Tyrosine-protein kinase ABL2
Also known as: ABL2, ABLL, ARG
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 also acts 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. 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 (By similarity).
Classification
- Family (Pfam)
- PF08919 F_actin_bind, PF07714 PK_Tyr_Ser-Thr, PF00017 SH2, PF00018 SH3_1
- InterPro
- ABL_SH2, F-actin-binding, Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tyr_kinase_AS, Tyr_kinase_cat_dom
- Functional cluster
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 9
- 2ECD NMR
- 2KK1 NMR
- 2XYN X-ray 2.81A
- 3GVU X-ray 2.05A
- 3HMI X-ray 1.65A
- 3ULR X-ray 1.65A
- 4EIH X-ray 1.20A
- 5NP3 X-ray 2.00A
- 5NP5 X-ray 1.40A
A predicted model is available from AlphaFold.
Gene Ontology · 33
- GO:0015629 actin cytoskeleton
- GO:0005829 cytosol
- GO:0005886 plasma membrane
- GO:0051015 actin filament binding
- GO:0003785 actin monomer binding
- GO:0005524 ATP binding
- GO:0008047 enzyme activator activity
- GO:0019899 enzyme binding
- GO:0000287 magnesium ion binding
- GO:0030145 manganese ion binding
- GO:0004715 non-membrane spanning protein tyrosine kinase activity
- GO:0001784 phosphotyrosine residue binding
- GO:0004672 protein kinase activity
- GO:0004713 protein tyrosine kinase activity
- GO:0007155 cell adhesion
- GO:0034599 cellular response to oxidative stress
- GO:0071300 cellular response to retinoic acid
- GO:0007173 epidermal growth factor receptor signaling pathway
- GO:0035640 exploration behavior
- GO:0035024 negative regulation of Rho protein signal transduction
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:1903905 positive regulation of establishment of T cell polarity
- GO:0010976 positive regulation of neuron projection development
- GO:2000406 positive regulation of T cell migration
- GO:0036211 protein modification process
- GO:0032956 regulation of actin cytoskeleton organization
- GO:0010506 regulation of autophagy
- GO:0030155 regulation of cell adhesion
- GO:2000145 regulation of cell motility
- GO:0030100 regulation of endocytosis
- GO:0007165 signal transduction
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Tyrosine-protein kinase ABL2 0.99
- Tyrosine-protein kinase ABL1 0.92
- Tyrosine-protein kinase ABL1 0.91
- Tyrosine-protein kinase transforming protein Abl 0.85
- Mitogen-activated protein kinase kinase kinase 9 0.81
- Mitogen-activated protein kinase kinase kinase 10 0.81
- Tyrosine-protein kinase transforming protein Src 0.78
- Mitogen-activated protein kinase kinase kinase 9 0.78
- Activated CDC42 kinase 1 0.78
- Tyrosine-protein kinase Src-2 0.77
- Activated CDC42 kinase 1 0.77
- Ack-related non-receptor tyrosine kinase 0.77
Co-cited proteins · studied together in the literature
- Tyrosine-protein kinase ABL2 5 shared papers
- Tyrosine-protein kinase ABL1 8 shared papers
- Src substrate cortactin 1 shared papers
- Tyrosine-protein kinase ABL1 3 shared papers
- Ras and Rab interactor 1 1 shared papers
- Proteasome subunit alpha type-7 1 shared papers
- CD44 antigen 1 shared papers
- Protein unc-119 homolog A 1 shared papers
- Adapter molecule crk 1 shared papers
Literature · 32 cited papers
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Lysozyme contamination facilitates crystallization of a heterotrimeric cortactin-Arg-lysozyme complex. Acta Crystallogr. F · 2012
- Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class. J. Med. Chem. · 2011
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- ABL tyrosine kinases: evolution of function, regulation, and specificity. Sci. Signal. · 2010
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
- Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
- Unc119 protects from Shigella infection by inhibiting the Abl family kinases. PLoS ONE · 2009
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- Abl kinases regulate autophagy by promoting the trafficking and function of lysosomal components. J. Biol. Chem. · 2008
- … and 20 more in the literature graph