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Overview

Uniprot ID	P00519
Protein Name	Tyrosine-protein kinase ABL1
Gene Name	ABL1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
689	RSPHLWKKSSTLTSS

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 (PubMed:22810897). 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' (PubMed:28428613). 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 also acts 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. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). 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). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity)

Protein Sequence

10 MLEICLKLVG 20 CKSKKGLSSS 30 SSCYLEEALQ 40 RPVASDFEPQ 50 GLSEAARWNS 60 KENLLAGPSE 70 NDPNLFVALY 80 DFVASGDNTL 90 SITKGEKLRV 100 LGYNHNGEWC 110 EAQTKNGQGW 120 VPSNYITPVN 130 SLEKHSWYHG 140 PVSRNAAEYL 150 LSSGINGSFL 160 VRESESSPGQ 170 RSISLRYEGR 180 VYHYRINTAS 190 DGKLYVSSES 200 RFNTLAELVH 210 HHSTVADGLI 220 TTLHYPAPKR 230 NKPTVYGVSP 240 NYDKWEMERT 250 DITMKHKLGG 260 GQYGEVYEGV 270 WKKYSLTVAV 280 KTLKEDTMEV 290 EEFLKEAAVM 300 KEIKHPNLVQ 310 LLGVCTREPP 320 FYIITEFMTY 330 GNLLDYLREC 340 NRQEVNAVVL 350 LYMATQISSA 360 MEYLEKKNFI 370 HRDLAARNCL 380 VGENHLVKVA 390 DFGLSRLMTG 400 DTYTAHAGAK 410 FPIKWTAPES 420 LAYNKFSIKS 430 DVWAFGVLLW 440 EIATYGMSPY 450 PGIDLSQVYE 460 LLEKDYRMER 470 PEGCPEKVYE 480 LMRACWQWNP 490 SDRPSFAEIH 500 QAFETMFQES 510 SISDEVEKEL 520 GKQGVRGAVS 530 TLLQAPELPT 540 KTRTSRRAAE 550 HRDTTDVPEM 560 PHSKGQGESD 570 PLDHEPAVSP 580 LLPRKERGPP 590 EGGLNEDERL 600 LPKDKKTNLF 610 SALIKKKKKT 620 APTPPKRSSS 630 FREMDGQPER 640 RGAGEEEGRD 650 ISNGALAFTP 660 LDTADPAKSP 670 KPSNGAGVPN 680 GALRESGGSG 690 FRSPHLWKKS 700 STLTSSRLAT 710 GEEEGGGSSS 720 KRFLRSCSAS 730 CVPHGAKDTE 740 WRSVTLPRDL 750 QSTGRQFDSS 760 TFGGHKSEKP 770 ALPRKRAGEN 780 RSDQVTRGTV 790 TPPPRLVKKN 800 EEAADEVFKD 810 IMESSPGSSP 820 PNLTPKPLRR 830 QVTVAPASGL 840 PHKEEAGKGS 850 ALGTPAAAEP 860 VTPTSKAGSG 870 APGGTSKGPA 880 EESRVRRHKH 890 SSESPGRDKG 900 KLSRLKPAPP 910 PPPAASAGKA 920 GGKPSQSPSQ 930 EAAGEAVLGA 940 KTKATSLVDA 950 VNSDAAKPSQ 960 PGEGLKKPVL 970 PATPKPQSAK 980 PSGTPISPAP 990 VPSTLPSASS 1000 ALAGDQPSST 1010 AFIPLISTRV 1020 SLRKTRQPPE 1030 RIASGAITKG 1040 VVLDSTEALC 1050 LAISRNSEQM 1060 ASHSAVLEAG 1070 KNLYTFCVSY 1080 VDSIQQMRNK 1090 FAFREAINKL 1100 ENNLRELQIC 1110 PATAGSGPAA 1120 TQDFSKLLSS 1130 VKEISDIVQR

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0015629	actin cytoskeleton
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0030425	dendrite
Cellular Component	GO:0098978	glutamatergic synapse
Cellular Component	GO:0030426	growth cone
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:0043025	neuronal cell body
Cellular Component	GO:0016604	nuclear body
Cellular Component	GO:0031965	nuclear membrane
Cellular Component	GO:0005730	nucleolus
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0048471	perinuclear region of cytoplasm
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0098794	postsynapse
Cellular Component	GO:0014069	postsynaptic density
Cellular Component	GO:0032991	protein-containing complex
Cellular Component	GO:0001726	ruffle
Molecular Function	GO:0051015	actin filament binding
Molecular Function	GO:0003785	actin monomer binding
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0000405	bubble DNA binding
Molecular Function	GO:0070097	delta-catenin binding
Molecular Function	GO:0003677	DNA binding
Molecular Function	GO:0008047	enzyme activator activity
Molecular Function	GO:0019899	enzyme binding
Molecular Function	GO:0046875	ephrin receptor binding
Molecular Function	GO:0000400	four-way junction DNA binding
Molecular Function	GO:0016301	kinase activity
Molecular Function	GO:0000287	magnesium ion binding
Molecular Function	GO:0030145	manganese ion binding
Molecular Function	GO:0051019	mitogen-activated protein kinase binding
Molecular Function	GO:0038191	neuropilin binding
Molecular Function	GO:0004515	nicotinate-nucleotide adenylyltransferase activity
Molecular Function	GO:0004715	non-membrane spanning protein tyrosine kinase activity
Molecular Function	GO:0001784	phosphotyrosine residue binding
Molecular Function	GO:0070064	proline-rich region binding
Molecular Function	GO:0004672	protein kinase activity
Molecular Function	GO:0005080	protein kinase C binding
Molecular Function	GO:0043539	protein serine/threonine kinase activator activity
Molecular Function	GO:0004674	protein serine/threonine kinase activity
Molecular Function	GO:0004713	protein tyrosine kinase activity
Molecular Function	GO:1990837	sequence-specific double-stranded DNA binding
Molecular Function	GO:0042169	SH2 domain binding
Molecular Function	GO:0019905	syntaxin binding
Molecular Function	GO:0003713	transcription coactivator activity
Biological Process	GO:0030036	actin cytoskeleton organization
Biological Process	GO:0030041	actin filament polymerization
Biological Process	GO:0008306	associative learning
Biological Process	GO:0006914	autophagy
Biological Process	GO:0060038	cardiac muscle cell proliferation
Biological Process	GO:0007155	cell adhesion
Biological Process	GO:1903351	cellular response to dopamine
Biological Process	GO:0070301	cellular response to hydrogen peroxide
Biological Process	GO:0034599	cellular response to oxidative stress
Biological Process	GO:0071560	cellular response to transforming growth factor beta stimulus
Biological Process	GO:0071103	DNA conformation change
Biological Process	GO:0006974	DNA damage response
Biological Process	GO:0043542	endothelial cell migration
Biological Process	GO:0048013	ephrin receptor signaling pathway
Biological Process	GO:0007173	epidermal growth factor receptor signaling pathway
Biological Process	GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
Biological Process	GO:0007229	integrin-mediated signaling pathway
Biological Process	GO:0035556	intracellular signal transduction
Biological Process	GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
Biological Process	GO:0006298	mismatch repair
Biological Process	GO:0051882	mitochondrial depolarization
Biological Process	GO:0000278	mitotic cell cycle
Biological Process	GO:0051450	myoblast proliferation
Biological Process	GO:2000042	negative regulation of double-strand break repair via homologous recombination
Biological Process	GO:1900272	negative regulation of long-term synaptic potentiation
Biological Process	GO:0051444	negative regulation of ubiquitin-protein transferase activity
Biological Process	GO:0038189	neuropilin signaling pathway
Biological Process	GO:0030845	phospholipase C-inhibiting G protein-coupled receptor signaling pathway
Biological Process	GO:0035791	platelet-derived growth factor receptor-beta signaling pathway
Biological Process	GO:1903210	podocyte apoptotic process
Biological Process	GO:0043065	positive regulation of apoptotic process
Biological Process	GO:1905555	positive regulation of blood vessel branching
Biological Process	GO:0090050	positive regulation of cell migration involved in sprouting angiogenesis
Biological Process	GO:0007204	positive regulation of cytosolic calcium ion concentration
Biological Process	GO:1900006	positive regulation of dendrite development
Biological Process	GO:0010595	positive regulation of endothelial cell migration
Biological Process	GO:1903905	positive regulation of establishment of T cell polarity
Biological Process	GO:1903055	positive regulation of extracellular matrix organization
Biological Process	GO:0048146	positive regulation of fibroblast proliferation
Biological Process	GO:0051894	positive regulation of focal adhesion assembly
Biological Process	GO:0043525	positive regulation of neuron apoptotic process
Biological Process	GO:0141214	positive regulation of phospholipase C/protein kinase C signal transduction
Biological Process	GO:0051496	positive regulation of stress fiber assembly
Biological Process	GO:1900026	positive regulation of substrate adhesion-dependent cell spreading
Biological Process	GO:2000406	positive regulation of T cell migration
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0045907	positive regulation of vasoconstriction
Biological Process	GO:1904518	protein localization to cytoplasmic microtubule plus-end
Biological Process	GO:0036211	protein modification process
Biological Process	GO:0032956	regulation of actin cytoskeleton organization
Biological Process	GO:0010506	regulation of autophagy
Biological Process	GO:0030516	regulation of axon extension
Biological Process	GO:0032489	regulation of Cdc42 protein signal transduction
Biological Process	GO:0030155	regulation of cell adhesion
Biological Process	GO:0051726	regulation of cell cycle
Biological Process	GO:2000145	regulation of cell motility
Biological Process	GO:0006355	regulation of DNA-templated transcription
Biological Process	GO:0030100	regulation of endocytosis
Biological Process	GO:1902036	regulation of hematopoietic stem cell differentiation
Biological Process	GO:0031113	regulation of microtubule polymerization
Biological Process	GO:1905244	regulation of modification of synaptic structure
Biological Process	GO:0099150	regulation of postsynaptic specialization assembly
Biological Process	GO:0045580	regulation of T cell differentiation
Biological Process	GO:0034976	response to endoplasmic reticulum stress
Biological Process	GO:0071871	response to epinephrine
Biological Process	GO:0006979	response to oxidative stress
Biological Process	GO:0009410	response to xenobiotic stimulus
Biological Process	GO:0042770	signal transduction in response to DNA damage
Biological Process	GO:0097706	vascular endothelial cell response to oscillatory fluid shear stress

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.