Biomedical subjects

Masuko Katoh

Publications and source records attributed to Masuko Katoh.

At least 55 records · Page 3Linked to original sources

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↗

PubMed2004

Identification and characterization of human FOXK1 gene in silico.

Forkhead-box (FOX) family transcription factors are implicated in carcinogenesis and embryogenesis. Here, we identified and characterized the human FOXK1 gene by using bioinformatics. Complete coding sequence of human FOXK1 cDNA was determined by assembling CB959941 EST, AW206906 EST, and 5'-truncated FLJ16099 (AK122663.1) cDNA. FOXK1 gene, consisting of nine exons, was mapped to human chromosome 7p22.1. Mouse Foxk1 (NM_199068.1) was an aberrant cDNA with frame shifts due to multiple insertions and deletions, while mouse IMAGE6853263 (BC060238.1) was a Foxk1 cDNA with a frame shift due to two base deletions. Complete coding sequence of mouse Foxk1 cDNA was determined by inserting CA nucleotides between nucleotide position 1628 and 1629 of BC060238.1. Foxk1 gene, consisting of nine exons, was mapped to mouse chromosome 5G2. Because interleukin enhancer-binding factor 1 (ILF1) gene at human chromosome 17q25.3 was the paralog of FOXK1 gene, ILF1 gene was designated the FOXK2 gene. Xenopus BC046369.1 cDNA was Foxk2 ortholog rather than Foxk1 ortholog. Human FOXK1 (733 aa) showed 88.7% total amino-acid identity with mouse Foxk1 (719 aa), 48.7% total amino-acid identity with human FOXK2, and 47.5% total amino-acid identity with Xenopus Foxk2. Forkhead associated (FHA) domain and FOX domain were conserved among human FOXK1, FOXK2, mouse FoxK1, and Xenopus Foxk2. At least 42 FOX family genes, including FOXK1, FOXN5 (FOXR1) and FOXN6 (FOXR2), have been identified within the human genome.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human CKTSF1B2 and CKTSF1B3 genes in silico.

Bone morphogenetic proteins (BMPs) are implicated in the regulation of morphogenesis and proliferation during embryogenesis and carcinogenesis. We have previously reported over-expression of BMP4 in diffuse-type gastric cancer cells. BMP signaling is regulated by tissue-specific expression of ligands and receptors as well as by secreted-type antagonists, such as CKTSF1B1 (Gremlin), CER1 (Cerberus 1), Noggin, SOSTDC1 (Ectodin), and Chordin. Here, we identified two novel genes related to CKTSF1B1 and CER1 by using bioinformatics. Two novel members of human CKTSF1B gene family were designated CKTSF1B2 (GREM2 or PRDC) and CKTSF1B3 (GREM3 or DANTE). FLJ21195 (BC046632.1) was the representative human CKTSF1B2 cDNA, and CKTSF1B2 gene was mapped to human chromosome 1q43. Human CKTSF1B2 showed 94.0% total amino-acid identity with mouse Cktsf1b2 (Prdc). FLJ38607 (AK095926.1) was the representative human CKTSF1B3 cDNA, and CKTSF1B3 gene was mapped to human chromosome 19p13.2. Human CKTSF1B3 showed 61.9% total amino-acid identity with mouse Cktsf1b2 (Dante). N-terminal signal peptide and DAN domain with nine cysteine residues were conserved among CKTSF1B1, CKTSF1B2, CKTSF1B3 and CER1. Phylogenetic analyses revealed that CKTSF1B2 was more related to CKTSF1B1, and that CKTSF1B3 was more related to CER1. CKTSF1B1, CKTSF1B2, CKTSF1B3 and CER1 constitute the CKTSF1B family among secreted-type cysteine knot superfamily proteins. This is the first report on identification and characterization of the human CKTSF1B2 and CKTSF1B3 genes.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of human TMEM25 and mouse Tmem25 genes in silico.

Immunoglobulin superfamily members are implicated in immune responses, growth factor signaling, and cell adhesion. IGSF4 (IGSF4A), homologous to IGSF4B, IGSF4C, IGSF4D, PVR, PVRL1, PVRL2, PVRL3 and PVRL4, is down-regulated in lung cancer. IGSF11, homologous to CXADR (CAR), ESAM and ASAM, is up-regulated in the intestinal-type gastric cancer. Here, we identified and characterized a novel member of the immunoglobulin superfamily, TMEM25, by using bioinformatics. BC042896 and AY358919 cDNAs were derived from human TMEM25 gene, while AK002841 cDNA was derived from mouse Tmem25 gene. TMEM25 isoform 1 (BC042896), consisting of exons 1-9, encoded a 366-aa transmembrane protein. TMEM25 isoform 2 (AY358919), consisting of exons 1-4 and 6-9, encoded a 322-aa secreted protein. Human TMEM25 gene was found to encode transmembrane-type as well as secreted-type proteins due to alternative splicing of exon-skipping type. TMEM25 mRNA was expressed in brain, including cerebellar cortex and hippocampus, as well as in neuroblastoma, brain tumors, and gastric cancer. Human TMEM25 isoform 1 showed 91.0% total-amino-acid identity with mouse Tmem25. TMEM25 was identified as a member of immunoglobulin superfamily, because codon 42-112 of TMEM25 was the C-2 type immunoglobulin domain homologous to Hemicentin (Fibulin-6, FIBL6), Titin (TTN), Sialoadhesin (SN) and Nephrin (NEPHS1). Human TMEM25 gene was located at the 11q23.3 oncogenomic recombination hotspot around the MLL amplicon and the neuroblastoma deleted region. TMEM25 is a target of pharmacogenomics in the field of oncology and regenerative medicine.

Alternative Splicing↗

PubMed2004

Identification and characterization of human HES2, HES3, and HES5 genes in silico.

MMTV induces the mouse mammary tumor through the dysregulation of Notch, Wnt, or Fgf signaling pathway. Activation of Notch signaling pathway leads to transcriptional activation of Hes family genes through the interaction between Notch intracellular domain and RBPSUH (CSL). Hes family proteins are mammalian homologs of Drosophila Hairy and Enhancer of split. Hes family of transcriptional repressors with basic Helix-loop-helix (bHLH) and Orange domains are implicated in the cell fate determination of stem cells (or precursor cells) by suppressing the expression of tissue-specific transcriptional activators. Human HES1, HES4, HES6, and HES7 genes have been reported by other groups. Here, we identified and characterized human HES2, HES3 and HES5 genes by using bioinformatics. FLJ33803 (AK091122.1) was the representative human HES2 cDNA. HES2 gene, encoding a 173-aa protein, was located within human genome sequence AL031848.11. HES3 gene, encoding a 186-aa protein, was identified within human genome sequence AL031847.17. HES5 gene, encoding a 166-aa protein, was identified within human genome sequence AL139246.20. HES2 and HES3 genes were mapped to human chromosome 1p36.31, while HES5 gene to 1p36.32. HES2 mRNA was expressed in placenta, pancreatic cancer, colon cancer with RER, cervical cancer, and in head and neck tumors. HES5 mRNA was expressed in fetal heart, and brain tumors. Human HES family proteins were found consisting of bHLH, Orange, Proline-rich domains, and WRPW motif. Phylogenetic analyses revealed that HES family proteins were distantly related except a paralog pair of HES1 and HES4. HES family genes are pharmacogenomic targets in the field of regenerative medicine and oncology.

Amino Acid Motifs↗

PubMed2004

Identification and characterization of human ARHGAP23 gene in silico.

ARHGAP family genes, such as FNBP2, SRGAP1/ARHGAP13, SRGAP2/ARHGAP14, ARHGAP4 and AHRGAP20/KIAA1391, encode GTPase activating proteins for Rho family proteins (RhoGAPs). Here, we identified and characterized the ARHGAP23 gene by using bioinformatics. KIAA1501 (AB040934.1) was a 5'-truncated partial cDNA derived from the ARHGAP23 gene. Complete coding sequence of human ARHGAP23 cDNA was determined by assembling BM806021 EST, BQ718622 EST, KIAA1501 partial cDNA, and AC115090.8 genome sequence corresponding to exons 7 and 25. ARHGAP23 gene encoded 1491-aa isoform 1 (without exon 23) and 1144-aa isoform 2 (with exon 23) due to alternative splicing. Isoform 2 was C-terminally truncated due to frame-shift within 23-bp exon 23. ARHGAP23 mRNA was expressed in placenta, prostate, hippocampus, brain medulla as well as in brain tumor, salivary gland tumor, head and neck tumor. Mouse 4933428G20 (NM_021493.1) was a 5'-truncated partial cDNA derived from Arhgap23 gene at mouse chromosome 11D. Human ARHGAP23, ARHGAP21 and Xenopus rGAP shared the common domain structure consisting of PDZ, Pleckstrin homology (PH), and RhoGAP domains. ARHGAP23-KIAA1684-MLLT6-RNF110-PIP5K2B-LASP1-PLXDC1-CACNB1 locus at human chromosome 17q12 and CACNB2-PLXDC2-LASP2-MLLT10-BMI1-PIP5K2A-KIAA1217-ARHGAP21 locus at human chromosome 10p12 were paralogous regions (paralogons) with internal inversion. MLLT6, MLLT10 and LASP1 genes are fusion partners of MLL gene in hematological malignancies, while RNF110, PIP5K2B, LASP1 and BMI1 genes are amplified in human tumors. Evolutionary recombination hotspots and oncogenomic recombination hotspots were co-localized around the ARHGAP23-CACNB1 locus and the ARHGAP21-CACNB2 locus.

Amino Acid Sequence↗