Application | Comment | Organism |
---|---|---|
medicine | nonreceptor tyrosine kinase c-Abl phosphorylates tyrosine 143 of parkin, which encodes a ubiquitin E3 ligase, related to autosomal recessive Parkinson disease. Phosphorylation inhibits parkins ubiquitin E3 ligase activity and protective function. Tyrosine phosphorylation of parkin by c-Abl is a major posttranslational modification that inhibits parkin function, possibly contributing to pathogenesis of sporadic Parkinson's disease | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
- |
Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
imatinib | a c-Abl-family kinase inhibitor, prevents the phosphorylation of substrate parkin, maintaining parkin in a catalytically active and protective state. The protective effects require parkin | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + [parkin]-Tyr143 | Homo sapiens | - |
ADP + [parkin]-phospho-Tyr143 | nonreceptor tyrosine kinase c-Abl phosphorylates tyrosine 143 of parkin, which encodes a ubiquitin E3 ligase, related to autosomal recessive Parkinson disease. Phosphorylation inhibits parkin's ubiquitin E3 ligase activity and protective function | ? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | in human postmortem Parkinson's disease brain, isoform c-Abl is active, substrate parkin is tyrosine-phosphorylated, and parkin substrates aminoacyl-tRNA synthetase-interacting multifunctional protein type 2, AIMP2, and fuse-binding protein 1, FBP1, accumulate in the substantia nigra and striatum | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + [parkin]-Tyr143 | - |
Homo sapiens | ADP + [parkin]-phospho-Tyr143 | nonreceptor tyrosine kinase c-Abl phosphorylates tyrosine 143 of parkin, which encodes a ubiquitin E3 ligase, related to autosomal recessive Parkinson disease. Phosphorylation inhibits parkin's ubiquitin E3 ligase activity and protective function | ? |
Synonyms | Comment | Organism |
---|---|---|
c-ABL | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | conditional knockout of isoform c-Abl in the nervous system prevents the phosphorylation of substrate parkin, the accumulation of parkin substrates aminoacyl-tRNA synthetase-interacting multifunctional protein type 2, AIMP2, and fuse-binding protein 1, FBP, and subsequent neurotoxicity in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication | Homo sapiens |