General Information of Binding Target of SBP (BTS) (ID: ST00108)
BTS Name
Tyrosine-protein kinase ABL1
Synonyms
EC 2.7.10.2; Abelson murine leukemia viral oncogene homolog 1; Abelson tyrosine-protein kinase 1; Proto-oncogene c-Abl; p150
BTS Type
Protein
Family
Protein kinase superfamily;
Tyr protein kinase family;
ABL subfamily
Gene Name
ABL1
Organism
Homo sapiens (Human)
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' 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. Regulates T-cell differentiation in a TBX21-dependent manner. Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity).
UniProt ID
P00519
UniProt Entry
ABL1_HUMAN
PFam
PF08919 ; PF07714 ; PF00017 ; PF00018
Gene ID
25
Sequence
MLEICLKLVGCKSKKGLSSSSSCYLEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSE
NDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVN
SLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTAS
DGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERT
DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQ
LLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFI
HRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKS
DVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP
SDRPSFAEIHQAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAE
HRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLF
SALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSP
KPSNGAGVPNGALRESGGSGFRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSAS
CVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTV
TPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGS
ALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPP
PPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPGEGLKKPVL
PATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPE
RIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNK
FAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR
Sequence Length
1130
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Cyclotide anti-Abl MTAbl06 Research Inhibitor N.A. Chronic myeloid leukaemia [ICD-11: 2B33.2]
SBP Info
[1]
Cyclotide anti-Abl MTAbl07 Research Inhibitor N.A. Chronic myeloid leukaemia [ICD-11: 2B33.2]
SBP Info
[1]
Cyclotide anti-Abl MTAbl13 Research Inhibitor N.A. Chronic myeloid leukaemia [ICD-11: 2B33.2]
SBP Info
[1]
Monobody anti-Abl HA4 Research Inhibitor Kd: 7 nM Research tool
SBP Info
[2], [3], [4]
Monobody anti-Abl-SH2 7c12 Research Inhibitor Kd: 50 nM Research tool
SBP Info
[5], [6], [7]
Monobody anti-Abl-SH2 AL2 Research Binder Kd: 70 nM Tools for identifying the unanticipated mode of monobody-target interactions
SBP Info
[7]
Monobody anti-Abl-SH2 AL38 Research Binder Kd: 11 nM Tools for identifying the unanticipated mode of monobody-target interactions
SBP Info
[7]
Monobody anti-Abl-SH2 AS15 Research Binder Kd: 9 nM Tools for identifying the unanticipated mode of monobody-target interactions
SBP Info
[7]
Monobody anti-Abl-SH2 AS25 Research Inhibitor Kd: 20 nM Research tool
SBP Info
[5], [6], [7]
Monobody anti-Abl-SH2 AS27 Research Inhibitor Kd: 3.7 nM Research tool
SBP Info
[5], [6], [7]
Monobody anti-Abl-SH2 GG10 Research Inhibitor Kd: 900 nM Chronic myeloid leukaemia [ICD-11: 2B33.2]
SBP Info
[6]
Monobody anti-Abl-SH2 GG3 Research Inhibitor Kd: 2540 nM Chronic myeloid leukaemia [ICD-11: 2B33.2]
SBP Info
[6]
Monobody anti-Abl-SH2 HA10 Research Inhibitor N.A. Research tool
SBP Info
[3], [8]
Monobody anti-Abl-SH2 HA16 Research Inhibitor N.A. Research tool
SBP Info
[3], [8]
Monobody anti-Abl-SH2 HA18 Research Inhibitor N.A. Research tool
SBP Info
[3], [8]
Monobody anti-Abl-SH2 SH13 Research Binder Kd: 6800 nM Tools for identifying the unanticipated mode of monobody-target interactions
SBP Info
[7]
References
1 Design of substrate-based BCR-ABL kinase inhibitors using the cyclotide scaffold. Sci Rep. 2015 Aug 12;5:12974.
2 Development of light-responsive protein binding in the monobody non-immunoglobulin scaffold. Nat Commun. 2020 Aug 13;11(1):4045.
3 A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain. Nat Struct Mol Biol. 2010 Apr;17(4):519-27.
4 Monobodies as possible next-generation protein therapeutics - a perspective. Swiss Med Wkly. 2017 Nov 20;147:w14545.
5 Monobodies and other synthetic binding proteins for expanding protein science. Protein Sci. 2017 May;26(5):910-924.
6 Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface. J Biol Chem. 2016 Apr 15;291(16):8836-47.
7 Teaching an old scaffold new tricks: monobodies constructed using alternative surfaces of the FN3 scaffold. J Mol Biol. 2012 Jan 13;415(2):393-405.
8 The fibronectin type III domain as a scaffold for novel binding proteins. J Mol Biol. 1998 Dec 11;284(4):1141-51.