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Protein

Tyrosine-protein kinase ABL2

Gene

Abl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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, ABI1.7 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Cofactori

Mg2+1 Publication, Mn2+1 Publication

Enzyme regulationi

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.By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei317ATPPROSITE-ProRule annotation1 Publication1
Active sitei409Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi294 – 302ATPPROSITE-ProRule annotationBy similarity9
Nucleotide bindingi362 – 368ATPPROSITE-ProRule annotation7

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • magnesium ion binding Source: UniProtKB
  • manganese ion binding Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • phosphotyrosine residue binding Source: MGI
  • protein tyrosine kinase activity Source: UniProtKB
  • signaling receptor binding Source: GO_Central

GO - Biological processi

  • actin cytoskeleton organization Source: UniProtKB
  • actin filament bundle assembly Source: MGI
  • actin filament organization Source: MGI
  • adult walking behavior Source: MGI
  • aggressive behavior Source: MGI
  • alpha-beta T cell differentiation Source: MGI
  • auditory behavior Source: MGI
  • Bergmann glial cell differentiation Source: MGI
  • cardiovascular system development Source: MGI
  • cell adhesion Source: UniProtKB-KW
  • cellular protein localization Source: MGI
  • cellular response to retinoic acid Source: MGI
  • cerebellum morphogenesis Source: MGI
  • dendrite morphogenesis Source: MGI
  • dendritic spine maintenance Source: MGI
  • epidermal growth factor receptor signaling pathway Source: MGI
  • exploration behavior Source: MGI
  • innate immune response Source: GO_Central
  • learning Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of cell-cell adhesion Source: MGI
  • negative regulation of endothelial cell apoptotic process Source: MGI
  • negative regulation of Rho protein signal transduction Source: MGI
  • neural tube closure Source: MGI
  • neuroepithelial cell differentiation Source: MGI
  • neuromuscular process controlling balance Source: MGI
  • neuron differentiation Source: MGI
  • neuron remodeling Source: MGI
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • phagocytosis Source: MGI
  • platelet-derived growth factor receptor signaling pathway Source: MGI
  • positive regulation of cytosolic calcium ion concentration Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of interferon-gamma secretion Source: MGI
  • positive regulation of interleukin-2 secretion Source: MGI
  • positive regulation of neuron projection development Source: MGI
  • positive regulation of oxidoreductase activity Source: MGI
  • positive regulation of phospholipase C activity Source: MGI
  • positive regulation of protein binding Source: MGI
  • positive regulation of Wnt signaling pathway, planar cell polarity pathway Source: MGI
  • post-embryonic development Source: MGI
  • protein phosphorylation Source: UniProtKB
  • regulation of cell proliferation Source: GO_Central
  • regulation of extracellular matrix organization Source: MGI
  • reproductive process Source: MGI
  • substrate-dependent cell migration, cell extension Source: MGI
  • visual learning Source: MGI

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processCell adhesion
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase ABL2 (EC:2.7.10.2)
Alternative name(s):
Abelson murine leukemia viral oncogene homolog 2
Abelson tyrosine-protein kinase 2
Abelson-related gene protein
Tyrosine-protein kinase ARG
Gene namesi
Name:Abl2Imported
Synonyms:Arg
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:87860 Abl2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Disruption phenotypei

Leads to defects in neuronal function.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi272Y → F: Minimal reduction in ability to autophosphorylate. 1 Publication1
Mutagenesisi317K → M: Loss of kinase activity. 1 Publication1
Mutagenesisi439Y → F: Partial reduction in ability to autophosphorylate. 1 Publication1
Mutagenesisi568Y → F: No reduction in ability to autophosphorylate. 1 Publication1
Mutagenesisi684Y → F: Minimal reduction in ability to autophosphorylate. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5222

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00002580192 – 1182Tyrosine-protein kinase ABL2Add BLAST1181

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei97PhosphoserineBy similarity1
Modified residuei116PhosphotyrosineBy similarity1
Modified residuei161PhosphotyrosineBy similarity1
Modified residuei174PhosphotyrosineBy similarity1
Modified residuei185PhosphotyrosineBy similarity1
Modified residuei218PhosphotyrosineBy similarity1
Modified residuei231PhosphotyrosineBy similarity1
Modified residuei261Phosphotyrosine; by ABL1 and autocatalysisBy similarity1
Modified residuei272Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei275PhosphoserineBy similarity1
Modified residuei299PhosphotyrosineBy similarity1
Modified residuei303PhosphotyrosineBy similarity1
Modified residuei439Phosphotyrosine; by autocatalysis and SRC-type Tyr-kinasesBy similarity1
Modified residuei459PhosphotyrosineBy similarity1
Modified residuei568Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei606PhosphoserineBy similarity1
Modified residuei621PhosphoserineCombined sources1
Modified residuei632PhosphoserineCombined sources1
Modified residuei634PhosphoserineBy similarity1
Modified residuei656PhosphoserineBy similarity1
Modified residuei670PhosphoserineBy similarity1
Modified residuei671PhosphoserineBy similarity1
Modified residuei672PhosphoserineBy similarity1
Modified residuei684Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei719PhosphotyrosineBy similarity1
Modified residuei778N6-acetyllysineBy similarity1
Modified residuei785PhosphoserineBy similarity1
Modified residuei802PhosphothreonineBy similarity1
Modified residuei819PhosphoserineBy similarity1
Modified residuei822PhosphoserineCombined sources1
Modified residuei915PhosphoserineBy similarity1
Modified residuei936PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress (By similarity). Phosphorylated by PDGFRB.By similarity2 Publications
Polyubiquitinated. Polyubiquitination of ABL2 leads to degradation (By similarity).By similarity

Keywords - PTMi

Acetylation, Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ4JIM5
MaxQBiQ4JIM5
PaxDbiQ4JIM5
PeptideAtlasiQ4JIM5
PRIDEiQ4JIM5

PTM databases

iPTMnetiQ4JIM5
PhosphoSitePlusiQ4JIM5

Expressioni

Tissue specificityi

Most abundant in adult mouse brain, especially in synapse-rich regions.1 Publication

Interactioni

Subunit structurei

Interacts with PSMA7. Interacts with CTTN (By similarity). Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-60989N
IntActiQ4JIM5, 4 interactors
STRINGi10090.ENSMUSP00000027888

Structurei

Secondary structure

11182
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi285 – 287Combined sources3
Beta strandi288 – 295Combined sources8
Beta strandi302 – 307Combined sources6
Helixi308 – 310Combined sources3
Beta strandi312 – 319Combined sources8
Helixi327 – 337Combined sources11
Beta strandi347 – 351Combined sources5
Beta strandi353 – 362Combined sources10
Helixi369 – 375Combined sources7
Turni378 – 380Combined sources3
Helixi383 – 402Combined sources20
Helixi412 – 414Combined sources3
Beta strandi415 – 417Combined sources3
Helixi419 – 421Combined sources3
Beta strandi423 – 425Combined sources3
Beta strandi435 – 437Combined sources3
Helixi449 – 451Combined sources3
Helixi454 – 459Combined sources6
Helixi464 – 479Combined sources16
Helixi491 – 493Combined sources3
Helixi494 – 499Combined sources6
Helixi512 – 521Combined sources10
Helixi526 – 528Combined sources3
Helixi532 – 545Combined sources14

3D structure databases

ProteinModelPortaliQ4JIM5
SMRiQ4JIM5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini107 – 167SH3PROSITE-ProRule annotationAdd BLAST61
Domaini173 – 263SH2PROSITE-ProRule annotationAdd BLAST91
Domaini288 – 539Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 106CAPAdd BLAST105
Regioni695 – 930F-actin-bindingAdd BLAST236
Regioni1020 – 1182F-actin-bindingAdd BLAST163

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi427 – 451Kinase activation loopBy similarityAdd BLAST25
Motifi659 – 661Nuclear localization signalSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi561 – 564Poly-Ser4
Compositional biasi735 – 741Poly-Gly7
Compositional biasi984 – 988Poly-Pro5

Domaini

Contains two distinct classes of F-actin-binding domains. Although both can each bind F-actin, the 2 are required to bundle actin filaments.2 Publications

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
HOGENOMiHOG000231988
HOVERGENiHBG004162
InParanoidiQ4JIM5
PhylomeDBiQ4JIM5

Family and domain databases

CDDicd09935 SH2_ABL, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR035837 ABL_SH2
IPR015015 F-actin_binding
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF08919 F_actin_bind, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00808 FABD, 1 hit
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q4JIM5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGQQVGRVGE APGLQQPQPR GIRGSSAARP SGRRRDPAGR TADAGFNVFT
60 70 80 90 100
QHDHFASCVE DGFEGDKTGG SSPEVLHRPF GCDAESQALN EAIRWSSKEN
110 120 130 140 150
LLGATESDPN LFVALYDFVA SGDNTLSITK GEKLRVLGYN QNGEWSEVRS
160 170 180 190 200
KNGQGWVPSN YITPVNSLEK HSWYHGPVSR SAAEYLLSSL INGSFLVRES
210 220 230 240 250
ESSPGQLSIS LRYEGRVYHY RINTTTDSKV YVTAESRFST LAELVHHHST
260 270 280 290 300
VADGLVTTLH YPAPKCNKPT VYGVSPIHDK WEMERTDITM KHKLGGGQYG
310 320 330 340 350
EVYVGVWKKY SLTVAVKTFK EDTMEVEEFL KEAAVMKEIK HPNLVQLLGV
360 370 380 390 400
CTLEPPFYIV TEYMPYGNLL DYLRECSREE VTAVVLLYMA TQISSAMEYL
410 420 430 440 450
EKKNFIHRDL AARNCLVGEN HVVKVADFGL SRLMTGDTYT AHAGAKFPIK
460 470 480 490 500
WTAPESLAYN TFSIKSDVWA FGVLLWEIAT YGMSPYPGID LSQVYDLLEK
510 520 530 540 550
GYRMEQPEGC PPKVYELMRA CWKWSPADRP SFAETHQAFE TMFHDSSISE
560 570 580 590 600
EVAEELGRTA SSSSVVPYLP RLPLLPSKTR TLRKQGENKE NLDGGLDAAE
610 620 630 640 650
SLASSSAPAG FIRSTQASSG SPALPRKQRD KSPSSLLEDA KETCFTRDRK
660 670 680 690 700
GGFFSSFMKK RNAPTPPKRS SSFREMENQP HKKYELTGNF SPVASLQNAD
710 720 730 740 750
GFSVAPSQQE PNLVPAKCYG GSFAQRNLCA DDDSGGGGGS GTAGGGWSGI
760 770 780 790 800
TGFFTPRLIK KTLGLRAGKP TASDDTSKPF PRSNSTSSMS SGLPEQDRMA
810 820 830 840 850
MTLPRNCQRS KLQLERTVST SSQPEENVDR ANDMLPKKSE EGAAPARERP
860 870 880 890 900
KAKLLPRGAT ALPLRAPDPA ITESDSPGVG VAGVAAAPKG KERNGGTRLG
910 920 930 940 950
VAGVPEDGEQ LGWSSPAKAV AVLPTTHNHK VPVLISPTLK HTPADVQLIG
960 970 980 990 1000
TDSQGNKFKL LSEHQVTSSG DKDRPRRVKP KCAPPPPPVM RLLQHPSTCS
1010 1020 1030 1040 1050
DPEEEPTAPP AGQHTPETQE GGKKAAPGPV PSSGKPGRPV MPPPQVPLPT
1060 1070 1080 1090 1100
SSISPAKMAN GTAGTKVALR KTKQAAEKIS ADKISKEALL ECADLLSSAI
1110 1120 1130 1140 1150
TEPVPNSQLV DTGHQLLDYC SGYVDSIPQT RNKFAFREAV SKLELSLQEL
1160 1170 1180
QVSSTAAGVP GTNPVLNNLL SCVQEISDVV QR
Length:1,182
Mass (Da):128,196
Last modified:August 2, 2005 - v1
Checksum:i08507298A9081228
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ084361 mRNA Translation: AAY86039.1
CCDSiCCDS15393.1
UniGeneiMm.329515

Similar proteinsi

Entry informationi

Entry nameiABL2_MOUSE
AccessioniPrimary (citable) accession number: Q4JIM5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: August 2, 2005
Last modified: May 23, 2018
This is version 113 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

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