LipidDB ID

LipidDB-9606-00697

Entry Name

UniProt Accession

P00519; A3KFJ3; Q13869; Q13870; Q16133; Q17R61; Q45F09;

Theoretical PI

8.84

Molecular Weight

122872.56

Genbank Protein ID

AAA51561.1; CAA34438.1; AAB60394.1; AAB60393.1; AAB60393.1; AAZ38718.1; CAM45752.1; CAM45752.1; CAM45754.1; CAM45756.1; CAM45756.1; EAW87948.1; AAI17452.1; AAD14034.1;

Genbank Nucleotide ID

M14752; X16416; U07563; U07563; U07561; DQ145721; AL359092; AL161733; AL161733; AL161733; AL359092; CH471090; BC117451; S69223;

Protein Name

Tyrosine-protein kinase ABL1

Protein Synonyms/Alias

2.7.10.2; Abelson murine leukemia viral oncogene homolog 1; Abelson tyrosine-protein kinase 1; Proto-oncogene c-Abl; p150;

Gene Name

ABL1

Gene Synonyms/Alias

ABL; JTK7;

Created Date

21-JUL-1986

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Fujita A, Shishido T, Yuan Y, Inamoto E, Narumiya S, Watanabe N. Imatinibmesylate (STI571)-induced cell edge translocation of kinase-active andkinase-defective Abelson kinase: requirements of myristoylation and src homology 3 domain. Mol Pharmacol. 2009 Jan;75(1):75-84. doi: 10.1124/mol.108.051706. Epub 2008 Oct 3.[PMID:18835981]
[2] Jackson P, Baltimore D. N-terminal mutations activate the leukemogenicpotential of the myristoylated form of c-abl. EMBO J. 1989 Feb;8(2):449-56.[PMID:2542016]
[3] Choi Y, Seeliger MA, Panjarian SB, Kim H, Deng X, Sim T, Couch B, Koleske AJ, Smithgall TE, Gray NS. N-myristoylated c-Abl tyrosine kinase localizes to theendoplasmic reticulum upon binding to an allosteric inhibitor. J Biol Chem. 2009 Oct 16;284(42):29005-14. doi: 10.1074/jbc.M109.026633. Epub 2009 Aug 13. PubMedPMID: 19679652; PubMed Central PMCID: PMC2781447.[PMID:19679652]

Functional Description

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.

Sequence Annotation

Domain: 61 121 SH3.
Domain: 127 217 SH2.
Domain: 242 493 Protein kinase.
Nucleotide-binding: 248 256 ATP.
Nucleotide-binding: 316 322 ATP.
Region: 1 60 CAP.
Region: 869 968 DNA-binding.
Region: 953 1130 F-actin-binding.
Motif: 381 405 Kinase activation loop.
Motif: 605 609 Nuclear localization signal 1.
Motif: 709 715 Nuclear localization signal 2.
Motif: 762 769 Nuclear localization signal 3.
Motif: 1090 1100 Nuclear export signal.
Active site: 363 363 Proton acceptor.
Binding site: 271 271 ATP.
Functional site: 26 27 Breakpoint for translocation to form BCR-ABL oncogene.
Modified residue: 50 50 Phosphoserine.
Modified residue: 70 70 Phosphotyrosine; by autocatalysis.
Modified residue: 115 115 Phosphotyrosine.
Modified residue: 128 128 Phosphotyrosine.
Modified residue: 139 139 Phosphotyrosine.
Modified residue: 172 172 Phosphotyrosine.
Modified residue: 185 185 Phosphotyrosine.
Modified residue: 215 215 Phosphotyrosine.
Modified residue: 226 226 Phosphotyrosine; by autocatalysis.
Modified residue: 253 253 Phosphotyrosine.
Modified residue: 257 257 Phosphotyrosine.
Modified residue: 264 264 Phosphotyrosine.
Modified residue: 392 392 Phosphothreonine.
Modified residue: 393 393 Phosphotyrosine; by autocatalysis andSRC-type Tyr-kinases.
Modified residue: 394 394 Phosphothreonine.
Modified residue: 446 446 Phosphoserine.
Modified residue: 469 469 Phosphotyrosine.
Modified residue: 569 569 Phosphoserine.
Modified residue: 613 613 Phosphothreonine.
Modified residue: 618 618 Phosphoserine; by PAK2.
Modified residue: 619 619 Phosphoserine; by PAK2.
Modified residue: 620 620 Phosphoserine.
Modified residue: 659 659 Phosphoserine.
Modified residue: 683 683 Phosphoserine.
Modified residue: 711 711 N6-acetyllysine; by EP300.
Modified residue: 718 718 Phosphoserine.
Modified residue: 735 735 Phosphothreonine.
Modified residue: 781 781 Phosphothreonine.
Modified residue: 805 805 Phosphoserine.
Modified residue: 809 809 Phosphoserine.
Modified residue: 814 814 Phosphothreonine.
Modified residue: 844 844 Phosphothreonine.
Modified residue: 852 852 Phosphothreonine.
Modified residue: 855 855 Phosphoserine.
Modified residue: 917 917 Phosphoserine.
Modified residue: 919 919 Phosphoserine.
Modified residue: 936 936 Phosphoserine.
Modified residue: 949 949 Phosphoserine.
Modified residue: 977 977 Phosphoserine.

Protein Length

1130 AA.

Protein Sequence
(Isoform 2)

FASTA
(Isoform 2)

Gene Ontology

GO:0015629; C:actin cytoskeleton; TAS:UniProtKB
GO:0031252; C:cell leading edge; IEA:Ensembl
GO:0005737; C:cytoplasm; TAS:UniProtKB
GO:0005829; C:cytosol; IDA:MGI
GO:0016020; C:membrane; IEA:UniProtKB-KW
GO:0005739; C:mitochondrion; NAS:ParkinsonsUK-UCL
GO:0005730; C:nucleolus; IDA:MGI
GO:0005634; C:nucleus; IDA:UniProtKB
GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB
GO:0003785; F:actin monomer binding; TAS:UniProtKB
GO:0005524; F:ATP binding; IDA:UniProtKB
GO:0003677; F:DNA binding; NAS:UniProtKB
GO:0000287; F:magnesium ion binding; IDA:UniProtKB
GO:0030145; F:manganese ion binding; IDA:UniProtKB
GO:0051019; F:mitogen-activated protein kinase binding; IPI:BHF-UCL
GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; TAS:UniProtKB
GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB
GO:0070064; F:proline-rich region binding; IDA:UniProtKB
GO:0008022; F:protein C-terminus binding; IPI:UniProtKB
GO:0004672; F:protein kinase activity; IDA:MGI
GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB
GO:0017124; F:SH3 domain binding; IPI:UniProtKB
GO:0019905; F:syntaxin binding; IPI:UniProtKB
GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB
GO:0006914; P:autophagy; IEA:UniProtKB-KW
GO:0007411; P:axon guidance; TAS:Reactome
GO:0007596; P:blood coagulation; TAS:Reactome
GO:0007155; P:cell adhesion; IEA:UniProtKB-KW
GO:0007050; P:cell cycle arrest; TAS:ParkinsonsUK-UCL
GO:0006464; P:cellular protein modification process; NAS:UniProtKB
GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB
GO:1903351; P:cellular response to dopamine; TAS:ParkinsonsUK-UCL
GO:0034599; P:cellular response to oxidative stress; TAS:ParkinsonsUK-UCL
GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB
GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome
GO:0045087; P:innate immune response; TAS:Reactome
GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; TAS:UniProtKB
GO:0006298; P:mismatch repair; TAS:ProtInc
GO:0051882; P:mitochondrial depolarization; TAS:ParkinsonsUK-UCL
GO:0007067; P:mitotic nuclear division; TAS:ParkinsonsUK-UCL
GO:0042692; P:muscle cell differentiation; TAS:Reactome
GO:1900275; P:negative regulation of phospholipase C activity; IMP:MGI
GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:BHF-UCL
GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; TAS:ParkinsonsUK-UCL
GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB
GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl
GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB
GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:MGI
GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome
GO:0051353; P:positive regulation of oxidoreductase activity; IDA:BHF-UCL
GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB
GO:2000249; P:regulation of actin cytoskeleton reorganization; TAS:UniProtKB
GO:0010506; P:regulation of autophagy; TAS:UniProtKB
GO:0030155; P:regulation of cell adhesion; TAS:UniProtKB
GO:2000145; P:regulation of cell motility; TAS:UniProtKB
GO:0030100; P:regulation of endocytosis; TAS:UniProtKB
GO:2001020; P:regulation of response to DNA damage stimulus; IDA:UniProtKB
GO:0006355; P:regulation of transcription, DNA-templated; TAS:ProtInc
GO:0006979; P:response to oxidative stress; IGI:MGI
GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB

Interpro

InterPro; IPR015015; F-actin_binding
InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom
InterPro; IPR000980; SH2
InterPro; IPR001452; SH3_domain
InterPro; IPR008266; Tyr_kinase_AS
InterPro; IPR020635; Tyr_kinase_cat_dom

Pfam

Pfam; PF08919; F_actin_bind;
Pfam; PF07714; Pkinase_Tyr;
Pfam; PF00017; SH2;
Pfam; PF00018; SH3_1;

SMART

SMART; SM00808; FABD;
SMART; SM00252; SH2;
SMART; SM00326; SH3;
SMART; SM00219; TyrKc;

PROSITE

PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00109; PROTEIN_KINASE_TYR;
PROSITE; PS50001; SH2;
PROSITE; PS50002; SH3;

PRINTS

PRINTS; PR00401; SH2DOMAIN;
PRINTS; PR00109; TYRKINASE;