Names & Taxonomy
- Uniprot ID:
- P42684
- Entry Name:
- ABL2_HUMAN
- Status:
- reviewed
- Protein Names:
- Abelson tyrosine-protein kinase 2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG)
- Gene Names:
- ABL2 ABLL ARG
- Gene Names Primary:
- ABL2
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1182
- Sequence:
- MGQQVGRVGEAPGLQQPQPRGIRGSSAARPSGRRRDPAGRTTETGFNIFTQHDHFASCVEDGFEGDKTGGSSPEALHRPYGCDVEPQALNEAIRWSSKENLLGATESDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNQNGEWSEVRSKNGQGWVPSNYITPVNSLEKHSWYHGPVSRSAAEYLLSSLINGSFLVRESESSPGQLSISLRYEGRVYHYRINTTADGKVYVTAESRFSTLAELVHHHSTVADGLVTTLHYPAPKCNKPTVYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTLEPPFYIVTEYMPYGNLLDYLRECNREEVTAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHVVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNTFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYDLLEKGYRMEQPEGCPPKVYELMRACWKWSPADRPSFAETHQAFETMFHDSSISEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQASSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPAQQEANLVPPKCYGGSFAQRNLCNDDGGGGGGSGTAGGGWSGITGFFTPRLIKKTLGLRAGKPTASDDTSKPFPRSNSTSSMSSGLPEQDRMAMTLPRNCQRSKLQLERTVSTSSQPEENVDRANDMLPKKSEESAAPSRERPKAKLLPRGATALPLRTPSGDLAITEKDPPGVGVAGVAAAPKGKEKNGGARLGMAGVPEDGEQPGWPSPAKAAPVLPTTHNHKVPVLISPTLKHTPADVQLIGTDSQGNKFKLLSEHQVTSSGDKDRPRRVKPKCAPPPPPVMRLLQHPSICSDPTEEPTALTAGQSTSETQEGGKKAALGAVPISGKAGRPVMPPPQVPLPTSSISPAKMANGTAGTKVALRKTKQAAEKISADKISKEALLECADLLSSALTEPVPNSQLVDTGHQLLDYCSGYVDCIPQTRNKFAFREAVSKLELSLQELQVSSAAAGVPGTNPVLNNLLSCVQEISDVVQR
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm, cytoskeleton.
Function
- Function:
- Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 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. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activity (By similarity).
- Active Site:
- ACT_SITE 409 409 Proton acceptor.
- Cross Reference Drug Bank:
- DB00171 DB01254
- Gene Ontology Go:
- actin cytoskeleton
cytosol
extrinsic component of cytoplasmic side of plasma membrane
actin filament binding
actin monomer binding
ATP binding
magnesium ion binding
manganese ion binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein tyrosine kinase activity
axon guidance
cell adhesion
cellular protein modification process
cellular response to retinoic acid
innate immune response
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of cytosolic calcium ion concentration
positive regulation of neuron projection development
positive regulation of oxidoreductase activity
positive regulation of phospholipase C activity
regulation of actin cytoskeleton reorganization
regulation of autophagy
regulation of cell adhesion
regulation of cell motility
regulation of cell proliferation
regulation of endocytosis
signal transduction
transmembrane receptor protein tyrosine kinase signaling pathway - Gene Ontology Biological Process:
- axon guidance
cell adhesion
cellular protein modification process
cellular response to retinoic acid
innate immune response
peptidyl-tyrosine autophosphorylation
peptidyl-tyrosine phosphorylation
positive regulation of cytosolic calcium ion concentration
positive regulation of neuron projection development
positive regulation of oxidoreductase activity
positive regulation of phospholipase C activity
regulation of actin cytoskeleton reorganization
regulation of autophagy
regulation of cell adhesion
regulation of cell motility
regulation of cell proliferation
regulation of endocytosis
signal transduction
transmembrane receptor protein tyrosine kinase signaling pathway - Gene Ontology Molecular Function:
- actin filament binding
actin monomer binding
ATP binding
magnesium ion binding
manganese ion binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein tyrosine kinase activity - Gene Ontology Cellular Component:
- actin cytoskeleton
cytosol
extrinsic component of cytoplasmic side of plasma membrane - Keywords:
- 3D-structure
ATP-binding
Acetylation
Alternative splicing
Cell adhesion
Complete proteome
Cytoplasm
Cytoskeleton
Kinase
Lipoprotein
Magnesium
Manganese
Metal-binding
Myristate
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
SH2 domain
SH3 domain
Transferase
Tyrosine-protein kinase
Ubl conjugation - Interacts With:
- Q8IZP0; P46108; P00533; P04626; P21860; Q15303; P06241; P62993; P10721; P16333; P27986; P19174; Q13671; Q15637; P12931