Aliases for ABL1 Gene
- ABL Proto-Oncogene 1, Non-Receptor Tyrosine Kinase 2 3 5
- V-Abl Abelson Murine Leukemia Viral Oncogene Homolog 1 2 3
- C-Abl Oncogene 1, Receptor Tyrosine Kinase 2 3
- Abelson Tyrosine-Protein Kinase 1 3 4
- Proto-Oncogene C-Abl 3 4
- EC 220.127.116.11 4 58
- JTK7 3 4
- P150 3 4
- ABL 3 4
- Abelson Murine Leukemia Viral Oncogene Homolog 1 4
- C-Abl Oncogene 1, Non-Receptor Tyrosine Kinase 2
External Ids for ABL1 Gene
Previous HGNC Symbols for ABL1 Gene
Previous GeneCards Identifiers for ABL1 Gene
This gene 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, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]
ABL1 is most relevant to cancer in its role in the BCR-ABL fusion protein that has become a signature of chronic myeloid leukemia (CML). Cells harboring this fusion have shown sensitivity to imatinib, greatly improving the prognostic outlook of the disease. However, additional mutations in ABL1 have been shown to confer resistance to imatinib. In these resistance cases, second-generation tyrosine kinase inhibitors such as dasatinib and nilotinib have exhibited some efficacy and are currently undergoing clinical trials for treating acquired resistance in CML.
GeneCards Summary for ABL1 Gene
ABL1 (ABL Proto-Oncogene 1, Non-Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with ABL1 include Congenital Heart Defects And Skeletal Malformations Syndrome and Leukemia, Chronic Myeloid, Somatic. Among its related pathways are DNA Double Strand Break Response and DNA Double-Strand Break Repair. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is ABL2.
UniProtKB/Swiss-Prot for ABL1 Gene
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.
The Abl family of non-receptor tyrosine kinases includes c-Abl (Abelson tyrosine kinase) and Arg (Abl2) subtypes. c-Abl is localized at many subcellular sites including the nucleus, cytoplasm, mitochondria and endoplasmic reticulum, where it interacts with several proteins.