Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

Abl1 (P00520) - Overview - Molecular Target Synopsis


Abl1, Tyrosine-protein kinase ABL1
Enzyme Classification
UniProt P00520

Also Known as ABL1_MOUSE, Abl1, Abl

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' (By similarity). 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-191' 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. Regulates T-cell differentiation in a TBX21-dependent manner (PubMed:21690296). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (PubMed:21690296). Interacts with INPPL1/SHIP2. Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16. Interacts with the 14-3-3 proteins, YWHAB, YWHAE, YWHAG, YWHAH, SFN AND YWHAZ; the interaction with 14-3-3 proteins requires phosphorylation on Thr-734 and sequesters ABL1 into the cytoplasm. Interacts (via SH3 domain) with CASP9; the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c-Abl activation (By similarity). Interacts with ABI1, ABI2, BCR, CRK, FYN, LYN, PSMA7 RAD9A, RAD51, RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Interacts with STX17; probably phosphorylates STX17 (By similarity). Interacts with ITGB1, HCK and FGR. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases (By similarity). Interacts with TBX21 (PubMed:21690296).

Inspect Structure
See all 3D Structures for Abl1

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform

Sub-cellular localization

UniProt: Abl1 is active in the following subcellular-locations: cytoplasm, cytoskeleton, mitochondrion, nucleus.
GO terms: Abl1 is active in the following subcellular-locations: actin cytoskeleton, cell leading edge, cytoplasm, cytosol, dendrite, endoplasmic reticulum, growth cone, mitochondrion, neuron projection, neuronal cell body, nuclear body, nucleolus, nucleoplasm, nucleus, perinuclear region of cytoplasm, protein-containing complex, ruffle, synapse.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project Abl1 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures

For Abl1 there are:
24 structures (45 chains) solved
22 are solved in complex with at least one small molecule ligand
9 are solved with an approved drug

Abl1 is solved in complex with the approved drug(s):

STI/IMATINIB (1IEP_A, 1IEP_B, 1OPJ_A, 1OPJ_B, 3K5V_A, 3K5V_B, 3MS9_A, 3MS9_B, 3MSS_A, 3MSS_B, 3MSS_C, 3MSS_D, 6HD4_A, 6HD4_B, 6HD6_A, 6HD6_B),

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

Abl1 has been screened with 44 compounds (49 bioactivities), 6 compounds have bioactivities that show binding affinity of <= 500nM (6 bioactivities). (see details)