Mouse Anti-ABL1 Recombinant Antibody (V2-179111) (CBMAB-A0354-YC)

ABL Proto-Oncogene 1, Non-Receptor Tyrosine Kinase

ABL1 is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain,

ABL Proto-Oncogene 1, Non-Receptor Tyrosine Kinase; V-Abl Abelson Murine Leukemia Viral Oncogene Homolog 1; C-Abl Oncogene 1, Receptor Tyrosine Kinase; Abelson Tyrosine-Protein Kinase 1; Proto-Oncogene C-Abl; EC 2.7.10.2; JTK7; P150; ABL; Abelson Murine L

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'. 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).

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
Circulatory system development
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 of actin cytoskeleton reorganization
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 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 production
Positive regulation of interleukin-2 production
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

Nucleus; Mitochondrion; Cytoskeleton. Shuttles between the nucleus and cytoplasm depending on environmental signals. Sequestered into the cytoplasm through interaction with 14-3-3 proteins. Localizes to mitochondria in response to oxidative stress (By similarity).
Isoform IB: Nucleus membrane. The myristoylated c-ABL protein is reported to be nuclear.

A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts. A chromosomal aberration involving ABL1 has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). A chromosomal aberration involving ABL1 is found in a form of acute lymphoblastic leukemia (PubMed:15361874). Translocation t(9;9)(q34;q34) with NUP214.
An autosomal dominant disorder characterized by congenital heart disease with atrial and ventricular septal defects, variable skeletal abnormalities, and failure to thrive. Skeletal defects include pectus excavatum, scoliosis, and finger contractures. Some patient exhibit joint laxity.

Acetylated at Lys-711 by EP300 which promotes the cytoplasmic translocation.
Phosphorylation at Tyr-70 by members of the SRC family of kinases disrupts SH3 domain-based autoinhibitory interactions and intermolecular associations, such as that with ABI1, and also enhances kinase activity. Phosphorylation at Tyr-226 and Tyr-393 correlate with increased activity. DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation (By similarity). Phosphorylation at Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division (By similarity). Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1. Phosphorylation on Thr-735 is required for binding 14-3-3 proteins for cytoplasmic translocation. Phosphorylated by PRKDC (By similarity).
Polyubiquitinated. Polyubiquitination of ABL1 leads to degradation.