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14-September-2008 18:38:51 - Abl gene V-abl Abelson murine leukemia viral oncogene homolog 1 PDB rendering based on 1ab2. Available structures: 1ab2, 1abo, 1abq, 1awo, 1bbz, 1fpu, 1iep, 1ju5, 1m52, 1opj, 1opk, 1opl, 1zzp, 2abl, 2e2b, 2f4j, 2fo0, 2g1t, 2g2f, 2g2h, 2g2i, 2gqg, 2hiw, 2hyy, 2hz0, 2hz4, 2hzi, 2hzn, 2o88 Identifiers Symbols ABL1; ABL; JTK7; bcr/abl; c-ABL; p150; v-abl External IDs OMIM: 189980 MGI: 87859 HomoloGene: 3783 Gene ontology Molecular function: nucleotide binding magnesium ion binding molecular_function DNA binding protein-tyrosine kinase activity ATP binding protein C-terminus binding transferase activity manganese ion binding Cellular component: cellular_component nucleus cytoskeleton Biological process: regulation of progression through cell cycle S-phase-specific transcription in mitotic cell cycle mismatch repair regulation of transcription, DNA-dependent cell adhesion intracellular signaling cascade biological_process DNA damage response, signal transduction resulting in induction of apoptosis peptidyl-tyrosine phosphorylation actin cytoskeleton organization and biogenesis RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 25 11350 Ensembl ENSG00000097007 ENSMUSG00000026842 Uniprot P00519 Q3SYK5 Refseq NM_005157 mRNA NP_005148 protein NM_009594 mRNA NP_033724 protein Location Chr 9: 132.58 - 132.75 Mb Chr 2: 31.51 - 31.63 Mb Pubmed search 1 2 The abl gene is associated with chronic myelogenous leukemia CML. The abl gene is located on the 9th chromosome. In CML, the gene is activated by being translocated within the bcr breakpoint cluster region gene on chromosome 22. This new abl/bcr chimeric gene encodes an unregulated, cytoplasm targeted tyrosine kinase which allows the cells to proliferate without being regulated by cytokines. This in turn allows the cell to become cancerous. The ABL1 protooncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response. Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t9;22 translocation results in the head-to-tail fusion of the BCR MIM:151410 and ABL1 genes present in many cases of chronic myelogeneous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function for ABL1. The ABL1 gene is expressed as either a 6- or 7-kb mRNA transcript, with alternatively spliced first exons spliced to the common exons 2-11.1 This gene is fused with the bcr gene in a Philadelphia chromosome, the characteristic abnormality in chronic myelogenous leukemia CML and rarely in some other leukemia forms. The bcr-abl transcript is also a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. The bcr-abl protein can be inhibited with the agent imatinib mesylate, which occupies the TK domain and inhibits bcr-abls influence on the cell cycle. Contents 1 References 2 Further reading 3 See also 4 External links References ^ Entrez Gene: ABL1 v-abl Abelson murine leukemia viral oncogene homolog 1. Further reading Clark, Stevens. Publications. Research Papers 1986-1989. http://www.humonc.wisc.edu/clark/publications_abstract1x.html Dunitz, Martin. Chronic Myeloid Leukaemia 2001. Taylor Francis, Limited. Published online via Ebrary.com Scott K Shore, Ramana V Tantravahi and E Premkumar Reddy. Transforming pathways activated by the v-Abl tyrosine kinase 9 Dec. 2002. http://www.nature.com/onc/journal/v21/n56/full/1206084a.html Shaul Y 2000. c-Abl: activation and nuclear targets.. Cell Death Differ. 7 1: 10-6. doi:10.1038/sj.cdd.4400626. PMID 10713716. Era T 2002. Bcr-Abl is a molecular switch for the decision for growth and differentiation in hematopoietic stem cells.. Int. J. Hematol. 76 1: 35-43. PMID 12138893. Pendergast AM 2003. The Abl family kinases: mechanisms of regulation and signaling.. Adv. Cancer Res. 85: 51-100. PMID 12374288. Keung YK, Beaty M, Steward W, et al. 2003. Chronic myelocytic leukemia with eosinophilia, t9;12q34;p13, and ETV6-ABL gene rearrangement: case report and review of the literature.. Cancer Genet. Cytogenet. 138 2: 139-42. PMID 12505259. Saglio G, Cilloni D 2005. Abl: the prototype of oncogenic fusion proteins.. Cell. Mol. Life Sci. 61 23: 2897-911. doi:10.1007/s00018-004-4271-0. PMID 15583852. Shaul Y, Ben-Yehoyada M 2005. Role of c-Abl in the DNA damage stress response.. Cell Res. 15 1: 33-5. doi:10.1038/sj.cr.7290261. PMID 15686624. Yoshida K 2007. Regulation for nuclear targeting of the Abl tyrosine kinase in response to DNA damage.. Adv. Exp. Med. Biol. 604: 155-65. PMID 17695727. See also BCR gene External links MeSH Genes,+abl Online 'Mendelian Inheritance in Man' OMIM 189980 ABL MeSH Abelson+Leukemia+Virus v d e Kinases: tyrosine kinases EC 2.7.10 2.7.10.1 Receptor tyrosine kinase 2.7.10.2 Abelson leukemia virus protein - c-Kit - C-MET - Flt3 - Janus kinase Janus kinase 1, Janus kinase 2, Janus kinase 3, Tyrosine kinase 2 - Src Lck - Syk - ZAP-70 Retrieved from http://en..org/wiki/Abl_gene Categories: Genes on chromosome 9 | Human proteins | Cell signaling | Signal transduction | Tyrosine kinases | EC 2.7.10 | Genes Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 8 July 2008, at 01:27
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