description
Intracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T cells. The ubiquitin-26S proteasome system plays a central role in the generation of these class I MHC antigens. Ubiquitination is the mechanism of adding ubiquitin to lysine residues on substrate protein leading to the formation of a polyubiquitinated substrate. This process involves three classes of enzyme, an E1 ubiquitin-activating enzyme, an E2 ubiquitin-conjugating enzyme, and an E3 ubiquitin ligase. Polyubiquitination through lysine-48 (K48) generally targets the substrate protein for proteasomal destruction. The protease responsible for the degradation of K48-polyubiquitinated proteins is the 26S proteasome. This proteasome is a two subunit protein complex composed of the 20S (catalytic core) and 19S (regulatory) proteasome complexes. The proteasome eliminates most of the foreign and non-functional proteins from the cell by degrading them into short peptides; only a small fraction of the peptides generated are of the correct length to be presented by the MHC class I system. It has been calculated that between 994 and 3122 protein molecules have to be degraded for the formation of a single, stable MHC class I complex at the cell surface, with an average effciency of 1 in 2000 (Kloetzel et al. 2004, Princiotta et al. 2003)

external resources
NCBI:1269193
REACTOME:R-HSA-983168
PUBMED:12648452
PUBMED:11917093
PUBMED:19489725
PUBMED:14734113
PUBMED:20351195
PUBMED:17145306

genes
BLMH , CBLB , CCNF , CDC20 , CDC27 , CDC34 , UBE2K , LMO7 , LNPEP , TRIM37 , NEDD4 , PRKN , PSMA1 , PSMA2 , PSMA3 , PSMA4 , PSMA5 , PSMA6 , PSMA7 , PSMB1 , PSMB2 , PSMB3 , PSMB4 , PSMB5 , PSMB6 , PSMB7 , PSMB8 , PSMB9 , PSMB10 , PSMC1 , PSMC2 , PSMC3 , PSMC4 , PSMC5 , PSMC6 , PSMD1 , PSMD2 , PSMD3 , PSMD4 , PSMD5 , PSMD7 , PSMD8 , PSMD9 , PSMD10 , PSMD11 , PSMD12 , PSMD13 , PSME1 , PSME2 , RBBP6 , RNF4 , RNF6 , RPS27A , FBXW4 , SIAH1 , SIAH2 , SKP1 , SKP2 , TRIM21 , ELOC , ELOB , TPP2 , UBA52 , UBB , UBC , UBA1 , UBA7 , UBE2A , UBE2B , UBE2D1 , UBE2D2 , UBE2D3 , UBE2E1 , UBE2E2 , UBE2G1 , UBE2G2 , UBE2H , UBE2L3 , UBE2N , UBE2V1 , UBE2V2 , UBE3A , VHL , ZBTB16 , SEM1 , CUL5 , GAN , CUL3 , CUL2 , CUL1 , SOCS1 , CDC23 , CDC16 , HERC3 , HERC2 , HERC1 , BTRC , SOCS3 , UBA3 , UBE2M , UBE2L6 , TRIP12 , UBE4A , PSMF1 , NPEPPS , RNF14 , RNF7 , DZIP3 , UBE3C , DCAF1 , KEAP1 , CUL7 , PSMD6 , PJA2 , AREL1 , KLHL21 , RBX1 , HUWE1 , RNF41 , PSME3 , PSMD14 , STUB1 , TRAIP , KLHL41 , ANAPC10 , UBAC1 , ARIH2 , UBE2E3 , LRRC41 , FBXW10 , ATG7 , RBCK1 , WWP1 , UBE2C , KLHL2 , UBOX5 , TRIM32 , FBXO21 , FBXL7 , PSME4 , FBXW11 , MGRN1 , UBR2 , NEDD4L , UBR4 , UFL1 , MKRN1 , FBXO7 , HECTD1 , ANAPC13 , RNF19A , RCHY1 , LTN1 , HERC4 , WSB1 , FBXW2 , FBXL21 , FBXL3 , FBXO2 , FBXL5 , FBXL4 , KLHL3 , FBXW8 , FBXO22 , FBXO10 , FBXO9 , FBXO6 , FBXO4 , RNF115 , KLHL20 , UBE2S , MYLIP , ANAPC2 , ANAPC4 , KLHL5 , ASB3 , RLIM , HERC5 , MEX3C , FZR1 , ANAPC5 , ANAPC7 , RNF138 , UBE2J1 , ANAPC11 , UBE2D4 , ASB1 , ASB4 , ASB2 , FBXO40 , BTBD1 , FBXW5 , FBXL19 , RNF111 , FBXL12 , UBE2R2 , HERC6 , DET1 , KLHL11 , RNF220 , UBA6 , UBE2W , FBXW7 , FBXL8 , TRIM36 , UBE2Q1 , RNF126 , RNF130 , RNF114 , KLHL9 , TRIM39 , SMURF1 , HECW2 , HACE1 , KLHL42 , SH3RF1 , RNF213 , RNF123 , UBE2O , PJA1 , RNF25 , KLHL25 , ANAPC1 , UNKL , SMURF2 , UBE2Z , FBXL15 , HECTD3 , ASB13 , FBXO31 , UBA5 , FBXL18 , SPSB1 , RNF34 , TRIM11 , ITCH , KBTBD7 , FBXO30 , TRAF7 , FBXW9 , KBTBD8 , TRIM63 , LNX1 , SPSB2 , KLHL22 , ZNRF1 , FBXL20 , TRIM4 , KBTBD6 , UBE3B , UBE3D , BTBD6 , KLHL13 , LRSAM1 , TRIM41 , LONRF1 , SPSB4 , ASB16 , UBE2Q2 , FBXO44 , TRIM9 , FBXO32 , FBXO17 , UBE2J2 , PSMB11 , LRR1 , FBXO27 , ASB17 , RNF19B , TRIM71 , TRIM50 , ASB10 , ASB11 , ASB5 , ASB6 , ASB7 , ASB8 , ASB9 , TRIM69 , UBE2F , MIB2 , ASB15 , ASB14 , ASB12 , HECTD2 , PSMA8 , FBXL14 , FBXL16 , UBE2U , FBXO41 , DTX3L , RNF217 , KCTD7 , CBLL2 , UBR1 , KCTD6 , FBXO15 , TRIM39-RPP21 , RNF182 , FBXL13 , ZNRF2 , CDC26 , RNF144B , FBXL22 , FBXW12 , KBTBD13 , ASB18 , C7orf76 , LOC100506136 , MIR4720 , MIR5193 ,