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FLASH GENE
Symbol ABL1 contributors: mct/shn - updated : 16-07-2016
HGNC name c-abl oncogene 1, receptor tyrosine kinase
HGNC id 76
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivemale systemtestis    Homo sapiens
Skin/Tegumentskin   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal highly
cells
SystemCellPubmedSpeciesStageRna symbol
Reproductivespermatozoa Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two Src homology domains SH3, SH2 (SH3 domain is involved in its interaction with talin and Vav)
  • a catalytic, protein tyrosine kinase domain
  • in the C terminal region three nuclear localization signals (NLS)
  • a DNA binding domain
  • a binding site for actin
  • a nuclear export signal (NES)
  • mono polymer tetramer
    HOMOLOGY
    interspecies ortholog to Abl1, Mus musculus
    ortholog to abl1, Danio rerio
    ortholog to ABL1, Pan troglodytes
    ortholog to Abl1, Rattusnorvegicus
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleolus
    text loss from the nucleus upon adhesion to fibronectin matrix
    basic FUNCTION
  • non receptor tyrosine kinase, involved in processes of cell differentiation, cell division, cell adhesion, and stress response
  • in brain, ABL1 is involved in neuronal plasticity, neurite outgrowth, and neurogenesis
  • playing a critical role for signaling transduction from various receptors in leukocytes
  • c-Abl promotes the induction of EGR1 through the MEK/ERK pathway in regulating apoptotic response to oxidative stress
  • playing a role in DNA repair as a regulator/coordinator of the DNA damage response
  • inducing apoptosis in response to DNA damage
  • required for beta(2) integrin-dependent neutrophil sustained adhesion and spreading
  • playing an essential role in the determination of cell fate that is related to its nuclear shuttling in response to DNA damage
  • plays a central role in the induction of NOX5 activity in response to H2O2
  • modulates innate immune response through MAVS phosphorylation
  • major regulator of PARK2 function (phosphorylates parkin on tyrosine 143)
  • participates in modulating PITX1 expression in the apoptotic response to DNA damage
  • is a nonreceptor protein tyrosine kinase that has a role in regulating smooth muscle cell proliferation and contraction
  • CELLULAR PROCESS cell cycle, division
    cell life, differentiation
    PHYSIOLOGICAL PROCESS
    text promoting cell cycle arrest by blocking the G/S transition-in a TP53 dependent way
    PATHWAY
    metabolism
    signaling
    a component
  • complex ABL1/ABI1/WASF2 as critical pathway for coupling stimulatory signals to actin cytoskeletal remodeling
  • BCR-ABL1 suppresses autophagy through ATF5-mediated regulation of MTOR transcription
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Philadelphia chromosome breakpoint, BCR (
  • cyclic AMP response element (CRE)-binding protein, CREB
  • abl-interactor 2, ABI2 (
  • Grb2 and mSos1 (
  • SHPTP1 (
  • ABL-associated protein 1, AAP1 (
  • v-crk sarcoma virus CT10 oncogene homolog (avian)-like, CRKL (
  • ataxia telangiectasia mutated, ATM (
  • phosphoprotein associated with glycosphingolipid, PAG (
  • Src family kinase Hck (
  • paxillin, PXN (
  • amphiphysin-like protein 1, ALP1 (
  • growth factor receptor-bound protein 10, GRB10 (
  • Janus kinase 1, Jak1 (
  • 70 kDa subunit of Ku antigen, Ku70 (
  • glucokinase (hexokinase 4) regulator, GCKR (
  • p73alpha (
  • Dok-like protein, DOKL (
  • P53 (
  • Trk nerve growth factor receptor (
  • TrkA (
  • rapamycin and FKBP-target 1, RAFT1 (
  • N-methyl-D-aspartic acid receptor NR2D subunit (
  • telomerase reverse transcriptase, TERT (
  • roundabout, axon guidance receptor, homolog 1, ROBO1 (
  • Cdk5 and Abl enzyme substrate, Cables (
  • WAVE-1 (
  • CD19 (
  • p21-activated protein kinase gamma-PAK (
  • hematopoietic progenitor kinase 1, HPK1 (
  • Fe65, X11, and mDab1 (
  • phospholipid scramblase 1, PLSCR1 (
  • proto-oncogene Vav (
  • RAN, member RAS oncogene family, RAN (
  • EPH receptor B2, EPHB2 (
  • Brain armadillo protein delta-catenin (
  • RAD9 homolog A (S. pombe), RAD9 (
  • anterior pharynx-defective 2, Aph2 (
  • BRCA1 (
  • damage-specific DNA binding protein 1, DDB1 (
  • IkappaBalpha (
  • Crk SH2 domain (
  • Arg/Abl-interacting protein ArgBP2 (
  • Arg protein-tyrosine kinases (
  • catalase (
  • glutathione peroxidase 1, GPx1 (
  • Ras and Rab interactor 1, RIN1 (
  • topoisomerase (DNA) II binding protein 1, TOPBP1 (
  • vinexin (
  • mucin 1, cell surface associated, MUC1 (
  • FGFR1OP and WRNIP1 (FGFR1OP significantly reduced ABL1-dependent phosphorylation of WRNIP1 and resulted in the promotion of cell cycle progression)
  • amplified in breast cancer 1 protein, AIB1 (
  • role for MSH5 in DNA damage response involving ABL1 and TP73, suggesting that mutations impairing this process could significantly affect normal cellular responses to anti-cancer treatments
  • CDON is important for full ABL1 kinase activity, and ABL1 is necessary for full activation of MAPK14, during myogenic differentiation
  • PARK2 (ABL1 SH3 domain is required for the interaction with parkin)
  • Atm and Atr in response to DNA damage (
  • EWSR1 depletion results in alternative splicing changes of genes involved in DNA repair and genotoxic stress signaling, including ABL1, CHEK2, and MAP4K2
  • H2O2-NOX5 regulation in human spermatozoa is mediated through a ABL1-dependent signaling pathway
  • mediates oxidative stress-induced neuronal cell death through phosphorylating STK4 at Y433
  • is a novel upstream activator of STK3 suggesting that the conserved ABL1-MST signaling cascade plays an important role in oxidative stress-induced neuronal cell death
  • KAT5 tyrosine phosphorylation is a key event in the sensing of genomic and chromatin perturbations, with a key role for ABL1 in such processes
  • functional relationship between ABL1 and CLASP2 is conserved and provides a means to control the CLASP2 association with the cytoskeleton
  • ABL1 protected HIPK2 from degradation mediated by the ubiquitin E3 ligase SIAH1
  • ABL1 phosphorylates SKI-interacting protein (SNW1), a nuclear cofactor of the transcription factor SMAD3
  • ERRFI1 may regulate the targeting of ABL1 to chromatin
  • cell & other
  • associates with chromatin after DNA damage in a manner dependent on its kinase activity, and functions during the early phase of RAD51 chromatin assembly, before RAD51 nucleoprotein filament formation
  • REGULATION
    activated by requiring mitogen-activated protein kinase kinase 6 activation (MAP2K6) for inducing apoptosis
    certain DNA-damaging agents from ionizing radiation to alkylating agents
    regulated by ATM
    beta(2) integrin engagement
    inhibited by ABL-associated protein 1, AAP1 (
    F-actin (
    repressed by TOPBP1, at both mRNA and protein levels
    ASSOCIATED DISORDERS
    corresponding disease(s) BCR-ABL
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    in chronic myelogenous leukemia cells, silenced by promoter methylation
    tumoral fusion translocation    
    translocation t(22;9)(q11;q34)and fusion with NUP214 in T-cell acute lymphoblastic leukemia
    tumoral fusion      
    EML1-ABL1 fusion due to a cryptic t(9;14)(q34;q32), in T-cell acute lymphoblastic leukemia (ALL)
    tumoral fusion      
    fusion gene involving ABL1 and NUP214, in T-cell acute lymphoblastic leukemia (T-ALL)
    tumoral fusion      
    BCR-ABL1 and ETV6-ABL1 in T-cell acute lymphoblastic leukemia
    tumoral fusion      
    with SFPQ in t(1;9)(p34;q34) and B cell progenitor acute lymphoid leukemia
    tumoral fusion      
    fusion gene SNX2-ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), arising from a t(5;9)(q22;q34) translocation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    ABL1 fusion proteins are sensitive to tyrosine kinase inhibitors, which can be included in future treatment strategy
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    inhibition of ABL1 may be a neuroprotective approach in the treatment of Parkinson disease
    ANIMAL & CELL MODELS
  • mice homozygous for the c-abl mutation became runted and died 1 to 2 weeks after birth (
  • mice homozygous for the c-abl mutation are severely affected, displaying increased perinatal mortality, runtedness, and abnormal spleen, head, eye development, and major reductions in B cell progenitors (
  • Abl-/- mice are osteoporotic with long bones containing thinner cortical bone and reduced trabecular bone volume (
  • c-Abl deficiency result in a broad spectrum of defects in cell response to genotoxic stress, including activation of Chk1 and Chk2, activation of p53, nuclear foci formation, apoptosis, and DNA repair (