Human Gene ABL2 (ENST00000392043.4) Description and Page Index
  Description: Homo sapiens ABL proto-oncogene 2, non-receptor tyrosine kinase (ABL2), transcript variant e, mRNA. (from RefSeq NM_001136001)
RefSeq Summary (NM_001136001): 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].
Gencode Transcript: ENST00000392043.4
Gencode Gene: ENSG00000143322.21
Transcript (Including UTRs)
   Position: hg38 chr1:179,110,805-179,229,684 Size: 118,880 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg38 chr1:179,110,805-179,229,397 Size: 118,593 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:179,110,805-179,229,684)mRNA (may differ from genome)Protein (542 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
LynxMGIneXtProtOMIMPubMedReactome
Stanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: ABL2_HUMAN
DESCRIPTION: RecName: Full=Abelson tyrosine-protein kinase 2; EC=2.7.10.2; AltName: Full=Abelson murine leukemia viral oncogene homolog 2; AltName: Full=Abelson-related gene protein; AltName: Full=Tyrosine-protein kinase ARG;
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 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.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
COFACTOR: Magnesium or manganese.
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. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activity (By similarity).
SUBUNIT: Interacts with PSMA7.
INTERACTION: P46108:CRK; NbExp=5; IntAct=EBI-1102694, EBI-886; P06241:FYN; NbExp=2; IntAct=EBI-1102694, EBI-515315; P62993:GRB2; NbExp=2; IntAct=EBI-1102694, EBI-401755; P16333:NCK1; NbExp=3; IntAct=EBI-1102694, EBI-389883; P27986:PIK3R1; NbExp=2; IntAct=EBI-1102694, EBI-79464; P19174:PLCG1; NbExp=4; IntAct=EBI-1102694, EBI-79387; Q13671:RIN1; NbExp=4; IntAct=EBI-1102694, EBI-366017; P12931:SRC; NbExp=2; IntAct=EBI-1102694, EBI-621482;
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
TISSUE SPECIFICITY: Widely expressed.
DOMAIN: Contains two distinct classes of F-actin-binding domains. Although both can bind F-actin, the 2 are required to bundle actin filaments (By similarity).
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress. Phosphorylated by PDGFRB (By similarity).
PTM: Polyubiquitinated. Polyubiquitination of ABL2 leads to degradation.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 1 SH3 domain.
SEQUENCE CAUTION: Sequence=CAD98092.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ABL2ID226.html";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/abl2/";
WEB RESOURCE: Name=CGP resequencing studies; URL="http://www.sanger.ac.uk/perl/genetics/CGP/cgp_viewer?action=gene&ln=ABL2";

-  MalaCards Disease Associations
  MalaCards Gene Search: ABL2
Diseases sorted by gene-association score: leukemia (15)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.80 RPKM in Cells - Transformed fibroblasts
Total median expression: 146.66 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -134.00287-0.467 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
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

Pfam Domains:
PF08919 - F-actin binding
PF07714 - Protein tyrosine kinase
PF00017 - SH2 domain
PF00018 - SH3 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2ECD
- NMR MuPIT

2KK1
- NMR MuPIT

2XYN
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3GVU - X-ray MuPIT 3HMI - X-ray MuPIT 3ULR - X-ray


ModBase Predicted Comparative 3D Structure on P42684
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0001784 phosphotyrosine binding
GO:0003785 actin monomer binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0030145 manganese ion binding
GO:0046872 metal ion binding
GO:0051015 actin filament binding

Biological Process:
GO:0006464 cellular protein modification process
GO:0006468 protein phosphorylation
GO:0007155 cell adhesion
GO:0007165 signal transduction
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0010506 regulation of autophagy
GO:0010863 positive regulation of phospholipase C activity
GO:0010976 positive regulation of neuron projection development
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0030100 regulation of endocytosis
GO:0030155 regulation of cell adhesion
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0042127 regulation of cell proliferation
GO:0045087 innate immune response
GO:0051353 positive regulation of oxidoreductase activity
GO:0071300 cellular response to retinoic acid
GO:2000145 regulation of cell motility
GO:2000249 regulation of actin cytoskeleton reorganization

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0015629 actin cytoskeleton
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane


-  Descriptions from all associated GenBank mRNAs
  M35296 - Human tyrosine kinase arg gene mRNA.
FJ542284 - Homo sapiens Abl2 isoform 1BLCTS mRNA, complete cds, alternatively spliced.
FJ542285 - Homo sapiens Abl2 isoform 1BSCTL mRNA, complete cds, alternatively spliced.
FJ542286 - Homo sapiens Abl2 isoform 1BSCTS mRNA, complete cds, alternatively spliced.
AK311045 - Homo sapiens cDNA, FLJ18087.
BX538317 - Homo sapiens mRNA; cDNA DKFZp686A02165 (from clone DKFZp686A02165).
BC065912 - Homo sapiens v-abl Abelson murine leukemia viral oncogene homolog 2 (arg, Abelson-related gene), mRNA (cDNA clone MGC:70756 IMAGE:5173213), complete cds.
FJ542283 - Homo sapiens Abl2 isoform 1ASCTS mRNA, complete cds, alternatively spliced.
AK225255 - Homo sapiens mRNA for v-abl Abelson murine leukemia viral oncogene homolog 2 isoform a variant, clone: DMC00952.
AK309549 - Homo sapiens cDNA, FLJ99590.
JD462910 - Sequence 443934 from Patent EP1572962.
JD217531 - Sequence 198555 from Patent EP1572962.
JD277330 - Sequence 258354 from Patent EP1572962.
JD218433 - Sequence 199457 from Patent EP1572962.
JD278522 - Sequence 259546 from Patent EP1572962.
JD076749 - Sequence 57773 from Patent EP1572962.
JD220317 - Sequence 201341 from Patent EP1572962.
JD162235 - Sequence 143259 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04012 - ErbB signaling pathway
hsa05416 - Viral myocarditis

Reactome (by CSHL, EBI, and GO)

Protein P42684 (Reactome details) participates in the following event(s):

R-HSA-376141 Interaction of ABL with ROBO1:SLIT2
R-HSA-428888 Phosphorylation of ROBO1 by ABL kinase
R-HSA-428883 Recruitment of CAP to ABL
R-HSA-428885 Activation of CLASP
R-HSA-428890 Role of ABL in ROBO-SLIT signaling
R-HSA-376176 Signaling by ROBO receptors
R-HSA-422475 Axon guidance
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: A0M8X0, ABL2_HUMAN, ABLL, ARG, B7UEF2, B7UEF3, B7UEF4, B7UEF5, NM_001136001, P42684, Q5T0X6, Q5W0C5, Q6NZY6, Q7Z301, uc009wxe.1, uc009wxe.2, uc009wxe.3, uc009wxe.4
UCSC ID: uc009wxe.4
RefSeq Accession: NM_001136001
Protein: P42684 (aka ABL2_HUMAN)
CCDS: CCDS44283.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.