Protein: Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) (P00520)
Organism: Mus musculus (Mouse)
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. 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. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1. Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity.
Subcellular location: Cytoplasm, cytoskeleton. Nucleus. Mitochondrion. Note=The myristoylated c-ABL protein is reported to be nuclear. Sequestered into the cytoplasm through interaction with 14-3-3 proteins (By similarity). Localizes to mitochondria in response to oxidative stress. {ECO:0000250}.
Sequence: MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTIYGVSPNYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVSAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSISDEVEKELGKRGTRGGAGSMLQAPELPTKTRTCRRAAEQKDAPDTPELLHTKGLGESDALDSEPAVSPLLPRKERGPPDGSLNEDERLLPRDRKTNLFSALIKKKKKMAPTPPKRSSSFREMDGQPDRRGASEDDSRELCNGPPALTSDAAEPTKSPKASNGAGVPNGAFREPGNSGFRSPHMWKKSSTLTGSRLAAAEEESGMSSSKRFLRSCSASCMPHGARDTEWRSVTLPRDLPSAGKQFDSSTFGGHKSEKPALPRKRTSESRSEQVAKSTAMPPPRLVKKNEEAAEEGFKDTESSPGSSPPSLTPKLLRRQVTASPSSGLSHKEEATKGSASGMGTPATAEPAPPSNKVGLSKASSEEMRVRRHKHSSESPGRDKGRLAKLKPAPPPPPACTGKAGKPAQSPSQEAGEAGGPTKTKCTSLAMDAVNTDPTKAGPPGEGLRKPVPPSVPKPQSTAKPPGTPTSPVSTPSTAPAPSPLAGDQQPSSAAFIPLISTRVSLRKTRQPPERIASGTITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAFREAINKLESNLRELQICPATASSGPAATQDFSKLLSSVKEISDIVRR
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [231-498]
- IPR036028: SH3-like domain superfamily (homologous_superfamily) [62-147]
- IPR050198: Non-receptor tyrosine kinases involved in cell signaling (family) [67-511]
- IPR015015: F-actin binding (domain) [997-1123]
- IPR001452: SH3 domain (domain) [61-121]
- IPR036860: SH2 domain superfamily (homologous_superfamily) [118-262]
- IPR001245: Serine-threonine/tyrosine-protein kinase, catalytic domain (domain) [242-492]
- IPR017441: Protein kinase, ATP binding site (binding_site) [248-271]
- IPR000719: Protein kinase domain (domain) [242-493]
- IPR008266: Tyrosine-protein kinase, active site (active_site) [359-371]
- IPR020635: Tyrosine-protein kinase, catalytic domain (domain) [242-493]
- IPR000980: SH2 domain (domain) [125-217]
- IPR035837: Tyrosine-protein kinase ABL, SH2 domain (domain) [123-216]
Interaction partners: - Adapter molecule crk
- Abl interactor 1
- E3 ubiquitin-protein ligase CBL
- Growth factor receptor-bound protein 2
- Crk-like protein
- Breakpoint cluster region protein
- Ras and Rab interactor 1
- Ephrin type-A receptor 5
- Ephrin type-B receptor 4
- SHC-transforming protein 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0043167 (ion binding), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0004672 (protein kinase activity), GO:0043169 (cation binding), GO:0016301 (kinase activity), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004713 (protein tyrosine kinase activity), GO:0046872 (metal ion binding), GO:0000287 (magnesium ion binding), GO:0046914 (transition metal ion binding), GO:0030145 (manganese ion binding)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0022414 (reproductive process), GO:0040007 (growth), GO:0048519 (negative regulation of biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0002376 (immune system process), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0023057 (negative regulation of signaling), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0035264 (multicellular organism growth), GO:0021700 (developmental maturation), GO:0048523 (negative regulation of cellular process), GO:0040012 (regulation of locomotion), GO:0048869 (cellular developmental process), GO:0009628 (response to abiotic stimulus), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0051234 (establishment of localization), GO:0033036 (macromolecule localization), GO:0065009 (regulation of molecular function), GO:0030029 (actin filament-based process), GO:0007154 (cell communication), GO:0048522 (positive regulation of cellular process), GO:0009605 (response to external stimulus), GO:0048589 (developmental growth), GO:0009653 (anatomical structure morphogenesis), GO:0048870 (cell motility), GO:0045321 (leukocyte activation), GO:0006807 (nitrogen compound metabolic process), GO:0009791 (post-embryonic development), GO:0050793 (regulation of developmental process), GO:0040017 (positive regulation of locomotion), GO:0023051 (regulation of signaling), GO:0007165 (signal transduction), GO:0023056 (positive regulation of signaling), GO:0001775 (cell activation), GO:0007275 (multicellular organism development), GO:0007155 (cell adhesion), GO:0002682 (regulation of immune system process), GO:0071704 (organic substance metabolic process), GO:0003008 (system process), GO:0044237 (cellular metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0048585 (negative regulation of response to stimulus), GO:0044238 (primary metabolic process), GO:0007610 (behavior), GO:0032989 (cellular component morphogenesis), GO:0044085 (cellular component biogenesis), GO:2000145 (regulation of cell motility), GO:0035148 (tube formation), GO:0009314 (response to radiation), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0001817 (regulation of cytokine production), GO:0007626 (locomotory behavior), GO:0007611 (learning or memory), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0032878 (regulation of establishment or maintenance of cell polarity), GO:0009790 (embryo development), GO:0050865 (regulation of cell activation), GO:0002118 (aggressive behavior), GO:0044093 (positive regulation of molecular function), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0030902 (hindbrain development), GO:0051649 (establishment of localization in cell), GO:0030534 (adult behavior), GO:0043170 (macromolecule metabolic process), GO:2000147 (positive regulation of cell motility), GO:0050867 (positive regulation of cell activation), GO:0010941 (regulation of cell death), GO:0060074 (synapse maturation), GO:0006810 (transport), GO:0007638 (mechanosensory behavior), GO:0070727 (cellular macromolecule localization), GO:0010647 (positive regulation of cell communication), GO:0050877 (nervous system process), GO:0009968 (negative regulation of signal transduction), GO:0048729 (tissue morphogenesis), GO:0060548 (negative regulation of cell death), GO:0002685 (regulation of leukocyte migration), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0030155 (regulation of cell adhesion), GO:0002694 (regulation of leukocyte activation), GO:0051098 (regulation of binding), GO:0046649 (lymphocyte activation), GO:0006793 (phosphorus metabolic process), GO:0071695 (anatomical structure maturation), GO:0035295 (tube development), GO:0000902 (cell morphogenesis), GO:0021549 (cerebellum development), GO:0007162 (negative regulation of cell adhesion), GO:0048469 (cell maturation), GO:0016043 (cellular component organization), GO:0007166 (cell surface receptor signaling pathway), GO:0001819 (positive regulation of cytokine production), GO:0021587 (cerebellum morphogenesis), GO:0051128 (regulation of cellular component organization), GO:0016477 (cell migration), GO:0035239 (tube morphogenesis), GO:0009967 (positive regulation of signal transduction), GO:0021575 (hindbrain morphogenesis), GO:0010648 (negative regulation of cell communication), GO:1901564 (organonitrogen compound metabolic process), GO:0035556 (intracellular signal transduction), GO:0098609 (cell-cell adhesion), GO:0051130 (positive regulation of cellular component organization), GO:0045785 (positive regulation of cell adhesion), GO:0022037 (metencephalon development), GO:0030036 (actin cytoskeleton organization), GO:0002687 (positive regulation of leukocyte migration), GO:0002696 (positive regulation of leukocyte activation), GO:0048598 (embryonic morphogenesis), GO:0009888 (tissue development), GO:0060322 (head development), GO:0010646 (regulation of cell communication), GO:0016358 (dendrite development), GO:0007632 (visual behavior), GO:0035640 (exploration behavior), GO:0009612 (response to mechanical stimulus), GO:0060562 (epithelial tube morphogenesis), GO:0030030 (cell projection organization), GO:0022409 (positive regulation of cell-cell adhesion), GO:0090659 (walking behavior), GO:0010001 (glial cell differentiation), GO:0043393 (regulation of protein binding), GO:0010468 (regulation of gene expression), GO:0043412 (macromolecule modification), GO:0051251 (positive regulation of lymphocyte activation), GO:0072359 (circulatory system development), GO:0071677 (positive regulation of mononuclear cell migration), GO:0030335 (positive regulation of cell migration), GO:1902533 (positive regulation of intracellular signal transduction), GO:0007264 (small GTPase mediated signal transduction), GO:0022408 (negative regulation of cell-cell adhesion), GO:0048858 (cell projection morphogenesis), GO:0007015 (actin filament organization), GO:0010996 (response to auditory stimulus), GO:0009416 (response to light stimulus), GO:0002521 (leukocyte differentiation), GO:0007167 (enzyme-linked receptor protein signaling pathway), GO:0031344 (regulation of cell projection organization), GO:0030111 (regulation of Wnt signaling pathway), GO:0007612 (learning), GO:2000114 (regulation of establishment of cell polarity), GO:0072175 (epithelial tube formation), GO:0006929 (substrate-dependent cell migration), GO:0036211 (protein modification process), GO:0008542 (visual learning), GO:0022008 (neurogenesis), GO:0060606 (tube closure), GO:0007249 (I-kappaB kinase/NF-kappaB signaling), GO:0008104 (protein localization), GO:0099173 (postsynapse organization), GO:0060429 (epithelium development), GO:0034330 (cell junction organization), GO:0097435 (supramolecular fiber organization), GO:0009792 (embryo development ending in birth or egg hatching), GO:0032743 (positive regulation of interleukin-2 production), GO:0032663 (regulation of interleukin-2 production), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0032990 (cell part morphogenesis), GO:0022407 (regulation of cell-cell adhesion), GO:0043954 (cellular component maintenance), GO:0002009 (morphogenesis of an epithelium), GO:0030334 (regulation of cell migration), GO:0032729 (positive regulation of type II interferon production), GO:0016331 (morphogenesis of embryonic epithelium), GO:0030098 (lymphocyte differentiation), GO:0048666 (neuron development), GO:0022607 (cellular component assembly), GO:0007420 (brain development), GO:0000904 (cell morphogenesis involved in differentiation), GO:0007399 (nervous system development), GO:1903053 (regulation of extracellular matrix organization), GO:0048813 (dendrite morphogenesis), GO:0007417 (central nervous system development), GO:0071675 (regulation of mononuclear cell migration)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0030054 (cell junction), GO:0045202 (synapse), GO:0098978 (glutamatergic synapse)