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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

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

The deubiquitinase (DUB) and tumor suppressor BAP1 catalyzes ubiquitin removal from histone H2A Lys-119 and coordinates cell proliferation, but how BAP1 partners modulate its function remains poorly understood. Here, we report that BAP1 forms two mutually exclusive complexes with the transcriptional regulators ASXL1 and ASXL2, which are necessary for maintaining proper protein levels of this DUB. Conversely, BAP1 is essential for maintaining ASXL2, but not ASXL1, protein stability. Notably, cancer-associated loss of BAP1 expression results in ASXL2 destabilization and hence loss of its function. ASXL1 and ASXL2 use their ASXM domains to interact with the C-terminal domain (CTD) of BAP1, and these interactions are required for ubiquitin binding and H2A deubiquitination. The deubiquitination-promoting effect of ASXM requires intramolecular interactions between catalytic and non-catalytic domains of BAP1, which generate a composite ubiquitin-binding interface (CUBI). Notably, the CUBI engages multiple interactions with ubiquitin involving (i) the ubiquitin carboxyl hydrolase catalytic domain of BAP1, which interacts with the hydrophobic patch of ubiquitin, and (ii) the CTD domain, which interacts with a charged patch of ubiquitin. Significantly, we identified cancer-associated mutations of BAP1 that disrupt the CUBI and notably an in-frame deletion in the CTD that inhibits its interaction with ASXL1/2 and DUB activity and deregulates cell proliferation. Moreover, we demonstrated that BAP1 interaction with ASXL2 regulates cell senescence and that ASXL2 cancer-associated mutations disrupt BAP1 DUB activity. Thus, inactivation of the BAP1/ASXL2 axis might contribute to cancer development.
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PMID:The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer. 2641 90