Abelson tyrosine-protein kinase 2 - Mus musculus (Mouse)

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Q4JIM5 (ABL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 72. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Abelson tyrosine-protein kinase 2
EC=2.7.10.2

Alternative name(s):
Abelson murine leukemia viral oncogene homolog 2
Abelson-related gene protein
Tyrosine-protein kinase ARG

Gene names

Name:	Abl2
Synonyms:	Arg

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1182 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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, receptor endocytosis, autophagy, DNA damage response and apoptosis. 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 or DOK1. Required for adhesion-dependent phosphorylation of ARHGAP35 which 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. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.8 Ref.9
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.2
Cofactor	Magnesium or manganese. Ref.2
Enzyme regulation	Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains By similarity. Inhibited by imatinib mesylate (Gleevec). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activity. Ref.2 Ref.6
Subunit structure	Interacts with PSMA7. Interacts with CTTN By similarity. Ref.2
Subcellular location	Cytoplasm › cytoskeleton Ref.1.
Tissue specificity	Most abundant in adult mouse brain, especially in synapse-rich regions. Ref.3
Domain	Contains two distinct classes of F-actin-binding domains. Although both can each bind F-actin, the 2 are required to bundle actin filaments. Ref.1 Ref.2 Ref.15
Post-translational modification	Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress By similarity. Phosphorylated by PDGFRB. Ref.2 Ref.6 Polyubiquitinated. Polyubiquitination of ABL2 leads to degradation By similarity.
Disruption phenotype	Leads to defects in neuronal function. Ref.3
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cytoplasm Cytoskeleton
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Magnesium Manganese Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin filament bundle assembly Inferred from direct assay Ref.1. Source: MGI cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.2. Source: UniProtKB
Cellular_component	actin cytoskeleton Inferred from direct assay Ref.1. Source: MGI cytoplasmic membrane-bounded vesicle Traceable author statement PubMed 10995551. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from direct assay Ref.2. Source: UniProtKB manganese ion binding Inferred from direct assay Ref.2. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1182

1182

Abelson tyrosine-protein kinase 2

PRO_0000258019

Regions

Domain

107 – 167

SH3

Domain

173 – 263

SH2

Domain

288 – 539

252

Protein kinase

Nucleotide binding

294 – 302

ATP By similarity UniProtKB P28523

Nucleotide binding

362 – 368

ATP By similarity

Region

1 – 106

106

CAP Ref.2

Region

695 – 930

236

F-actin-binding

Region

1020 – 1182

163

F-actin-binding

Motif

427 – 451

Kinase activation loop By similarity

Motif

659 – 661

Nuclear localization signal Potential

Compositional bias

561 – 564

Poly-Ser

Compositional bias

735 – 741

Poly-Gly

Compositional bias

984 – 988

Poly-Pro

Sites

Active site

409

Proton acceptor By similarity UniProtKB P28523

Binding site

317

ATP Ref.2

Amino acid modifications

Modified residue

261

Phosphotyrosine; by ABL1 and autocatalysis By similarity

Modified residue

272

Phosphotyrosine; by autocatalysis Ref.2

Modified residue

275

Phosphoserine By similarity

Modified residue

439

Phosphotyrosine; by autocatalysis and SRC-type Tyr-kinases By similarity Ref.2

Modified residue

568

Phosphotyrosine; by autocatalysis Ref.2

Modified residue

621

Phosphoserine By similarity

Modified residue

632

Phosphoserine Ref.11

Modified residue

634

Phosphoserine By similarity

Modified residue

656

Phosphoserine By similarity

Modified residue

684

Phosphotyrosine; by autocatalysis Ref.2

Modified residue

719

Phosphotyrosine By similarity

Modified residue

819

Phosphoserine By similarity

Modified residue

822

Phosphoserine By similarity

Modified residue

915

Phosphoserine By similarity

Modified residue

936

Phosphoserine By similarity

Lipidation

N-myristoyl glycine By similarity UniProtKB P00519

Experimental info

Mutagenesis

272

Y → F: Minimal reduction in ability to autophosphorylate. Ref.2

Mutagenesis

317

K → M: Loss of kinase activity. Ref.2

Mutagenesis

439

Y → F: Partial reduction in ability to autophosphorylate. Ref.2

Mutagenesis

568

Y → F: No reduction in ability to autophosphorylate. Ref.2

Mutagenesis

684

Y → F: Minimal reduction in ability to autophosphorylate. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

Q4JIM5 [UniParc].

Last modified August 2, 2005. Version 1.
Checksum: 08507298A9081228
Show »

FASTA

1,182

128,196

        10         20         30         40         50         60 
MGQQVGRVGE APGLQQPQPR GIRGSSAARP SGRRRDPAGR TADAGFNVFT QHDHFASCVE 

        70         80         90        100        110        120 
DGFEGDKTGG SSPEVLHRPF GCDAESQALN EAIRWSSKEN LLGATESDPN LFVALYDFVA 

       130        140        150        160        170        180 
SGDNTLSITK GEKLRVLGYN QNGEWSEVRS KNGQGWVPSN YITPVNSLEK HSWYHGPVSR 

       190        200        210        220        230        240 
SAAEYLLSSL INGSFLVRES ESSPGQLSIS LRYEGRVYHY RINTTTDSKV YVTAESRFST 

       250        260        270        280        290        300 
LAELVHHHST VADGLVTTLH YPAPKCNKPT VYGVSPIHDK WEMERTDITM KHKLGGGQYG 

       310        320        330        340        350        360 
EVYVGVWKKY SLTVAVKTFK EDTMEVEEFL KEAAVMKEIK HPNLVQLLGV CTLEPPFYIV 

       370        380        390        400        410        420 
TEYMPYGNLL DYLRECSREE VTAVVLLYMA TQISSAMEYL EKKNFIHRDL AARNCLVGEN 

       430        440        450        460        470        480 
HVVKVADFGL SRLMTGDTYT AHAGAKFPIK WTAPESLAYN TFSIKSDVWA FGVLLWEIAT 

       490        500        510        520        530        540 
YGMSPYPGID LSQVYDLLEK GYRMEQPEGC PPKVYELMRA CWKWSPADRP SFAETHQAFE 

       550        560        570        580        590        600 
TMFHDSSISE EVAEELGRTA SSSSVVPYLP RLPLLPSKTR TLRKQGENKE NLDGGLDAAE 

       610        620        630        640        650        660 
SLASSSAPAG FIRSTQASSG SPALPRKQRD KSPSSLLEDA KETCFTRDRK GGFFSSFMKK 

       670        680        690        700        710        720 
RNAPTPPKRS SSFREMENQP HKKYELTGNF SPVASLQNAD GFSVAPSQQE PNLVPAKCYG 

       730        740        750        760        770        780 
GSFAQRNLCA DDDSGGGGGS GTAGGGWSGI TGFFTPRLIK KTLGLRAGKP TASDDTSKPF 

       790        800        810        820        830        840 
PRSNSTSSMS SGLPEQDRMA MTLPRNCQRS KLQLERTVST SSQPEENVDR ANDMLPKKSE 

       850        860        870        880        890        900 
EGAAPARERP KAKLLPRGAT ALPLRAPDPA ITESDSPGVG VAGVAAAPKG KERNGGTRLG 

       910        920        930        940        950        960 
VAGVPEDGEQ LGWSSPAKAV AVLPTTHNHK VPVLISPTLK HTPADVQLIG TDSQGNKFKL 

       970        980        990       1000       1010       1020 
LSEHQVTSSG DKDRPRRVKP KCAPPPPPVM RLLQHPSTCS DPEEEPTAPP AGQHTPETQE 

      1030       1040       1050       1060       1070       1080 
GGKKAAPGPV PSSGKPGRPV MPPPQVPLPT SSISPAKMAN GTAGTKVALR KTKQAAEKIS 

      1090       1100       1110       1120       1130       1140 
ADKISKEALL ECADLLSSAI TEPVPNSQLV DTGHQLLDYC SGYVDSIPQT RNKFAFREAV 

      1150       1160       1170       1180 
SKLELSLQEL QVSSTAAGVP GTNPVLNNLL SCVQEISDVV QR

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Abl-related gene (Arg) nonreceptor tyrosine kinase uses two F-actin-binding domains to bundle F-actin." Wang Y., Miller A.L., Mooseker M.S., Koleske A.J. Proc. Natl. Acad. Sci. U.S.A. 98:14865-14870(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DOMAIN, SUBCELLULAR LOCATION, ACTIN-BINDING. Strain: 129/SvJ.
[2]	"Two distinct phosphorylation pathways have additive effects on Abl family kinase activation." Tanis K.Q., Veach D., Duewel H.S., Bornmann W.G., Koleske A.J. Mol. Cell. Biol. 23:3884-3896(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CAP DOMAIN, FUNCTION, ENZYME REGULATION, INTERACTION WITH CRK, AUTOPHOSPHORYLATION AT TYR-272; TYR-439; TYR-568 AND TYR-684, MUTAGENESIS OF TYR-272; LYS-317; TYR-439; TYR-568 AND TYR-684. Strain: 129/SvJ.
[3]	"Essential roles for the Abl and Arg tyrosine kinases in neurulation." Koleske A.J., Gifford A.M., Scott M.L., Nee M., Bronson R.T., Miczek K.A., Baltimore D. Neuron 21:1259-1272(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, FUNCTION.
[4]	"Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes." Kain K.H., Klemke R.L. J. Biol. Chem. 276:16185-16192(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Regulation of F-actin-dependent processes by the Abl family of tyrosine kinases." Woodring P.J., Hunter T., Wang J.Y. J. Cell Sci. 116:2613-2626(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[6]	"Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor." Plattner R., Koleske A.J., Kazlauskas A., Pendergast A.M. Mol. Cell. Biol. 24:2573-2583(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION.
[7]	"How do Abl family kinases regulate cell shape and movement?" Hernandez S.E., Krishnaswami M., Miller A.L., Koleske A.J. Trends Cell Biol. 14:36-44(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[8]	"Integrin signaling through Arg activates p190RhoGAP by promoting its binding to p120RasGAP and recruitment to the membrane." Bradley W.D., Hernandez S.E., Settleman J., Koleske A.J. Mol. Biol. Cell 17:4827-4836(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Use of a chemical genetic technique to identify myosin IIb as a substrate of the Abl-related gene (Arg) tyrosine kinase." Boyle S.N., Koleske A.J. Biochemistry 46:11614-11620(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-936, MASS SPECTROMETRY. Tissue: Brain cortex.
[11]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632, MASS SPECTROMETRY. Tissue: Melanoma.
[12]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-621, MASS SPECTROMETRY. Tissue: Macrophage.
[13]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-439, MASS SPECTROMETRY. Tissue: Brain.
[14]	"Emerging roles of Abl family tyrosine kinases in microbial pathogenesis." Backert S., Feller S.M., Wessler S. Trends Biochem. Sci. 33:80-90(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[15]	"ABL tyrosine kinases: evolution of function, regulation, and specificity." Colicelli J. Sci. Signal. 3:RE6-RE6(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION, DOMAIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ084361 mRNA. Translation: AAY86039.1.
IPI	IPI00117039.
UniGene	Mm.329515.
3D structure databases
ProteinModelPortal	Q4JIM5.
SMR	Q4JIM5. Positions 110-558, 1058-1182.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000027888.
PTM databases
PhosphoSite	Q4JIM5.
Proteomic databases
PaxDb	Q4JIM5.
PRIDE	Q4JIM5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:87860. Abl2.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000231988.
HOVERGEN	HBG004162.
InParanoid	Q4JIM5.
OrthoDB	EOG4NS39R.
Gene expression databases
Genevestigator	Q4JIM5.
GermOnline	ENSMUSG00000026596. Mus musculus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR015015. F-actin_binding. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR001452. SH3_domain. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. [Graphical view]
Pfam	PF08919. F_actin_bind. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00109. TYRKINASE.
SMART	SM00808. FABD. 1 hit. SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50001. SH2. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5222.
ChiTaRS	ABL2. mouse.
SOURCE	Search...

Entry information

Entry name

ABL2_MOUSE

Accession

Primary (citable) accession number: Q4JIM5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	August 2, 2005
Last modified:	May 29, 2013
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents