Abl
an ubiquitous and highly conserved, proto-oncogenic non-receptor tyrosine kinase that plays a role in many key processes including cell growth and survival, actin remodeling, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Negatively regulated by its SH3 domain. Deletion of the SH3 domain turns ABL1 into an oncogene. The Philadelphia 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). Is inhibited by active-site binding small molecules such as imatinib (Gleevec), Dasatinib, Nilotinib, Bosutinib, Ponatinib, and Bafetinib. Compounds such as GNF-2 that bind the myristate-binding pocket of Abl allosterically inhibit Abl kinase activity. Modulates the endocytosis of activated B-cell receptor complexes. Regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Mitochondrial dysfunction and cell death in response to oxidative stress. Translocates to the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Regulates T-cell differentiation in a TBX21-dependent manner. Two alternatively-spliced human isoforms have been described: one that is N-terminally myristoylated and the other not due to an alternative splicing of the first exon. Note: This description may include information from UniProtKB.
Protein type: Abl family; EC 2.7.10.2; Kinase, protein; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); TK group
Molecular Function: actin filament binding; ATP binding; bubble DNA binding; delta-catenin binding; DNA binding; ephrin receptor binding; four-way junction DNA binding; kinase activity; magnesium ion binding; manganese ion binding; metal ion binding; mitogen-activated protein kinase binding; neuropilin binding; non-membrane spanning protein tyrosine kinase activity; nucleotide binding; phosphotyrosine residue binding; proline-rich region binding; protein binding; protein domain specific binding; protein kinase activity; protein kinase binding; protein kinase C binding; protein self-association; protein tyrosine kinase activity; sequence-specific double-stranded DNA binding; SH2 domain binding; SH3 domain binding; syntaxin binding; transferase activity
Biological Process: actin cytoskeleton organization; actin filament polymerization; activated T cell proliferation; activation of protein kinase C activity; alpha-beta T cell differentiation; apoptotic process; autophagy; B cell proliferation; B cell proliferation involved in immune response; B cell receptor signaling pathway; B-1 B cell homeostasis; Bergmann glial cell differentiation; BMP signaling pathway; cell adhesion; cell-cell adhesion; cellular response to hydrogen peroxide; cellular response to lipopolysaccharide; cellular senescence; cerebellum morphogenesis; circulatory system development; DN4 thymocyte differentiation; DNA conformation change; DNA damage response; DNA repair; endocytosis; endothelial cell migration; epidermal growth factor receptor signaling pathway; ERK1 and ERK2 cascade; establishment of localization in cell; I-kappaB kinase/NF-kappaB signaling; integrin-mediated signaling pathway; interleukin-2 production; learning or memory; microspike assembly; negative regulation of BMP signaling pathway; negative regulation of cell-cell adhesion; negative regulation of cellular senescence; negative regulation of double-strand break repair via homologous recombination; negative regulation of endothelial cell apoptotic process; negative regulation of ERK1 and ERK2 cascade; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of long-term synaptic potentiation; negative regulation of mitotic cell cycle; negative regulation of phospholipase C activity; negative regulation of protein serine/threonine kinase activity; negative regulation of ubiquitin-protein transferase activity; neural tube closure; neuroepithelial cell differentiation; neuromuscular process controlling balance; neuron apoptotic process; neuron differentiation; neuropilin signaling pathway; peptidyl-tyrosine autophosphorylation; peptidyl-tyrosine phosphorylation; phagocytosis; phosphorylation; platelet-derived growth factor receptor signaling pathway; platelet-derived growth factor receptor-beta signaling pathway; podocyte apoptotic process; positive regulation of actin filament binding; positive regulation of apoptotic process; positive regulation of blood vessel branching; positive regulation of cell migration involved in sprouting angiogenesis; positive regulation of cytosolic calcium ion concentration; positive regulation of dendrite development; positive regulation of endothelial cell migration; positive regulation of ERK1 and ERK2 cascade; positive regulation of establishment of T cell polarity; positive regulation of extracellular matrix organization; positive regulation of fibroblast proliferation; positive regulation of focal adhesion assembly; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of interleukin-2 production; positive regulation of microtubule binding; positive regulation of mitotic cell cycle; positive regulation of neuron apoptotic process; positive regulation of osteoblast proliferation; positive regulation of oxidoreductase activity; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of protein phosphorylation; positive regulation of release of sequestered calcium ion into cytosol; positive regulation of stress fiber assembly; positive regulation of substrate adhesion-dependent cell spreading; positive regulation of T cell migration; positive regulation of type II interferon production; positive regulation of vasoconstriction; positive regulation of Wnt signaling pathway, planar cell polarity pathway; post-embryonic development; protein autophosphorylation; protein localization to cytoplasmic microtubule plus-end; protein phosphorylation; regulation of actin cytoskeleton organization; regulation of apoptotic process; regulation of axon extension; regulation of Cdc42 protein signal transduction; regulation of cell cycle; regulation of cell population proliferation; regulation of cellular senescence; regulation of extracellular matrix organization; regulation of microtubule polymerization; regulation of modification of synaptic structure; regulation of T cell differentiation; response to endoplasmic reticulum stress; response to oxidative stress; signal transduction in response to DNA damage; spleen development; substrate adhesion-dependent cell spreading; T cell receptor signaling pathway; thymus development; transitional one stage B cell differentiation; type II interferon production
