ABL1 Active Protein

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 t(9;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. [provided by RefSeq, Jul 2008]

Abl: an ubiquitously expressed and highly conserved proto-oncogenic tyrosine kinase. c-Abl protein is distributed in both the nucleus and the cytoplasm of cells. Negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. It has been implicated in regulation of cell proliferation, differentiation, apoptosis, cell adhesion and stress response. The Philadephia chromosome translocation t(9;22)(q34;q11) creates a Bcr-Abl fusion protein, responsible for 90% of chronic myelogenous leukemia (CML) and ~25% of acute lymphoblastic leukemia (ALL). Inhibitors: Gleevec (imatinib, Glivec), Dasatinib. Two alternatively-spliced isoforms have been described.

Protein type: Protein kinase, tyrosine (non-receptor); Protein kinase, TK; Kinase, protein; Oncoprotein; EC 2.7.10.2; TK group; Abl family

Chromosomal Location of Human Ortholog: 9q34.1

Cellular Component: nucleoplasm; nuclear membrane; extrinsic to internal side of plasma membrane; mitochondrion; perinuclear region of cytoplasm; cytoplasm; leading edge; nucleolus; nucleus; cytosol; actin cytoskeleton

Molecular Function: protein C-terminus binding; actin monomer binding; magnesium ion binding; non-membrane spanning protein tyrosine kinase activity; protein kinase activity; actin filament binding; protein binding; DNA binding; syntaxin binding; protein-tyrosine kinase activity; manganese ion binding; mitogen-activated protein kinase binding; nicotinate-nucleotide adenylyltransferase activity; SH3 domain binding; ATP binding; receptor binding

Biological Process: DNA damage induced protein phosphorylation; positive regulation of apoptosis; cerebellum morphogenesis; negative regulation of BMP signaling pathway; elevation of cytosolic calcium ion concentration; transitional one stage B cell differentiation; B cell receptor signaling pathway; regulation of endocytosis; negative regulation of mitotic cell cycle; cell cycle arrest; neuromuscular process controlling balance; positive regulation of oxidoreductase activity; spleen development; mitosis; positive regulation of I-kappaB kinase/NF-kappaB cascade; negative regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of peptidyl-tyrosine phosphorylation; muscle cell differentiation; DNA damage response, signal transduction resulting in induction of apoptosis; positive regulation of osteoblast proliferation; negative regulation of ubiquitin-protein ligase activity; autophagy; response to oxidative stress; actin cytoskeleton organization and biogenesis; axon guidance; peptidyl-tyrosine phosphorylation; alpha-beta T cell differentiation; platelet-derived growth factor receptor signaling pathway; mitochondrial depolarization; positive regulation of mitotic cell cycle; Bergmann glial cell differentiation; regulation of transcription, DNA-dependent; collateral sprouting; cell differentiation; B cell proliferation during immune response; epidermal growth factor receptor signaling pathway; regulation of cell adhesion; cell migration; mismatch repair; thymus development; DNA damage response, signal transduction; B-1 B cell homeostasis; activated T cell proliferation; protein modification process; regulation of cell proliferation; microspike biogenesis; innate immune response; positive regulation of muscle cell differentiation; regulation of autophagy; positive regulation of release of sequestered calcium ion into cytosol; negative regulation of cell-cell adhesion; blood coagulation; response to DNA damage stimulus

Disease: Leukemia, Chronic Myeloid