ABL1 - Tyrosine-protein kinase ABL1 - human protein (Function)
 
Home Recent activites arrow-down favorite My favorites arrow-down favorite My labels arrow-down Downloads
Back to ...  
Publication View
Protein
Gene
References

 
ABL1 »  Tyrosine-protein kinase ABL1   [ EC 2.7.10.2 ]
 
Protein also known as:  Abelson murine leukemia viral oncogene homolog 1.
Gene name:  ABL1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 652 2
GENE REF ISO

Function

 show evidences
Overview 
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.  
23
  • UniProtKB
GO molecular function 
Actin monomer bindingdefinition[GO:0003785]  
1
  • UniProtKB
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB
DNA bindingdefinition[GO:0003677]  
1
  • UniProtKB
Magnesium ion bindingdefinition[GO:0000287]  
1
  • UniProtKB
Manganese ion bindingdefinition[GO:0030145]  
1
  • UniProtKB
Mitogen-activated protein kinase bindingdefinition[GO:0051019]  
1
  • BHF-UCL
Nicotinate-nucleotide adenylyltransferase activitydefinition[GO:0004515]  
1
  • UniProtKB
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • UniProtKB
Proline-rich region bindingdefinition[GO:0070064]  
2
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
35
  • IntAct
  • UniProtKB
  • BHF-UCL
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • UniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • MGI
Protein tyrosine kinase activitydefinition[GO:0004713]  
7
  • MGI
  • UniProtKB
  • BHF-UCL
Receptor bindingdefinition[GO:0005102]  
1
  • RefGenome
SH3 domain bindingdefinition[GO:0017124]  
1
  • UniProtKB
Syntaxin bindingdefinition[GO:0019905]  
1
  • UniProtKB
GO biological process 
Actin cytoskeleton organizationdefinition[GO:0030036]  
1
  • Ortholog Curator
Autophagydefinition[GO:0006914]  
1
  • UniProtKB KW
Cell adhesiondefinition[GO:0007155]  
1
  • UniProtKB KW
Cell cycle arrestdefinition[GO:0007050]  
1
  • ParkinsonsUK-UCL
Cell differentiationdefinition[GO:0030154]  
1
  • RefGenome
Cell migrationdefinition[GO:0016477]  
1
  • RefGenome
Cellular protein modification processdefinition[GO:0006464]  
1
  • UniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • UniProtKB
Cellular response to dopaminedefinition[GO:1903351]  
1
  • ParkinsonsUK-UCL
Cellular response to oxidative stressdefinition[GO:0034599]  
1
  • ParkinsonsUK-UCL
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
1
  • UniProtKB
Epidermal growth factor receptor signaling pathwaydefinition[GO:0007173]  
1
  • RefGenome
Innate immune responsedefinition[GO:0045087]  
1
  • RefGenome
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
1
  • UniProtKB
Mismatch repairdefinition[GO:0006298]  
1
  • PINC
Mitochondrial depolarizationdefinition[GO:0051882]  
1
  • ParkinsonsUK-UCL
Mitotic nuclear divisiondefinition[GO:0007067]  
1
  • ParkinsonsUK-UCL
Negative regulation of phospholipase C activitydefinition[GO:1900275]  
1
  • MGI
Negative regulation of protein serine/threonine kinase activitydefinition[GO:0071901]  
1
  • BHF-UCL
Negative regulation of ubiquitin-protein transferase activitydefinition[GO:0051444]  
3
  • ParkinsonsUK-UCL
  • MGI
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • RefGenome
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
5
  • ParkinsonsUK-UCL
  • BHF-UCL
  • UniProtKB
Platelet-derived growth factor receptor signaling pathwaydefinition[GO:0048008]  
1
  • RefGenome
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • UniProtKB
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204]  
1
  • MGI
Positive regulation of oxidoreductase activitydefinition[GO:0051353]  
1
  • BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • UniProtKB
Regulation of actin cytoskeleton reorganizationdefinition[GO:2000249]  
1
  • UniProtKB
Regulation of autophagydefinition[GO:0010506]  
1
  • UniProtKB
Regulation of cell adhesiondefinition[GO:0030155]  
1
  • UniProtKB
Regulation of cell motilitydefinition[GO:2000145]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • RefGenome
Regulation of endocytosisdefinition[GO:0030100]  
1
  • UniProtKB
Regulation of response to DNA damage stimulusdefinition[GO:2001020]  
1
  • UniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • PINC
Response to oxidative stressdefinition[GO:0006979]  
1
  • MGI
Signal transduction in response to DNA damagedefinition[GO:0042770]  
2
  • UniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
3
  • UniProtKB
  • PROSITE-ProRule
It requires the following cofactor
 Mg(2+)  
1
  • UniProtKB
It is regulated in the following manner
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.  
6
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Axon guidance  hsa04360+25  
Cell cycle  hsa04110+25  
Chronic myeloid leukemia  hsa05220+25  
ErbB signaling pathway  hsa04012+25  
Neurotrophin signaling pathway  hsa04722+25  
Pathogenic Escherichia coli infection  hsa05130+25  
Pathways in cancer  hsa05200+25  
Shigellosis  hsa05131+25  
Viral myocarditis  hsa05416+25  
According to Reactome, this protein belongs to the following pathways:
CDO in myogenesis  REACT_21402  
Factors involved in megakaryocyte development and platelet production  REACT_24970  
Regulation of actin dynamics for phagocytic cup formation  REACT_160086  
Role of Abl in Robo-Slit signaling  REACT_19230  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Autophagy  definition   [KW-0072]
Cell adhesion  definition   [KW-0130]
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Endocytosis  definition   [KW-0254]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: ABL_(gene)
GenomeRNAi: 25
PRO: PR:P00519
Chemistry
GuidetoPHARMACOLOGY: 1923