Tchem ABL2 Tyrosine-protein kinase ABL2

Protein Summary

Description

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 acts also 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. This gene encodes a member of the Abelson family of nonreceptor tyrosine protein kinases. The protein is highly similar to the c-abl oncogene 1 protein, including the tyrosine kinase, SH2 and SH3 domains, and it plays a role in cytoskeletal rearrangements through its C-terminal F-actin- and microtubule-binding sequences. This gene is expressed in both normal and tumor cells, and is involved in translocation with the ets variant 6 gene in leukemia. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

Uniprot Accession IDs

• P42684
• A0M8X0
• B7UEF2
• B7UEF3
• B7UEF4
• B7UEF5
• Q5T0X6
• Q5W0C5
• Q6NZY6
• Q7Z301

Gene Name

• ABL2

Ensembl ID

• ENST00000344730
• ENSP00000339209
• ENSG00000143322
• ENST00000367623
• ENSP00000356595
• ENST00000392043
• ENSP00000375897
• ENST00000502732
• ENSP00000427562
• ENST00000504405
• ENSP00000426831
• ENST00000507173
• ENSP00000423413
• ENST00000511413
• ENSP00000424697
• ENST00000512653
• ENSP00000423578

Symbol

• ABLL
• ARG
• ARG
• ABLL

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
drug perturbation	0.99
molecular function	0.99
protein domain	0.99
kinase perturbation	0.97

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Abl Family / Abelson Tyrosine-protein Kinase 2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 98.51   (req: < 5)

Gene RIFs: 28   (req: <= 3)

Antibodies: 446   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 98.51   (req: >= 5)

Gene RIFs: 28   (req: > 3)

Antibodies: 446   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 26

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 19

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 5

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (5)

Explore Approved Drugs

1 – 5 of 5

bosutinib

ABL2Tchem Kinase

INHIBITOR pKd : 8.38

dasatinib

ABL2Tchem Kinase

INHIBITOR pKd : 7.89

ponatinib

ABL2Tchem Kinase

INHIBITOR pKi : 8.8

imatinib

ABL2Tchem Kinase

INHIBITOR pKd : 7.89

nilotinib

ABL2Tchem Kinase

INHIBITOR pKd : 8.44

Active Ligands (19)

Explore Active Ligands

1 – 10 of 19

staurosporine

ABL2Tchem Kinase

pKd : 7.89

foretinib

ABL2Tchem Kinase

pKd : 7.92

AST-487

ABL2Tchem Kinase

pKd : 7.77

PD-173955

ABL2Tchem Kinase

pKd : 7.92

TG-100572

ABL2Tchem Kinase

pKd : 9.05

XL-228

ABL2Tchem Kinase

pKd : 7.58

tozasertib

ABL2Tchem Kinase

pKd : 7.55

danusertib

ABL2Tchem Kinase

pKd : 7.75

pexmetinib

ABL2Tchem Kinase

pKd : 6.17

CHEMBL4462318

ABL2Tchem Kinase

pKd : 7.85

Protein-Protein Interactions (93)

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1 – 10 of 93

• See Interactions on String-DB

NCK2

Tbio

Novelty:  0.02220251

p_int:  0.999998288

p_ni:  0.000001712

Score:  0.342

Data Source:  BioPlex,STRINGDB

RIN1

Tbio

Novelty:  0.02401084

p_int:  0.999982327

p_ni:  0.00001767

p_wrong:  3e-9

Score:  0.929

Data Source:  BioPlex,STRINGDB

HSPA8

Tchem

Novelty:  0.00081014

p_int:  0.999954485

p_ni:  0.000045368

p_wrong:  1.46e-7

Score:  0.294

Data Source:  BioPlex,STRINGDB

HSPBP1

Tbio

Novelty:  0.01176285

p_int:  0.999951777

p_ni:  0.000013179

p_wrong:  0.000035045

Score:  0.396

Data Source:  BioPlex,STRINGDB

ABI2

Tbio

Novelty:  0.02324355

p_int:  0.9999404

p_ni:  0.000059586

p_wrong:  1.3e-8

Score:  0.915

Data Source:  BioPlex,STRINGDB

NCK1

Tbio

Novelty:  0.00352084

p_int:  0.999586506

p_ni:  0.00036636

p_wrong:  0.000047134

Score:  0.961

Data Source:  BioPlex,STRINGDB

BAG5

Tbio

Novelty:  0.0318404

p_int:  0.999333008

p_ni:  0.00053023

p_wrong:  0.000136763

Score:  0.538

Data Source:  BioPlex,STRINGDB

CRK

Tchem

Novelty:  0.00238512

Score:  0.979

Data Source:  STRINGDB

CRKL

Tbio

Novelty:  0.0051181

Score:  0.959

Data Source:  STRINGDB

PSMA7

Tbio

Family:  Enzyme

Novelty:  0.01385043

Score:  0.958

Data Source:  STRINGDB

Nearest Tclin Targets (1)

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Upstream (1)

1 – 1 of 1

EGFR

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  2

1: ErbB signaling pathway

2: Ras signaling pathway

Pathways (382)

Reactome (4)

KEGG (3)

PathwayCommons (1)

WikiPathways (374)

Axon guidance (R-HSA-422475)

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1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Role of ABL in ROBO-SLIT signaling	8 targets	R-HSA-428890
Reactome	Signaling by ROBO receptors	220 targets	R-HSA-376176

Name	Explore in Pharos	Explore in Source
Axon guidance	533 targets	R-HSA-422475
Developmental Biology	1055 targets	R-HSA-1266738
Role of ABL in ROBO-SLIT signaling	8 targets	R-HSA-428890
Signaling by ROBO receptors	220 targets	R-HSA-376176

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (28)

Functions (9)

Components (2)

Processes (17)

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1 – 9 of 9

GO Term	Evidence	Assigned by
magnesium ion binding	Inferred from Direct Assay (IDA)	UniProtKB
manganese ion binding	Inferred from Direct Assay (IDA)	UniProtKB
protein tyrosine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
phosphotyrosine residue binding	Inferred from Physical Interaction (IPI)	CAFA
non-membrane spanning protein tyrosine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
actin filament binding	Traceable Author Statement (TAS)	UniProtKB
actin monomer binding	Traceable Author Statement (TAS)	UniProtKB
protein kinase activity	Traceable Author Statement (TAS)	ProtInc
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (2)

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1 – 2 of 2

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	3	2	3		93.7
type II diabetes mellitus	EFO_0001360	1	1	1		2.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 2 of 2

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	3		93.7
type II diabetes mellitus	EFO_0001360	1		2.3

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
ATP-binding
Cell adhesion
Complete proteome
Cytoplasm
Cytoskeleton
Kinase
Lipoprotein

GWAS Trait Find Similar Targets

No Header	No Header
testosterone measurement
type II diabetes mellitus

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
growth/size/body region phenotype
nervous system phenotype
reproductive system phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	ABL proto-oncogene 2, non-receptor tyrosine kinase	VGNC:12980	457552
Macaque	ABL proto-oncogene 2, non-receptor tyrosine kinase		717037
Mouse	v-abl Abelson murine leukemia viral oncogene 2 (arg, Abelson-related gene)	MGI:87860	11352
Rat	ABL proto-oncogene 2, non-receptor tyrosine kinase	RGD:1590898	304883
Dog	ABL proto-oncogene 2, non-receptor tyrosine kinase	VGNC:53323	480052

Species	Name	OMA	EggNOG	Inparanoid
Chimp	ABL proto-oncogene 2, non-receptor tyrosine kinase
Macaque	ABL proto-oncogene 2, non-receptor tyrosine kinase
Mouse	v-abl Abelson murine leukemia viral oncogene 2 (arg, Abelson-related gene)
Rat	ABL proto-oncogene 2, non-receptor tyrosine kinase
Dog	ABL proto-oncogene 2, non-receptor tyrosine kinase

Publication Statistics

PubMed Score 98.51

PubMed score by year

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PubTator Score 45.67

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Patents

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Related Publications

Text Mined References (75)

GeneRif Annotations (28)

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PMID	Year	Title