ABL1
Entrez ID: 25
Full name: ABL proto-oncogene 1, non-receptor tyrosine kinase
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: TK: Abl
Chromosomal location: 9q34.12
Substructure location: Gatekeeper: 315 A-loop: 380...404 G-loop: 245...256 αC-helix: 248...251
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ABL1
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remo...
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner. Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity).
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GO - Biological processes (BP):
actin cytoskeleton organization, actin filament branching, activated T cell proliferation, activation of protein kinase C activity, alpha-beta T cell differentiation, autophagy, B-1 B cell homeostasis, B cell proliferation involved in immune response, B cell receptor signaling pathway, Bergmann glia...
actin cytoskeleton organization, actin filament branching, activated T cell proliferation, activation of protein kinase C activity, alpha-beta T cell differentiation, autophagy, B-1 B cell homeostasis, B cell proliferation involved in immune response, B cell receptor signaling pathway, Bergmann glial cell differentiation, cardiovascular system development, cell cycle arrest, cellular protein modification process, cellular response to DNA damage stimulus, cellular response to dopamine, cellular response to hydrogen peroxide, cellular response to lipopolysaccharide, cellular response to oxidative stress, cerebellum morphogenesis, collateral sprouting, DNA conformation change, DNA damage induced protein phosphorylation, endocytosis, endothelial cell migration, epidermal growth factor receptor signaling pathway, establishment of protein localization, Fc-gamma receptor signaling pathway involved in phagocytosis, integrin-mediated signaling pathway, intrinsic apoptotic signaling pathway in response to DNA damage, microspike assembly, mismatch repair, mitochondrial depolarization, mitotic cell cycle, negative regulation of BMP signaling pathway, negative regulation of cell-cell adhesion, negative regulation of cellular senescence, 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, neuropilin signaling pathway, peptidyl-tyrosine autophosphorylation, peptidyl-tyrosine phosphorylation, platelet-derived growth factor receptor-beta signaling pathway, positive regulation blood vessel branching, positive regulation of actin cytoskeleton reorganization, positive regulation of actin filament binding, positive regulation of apoptotic process, positive regulation of cell migration involved in sprouting angiogenesis, positive regulation of cytosolic calcium ion concentration, positive regulation of endothelial cell migration, positive regulation of ERK1 and ERK2 cascade, positive regulation of focal adhesion assembly, positive regulation of I-kappaB kinase/NF-kappaB signaling, positive regulation of interferon-gamma secretion, positive regulation of interleukin-2 secretion, positive regulation of microtubule binding, positive regulation of mitotic cell cycle, positive regulation of muscle cell differentiation, positive regulation of neuron death, 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 transcription by RNA polymerase II, positive regulation of Wnt signaling pathway, planar cell polarity pathway, post-embryonic development, protein autophosphorylation, protein phosphorylation, regulation of actin cytoskeleton organization, regulation of actin cytoskeleton reorganization, regulation of apoptotic process, regulation of autophagy, regulation of axon extension, regulation of Cdc42 protein signal transduction, regulation of cell adhesion, regulation of cell motility, regulation of endocytosis, regulation of extracellular matrix organization, regulation of hematopoietic stem cell differentiation, regulation of microtubule polymerization, regulation of modification of synaptic structure, regulation of response to DNA damage stimulus, regulation of T cell differentiation, regulation of transcription, DNA-templated, 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
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GO - Molecular function (MF):
actin filament binding, actin monomer binding, ATP binding, bubble DNA binding, DNA binding, ephrin receptor binding, four-way junction DNA binding, kinase activity, magnesium ion binding, manganese ion binding, mitogen-activated protein kinase binding, neuropilin binding, nicotinate-nucleotide aden...
actin filament binding, actin monomer binding, ATP binding, bubble DNA binding, DNA binding, ephrin receptor binding, four-way junction DNA binding, kinase activity, magnesium ion binding, manganese ion binding, mitogen-activated protein kinase binding, neuropilin binding, nicotinate-nucleotide adenylyltransferase activity, non-membrane spanning protein tyrosine kinase activity, phosphotyrosine residue binding, proline-rich region binding, protein C-terminus binding, protein kinase activity, protein kinase C binding, protein tyrosine kinase activity, sequence-specific double-stranded DNA binding, SH2 domain binding, SH3 domain binding, syntaxin binding, transcription coactivator activity
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GO - Cellular component (CC):
actin cytoskeleton, cytosol, mitochondrion, nuclear body, nuclear membrane, nucleolus, nucleoplasm, nucleus, cell, cell leading edge, cytoplasm, dendrite, neuronal cell body, perinuclear region of cytoplasm, postsynapse, protein-containing complex...
actin cytoskeleton, cytosol, mitochondrion, nuclear body, nuclear membrane, nucleolus, nucleoplasm, nucleus, cell, cell leading edge, cytoplasm, dendrite, neuronal cell body, perinuclear region of cytoplasm, postsynapse, protein-containing complex
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ABL proto-oncogene 1, non-receptor tyrosine kinase
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*NOTE: the Kaplan plots were collected from OncoLnc