Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Identification and characterization of ASXL2 gene in silico. 1288 26

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.
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PMID:Identification and characterization of human MPP7 gene and mouse Mpp7 gene in silico. 1471 43

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.
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PMID:Identification and characterization of human LLGL4 gene and mouse Llgl4 gene in silico. 1476 61

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.
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PMID:Identification and characterization of ASXL3 gene in silico. 1513 7

CXXC4 gene encodes Dishevelled-binding protein, functioning as a negative regulator of WNT - beta-catenin signaling pathway. CXXC5, encoding CXXC finger (PHD domain) protein, is the paralog of CXXC4. CXXC6, MLL, DNMT1, ASXL1, ASXL2, and ASXL3 are cancer-associated genes belonging to the CXXC gene family. Here, we identified and characterized CXXC10 (CXXL4L or CXXC6L) gene by using bioinformatics. Complete coding sequence of human CXXC10 cDNA was determined by assembling AI438961 EST, AC073046.7 genome sequence, BX492895 EST, and MGC22014 5'-truncated cDNA. CXXC10 gene products derived from nucleotide positions 428-739 and 811-3624 were designated CXXC10-1 and CXXC10-2, respectively. CXXC10-1 (103 aa) was homologous to CXXC4 and CXXC6 within the CXXC domain. CXXC10-2 (937 aa) was homologous to CXXC6, and KIAA1546. Complete coding sequence of KIAA1546 cDNA was determined by assembling BF900449 EST, IMAGE3536481 partial cDNA, and KIAA1546 5'-truncated cDNA (AB046766.1). LCXH1 domain (codon 1-273 of CXXC10-2) and LCXH2 domain (codon 778-854 of CXXC10-2) were conserved among CXXC10-2, KIAA1546, and CXXC6. CXXC4 and KIAA1546 genes were closely linked in head to head manner with an interval of about 700 kb. CXXC10 locus at 2p13.1, CXXC4-KIAA1546 locus at 4q24, and CXXC6 locus at 10q21.3 were paralogous regions within the human genome. Because CXXC4 and KIAA1546 genes were located in the opposite direction, intragenetic inversion might be generated within the ancestral CXXC4-KIAA1546 locus during evolution. This is the first report on CXXC10 gene as well as on the CXXC10, CXXC4-KIAA1546, and CXXC6 paralogs.
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PMID:Identification and characterization of human CXXC10 gene in silico. 1537 72

Ultraconservation has been variously defined to describe sequences that have remained identical or nearly so over long periods of evolution to a degree that is higher than expected for sequences under typical constraints associated with protein-coding sequences, splice sites, or transcription factor binding sites. Most intergenic ultraconserved elements (UCE) appear to be tissue-specific enhancers, whereas another class of intragenic UCEs is involved in regulation of gene expression by means of alternative splicing. In this study we define a set of 2827 short ultraconserved promoter regions (SUPR) in 5 kb upstream regions of 1268 human protein-coding genes using a definition of 98% identity for at least 30 bp in 7 mammalian species. Our analysis shows that SUPRs are enriched in genes playing a role in regulation and development. Many of the genes having a SUPR-containing promoter have additional alternative promoters that do not contain SUPRs. Comparison of such promoters by CAGE tag, EST, and Solexa read analysis revealed that SUPR-associated transcripts show a significantly higher mean expression than transcripts associated with non-SUPR-containing promoters. The same was true for the comparison between all SUPR-associated and non-SUPR-associated transcripts on a genome-wide basis. SUPR-associated genes show a highly significant tendency to occur in regions that are also enriched for intergenic short ultraconserved elements (SUE) in the vicinity of developmental genes. A number of predicted transcription factor binding sites (TFBS) are overrepresented in SUPRs and SUEs, including those for transcription factors of the homeodomain family, but in contrast to SUEs, SUPRs are also enriched in core-promoter motifs. These observations suggest that SUPRs delineate a distinct class of ultraconserved sequences.
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PMID:Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts. 1966 May 40

Since the inception of next-generation mRNA sequencing (RNA-Seq) technology, various attempts have been made to utilize RNA-Seq data in assembling full-length mRNA isoforms de novo and estimating abundance of isoforms. However, for genes with more than a few exons, the problem tends to be challenging and often involves identifiability issues in statistical modeling. We have developed a statistical method called "sparse linear modeling of RNA-Seq data for isoform discovery and abundance estimation" (SLIDE) that takes exon boundaries and RNA-Seq data as input to discern the set of mRNA isoforms that are most likely to present in an RNA-Seq sample. SLIDE is based on a linear model with a design matrix that models the sampling probability of RNA-Seq reads from different mRNA isoforms. To tackle the model unidentifiability issue, SLIDE uses a modified Lasso procedure for parameter estimation. Compared with deterministic isoform assembly algorithms (e.g., Cufflinks), SLIDE considers the stochastic aspects of RNA-Seq reads in exons from different isoforms and thus has increased power in detecting more novel isoforms. Another advantage of SLIDE is its flexibility of incorporating other transcriptomic data such as RACE, CAGE, and EST into its model to further increase isoform discovery accuracy. SLIDE can also work downstream of other RNA-Seq assembly algorithms to integrate newly discovered genes and exons. Besides isoform discovery, SLIDE sequentially uses the same linear model to estimate the abundance of discovered isoforms. Simulation and real data studies show that SLIDE performs as well as or better than major competitors in both isoform discovery and abundance estimation. The SLIDE software package is available at https://sites.google.com/site/jingyijli/SLIDE.zip.
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PMID:Sparse linear modeling of next-generation mRNA sequencing (RNA-Seq) data for isoform discovery and abundance estimation. 2213 61

Several classes of exclusively--or at least predominantly--unspliced non-coding RNAs have been described in the last years, including totally and partially intronic transcripts and long intergenic RNAs. Functionally, they appear to be involved in regulating gene expression, at least in part by associating with the chromatin. Intron-less transcripts have received little attention, even though recent findings indicate that intron-less protein-coding genes have several features that set them apart from the more abundant and much better understood spliced mRNAs. Even less is known about unspliced non-coding transcripts. Thus we systematically analyze the distribution of unspliced ESTs in the human genome. These form a large source of transcriptomic data that is almost always excluded from detailed studies. Most unspliced ESTs appear in clusters overlapping, or located in the close vicinity of, annotated RefSeq genes. Partially intronic unspliced ESTs show complex patterns of overlap with the intron/exon structure of the RefSeq gene. Distinctive patterns of CAGE tags indicate that a large class of unspliced EST clusters is forming long extensions of 3'UTRs, at least several hundreds of which probably appear also as independent 3'UTR-associated RNAs.
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PMID:Hidden treasures in unspliced EST data. 2248 13