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
ID:ABL2_HUMAN DESCRIPTION: RecName: Full=Abelson tyrosine-protein kinase 2; EC=18.104.22.168; 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";
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.
ModBase Predicted Comparative 3D Structure on P42684
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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.