Target name

P00519: Tyrosine-protein kinase ABL1

  Protein function

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.

  Database links

Uniprot primary ID P00519
PDB ID 2G2F 2F4J 4XEY 1AB2 2HZI 2G2I 2G2H 3QRJ 3QRK 3QRI 1ABL 1ZZP 4JJD 4WA9 4JJB 4JJC 2O88 2E2B 1AWO 3CS9 1JU5 2ABL 4J9E 4J9D 4J9G 4J9F 4J9C 4J9B 4TWP 4J9I 4J9H 1OPL 3K2M 2FO0 3EG1 3EG0 3EG3 1BBZ 3UE4 2HYY 2G1T 3PYY 2V7A 2GQG 3EG2 2HZ4 3EGU 2HZ0 3T04 3UYO 2HIW
DrugBank ID DB00619 DB04868 DB06616 DB00171 DB08901 DB08896 DB01254
BioGrid ID 106543
PharmGKB ID PA24413
KEGG ID hsa:25
Entrez Gene (Gene ID) 25
STRING 9606ENSP00000361423
MINT MINT-7236141
IntAct P00519
DMDM 85681908
BREDNA 27102
Rectome R-HSA-983231 R-HSA-375170 R-HSA-5663213 R-HSA-2029482 R-HSA-428890
SignaLink P00519
BindingDB P00519

  Model Performance Metrics

Fingerprint type F1_CV AUC_CV Accuracy_CV Sensitivity_CV Specificity_CV F1_test AUC_test Accuracy_test Sensitivity_test Specificity_test Download model
FP2 fingerprints 0.798 0.836 0.799 0.790 0.808 0.797 0.837 0.801 0.785 0.817 Download
MACCS fingerprints 0.764 0.830 0.752 0.800 0.703 0.783 0.853 0.783 0.833 0.738 Download
Daylight fingerprints 0.763 0.781 0.755 0.787 0.724 0.746 0.760 0.736 0.790 0.684 Download
ECFP2 fingerprints 0.817 0.877 0.817 0.814 0.820 0.811 0.878 0.814 0.813 0.816 Download
ECFP4 fingerprints 0.821 0.887 0.832 0.768 0.896 0.798 0.888 0.812 0.758 0.864 Download
ECFP6 fingerprints 0.804 0.877 0.824 0.721 0.927 0.788 0.881 0.810 0.721 0.895 Download

  Download datasets

Positive dataset Negative dataset

Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

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