ABL1 - Tyrosine-protein kinase ABL1 - human protein (Function)
 
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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
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1 603 2
GENE REF ISO

Function

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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.  
22
  • CuratedUniProtKB
GO molecular function 
Actin monomer bindingdefinition[GO:0003785]  
1
  • TASUniProtKB
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
DNA bindingdefinition[GO:0003677]  
1
  • NASUniProtKB
Magnesium ion bindingdefinition[GO:0000287]  
1
  • IDAUniProtKB
Manganese ion bindingdefinition[GO:0030145]  
1
  • IDAUniProtKB
Mitogen-activated protein kinase bindingdefinition[GO:0051019]  
1
  • IPIBHF-UCL
Nicotinate-nucleotide adenylyltransferase activitydefinition[GO:0004515]  
1
  • TASUniProtKB
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • IDAUniProtKB
Proline-rich region bindingdefinition[GO:0070064]  
2
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
32
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • IPIUniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
5
  • IDAUniProtKB
  • IDABHF-UCL
SH3 domain bindingdefinition[GO:0017124]  
1
  • IPIUniProtKB
Syntaxin bindingdefinition[GO:0019905]  
1
  • IPIUniProtKB
GO biological process 
Actin cytoskeleton organizationdefinition[GO:0030036]  
  • ISSOrtholog Curator
Autophagydefinition[GO:0006914]  
  • IEAUniProtKB KW
Cell adhesiondefinition[GO:0007155]  
  • IEAUniProtKB KW
Cellular protein modification processdefinition[GO:0006464]  
1
  • NASUniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • IDAUniProtKB
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
1
  • IDAUniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
1
  • TASUniProtKB
Mismatch repairdefinition[GO:0006298]  
1
  • TASPINC
Negative regulation of protein serine/threonine kinase activitydefinition[GO:0071901]  
1
  • IDABHF-UCL
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
3
  • IDABHF-UCL
  • IDAUniProtKB
Platelet-derived growth factor receptor signaling pathwaydefinition[GO:0048008] silver  
  • IEAOrtholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • IDAUniProtKB
Positive regulation of oxidoreductase activitydefinition[GO:0051353]  
1
  • IDABHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • IDAUniProtKB
Regulation of actin cytoskeleton reorganizationdefinition[GO:2000249]  
1
  • TASUniProtKB
Regulation of autophagydefinition[GO:0010506]  
1
  • TASUniProtKB
Regulation of cell adhesiondefinition[GO:0030155]  
1
  • TASUniProtKB
Regulation of cell cycledefinition[GO:0051726] silver  
  • IEAOrtholog Compara
Regulation of cell motilitydefinition[GO:2000145]  
1
  • TASUniProtKB
Regulation of endocytosisdefinition[GO:0030100]  
1
  • TASUniProtKB
Regulation of response to DNA damage stimulusdefinition[GO:2001020]  
1
  • IDAUniProtKB
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • TASPINC
Signal transduction in response to DNA damagedefinition[GO:0042770]  
2
  • IDAUniProtKB
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.  
1
  • CuratedUniProtKB
It requires the following cofactor
Magnesium or manganese.  
  • CuratedUniProtKB
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.  
5
  • CuratedUniProtKB
 
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