mutant chimeric proteins

Summary

Summary: Proteins produced from GENES that have mutated by the fusing of protein coding regions of more than one gene. Such hybrid proteins are responsible for some instances of ANTIBIOTIC RESISTANCE and defective biological processes such as NEOPLASMS.

Top Publications

  1. Frenkel Morgenstern M, Lacroix V, Ezkurdia I, Levin Y, Gabashvili A, Prilusky J, et al. Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts. Genome Res. 2012;22:1231-42 pubmed publisher
    ..Taken together, these findings establish that some chimeric RNAs are translated into potentially functional proteins in humans. ..
  2. Brennan G, Kozyrev Y, Hu S. TRIMCyp expression in Old World primates Macaca nemestrina and Macaca fascicularis. Proc Natl Acad Sci U S A. 2008;105:3569-74 pubmed publisher
    ..Convergent evolution of TRIMCyp in both Old World and New World primates suggests that TRIMCyp may have provided evolutionary advantages...
  3. Jena B, Maiti S, Huls H, Singh H, Lee D, Champlin R, et al. Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials. PLoS ONE. 2013;8:e57838 pubmed publisher
    ..The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy. ..
  4. Kim N, Kim P, Nam S, Shin S, Lee S. ChimerDB--a knowledgebase for fusion sequences. Nucleic Acids Res. 2006;34:D21-4 pubmed
    ..The database is available at http://genome.ewha.ac.kr/ChimerDB/ for human, mouse and rat genomes. ..
  5. Wilson S, Webb B, Ylinen L, Verschoor E, Heeney J, Towers G. Independent evolution of an antiviral TRIMCyp in rhesus macaques. Proc Natl Acad Sci U S A. 2008;105:3557-62 pubmed publisher
    ..The lack of activity against HIV-1 suggests that Mamu7 homozygous animals will be null for TRIM5-mediated restriction of HIV-1 and could contribute to improved animal models for HIV/AIDS. ..
  6. Frenkel Morgenstern M, Valencia A. Novel domain combinations in proteins encoded by chimeric transcripts. Bioinformatics. 2012;28:i67-74 pubmed publisher
    ..our scripts are available upon request. ..
  7. Asmann Y, Hossain A, Necela B, Middha S, Kalari K, Sun Z, et al. A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell lines. Nucleic Acids Res. 2011;39:e100 pubmed publisher
    ..Executables in PERL are available for download from our web site: http://mayoresearch.mayo.edu/mayo/research/biostat/stand-alone-packages.cfm. ..
  8. Liao C, Kuang Y, Liu H, Zheng Y, Su B. A novel fusion gene, TRIM5-Cyclophilin A in the pig-tailed macaque determines its susceptibility to HIV-1 infection. AIDS. 2007;21 Suppl 8:S19-26 pubmed publisher
  9. Newman R, Hall L, Kirmaier A, Pozzi L, Pery E, Farzan M, et al. Evolution of a TRIM5-CypA splice isoform in old world monkeys. PLoS Pathog. 2008;4:e1000003 pubmed publisher
    ..Whether the formation of novel genes through alternative splicing has played a wider role in the evolution of the TRIM family remains to be investigated...

More Information

Publications62

  1. Nakayama E, Shioda T. Anti-retroviral activity of TRIM5 alpha. Rev Med Virol. 2010;20:77-92 pubmed publisher
    ..Accurate structural analysis of the binding surface between the viral capsid protein and TRIM5 alpha SPRY is thus required for the development of new antiretroviral drugs that enhance anti-HIV-1 activity of human TRIM5 alpha. ..
  2. Venables J, Strain L, Routledge D, Bourn D, Powell H, Warwicker P, et al. Atypical haemolytic uraemic syndrome associated with a hybrid complement gene. PLoS Med. 2006;3:e431 pubmed
    ..In this study we tested the hypothesis that nonallelic homologous recombination between low-copy repeats in the RCA cluster could result in the formation of a hybrid CFH/CFHL1 gene that predisposes to the development of aHUS...
  3. Virgen C, Kratovac Z, Bieniasz P, Hatziioannou T. Independent genesis of chimeric TRIM5-cyclophilin proteins in two primate species. Proc Natl Acad Sci U S A. 2008;105:3563-8 pubmed publisher
    ..Overall, an intuitively unlikely evolutionary event has, in fact, occurred at least twice in primates and represents a striking example of convergent evolution in divergent species. ..
  4. Li H, Wang J, Mor G, Sklar J. A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells. Science. 2008;321:1357-61 pubmed publisher
    ..These observations suggest that certain gene fusions may be pro-neoplastic owing to constitutive expression of chimeric gene products normally generated by trans-splicing of RNAs in developing tissues. ..
  5. Kuang Y, Tang X, Liu F, Jiang X, Zhang Y, Gao G, et al. Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina), a primate species susceptible to Human Immunodeficiency Virus type 1 infection. Retrovirology. 2009;6:58 pubmed publisher
    ..The susceptibility of M. leonina to HIV-1 infection is due to the dysfunctional TRIM5-CypA fusion in the TRIM5 locus. This finding should broaden our perspective in developing better HIV/AIDS non-human primate animal models. ..
  6. Wang W, Zheng H, Fan C, Li J, Shi J, Cai Z, et al. High rate of chimeric gene origination by retroposition in plant genomes. Plant Cell. 2006;18:1791-802 pubmed
    ..These observations suggest that retroposition is an important mechanism that governs gene evolution in rice and other grass species. ..
  7. Jones C, Custer A, Begun D. Origin and evolution of a chimeric fusion gene in Drosophila subobscura, D. madeirensis and D. guanche. Genetics. 2005;170:207-19 pubmed publisher
    ..We present a model for the origin of this new gene and discuss genetic and evolutionary factors affecting the evolution of new genes and functions...
  8. Isa M, Ohta Y, Namiki S, Hirose K. Artificial control of subtype-specific platelet-derived growth factor-receptor signaling. J Pharmacol Sci. 2009;111:312-6 pubmed
    ..Our method is expected to be useful to understand the subtype-specific roles of PDGFRs in various cellular functions. ..
  9. Cardenas J, Rivero S, Goud B, Bornens M, Rios R. Golgi localisation of GMAP210 requires two distinct cis-membrane binding mechanisms. BMC Biol. 2009;7:56 pubmed publisher
  10. Kotorashvili A, Russo S, Mulugeta S, Guttentag S, Beers M. Anterograde transport of surfactant protein C proprotein to distal processing compartments requires PPDY-mediated association with Nedd4 ubiquitin ligases. J Biol Chem. 2009;284:16667-78 pubmed publisher
    ..We speculate that the Nedd4/proSP-C tandem is part of a larger protein complex containing a ubiquitinated component that further directs its transport. ..
  11. Loskog A, Giandomenico V, Rossig C, Pule M, Dotti G, Brenner M. Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Leukemia. 2006;20:1819-28 pubmed
    ..These effects are seen whether the chimeric T cells are derived from normal donors or from patients with B-cell chronic lymphocytic leukemia, indicating the potential for clinical application in B cell malignancies. ..
  12. Kaiserman D, Bird P. Analysis of vertebrate genomes suggests a new model for clade B serpin evolution. BMC Genomics. 2005;6:167 pubmed
    ..Both structures were then duplicated at a single locus until a chromosomal breakage occurred at some point along the mammalian lineage resulting in the two modern loci. ..
  13. Rossetti S, VAN Unen L, Sacchi N, Hoogeveen A. Novel RNA-binding properties of the MTG chromatin regulatory proteins. BMC Mol Biol. 2008;9:93 pubmed publisher
    ..Both wild type MTGs and chimeric AML1-MTG proteins display in vitro RNA-binding properties, thus opening new perspectives on the possible involvement of an RNA component in MTG-mediated chromatin regulation. ..
  14. Cui Y, Tae H, Norris N, Karunasekara Y, Pouliquin P, Board P, et al. A dihydropyridine receptor alpha1s loop region critical for skeletal muscle contraction is intrinsically unstructured and binds to a SPRY domain of the type 1 ryanodine receptor. Int J Biochem Cell Biol. 2009;41:677-86 pubmed publisher
    ..Thus the second SPRY domain is an in vitro binding site for the II-III loop. The possible in vivo role of this region is discussed. ..
  15. James S, Greenberg P, Jensen M, Lin Y, Wang J, Budde L, et al. Mathematical modeling of chimeric TCR triggering predicts the magnitude of target lysis and its impairment by TCR downmodulation. J Immunol. 2010;184:4284-94 pubmed publisher
  16. Molzan M, Ottmann C. Subcellular localization of full-length human myeloid leukemia factor 1 (MLF1) is independent of 14-3-3 proteins. Cell Mol Biol Lett. 2013;18:137-48 pubmed publisher
    ..Surprisingly, we found that the subcellular localization of full-length human MLF1 is 14-3-3-independent, and is probably regulated by other as-yet-unknown proteins. ..
  17. Kiptoo P, Büyüktimkin B, Badawi A, Stewart J, Ridwan R, Siahaan T. Controlling immune response and demyelination using highly potent bifunctional peptide inhibitors in the suppression of experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2013;172:23-36 pubmed publisher
    ..Also, we observed significantly less demyelination in PLP-cIBR-treated mice compared to the control, further indicating that PLP-cIBR promoted protection against demyelination. ..
  18. Ahn M, Lee J, Gustafsson A, Enriquez A, Lancaster E, Sul J, et al. Cx29 and Cx32, two connexins expressed by myelinating glia, do not interact and are functionally distinct. J Neurosci Res. 2008;86:992-1006 pubmed
    ..Substituting the intracellular loop and/or tail of Cx32 with those of Cx29 appears to prevent Cx32 from forming functional gap junctions. ..
  19. Irvine K, Burns C, Wilks A, Su S, Hume D, Sweet M. A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations. FASEB J. 2006;20:1921-3 pubmed
    ..CSF-1R inhibitors such as CYC10268 provide a powerful tool to dissect the role of the CSF-1/CSF-1R signaling system in a range of biological systems and have potential for a number of therapeutic applications. ..
  20. Zhan X, Li C, Guo W, Jiang Y. PROKARYOTIC EXPRESSION AND BIOACTIVITY EVALUATION OF THE CHIMERIC GENE DERIVED FROM THE GROUP 1 ALLERGENS OF DUST MITES. Nutr Hosp. 2015;32:2771-6 pubmed publisher
  21. Catalano A, Dawson M, Somana K, Opat S, Schwarer A, Campbell L, et al. The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia. Blood. 2007;110:4073-6 pubmed
    ..This trial was registered at www.actr.org.au with the Australian Clinical Trials Registry as number 12605000070639. ..
  22. Yamada K, Muramatsu M, Saito D, Sato Oka M, Saito M, Moriyama T, et al. Characterization of the C-terminal diglycine motif of SUMO-1/3. Biosci Biotechnol Biochem. 2012;76:1035-7 pubmed
    ..In this study we found that the SUMO-1/3-AA/-GS/-GN/-GA mutant can form sodium dodecyl sulfate (SDS)-dithiothreitol (DTT)-resistant complexes with cellular proteins, indicating that the GG motif is not strictly required for SUMOylation. ..
  23. Zhang C, Fan K, Zhang W, Zhu R, Zhang L, Wei D. Structure-based characterization of canine-human chimeric uricases and its evolutionary implications. Biochimie. 2012;94:1412-20 pubmed publisher
    ..The loss of hominoid uricase should be caused by progressive multistep mutations rather than a single mutation event. ..
  24. Kenig M, Jenko Kokalj S, Tusek Znidaric M, Pompe Novak M, Guncar G, Turk D, et al. Folding and amyloid-fibril formation for a series of human stefins' chimeras: any correlation?. Proteins. 2006;62:918-27 pubmed
    ..Instead, the propensity to fibrillize is related to selected parts of structure, such as the beta-sheet of stefin B, and can be predicted reasonably well by calculating the beta-strand propensity of the denatured states. ..
  25. Rogers R, Bedford T, Lyons A, Hartl D. Adaptive impact of the chimeric gene Quetzalcoatl in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2010;107:10943-8 pubmed publisher
    ..Together, these results show that chimeric genes can produce structural and regulatory changes in a single mutational step and may be a major factor in adaptive evolution. ..
  26. Ray D, Shi P. Recent advances in flavivirus antiviral drug discovery and vaccine development. Recent Pat Antiinfect Drug Discov. 2006;1:45-55 pubmed
    ..In this article we review recent advances made in the areas of (i) flavivirus vaccine development, and (ii) antiflavivirus drug discovery reported in literature and patents, and highlight strategies used in these investigations. ..
  27. Brito V, Mellal K, Portelance S, Pérez A, Soto Y, Deblois D, et al. Induction of anti-anti-idiotype antibodies against sulfated glycosaminoglycans reduces atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2012;32:2847-54 pubmed publisher
    ..The present study supports use of active immunization and the mounting of an idiotypic antibody network response against glycosaminoglycans as a novel approach to target atherosclerosis. ..
  28. Zhao Y, Qin W, Zhang J, Hu Z, Tong J, Ding C, et al. HCV IRES-mediated core expression in zebrafish. PLoS ONE. 2013;8:e56985 pubmed publisher
    ..These findings demonstrate the feasibility of the zebrafish model for screening of anti-HCV drugs targeting to HCV-IRES. The zebrafish system provides a novel evidence of using zebrafish as a HCV model organism. ..
  29. Rezvanpour A, Phillips J, Shaw G. Design of high-affinity S100-target hybrid proteins. Protein Sci. 2009;18:2528-36 pubmed publisher
    ..Since cleavage of the S100 hybrid protein is not necessary for structural characterization, this approach may be useful as a scaffold for larger S100 complexes. ..
  30. Walz C, Haferlach C, Hänel A, Metzgeroth G, Erben P, Gosenca D, et al. Identification of a MYO18A-PDGFRB fusion gene in an eosinophilia-associated atypical myeloproliferative neoplasm with a t(5;17)(q33-34;q11.2). Genes Chromosomes Cancer. 2009;48:179-83 pubmed publisher
    ..Patients with PDGFRB fusions genes are excellent candidates for treatment with imatinib; complete cytogenetic and even molecular remissions are common while primary or secondary resistance seems to be very rare. ..
  31. Foss S, Li H, Santos M, Edwards R, Voglmaier S. Multiple dileucine-like motifs direct VGLUT1 trafficking. J Neurosci. 2013;33:10647-60 pubmed publisher
    ..Consistent with these differences in trafficking signals, wild-type VGLUT1 and VGLUT2 differ in their response to stimulation. ..
  32. Claus C, Tzeng W, Liebert U, Frey T. Analysis of the selective advantage conferred by a C-E1 fusion protein synthesized by rubella virus DI RNAs. Virology. 2007;369:19-34 pubmed
  33. Schubert C, Schalk Hihi C, Struble G, Ma H, Petrounia I, Brandt B, et al. Crystal structure of the tyrosine kinase domain of colony-stimulating factor-1 receptor (cFMS) in complex with two inhibitors. J Biol Chem. 2007;282:4094-101 pubmed
  34. Proszynski T, Klemm R, Gravert M, Hsu P, Gloor Y, Wagner J, et al. A genome-wide visual screen reveals a role for sphingolipids and ergosterol in cell surface delivery in yeast. Proc Natl Acad Sci U S A. 2005;102:17981-6 pubmed
    ..This visual screening method can now be used for different cargo proteins to search in a genome-wide fashion for machinery involved in post-Golgi sorting. ..
  35. Moiani A, Mavilio F. Alternative splicing caused by lentiviral integration in the human genome. Methods Enzymol. 2012;507:155-69 pubmed publisher
  36. Das S, Nayak D, Zhou Y, Pattnaik A. Visualization of intracellular transport of vesicular stomatitis virus nucleocapsids in living cells. J Virol. 2006;80:6368-77 pubmed
    ..These findings are compatible with a model in which the progeny viral nucleocapsids are transported toward the cell periphery by MT and the transport may be facilitated by mitochondria. ..
  37. Fang W, Wei Y, Kang Y, Landweber L. Detection of a common chimeric transcript between human chromosomes 7 and 16. Biol Direct. 2012;7:49 pubmed publisher
    ..The fusion sequence at the novel exon-exon boundary, and the absence of corresponding DNA rearrangement suggest that this chimeric RNA is likely produced by trans-splicing in human cells. ..
  38. Goihberg E, Peretz M, Tel Or S, Dym O, Shimon L, Frolow F, et al. Biochemical and structural properties of chimeras constructed by exchange of cofactor-binding domains in alcohol dehydrogenases from thermophilic and mesophilic microorganisms. Biochemistry. 2010;49:1943-53 pubmed publisher
  39. Bentley M, Gaweska H, Kielec J, McCafferty D. Engineering the substrate specificity of Staphylococcus aureus Sortase A. The beta6/beta7 loop from SrtB confers NPQTN recognition to SrtA. J Biol Chem. 2007;282:6571-81 pubmed
    ..These results indicate that the beta6/beta7 loop is an important site for substrate recognition in sortases. ..
  40. MacDonald D, Cross N. Chronic myeloproliferative disorders: the role of tyrosine kinases in pathogenesis, diagnosis and therapy. Pathobiology. 2007;74:81-8 pubmed
    ..The second group of tyrosine kinase abnormalities are point mutations in JAK2, a cytosolic TK. This abnormality is seen in 30-97% of cases of MPD with the phenotype PV, ET or CIMF. ..
  41. Zabala G, Vodkin L. Novel exon combinations generated by alternative splicing of gene fragments mobilized by a CACTA transposon in Glycine max. BMC Plant Biol. 2007;7:38 pubmed
    ..The multiplicity and randomness of these events provide some insights into the origin and mechanism of alternatively spliced genes. ..
  42. Leelawatwattana L, Praphanphoj V, Prapunpoj P. Effect of the N-terminal sequence on the binding affinity of transthyretin for human retinol-binding protein. FEBS J. 2011;278:3337-47 pubmed publisher
    ..03 ± 0.68 ?m) in which its N-terminal region was shorter and less hydrophobic. These results suggest an influence of the N-terminal primary structure of TTR on its function as a co-carrier for retinol with RBP. ..
  43. Lu X, Xu Y, Zhang F, Shin Y. Synaptotagmin I and Ca(2+) promote half fusion more than full fusion in SNARE-mediated bilayer fusion. FEBS Lett. 2006;580:2238-46 pubmed
    ..With these hybrid SNAREs, we demonstrated that the interaction between the SNARE motifs of neuronal proteins and Syt.Ca(2+) was required for the stimulation of fusion. ..
  44. Spencer D, Cavalier M, Kalpatthi R, Quigley D. Inverted and deleted chromosome 16 with deletion of 3'CBFB identified by fluorescence in situ hybridization. Cancer Genet Cytogenet. 2007;179:82-4 pubmed
  45. Jung J, Kim H, Kim T, Shin B, Park G, Park S, et al. C-terminal substitution of HBV core proteins with those from DHBV reveals that arginine-rich 167RRRSQSPRR175 domain is critical for HBV replication. PLoS ONE. 2012;7:e41087 pubmed publisher
    ..Five amino acids differing between viral species (underlined above) were tested for replication rescue; R169 and R175 were found to be important. ..
  46. Marzi A, Akhavan A, Simmons G, Gramberg T, Hofmann H, Bates P, et al. The signal peptide of the ebolavirus glycoprotein influences interaction with the cellular lectins DC-SIGN and DC-SIGNR. J Virol. 2006;80:6305-17 pubmed publisher
    ..In summary, we identified the level of GP incorporation into virions and signal peptide-controlled glycosylation of GP as determinants of attachment factor engagement...
  47. Kamtekar S, Ho R, Cocco M, Li W, Wenwieser S, Boocock M, et al. Implications of structures of synaptic tetramers of gamma delta resolvase for the mechanism of recombination. Proc Natl Acad Sci U S A. 2006;103:10642-7 pubmed publisher
  48. Masson E, Le Maréchal C, Delcenserie R, Chen J, Ferec C. Hereditary pancreatitis caused by a double gain-of-function trypsinogen mutation. Hum Genet. 2008;123:521-9 pubmed publisher
    ..Our finding should also stimulate more interest in analyzing both types of genetic variation whenever one tries to determine the contribution of a specific locus to a given disease phenotype. ..
  49. Plebani R, Oliver G, Trerotola M, Guerra E, Cantanelli P, Apicella L, et al. Long-range transcriptome sequencing reveals cancer cell growth regulatory chimeric mRNA. Neoplasia. 2012;14:1087-96 pubmed
    ..Replication-controlling chimeras were found to be expressed by most cancers from breast, ovary, colon, uterus, kidney, lung, and stomach, suggesting a widespread role in tumor development. ..
  50. Liu H, Sun X, Zhang S, Ge W, Zhu Y, Zhang J, et al. The dominant negative mutant Artemis enhances tumor cell radiosensitivity. Radiother Oncol. 2011;101:66-72 pubmed publisher
    ..It is the first time to modulate tumor cell radiosensitivity via targeting Artemis. This novel mechanism of radiosensitivity strongly suggests the potential role of Artemis in cancer therapy. ..
  51. Tolmachov O, Coutelle C. Covalent attachment of multifunctional chimeric terminal proteins to 5' DNA ends: A potential new strategy for assembly of synthetic therapeutic gene vectors. Med Hypotheses. 2007;68:328-31 pubmed
  52. Bachtarzi H, Stevenson M, Fisher K. Cancer gene therapy with targeted adenoviruses. Expert Opin Drug Deliv. 2008;5:1231-40 pubmed
    ..However, there are still some limitations that need special consideration before adenovirus-targeted cancer gene therapy emerges as a routine treatment in the clinical setting. ..
  53. Masuda S, Nakatani Y, Ren S, Tanaka M. Blue light-mediated manipulation of transcription factor activity in vivo. ACS Chem Biol. 2013;8:2649-53 pubmed publisher
    ..When applied to zebrafish embryos, PICCORO permitted regulation of the activity of the mutant No Tail in response to 472-nm light provided by a light-emitting diode. ..