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  3. ABL1

ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)

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The Function of 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 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. 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.

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Protein names

Recommended name:

Tyrosine-protein kinase ABL1

Alternative name(s):

Abelson murine leukemia viral oncogene homolog 1
Abelson tyrosine-protein kinase 1
Proto-oncogene c-Abl
p150

ABL1 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS10901296 (ABL1) ??
  2. RS2070997 (ABL1) ??

Top Gene-Substance Interactions

ABL1 Interacts with These Diseases

Disease Score

Substances That Increase ABL1

Substances Interaction Organism Category

Substances That Decrease ABL1

Substances Interaction Organism Category

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • FOXO3
  • FOXO3a
  • STAT3
  • c-Myc
  • STAT1
  • STAT1alpha
  • c-Rel
  • GATA-3

Tissue specificity:

Widely expressed.

Gene Pathways:

  • Immune System
  • Pathways in cancer
  • Hemostasis
  • Pathogenic Escherichia coli infection
  • Axon guidance
  • Neurotrophin signaling pathway
  • Chronic myeloid leukemia
  • Shigellosis
  • Viral myocarditis

Enzyme Regulation:

Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage. Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits also the tyrosine kinase activity (By similarity). Inhibited by ABI1, whose activity is controlled by ABL1 itself through tyrosine phosphorylation. Also inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML), and by VX-680, an inhibitor that acts also on imatinib-resistant mutants.

Molecular Function:

  • Actin Monomer Binding
  • Atp Binding
  • Dna Binding
  • Magnesium Ion Binding
  • Manganese Ion Binding
  • Mitogen-Activated Protein Kinase Binding
  • Nicotinate-Nucleotide Adenylyltransferase Activity
  • Non-Membrane Spanning Protein Tyrosine Kinase Activity
  • Proline-Rich Region Binding
  • Protein C-Terminus Binding
  • Protein Kinase C Binding
  • Protein Tyrosine Kinase Activity
  • Sh3 Domain Binding
  • Syntaxin Binding

Biological Processes:

  • 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
  • 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 Damage Induced Protein Phosphorylation
  • Epidermal Growth Factor Receptor Signaling Pathway
  • Establishment Of Protein Localization
  • Fc-Gamma Receptor Signaling Pathway Involved In Phagocytosis
  • Innate Immune Response
  • Intrinsic Apoptotic Signaling Pathway In Response To Dna Damage
  • Microspike Assembly
  • Mismatch Repair
  • Mitochondrial Depolarization
  • Mitotic Nuclear Division
  • 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 Mitotic Cell Cycle
  • Negative Regulation Of Phospholipase C Activity
  • Negative Regulation Of Protein Serine/Threonine Kinase Activity
  • Negative Regulation Of Ubiquitin-Protein Transferase Activity
  • Neuromuscular Process Controlling Balance
  • Peptidyl-Tyrosine Autophosphorylation
  • Peptidyl-Tyrosine Phosphorylation
  • Platelet-Derived Growth Factor Receptor-Beta Signaling Pathway
  • Positive Regulation Of Actin Filament Binding
  • Positive Regulation Of Apoptotic Process
  • Positive Regulation Of Cytosolic Calcium Ion Concentration
  • Positive Regulation Of Erk1 And Erk2 Cascade
  • 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 Wnt Signaling Pathway, Planar Cell Polarity Pathway
  • Protein Autophosphorylation
  • Regulation Of Actin Cytoskeleton Organization
  • Regulation Of Actin Cytoskeleton Reorganization
  • Regulation Of Autophagy
  • Regulation Of Axon Extension
  • Regulation Of Cell Adhesion
  • Regulation Of Cell Motility
  • Regulation Of Cell Proliferation
  • Regulation Of Endocytosis
  • Regulation Of Extracellular Matrix Organization
  • Regulation Of Microtubule Polymerization
  • Regulation Of Response To Dna Damage Stimulus
  • Regulation Of Transcription, Dna-Templated
  • Response To Oxidative Stress
  • Signal Transduction In Response To Dna Damage
  • Spleen Development
  • Substrate Adhesion-Dependent Cell Spreading
  • Thymus Development
  • Transitional One Stage B Cell Differentiation

Drug Bank:

  • Adenosine Triphosphate
  • Imatinib
  • Nilotinib
  • Ponatinib
  • Regorafenib
  • Bosutinib
  • Dasatinib
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| Abelson murine leukemia oncogene| Abelson murine leukemia viral oncogene 1-like protein| abelson murine leukemia viral oncogene homolog 1| Abelson murine leukemia viral (v-abl) oncogene homolog 1| Abelson tyrosine-protein kinase 1| Abl| AS27_01606| AS28_01153| bcr/abl| bcr/c-abl oncogene protein| c-abl| c-ABL1| c-abl oncogene 1, non-receptor tyrosine kinase| c-abl oncogene 1, receptor tyrosine kinase| c-abl oncoprotein 1, receptor tyrosine kinase| c-abl protein, type I| c-abl protein, type II| c-abl protein, type III| EH28_08971| H920_06685| I79_022766| JTK7| M91_15851| M959_09404| MDA_GLEAN10011219| N300_09310| N301_05310| N302_13132| N303_06132| N305_08970| N306_14769| N307_02480| N308_09276| N310_02990| N311_05821| N312_13493| N320_05420| N321_09312| N322_03953| N324_04265| N325_05681| N326_05069| N327_00954| N328_09054| N329_05370| N330_00892| N331_05850| N332_01067| N333_04720| N334_08332| N335_09034| N336_02603| N339_12434| N340_00756| N341_05339| p150| PAL_GLEAN10012549| PANDA_003253| proto-oncogene c-Abl| proto-oncogene tyrosine-protein kinase ABL1| Tyrosine-protein kinase ABL1| Tyrosine-protein kinase transforming protein Abl| UY3_08252| v-abl| v-abl Abelson murine leukemia oncogene 1| v-abl Abelson murine leukemia viral oncogene 1| v-abl Abelson murine leukemia viral oncogene homolog 1| v-abl Abelson murine leukemia viral oncogene-like 1| Y1Q_004344| Y956_02069| Z169_11685| abl1

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