Entry Name Ubiquitin mediated proteolysis - Homo sapiens (human)
Description Protein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to proteins being degraded is performed by a reaction cascade consisting of three enzymes, named E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin ligase). Each E3 has specificity to its substrate, or proteins to be targeted by ubiquitination. Many E3s are discovered in eukaryotes and they are classified into four types: HECT type, U-box type, single RING-finger type, and multi-subunit RING-finger type. Multi-subunit RING-finger E3s are exemplified by cullin-Rbx E3s and APC/C. They consist of a RING-finger-containing subunit (RBX1 or RBX2) that functions to bind E2s, a scaffold-like cullin molecule, adaptor proteins, and a target recognizing subunit that binds substrates.
Class Genetic Information Processing; Folding, sorting and degradationBRITE hierarchy
Pathway map Drug D12418 Siremadlin succinate (USAN)
D12622 Milademetan tosylate (USAN)
D12842 Brigimadlin (JAN/USAN/INN)
Other DBs Organism Homo sapiens (human) [GN:
hsa ]
Gene 10393 ANAPC10; anaphase-promoting complex subunit 10 isoform 1 [KO:K03357 ]
10401 PIAS3; E3 SUMO-protein ligase PIAS3 [KO:K16064 ] [EC:2.3.2.-]
11060 WWP2; NEDD4-like E3 ubiquitin-protein ligase WWP2 isoform WWP2-FL [KO:K05630 ] [EC:2.3.2.26 ]
1161 ERCC8; DNA excision repair protein ERCC-8 isoform 1 [KO:K10570 ]
119504 ANAPC16; anaphase-promoting complex subunit 16 isoform 1 [KO:K25229 ]
1642 DDB1; DNA damage-binding protein 1 [KO:K10610 ]
1643 DDB2; DNA damage-binding protein 2 isoform WT [KO:K10140 ]
23221 RHOBTB2; rho-related BTB domain-containing protein 2 isoform 3 [KO:K07868 ]
23291 FBXW11; F-box/WD repeat-containing protein 11 isoform C [KO:K03362 ]
23759 PPIL2; RING-type E3 ubiquitin-protein ligase PPIL2 isoform a [KO:K10598 ] [EC:5.2.1.8 ]
246184 CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359 ]
25847 ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456 ]
25898 RCHY1; RING finger and CHY zinc finger domain-containing protein 1 isoform 1 [KO:K10144 ] [EC:2.3.2.27 ]
25906 ANAPC15; anaphase-promoting complex subunit 15 isoform b [KO:K25228 ]
26259 FBXW8; F-box/WD repeat-containing protein 8 isoform 1 [KO:K10264 ]
26272 FBXO4; F-box only protein 4 isoform 1 [KO:K10291 ]
29882 ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349 ]
29945 ANAPC4; anaphase-promoting complex subunit 4 isoform 2 [KO:K03351 ]
329 BIRC2; baculoviral IAP repeat-containing protein 2 isoform 1 [KO:K16060 ]
330 BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060 ]
51343 FZR1; fizzy-related protein homolog isoform 1 [KO:K03364 ]
51433 ANAPC5; anaphase-promoting complex subunit 5 isoform a [KO:K03352 ]
51434 ANAPC7; anaphase-promoting complex subunit 7 isoform a [KO:K03354 ]
51529 ANAPC11; anaphase-promoting complex subunit 11 isoform 2 [KO:K03358 ]
5371 PML; protein PML isoform 1 [KO:K10054 ] [EC:2.3.2.-]
55294 FBXW7; F-box/WD repeat-containing protein 7 isoform 1 [KO:K10260 ]
57448 BIRC6; dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 isoform 1 [KO:K10586 ] [EC:2.3.2.23 ]
6233 RPS27A; ubiquitin-ribosomal protein eS31 fusion protein precursor [KO:K02977 ]
64682 ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348 ]
6500 SKP1; S-phase kinase-associated protein 1 isoform b [KO:K03094 ]
6502 SKP2; S-phase kinase-associated protein 2 isoform 1 [KO:K03875 ]
672 BRCA1; breast cancer type 1 susceptibility protein isoform 1 [KO:K10605 ] [EC:2.3.2.27 ]
7311 UBA52; ubiquitin-ribosomal protein eL40 fusion protein isoform 1 precursor [KO:K02927 ]
7317 UBA1; ubiquitin-like modifier-activating enzyme 1 isoform 1 [KO:K03178 ] [EC:6.2.1.45 ]
7329 UBE2I; SUMO-conjugating enzyme UBC9 [KO:K10577 ]
7428 VHL; von Hippel-Lindau disease tumor suppressor isoform 1 [KO:K03871 ]
79444 BIRC7; baculoviral IAP repeat-containing protein 7 isoform alpha [KO:K16061 ]
8554 PIAS1; E3 SUMO-protein ligase PIAS1 isoform 2 [KO:K04706 ] [EC:2.3.2.-]
8651 SOCS1; suppressor of cytokine signaling 1 [KO:K04694 ]
8697 CDC23; cell division cycle protein 23 homolog [KO:K03355 ]
8881 CDC16; cell division cycle protein 16 homolog isoform 1 [KO:K03353 ]
8916 HERC3; probable E3 ubiquitin-protein ligase HERC3 isoform 1 [KO:K10614 ] [EC:2.3.2.26 ]
8945 BTRC; F-box/WD repeat-containing protein 1A isoform 1 [KO:K03362 ]
9021 SOCS3; suppressor of cytokine signaling 3 [KO:K04696 ]
90293 KLHL13; kelch-like protein 13 isoform a [KO:K10447 ]
9039 UBA3; NEDD8-activating enzyme E1 catalytic subunit isoform 1 [KO:K10686 ] [EC:6.2.1.64 ]
9063 PIAS2; E3 SUMO-protein ligase PIAS2 isoform beta [KO:K16063 ] [EC:2.3.2.-]
9616 RNF7; RING-box protein 2 isoform 1 [KO:K10611 ]
9817 KEAP1; kelch-like ECH-associated protein 1 [KO:K10456 ]
9886 RHOBTB1; rho-related BTB domain-containing protein 1 isoform 1 [KO:K07868 ]
991 CDC20; cell division cycle protein 20 homolog [KO:K03363 ]
996 CDC27; cell division cycle protein 27 homolog isoform 2 [KO:K03350 ]
Reference Authors Kamura T.
Title [Cullin-based E3 family]
Journal Tanpakushitsu Kakusan Koso 51:1167-72 (2006)
Reference Authors Matsuda N.
Title [Overview: hereditary disorders caused by dysfunction of ubiquitylation]
Journal Tanpakushitsu Kakusan Koso 51:1402-7 (2006)
Reference Authors Tokunaga F.
Title [E2 ubiquitin-conjugating enzymes: structures and functions]
Journal Tanpakushitsu Kakusan Koso 51:1150-6 (2006)
Reference Authors Nalepa G, Rolfe M, Harper JW.
Title Drug discovery in the ubiquitin-proteasome system.
Journal Reference Authors Hsu YJ, Goodman SR.
Title Spectrin and ubiquitination: a review.
Journal Cell Mol Biol (Noisy-le-grand) Suppl 51:OL801-7 (2005)
Reference Authors Hatakeyama S, Nakayama KI.
Title Ubiquitylation as a quality control system for intracellular proteins.
Journal Reference Authors Lee J, Zhou P.
Title DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase.
Journal Related KO pathway
