016.1) and KIAA1444 (NM_032512.1) cDNAs were derived from human PDZRN4L (also known as PDZRN5, LNX4L, or LNX5) gene. FLJ45072 was the representative PDZRN4L cDNA, while KIAA1444 was a 5'-truncated partial PDZRN4L cDNA. MGC67228 (BC056462.1) and B230341P03 (AK046101.1) cDNAs were derived from mouse Pdzrn4l gene. MGC67228 was a 5'-truncated partial Pdzrn4l cDNA, while B230341P03 was an aberrant Pdzrn4l cDNA with exon skipping and insertions within the coding region. PDZRN4L gene, consisting of at least 8 exons, was located at human chromosome Xq28. Exons 1-8 of PDZRN4L gene corresponded to exons 1b, 4-10 of PDZRN4 gene. Because the regions corresponding to exons 1-3 of PDZRN4 gene were not identified within human genome sequences around the PDZRN4L gene, PDZRN4L isoform with RING finger domain was not identified. Human PDZRN4L (769 aa) showed 93.0% total-amino-acid identity with mouse Pdzrn4l (772 aa), and 49.9% total-amino-acid identity with human PDZRN4S. PDZ, PR34H1 and PR34H2 domains were conserved between PDZRN4L and PDZRN4S. This is the first report on human PDZRN4L and mouse Pdzrn4l genes.

Alternative Splicing↗

PubMed2004

Identification and characterization of human FHDC1, mouse Fhdc1 and zebrafish fhdc1 genes in silico.

Formin homology proteins, implicated in organogenesis and carcinogenesis, are actin regulators with scaffold function. FMNL1, FMNL2, FMNL3, DIAPH1, DIAPH2, DIAPH3, DAAM1 and DAAM2 are FDD-type Formin homology proteins, while FHOD1, FHOD3, GRID2IP, Fmn1 and Fmn2 are non-FDD-type Formin homology proteins. Here, we identified human FHDC1 gene and vertebrate FHDC1 orthologs by using bioinformatics. The complete coding sequence of human FHDC1 cDNA was determined by assembling 3'-recombinated FLJ35083 chimeric cDNA and 5'-truncated KIAA1727 (AB051514.1) partial cDNA. The complete coding sequence of mouse Fhdc1 cDNA was determined by assembling 3'-truncated CD555494 EST and 5'-truncated 6330505N24 (AK031946.1) partial cDNA. The complete coding sequence of zebrafish fhdc1 cDNA was determined by assembling fhdc1 exons within zebrafish genome clone DKEY-4A14 (BX571710.4). FHDC1 gene was located at human chromosome 4q31.3, and Fhdc1 gene at mouse chromosome 3F1. Human FHDC1 (1143 aa) showed 73.3% total amino-acid identity with mouse Fhdc1 (1148 aa), and 43.4% total amino-acid identity with zebrafish Fhdc1 (1165 aa). FDCH1-FDCH5 domains were identified as novel conserved regions among vertebrate FHDC1 orthologs. Human FHDC1, mouse Fhdc1, and zebrafish Fhdc1 were non-FDD-type Formin homology proteins with FH1 and FH2 domains in the N-terminal part as well as with FDCH1, FDCH2, FDCH3, FDCH4, and FDCH5 domains in the C-terminal part. This is the first report on the identification and characterization of the human FHDC1, mouse Fhdc1 and zebrafish fhdc1 genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human FOXN6, mouse Foxn6, and rat Foxn6 genes in silico.

Forkhead-box (FOX) transcription factors are implicated in carcinogenesis through gene amplification, retroviral integration, or chromosomal translocation. FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4 and FOXN5 (FOXR1) constitute the FOXN family. Here, we identified and characterized human FOXN6 (FOXR2) and rodent Foxn6 (Foxr2) orthologs by using bioinformatics. Human FOXN6 gene was identified within human genome sequence RP11-167P23 (AL159987.19), mouse Foxn6 gene within mouse genome sequence RP23-180D16 (AL672293.14), and rat Foxn6 gene within rat genome sequence CH230-264B14 (AC106980.5). FOXN6, RRAGB (RAGB), and KLF8 genes were clustered at human chromosome Xp11.21. Foxn6, Rragb, and Klf8 genes were also clustered at mouse chromosome XF3 as well as at rat chromosome Xq14. Human FOXN6 mRNA was expressed in breast cancer cell line and primary breast cancer. Mouse Foxn6 mRNA was expressed in E9.5 embryo. Human FOXN6 (286 aa) showed 57.7% total-amino-acid identity with human FOXN5, 53.8% total-amino-acid identity with mouse Foxn6 (277 aa), and 52.4% total-amino-acid identity with rat Foxn6 (277 aa). Codon 167-248 of human FOXN6 was the Forkhead domain. FN56 domain (codon 1-69 of FOXN6) was identified as a novel domain conserved among FOXN6 and FOXN5 orthologs. Mammalian FOXN6 orthologs were found consisting of FN56 and FOX domains. Phylogenetic analyses revealed that FOXN family proteins are classified into three subfamilies: i) FOXN6 and FOXN5 orthologs; ii) FOXN1 and FOXN4 orthologs; iii) FOXN2 and FOXN3 orthologs. This is the first report on human FOXN6, mouse Foxn6, and rat Foxn6 genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human TP53I5 and mouse Tp53i5 genes in silico.

TP53 gene, encoding tumor protein P53, is frequently inactivated in various types of human cancer, including colorectal, lung, and gastric cancer. Cancer cells with TP53 mutation acquire malignant potentials, such as selective growth advantage, genomic instability, resistance to apoptosis, and promotion of angiogenesis. U33271 partial cDNA isolated from HPV-18 E6/E7 immortalized keratinocytes is derived from one of P53-traget genes. Here, we identified and characterized the TP53I5 (tumor protein P53 inducible protein 5) gene corresponding to U33271 partial cDNA by using bioinformatics. FLJ23270 (AK026923.1) was the representative human TP53I5 cDNA. TP53I5 gene, consisting of 23 exons, was located at human chromosome 11p15.5. TP53I5 mRNA was expressed in human colorectal, lung, and breast cancer. IMAGE5352905 (BC025477.1) and IMAGE6508837 (NM_178381.2) were aberrant mouse Tp53i5 cDNAs with multiple frameshifts due to retention of intronic sequences. Complete coding sequence of mouse Tp53i5 cDNA was determined by assembling nucleotide positions 1-1213, 1293-1740, 1745-2045, and 2071-3088 of BC025477.1. Tp53i5 gene was located at mouse chromosome 7F5. Human TP53I5 (782 aa) and mouse Tp53i5 (747 aa), showing 71.1% total-amino-acid identity, were eight-transmembrane proteins with N- and C-terminal tails facing the cytoplasm. TP53I5 orthologs were homologous to TMEM16A (FLJ10261 or ORAOV2), TMEM16B, TMEM16C, TMEM16D, TMEM16E and TMEM16F with the TM16H1, TM16H2, and TM16H3 domains. TP53I5 was identified as a novel member of the TMEM16 family based on membrane topology and TM16H1-3 domains. This is the first report on the human TP53I5 and mouse Tp53i5 genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of the human FMN1 gene in silico.

Mouse Formin (Fmn1) protein plays a key role in limb morphogenesis. Fmn1 is one of the actin regulators with scaffold function, interacting with Profilin, SRC, EMS1, FNBP1, FNBP2, FNBP3, FNBP4, WBP4 and alpha-catenin. Fmn1, Fmn2, FHOD1, FHOD3, GRID2IP and FHDC1 are non-FDD-type Formin homology proteins, while FMNL1, FMNL2, FMNL3, DIAPH1, DIAPH2, DIAPH3, DAAM1 and DAAM2 are FDD-type Formin homology proteins. Here, we identified the human FMN1 gene by using bioinformatics. The complete coding sequence of human FMN1 cDNA was determined by assembling AC055874.8 genome sequence (nucleotide position 178207-180073), AI040235 EST (complementary sequence for nucleotide position 331-156) and FLJ45135 cDNA (nucleotide position 319-3310). FMN1 isoform 1 (exons 1-18) and FMN isoform 2 (exons 1b and 3-18) were transcribed due to alternative splicing of the alternative promoter type. The FMN1 gene at human chromosome 15q13.3 was located between CKTSF1B1 (Gremlin) and RYR3 genes. The Xenopus fmn1 gene was identified within the Xenopus genome sequence CH216-24N20 (AC147835.1). The FMH1 domain (codon 1-120 of FMN1) and FMH2 domain (codon 683-835 of FMN1) were identified as novel regions conserved among human FMN1, mouse Fmn1, and Xenopus fmn1. The FMH2 domain was almost identical to the alpha-catenin binding domain of mouse Fmn1. Human FMN1 (1419 aa), showing 77.1% total amino-acid identity with mouse Fmn1, was found consisting of FMH1, FMH2, FH1 and FH2 domains. This is the first report on the identification and characterization of the human FMN1 gene as well as the FMH1 and FMH2 domains.

Amino Acid Sequence↗