LipidDB ID

LipidDB-10090-00682

Entry Name

UniProt Accession

P00520; P97896; Q61252; Q61253; Q61254; Q61255; Q61256; Q61257; Q61258; Q61259; Q61260; Q61261; Q6PCM5; Q8C1X4;

Theoretical PI

8.86

Molecular Weight

122672.54

Genbank Protein ID

AAA88241.1; BAC41088.1; AAH59260.1; AAB60451.1; AAB60451.1; AAB60450.1; AAB60450.1; AAB60448.1; AAB60448.1; AAB60449.1; AAB60449.1; CAA30411.1; CAA30412.1; CAA30413.1; CAA30414.1; AAA37136.1; AAA37137.1; AAA37138.1; AAA37134.1; AAA37135.1;

Genbank Nucleotide ID

J02995; AK090095; BC059260; U14721; U14720; U14721; U14720; U14721; U13835; U14721; U13835; X07539; X07539; X07540; X07541; M12263; M12264; M12265; M12266; K03228;

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;

Created Date

21-JUL-1986

Organism

Mus musculus (Mouse)

NCBI Taxa ID

10090

Reference

[1] 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]
[2] 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]

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-191' 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.

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: 863 961 DNA-binding.
Region: 945 1123 F-actin-binding.
Motif: 381 405 Kinase activation loop.
Motif: 605 609 Nuclear localization signal 1.
Motif: 708 714 Nuclear localization signal 2.
Motif: 761 768 Nuclear localization signal 3.
Motif: 1083 1093 Nuclear export signal.
Active site: 363 363 Proton acceptor.
Binding site: 271 271 ATP.
Modified residue: 50 50 Phosphoserine.
Modified residue: 70 70 Phosphotyrosine; by autocatalysis.
Modified residue: 185 185 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: 547 547 Phosphothreonine.
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: 658 658 Phosphoserine.
Modified residue: 682 682 Phosphoserine.
Modified residue: 710 710 N6-acetyllysine; by EP300.
Modified residue: 717 717 Phosphoserine.
Modified residue: 734 734 Phosphothreonine.
Modified residue: 803 803 Phosphoserine.
Modified residue: 807 807 Phosphoserine.
Modified residue: 812 812 Phosphothreonine.
Modified residue: 844 844 Phosphothreonine.
Modified residue: 909 909 Phosphoserine.
Modified residue: 911 911 Phosphoserine.
Modified residue: 927 927 Phosphoserine.
Modified residue: 970 970 Phosphoserine.

Protein Length

1123 AA.

Protein Sequence
(Isoform 4)

FASTA
(Isoform 4)

Gene Ontology

GO:0015629; C:actin cytoskeleton; IDA:MGI
GO:0031252; C:cell leading edge; IDA:MGI
GO:0005737; C:cytoplasm; IDA:UniProtKB
GO:0005829; C:cytosol; ISA:MGI
GO:0005739; C:mitochondrion; IEA:UniProtKB-KW
GO:0005730; C:nucleolus; IEA:Ensembl
GO:0005634; C:nucleus; IDA:UniProtKB
GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl
GO:0051015; F:actin filament binding; IDA:MGI
GO:0005524; F:ATP binding; IDA:UniProtKB
GO:0003677; F:DNA binding; IEA:UniProtKB-KW
GO:0016301; F:kinase activity; IDA:MGI
GO:0000287; F:magnesium ion binding; IDA:UniProtKB
GO:0030145; F:manganese ion binding; IDA:UniProtKB
GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC
GO:0070064; F:proline-rich region binding; ISS:UniProtKB
GO:0019904; F:protein domain specific binding; IPI:MGI
GO:0004672; F:protein kinase activity; IDA:MGI
GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB
GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB
GO:0090135; P:actin filament branching; IMP:MGI
GO:0050798; P:activated T cell proliferation; IMP:MGI
GO:0046632; P:alpha-beta T cell differentiation; IGI:MGI
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW
GO:0006914; P:autophagy; IEA:UniProtKB-KW
GO:0042100; P:B cell proliferation; IMP:MGI
GO:0002322; P:B cell proliferation involved in immune response; IMP:MGI
GO:0050853; P:B cell receptor signaling pathway; IMP:MGI
GO:0001922; P:B-1 B cell homeostasis; IMP:MGI
GO:0060020; P:Bergmann glial cell differentiation; IGI:MGI
GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB
GO:0071222; P:cellular response to lipopolysaccharide; IMP:MGI
GO:0021587; P:cerebellum morphogenesis; IGI:MGI
GO:0048668; P:collateral sprouting; IMP:MGI
GO:0006975; P:DNA damage induced protein phosphorylation; IEA:Ensembl
GO:0006281; P:DNA repair; IEA:UniProtKB-KW
GO:0007173; P:epidermal growth factor receptor signaling pathway; IGI:MGI
GO:0030035; P:microspike assembly; IDA:MGI
GO:0030514; P:negative regulation of BMP signaling pathway; IMP:MGI
GO:0022408; P:negative regulation of cell-cell adhesion; IGI:MGI
GO:2000773; P:negative regulation of cellular senescence; IGI:MGI
GO:2000352; P:negative regulation of endothelial cell apoptotic process; IGI:MGI
GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:MGI
GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:MGI
GO:0045930; P:negative regulation of mitotic cell cycle; IDA:MGI
GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IEA:Ensembl
GO:0050885; P:neuromuscular process controlling balance; IGI:MGI
GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB
GO:0006909; P:phagocytosis; IMP:MGI
GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:MGI
GO:0043065; P:positive regulation of apoptotic process; IMP:MGI
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:MGI
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IGI:MGI
GO:1902715; P:positive regulation of interferon-gamma secretion; IGI:MGI
GO:1900042; P:positive regulation of interleukin-2 secretion; IGI:MGI
GO:0045931; P:positive regulation of mitotic cell cycle; IGI:MGI
GO:1901216; P:positive regulation of neuron death; IMP:MGI
GO:0033690; P:positive regulation of osteoblast proliferation; IMP:MGI
GO:0051353; P:positive regulation of oxidoreductase activity; IEA:Ensembl
GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB
GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IGI:MGI
GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IGI:MGI
GO:0032956; P:regulation of actin cytoskeleton organization; IGI:MGI
GO:0051726; P:regulation of cell cycle; IDA:MGI
GO:2000772; P:regulation of cellular senescence; IGI:MGI
GO:1903053; P:regulation of extracellular matrix organization; IGI:MGI
GO:2001020; P:regulation of response to DNA damage stimulus; IEA:Ensembl
GO:0006979; P:response to oxidative stress; IMP:MGI
GO:0042770; P:signal transduction in response to DNA damage; ISS:UniProtKB
GO:0048536; P:spleen development; IMP:MGI
GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:MGI
GO:0048538; P:thymus development; IMP:MGI
GO:0002333; P:transitional one stage B cell differentiation; IMP:MGI

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;