Proteolysis/ Ubiquitin Pathway

Curator(s): Peter D'Adamo

The Ubiquitin Proteasome Pathway (UPP) is the principal mechanism for protein catabolism in the mammalian cytosol and nucleus.Modulation of protein activities by ubiquitin-dependent modification regulates the turnover, degradation and function of many cellular proteins. Ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin-protein ligase (E3) catalyze the conjugation of the protein Ubiquitin to a variety of biologically significant protein substrates for targeted degradation through the 26S proteasome, as well as for nonproteolytic regulation of their functions or subcellular localizations.The highly regulated UPP affects a wide variety of cellular processes and substrates and defects in the system can result in the pathogenesis of several important human diseases.    
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Proteolysis/ Ubiquitin Pathway cluster_ER ER ubiquitin-like modifier activating enzyme 1 UBA1 Ubiquitin UBA1->Ubiquitin ubiquitin-conjugating enzyme E2D 1 UBE2D1 UBE2D1->Ubiquitin UBCH8 UBCH8->Ubiquitin Parkin UBCH8->Parkin UBCH13 UBCH13->Ubiquitin node1 1 Ubiquitin->node1 Ubiquitin Ubiquitin->Parkin TNF receptor-associated factor 6 TRAF6 Ubiquitin->TRAF6 Synphilin 1 Ubiquitin->Synphilin 1 Septin 5 Ubiquitin->Septin 5 node5 Ataxin-3 Ubiquitin->node5 G protein-coupled receptor 37 (endothelin receptor type B-like) GPR37 Ubiquitin->GPR37 Parkin->Ubiquitin Cyclin E Parkin->Cyclin E node9 a-Tubulin Parkin->node9 node10 B-Tubulin Parkin->node10 node2 3 TRAF6->UBCH13 TRAF6->Ubiquitin TRAF6->node2 TRAF6 ubiquitin-conjugating enzyme E2 variant 1 UBE2V1 TRAF6->UBE2V1 node3 1 E3 Ligase E3 Ligase->Ubiquitin E3 Ligase->node3 E3 Ligase cullin 1 CUL1 CUL1->Parkin CUL1->E3 Ligase S-phase kinase-associated protein 2 (p45) SKP2 SKP2->CUL1 S-phase kinase-associated protein 1 SKP1 SKP1->SKP2 F-box and WD repeat domain containing 7 FBXW7 SKP1->FBXW7 FBXW7->Parkin FBXW7->CUL1 FBXW7->Cyclin E ring-box 1,E3 ubiquitin protein ligase RBX1 RBX1->E3 Ligase UBE2V1->UBCH13 node4 11 ATP node11 1 ATP->node11 node6 Proteolysis/ Ubiquitin Pathway Synphilin 1->node6 Septin 5->node6 node5->node6 node7 2 caspase 1,apoptosis-related cysteine peptidase (interleukin 1,beta,convertase) CASP1 CASP1->Parkin CASP1->node7 CASP1 node8 6 caspase 8,apoptosis-related cysteine peptidase CASP8 CASP8->Parkin CASP8->node8 CASP8 calcium/calmodulin-dependent serine protein kinase (MAGUK family) CASK CASK->Parkin Cyclin E->node6 node9->node6 node10->node6 node11->UBA1 node12 Inhibitors of ubiquinin activation/transfer node12->node11 node13 22 node14 26S Proteasome node14->node6 node14->node13 26S Proteasome CHIP CHIP->Parkin CHIP->GPR37 HSP70 CHIP->HSP70 GPR37->node6 HSP70->Parkin HSP70->node4 HSP70 UBCH6 UBCH6->Ubiquitin UBCH6->Parkin UBCH7 UBCH7->Ubiquitin UBCH7->Parkin print "