UniProt functional annotation for Q4JIM5



	UniProt functional annotation for Q4JIM5

UniProt code: Q4JIM5.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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. {ECO:0000269|PubMed:11279004, ECO:0000269|PubMed:11752434, ECO:0000269|PubMed:12748290, ECO:0000269|PubMed:14993293, ECO:0000269|PubMed:16971514, ECO:0000269|PubMed:17892306, ECO:0000269|PubMed:9883720}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:12748290};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:12748290}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:12748290};

Activity 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. {ECO:0000250, ECO:0000269|PubMed:12748290, ECO:0000269|PubMed:14993293}.

Subunit: 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). {ECO:0000250}.

Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11752434}.

Tissue specificity: Most abundant in adult mouse brain, especially in synapse-rich regions. {ECO:0000269|PubMed:9883720}.

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. {ECO:0000269|PubMed:11752434, ECO:0000269|PubMed:20841568}.

Ptm: Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress (By similarity). Phosphorylated by PDGFRB. {ECO:0000250, ECO:0000269|PubMed:12748290, ECO:0000269|PubMed:14993293}.

Ptm: Polyubiquitinated. Polyubiquitination of ABL2 leads to degradation (By similarity). {ECO:0000250}.

Disruption phenotype: Leads to defects in neuronal function. {ECO:0000269|PubMed:9883720}.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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. {ECO:0000269\|PubMed:11279004, ECO:0000269\|PubMed:11752434, ECO:0000269\|PubMed:12748290, ECO:0000269\|PubMed:14993293, ECO:0000269\|PubMed:16971514, ECO:0000269\|PubMed:17892306, ECO:0000269\|PubMed:9883720}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000255\|PROSITE-ProRule:PRU10028, ECO:0000269\|PubMed:12748290};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:12748290}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:12748290};
Activity 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. {ECO:0000250, ECO:0000269\|PubMed:12748290, ECO:0000269\|PubMed:14993293}.
Subunit:		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). {ECO:0000250}.
Subcellular location:		Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:11752434}.
Tissue specificity:		Most abundant in adult mouse brain, especially in synapse-rich regions. {ECO:0000269\|PubMed:9883720}.
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. {ECO:0000269\|PubMed:11752434, ECO:0000269\|PubMed:20841568}.
Ptm:		Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress (By similarity). Phosphorylated by PDGFRB. {ECO:0000250, ECO:0000269\|PubMed:12748290, ECO:0000269\|PubMed:14993293}.
Ptm:		Polyubiquitinated. Polyubiquitination of ABL2 leads to degradation (By similarity). {ECO:0000250}.
Disruption phenotype:		Leads to defects in neuronal function. {ECO:0000269\|PubMed:9883720}.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00159}.