Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q4JIM5 (ABL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1182 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Cytoplasmcytoskeleton 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.12

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 processCell adhesion
   Cellular componentCytoplasm
Cytoskeleton
   DomainSH2 domain
SH3 domain
   LigandATP-binding
Magnesium
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMLipoprotein
Myristate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from direct assay Ref.1. Source: UniProtKB

actin filament bundle assembly

Inferred from direct assay Ref.1. Source: MGI

actin filament organization

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

protein phosphorylation

Inferred from direct assay Ref.2. Source: UniProtKB

   Cellular_componentactin cytoskeleton

Inferred from direct assay Ref.1. Source: MGI

cytoplasmic membrane-bounded vesicle

Traceable author statement PubMed 10995551. Source: MGI

   Molecular_functionATP 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: UniProtKB-EC

protein tyrosine kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 11821181Abelson tyrosine-protein kinase 2
PRO_0000258019

Regions

Domain107 – 16761SH3
Domain173 – 26391SH2
Domain288 – 539252Protein kinase
Nucleotide binding294 – 3029ATP By similarity UniProtKB P28523
Nucleotide binding362 – 3687ATP By similarity
Region2 – 106105CAP
Region695 – 930236F-actin-binding
Region1020 – 1182163F-actin-binding
Motif427 – 45125Kinase activation loop By similarity
Motif659 – 6613Nuclear localization signal Potential
Compositional bias561 – 5644Poly-Ser
Compositional bias735 – 7417Poly-Gly
Compositional bias984 – 9885Poly-Pro

Sites

Active site4091Proton acceptor By similarity UniProtKB P28523
Binding site3171ATP Ref.2

Amino acid modifications

Modified residue2611Phosphotyrosine; by ABL1 and autocatalysis By similarity
Modified residue2721Phosphotyrosine; by autocatalysis Ref.2
Modified residue2751Phosphoserine By similarity
Modified residue4391Phosphotyrosine; by autocatalysis and SRC-type Tyr-kinases By similarity Ref.2
Modified residue5681Phosphotyrosine; by autocatalysis Ref.2
Modified residue6211Phosphoserine Ref.11
Modified residue6321Phosphoserine Ref.11
Modified residue6341Phosphoserine By similarity
Modified residue6561Phosphoserine By similarity
Modified residue6841Phosphotyrosine; by autocatalysis Ref.2
Modified residue7191Phosphotyrosine By similarity
Modified residue8191Phosphoserine By similarity
Modified residue8221Phosphoserine By similarity
Modified residue9151Phosphoserine By similarity
Modified residue9361Phosphoserine Ref.11
Lipidation21N-myristoyl glycine By similarity UniProtKB P00519

Experimental info

Mutagenesis2721Y → F: Minimal reduction in ability to autophosphorylate. Ref.2
Mutagenesis3171K → M: Loss of kinase activity. Ref.2
Mutagenesis4391Y → F: Partial reduction in ability to autophosphorylate. Ref.2
Mutagenesis5681Y → F: No reduction in ability to autophosphorylate. Ref.2
Mutagenesis6841Y → F: Minimal reduction in ability to autophosphorylate. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q4JIM5 [UniParc].

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

FASTA1,182128,196
        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' 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, PHOSPHORYLATION 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]"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.
[11]"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; SER-632 AND SER-936, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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.
CCDSCCDS15393.1.
UniGeneMm.329515.

3D structure databases

ProteinModelPortalQ4JIM5.
SMRQ4JIM5. Positions 108-558, 1058-1182.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ4JIM5. 2 interactions.
STRING10090.ENSMUSP00000027888.

Chemistry

ChEMBLCHEMBL5222.

PTM databases

PhosphoSiteQ4JIM5.

Proteomic databases

MaxQBQ4JIM5.
PaxDbQ4JIM5.
PRIDEQ4JIM5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:87860. Abl2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000231988.
HOVERGENHBG004162.
InParanoidQ4JIM5.
PhylomeDBQ4JIM5.

Gene expression databases

GenevestigatorQ4JIM5.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR015015. F-actin_binding.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamPF08919. F_actin_bind. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTSM00808. FABD. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

ChiTaRSABL2. mouse.
PROQ4JIM5.
SOURCESearch...

Entry information

Entry nameABL2_MOUSE
AccessionPrimary (citable) accession number: Q4JIM5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: August 2, 2005
Last modified: July 9, 2014
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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