EC Number   |
General Information |
Reference |
|---|
   6.3.1.19 | physiological function |
bacteria use an intrinsically disordered protein, Pup, to mark proteins for destruction. The protein degradation machinery of Mycobacterium tuberculosis includes a proteasome and a ubiquitin-like protein (Pup). Proteasome accessory factor A (PafA) attaches Pup to proteins to target them for degradation by the proteasome. PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log). This apparent transpupylation reaction requires a previously unrecognized depupylase activity in PafA, and, surprisingly, this depupylase activity is much more efficient than the activity of the dedicated depupylase Dop (deamidase of Pup). Thus, PafA can potentially use both newly synthesized Pup and recycled Pup to doom proteins for degradation. In contrast, enzyme Dop, in addition to deamidating PupGln to PupGlu, can remove Pup from proteins, which can rescue them from proteasomal degradation. PafA, unlike Dop, can-not deamidate PupGln to PupGlu, thus, PafA amidase activity appears to be limited to pupylated proteins |
-, 745678 |
| 6.3.1.19 | physiological function |
enzyme PafA, the prokaryotic ubiquitin-like protein (Pup) ligase, catalyzes the Pup modification of bacterial proteins and targets the substrates for proteasomal degradation. Mycobacterium smegmatis PafA can be poly-pupylated. Self-pupylation of PafA is reversely regulated by Dop, a dual-functional enzyme, functioning as deaminase to convert PupQ to PupE and also as depupylase to remove Pup from the pupylated proteins. The self-pupylation of PafA is involved in the regulation of its stability |
-, 746202 |
| 6.3.1.19 | malfunction |
in a pafA knockout strain pupylated proteins are undetectable and proteasomal substrate proteins accumulate |
-, 729308 |
| 6.3.1.19 | physiological function |
in Mycobacterium tuberculosis Pup tagging is important for virulence |
-, 730010 |
| 6.3.1.19 | evolution |
PafA is a member of the glutamine synthetase (GS) family of proteins |
-, 745678 |
| 6.3.1.19 | metabolism |
posttranslational regulation of coordinated enzyme activities in the prokaryotic ubiquitin-like protein (Pup)-proteasome system (PPS), overview. Pup, a ubiquitin analogue, is conjugated to proteins through the activities of two enzymes, Dop (deamidase of Pup) and PafA (proteasome accessory factor A), the Pup ligase. The depupylase activity of Dop counteracts the actions of PafA. tight Pup binding and the limited degree of Dop interaction with high-molecular-weight pupylated proteins results in preferred Pup deamidation over protein depupylation by enzyme Dop. Dop is depleted in the absence of Pup in stationary-phase cells. Pup-PanB and Pup-IdeR act as tight-binding competitors versus Pup binding by Dop. Pup binding stabilizes Dop and prevents its depletion. PafA and Dop generate a high-molecular-weight pupylome |
-, 746316 |
| 6.3.1.19 | metabolism |
prokaryotic ubiquitin-like protein (Pup) is a post-translational modifier that attaches to more than 50 proteins in Mycobacteria. Proteasome accessory factor A (PafA) is responsible for Pup conjugation to substrates |
-, 729641 |
| 6.3.1.19 | physiological function |
prokaryotic ubiquitin-like protein (Pup) is a small protein that can be covalently attached to lysine side chains of cellular proteins by Pup ligase PafA. Pupylation serves as a recruitment tool for proteasomal degradation. For Mycobacterium tuberculosis, pupylation and the recruitment of pupylated substrates to the proteasome support persistence inside host macrophages during pathogenesis. Pup serves as both recognition and threading element in proteasomal degradation of pupylated substrates. The degradation substrate covalently modified with Pup is recruited to the Mpa-proteasome complex by docking to the Mpa coiled-coil domain, which triggers Pup to undergo a disorder-to-order transition, forming an extended helix that associates into a shared three-stranded coil with the Mpa N-terminal coiled-coil domains. The disordered N-terminal region of Pup points into the Mpa central pore, where it is engaged by the ATPase-driven pore loops for unfolding and directional translocation into the proteasome core for degradation. Structure-function analysis, overview |
-, 745555 |
| 6.3.1.19 | physiological function |
prokaryotic ubiquitin-like protein (Pup) is a small protein that can be covalently attached to lysine side chains of cellular proteins by Pup ligase PafA. Pupylation serves as a recruitment tool for proteasomal degradation. Pup serves as both recognition and threading element in proteasomal degradation of pupylated substrates. The degradation substrate covalently modified with Pup is recruited to the Mpa-proteasome complex by docking to the Mpa coiled-coil domain, which triggers Pup to undergo a disorder-to-order transition, forming an extended helix that associates into a shared three-stranded coil with the Mpa N-terminal coiled-coil domains. The disordered N-terminal region of Pup points into the Mpa central pore, where it is engaged by the ATPase-driven pore loops for unfolding and directional translocation into the proteasome core for degradation. Structure-function analysis, overview |
-, 745555 |
| 6.3.1.19 | physiological function |
prokaryotic ubiquitin-like protein, Pup, is conjugated to proteins by PafA, the only Pup ligase identified thus far, through the formation of an iso-peptide bond between the gamma-carboxylate of a glutamate side chain at the C terminus of Pup and the epsilon-amine of a lysine residue on the target protein. Pupylation is a cytoplasmic signal for proteasomal degradation. Pup ligase PafA conjugates the small protein Pup to lysine side chains of target proteins. Mono-Pup moieties are almost exclusively observed in vivo and are sufficient as degradation tags |
-, 744878 |
