Names & Taxonomy

Uniprot ID:
P00519
Entry Name:
ABL1_HUMAN
Status:
reviewed
Protein Names:
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)
Gene Names:
ABL1 ABL JTK7
Gene Names Primary:
ABL1
Organism:
Homo sapiens (Human)

Structure

Length:
1130
Sequence:
MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSASCVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTVTPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGSALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPPPPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPGEGLKKPVLPATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPERIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm, cytoskeleton. Nucleus. Mitochondrion

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Cofactor:
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
Enzyme Regulation:
ENZYME REGULATION: 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.
Active Site:
ACT_SITE 363 363 Proton acceptor.
Cross Reference Drug Bank:
DB00171 DB06616 DB01254 DB00619 DB04868 DB08901 DB08896
Gene Ontology Go:
actin cytoskeleton
cell leading edge
cytoplasm
cytosol
extrinsic component of cytoplasmic side of plasma membrane
mitochondrion
nuclear membrane
nucleolus
nucleoplasm
nucleus
perinuclear region of cytoplasm
actin monomer binding
ATP binding
DNA binding
magnesium ion binding
manganese ion binding
mitogen-activated protein kinase binding
nicotinate-nucleotide adenylyltransferase activity
non-membrane spanning protein tyrosine kinase activity
proline-rich region binding
protein C-terminus binding
protein kinase activity
protein kinase C binding
protein tyrosine kinase activity
SH3 domain binding
syntaxin binding
actin cytoskeleton organization
actin filament branching
activated T cell proliferation
activation of protein kinase C activity
alpha-beta T cell differentiation
autophagy
axon guidance
B cell proliferation involved in immune response
B cell receptor signaling pathway
B-1 B cell homeostasis
Bergmann glial cell differentiation
blood coagulation
cell cycle arrest
cellular protein modification process
cellular response to DNA damage stimulus
cellular response to dopamine
cellular response to hydrogen peroxide
cellular response to lipopolysaccharide
cellular response to oxidative stress
cerebellum morphogenesis
collateral sprouting
DNA damage induced protein phosphorylation
DNA repair
double-strand break repair
double-strand break repair via homologous recombination
epidermal growth factor receptor signaling pathway
establishment of protein localization
Fc-gamma receptor signaling pathway involved in phagocytosis
innate immune response
intrinsic apoptotic signaling pathway in response to DNA damage
microspike assembly
mismatch repair
mitochondrial depolarization
mitotic nuclear division
muscle cell differentiation
negative regulation of BMP signaling pathway
negative regulation of cell-cell adhesion
negative regulation of cellular senescence
negative regulation of endothelial cell apoptotic process
negative regulation of ERK1 and ERK2 cascade
negative regulation of I-kappaB kinase/NF-kappaB signaling
negative regulation of mitotic cell cycle
negative regulation of phospholipase C activity
negative regulation of protein serine/threonine kinase activity
negative regulation of ubiquitin-protein transferase activity
neuromuscular process controlling balance
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
platelet-derived growth factor receptor-beta signaling pathway
positive regulation of actin filament binding
positive regulation of apoptotic process
positive regulation of cytosolic calcium ion concentration
positive regulation of ERK1 and ERK2 cascade
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of interferon-gamma secretion
positive regulation of interleukin-2 secretion
positive regulation of microtubule binding
positive regulation of mitotic cell cycle
positive regulation of muscle cell differentiation
positive regulation of neuron death
positive regulation of osteoblast proliferation
positive regulation of oxidoreductase activity
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of protein phosphorylation
positive regulation of release of sequestered calcium ion into cytosol
positive regulation of Wnt signaling pathway, planar cell polarity pathway
protein autophosphorylation
regulation of actin cytoskeleton organization
regulation of actin cytoskeleton reorganization
regulation of autophagy
regulation of axon extension
regulation of cell adhesion
regulation of cell motility
regulation of cell proliferation
regulation of endocytosis
regulation of extracellular matrix organization
regulation of microtubule polymerization
regulation of response to DNA damage stimulus
regulation of transcription, DNA-templated
response to oxidative stress
signal transduction in response to DNA damage
small GTPase mediated signal transduction
spleen development
substrate adhesion-dependent cell spreading
thymus development
transitional one stage B cell differentiation
Gene Ontology Biological Process:
actin cytoskeleton organization
actin filament branching
activated T cell proliferation
activation of protein kinase C activity
alpha-beta T cell differentiation
autophagy
axon guidance
B-1 B cell homeostasis
B cell proliferation involved in immune response
B cell receptor signaling pathway
Bergmann glial cell differentiation
blood coagulation
cell cycle arrest
cellular protein modification process
cellular response to DNA damage stimulus
cellular response to dopamine
cellular response to hydrogen peroxide
cellular response to lipopolysaccharide
cellular response to oxidative stress
cerebellum morphogenesis
collateral sprouting
DNA damage induced protein phosphorylation
DNA repair
double-strand break repair
double-strand break repair via homologous recombination
epidermal growth factor receptor signaling pathway
establishment of protein localization
Fc-gamma receptor signaling pathway involved in phagocytosis
innate immune response
intrinsic apoptotic signaling pathway in response to DNA damage
microspike assembly
mismatch repair
mitochondrial depolarization
mitotic nuclear division
muscle cell differentiation
negative regulation of BMP signaling pathway
negative regulation of cell-cell adhesion
negative regulation of cellular senescence
negative regulation of endothelial cell apoptotic process
negative regulation of ERK1 and ERK2 cascade
negative regulation of I-kappaB kinase/NF-kappaB signaling
negative regulation of mitotic cell cycle
negative regulation of phospholipase C activity
negative regulation of protein serine/threonine kinase activity
negative regulation of ubiquitin-protein transferase activity
neuromuscular process controlling balance
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
platelet-derived growth factor receptor-beta signaling pathway
positive regulation of actin filament binding
positive regulation of apoptotic process
positive regulation of cytosolic calcium ion concentration
positive regulation of ERK1 and ERK2 cascade
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of interferon-gamma secretion
positive regulation of interleukin-2 secretion
positive regulation of microtubule binding
positive regulation of mitotic cell cycle
positive regulation of muscle cell differentiation
positive regulation of neuron death
positive regulation of osteoblast proliferation
positive regulation of oxidoreductase activity
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of protein phosphorylation
positive regulation of release of sequestered calcium ion into cytosol
positive regulation of Wnt signaling pathway, planar cell polarity pathway
protein autophosphorylation
regulation of actin cytoskeleton organization
regulation of actin cytoskeleton reorganization
regulation of autophagy
regulation of axon extension
regulation of cell adhesion
regulation of cell motility
regulation of cell proliferation
regulation of endocytosis
regulation of extracellular matrix organization
regulation of microtubule polymerization
regulation of response to DNA damage stimulus
regulation of transcription, DNA-templated
response to oxidative stress
signal transduction in response to DNA damage
small GTPase mediated signal transduction
spleen development
substrate adhesion-dependent cell spreading
thymus development
transitional one stage B cell differentiation
Gene Ontology Molecular Function:
actin monomer binding
ATP binding
DNA binding
magnesium ion binding
manganese ion binding
mitogen-activated protein kinase binding
nicotinate-nucleotide adenylyltransferase activity
non-membrane spanning protein tyrosine kinase activity
proline-rich region binding
protein C-terminus binding
protein kinase activity
protein kinase C binding
protein tyrosine kinase activity
SH3 domain binding
syntaxin binding
Gene Ontology Cellular Component:
actin cytoskeleton
cell leading edge
cytoplasm
cytosol
extrinsic component of cytoplasmic side of plasma membrane
mitochondrion
nuclear membrane
nucleolus
nucleoplasm
nucleus
perinuclear region of cytoplasm
Keywords:
3D-structure
ATP-binding
Acetylation
Alternative splicing
Apoptosis
Autophagy
Cell adhesion
Chromosomal rearrangement
Complete proteome
Cytoplasm
Cytoskeleton
DNA damage
DNA repair
DNA-binding
Endocytosis
Kinase
Lipoprotein
Magnesium
Manganese
Membrane
Metal-binding
Mitochondrion
Myristate
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
SH2 domain
SH3 domain
Transferase
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
Q8IZP0; Q9NYB9; P10275; Q4KMG0; O35158; P46108; P46109; P35222; P00533; P04626; Q14315; P05107; P10721; Q38SD2; Q92918; Q7Z434; O43196; P15941; P16333; O43900; Q13905; Q86UR5; Q13671; P31947; Q15464; O75751; P37840; Q9BX66; O60504-2; Q07890; P12931; Q9Y4G6; P11387; P15498; P63104

Publication

PubMed ID:
3021337 2687768 7665185 15164053 15489334 2825022 6191223 7545908 2542016 2183353 9037071 9144171 9461559 10194451 10391250 10325413 11114745 11374898 12379650 11971963 12475393 12531427 12672821 12775773 15302586 15556646 15031292 15686624 15886098 15657060 15696159 17081983 16648821 16912036 16943190 16678104 17306540 17623672 18161990 18328268 18945674 18775435 18691976 18669648 18182299 19413330 19891780 19369195 19381274 19690332 20417104 20861316 20841568 21269460 23006999 24275569 1505033 1281542 7892170 8590002 9698566 12384576 12654251 16424036 16543148 16640460 17164530 17452790 19906645 20357770 17344846