Ubiqutin (Ub) is initially produced as a 229-a.a. Polyubiquitin-B (UniProt P0CG47) precursor protein encoded by the UBB gene (Gene ID 7314) or a 685-a.a. Polyubiquitin-C precursor protein (UniProt P0CG48) encoded by the UBC gene (Gene ID 7316) in human. The C-termini of Polyubiquitin-B (Cys229) and Polyubiquitin-C (Val685) are post-translationally removed, followed by additional posttranslational cleavages to yield multiple copies of idential 76-amino acid ubiquitin (also known as high mobility group nonhistone protein HMG-20) molecules (three copies per Polyubiquitin-B and nine copies per Polyubiquitin-C). Covalent modifications of target proteins via different Ub Lys residues are well documented events during cellular DNA repair, ER-associated degradation (ERAD), transcription activation, lysosomal and proteasomal degradation. PINK1 (PTEN induced putative kinase 1) is a Ser/Thr kinase that specifically accumulates in depolarized mitochondria, where it acts as a positive regulator of parkin (Park2) E3 ubiquitin (Ub) ligase activity by phosphorylating Ub at Ser65 as well as the corresponding Ser residue in parkin N-terminal Ub-like (UBL) domain. Phosphorylated Ub interacts with phosphorylated parkin at its GINGO0 domain in an allosteric manner, inducing a conformation change and exposing parkin RING2 domain catalytic cysteine for full ligase activity. NMR based conformation study reveals that Ser65-phosphorylated Ub exists in two conformations in solution. The major conformation displays altered surface properties, while the second phosphoUb conformation exhibits a retracted C-terminal tail by two residues into the Ub core. Ub Ser65 phosphorylation has little effect toward E1-mediated E2 charging and mainly affects the discharging of E2 enzymes to form polyUb chains. In addition, the majority of deubiquitinases (DUBs), including USP8, USP15 and USP30, are shown to exhibit impaired activity against Lys63-linked poly-phosphoUb.
Synonyms: Ubiqutin, Ser65 phosphorylated, Ub, Ser65 phosphorylated
Application: The unconjugated antibody (Cat. No. AB1513-I) is also available for Immunocytochemistry and Western Blotting applications.
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Other Notes: Concentration: Please refer to lot specific datasheet.