KEGG   PATHWAY: ko04120
ko04120                     Pathway                                

Ubiquitin mediated proteolysis
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.
Genetic Information Processing; Folding, sorting and degradation
Pathway map
ko04120  Ubiquitin mediated proteolysis

H00509  3M syndrome
H00559  von Hippel-Lindau syndrome
H00583  Opitz-GBBB syndrome
H00593  Limb-girdle muscular dystrophy
H00658  Syndromic X-linked mental retardation
H01232  Syndromic multisystem autoimmune disease
H01289  Mulibrey nanism
H01732  Angelman syndrome
H02131  UV-sensitive syndrome
H02298  Macrocephaly, dysmorphic facies, and psychomotor retardation
Other DBs
GO: 0016567
K04551  ubiquitin B
K08770  ubiquitin C
K02927  ubiquitin-large subunit ribosomal protein L40e
K02977  ubiquitin-small subunit ribosomal protein S27Ae
K03178  ubiquitin-activating enzyme E1 [EC:]
K10684  ubiquitin-like 1-activating enzyme E1 A [EC:]
K10685  ubiquitin-like 1-activating enzyme E1 B [EC:]
K10686  NEDD8-activating enzyme E1 [EC:]
K10698  ubiquitin-activating enzyme E1-like [EC:]
K10699  ubiquitin-activating enzyme E1-like protein 2 [EC:]
K10573  ubiquitin-conjugating enzyme E2 A [EC:]
K10574  ubiquitin-conjugating enzyme E2 B [EC:]
K06688  ubiquitin-conjugating enzyme E2 C [EC:]
K06689  ubiquitin-conjugating enzyme E2 D [EC:]
K20217  ubiquitin-conjugating enzyme E2 E [EC:]
K10687  ubiquitin-conjugating enzyme E2 F [EC:]
K10575  ubiquitin-conjugating enzyme E2 G1 [EC:]
K04555  ubiquitin-conjugating enzyme E2 G2 [EC:]
K10576  ubiquitin-conjugating enzyme E2 H [EC:]
K10577  ubiquitin-conjugating enzyme E2 I
K10578  ubiquitin-conjugating enzyme E2 J1 [EC:]
K04554  ubiquitin-conjugating enzyme E2 J2 [EC:]
K04552  ubiquitin-conjugating enzyme E2 L3 [EC:]
K04553  ubiquitin-conjugating enzyme E2 L6 [EC:]
K10579  ubiquitin-conjugating enzyme E2 M [EC:]
K10580  ubiquitin-conjugating enzyme E2 N [EC:]
K10581  ubiquitin-conjugating enzyme E2 O [EC:]
K10582  ubiquitin-conjugating enzyme E2 Q [EC:]
K02207  ubiquitin-conjugating enzyme E2 R [EC:]
K10583  ubiquitin-conjugating enzyme E2 S [EC:]
K10584  ubiquitin-conjugating enzyme E2 U [EC:]
K10688  ubiquitin-conjugating enzyme E2 W [EC:]
K10585  ubiquitin-conjugating enzyme E2 Z [EC:]
K04649  ubiquitin-conjugating enzyme (huntingtin interacting protein 2) [EC:]
K10586  baculoviral IAP repeat-containing protein 6 (apollon) [EC:]
K10587  ubiquitin-protein ligase E3 A [EC:]
K10588  ubiquitin-protein ligase E3 B [EC:]
K10589  ubiquitin-protein ligase E3 C [EC:]
K04678  E3 ubiquitin ligase SMURF1/2 [EC:]
K05632  E3 ubiquitin-protein ligase Itchy [EC:]
K05633  NEDD4-like E3 ubiquitin-protein ligase WWP1 [EC:]
K05630  NEDD4-like E3 ubiquitin-protein ligase WWP2 [EC:]
K10590  E3 ubiquitin-protein ligase TRIP12 [EC:]
K10591  E3 ubiquitin-protein ligase NEDD4 [EC:]
K13305  E3 ubiquitin-protein ligase NEDD4-like [EC:]
K10592  E3 ubiquitin-protein ligase HUWE1 [EC:]
K10593  E3 ubiquitin-protein ligase EDD1 [EC:]
K10594  E3 ubiquitin-protein ligase HERC1 [EC:]
K10595  E3 ubiquitin-protein ligase HERC2 [EC:]
K10614  E3 ubiquitin-protein ligase HERC3 [EC:]
K10615  E3 ubiquitin-protein ligase HERC4 [EC:]
K10596  ubiquitin conjugation factor E4 A [EC:]
K10597  ubiquitin conjugation factor E4 B [EC:]
K09561  STIP1 homology and U-box containing protein 1 [EC:]
K10598  peptidyl-prolyl cis-trans isomerase-like 2 [EC:]
K10599  pre-mRNA-processing factor 19 [EC:]
K10600  U-box domain-containing protein 5
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:]
K04707  E3 ubiquitin-protein ligase CBL [EC:]
K22517  E3 ubiquitin-protein ligase CBL-B [EC:]
K22518  E3 ubiquitin-protein ligase CBL-C [EC:]
K04556  parkin [EC:]
K04506  E3 ubiquitin-protein ligase SIAH1 [EC:]
K10054  probable transcription factor PML
K03175  TNF receptor-associated factor 6 [EC:]
K04416  mitogen-activated protein kinase kinase kinase 1 [EC:]
K10143  E3 ubiquitin-protein ligase RFWD2 [EC:]
K10144  RING finger and CHY zinc finger domain-containing protein 1 [EC:]
K16060  baculoviral IAP repeat-containing protein 2/3
K04725  E3 ubiquitin-protein ligase XIAP [EC:]
K16061  baculoviral IAP repeat-containing protein 7/8
K04706  E3 SUMO-protein ligase PIAS1 [EC:2.3.2.-]
K16063  E3 SUMO-protein ligase PIAS2 [EC:2.3.2.-]
K16064  E3 SUMO-protein ligase PIAS3 [EC:2.3.2.-]
K16065  E3 SUMO-protein ligase PIAS4 [EC:]
K10601  E3 ubiquitin-protein ligase synoviolin [EC:]
K10602  E3 ubiquitin-protein ligase NHLRC1 [EC:]
K10603  autoimmune regulator
K10604  E3 ubiquitin-protein ligase MGRN1 [EC:]
K10605  breast cancer type 1 susceptibility protein [EC:]
K10606  E3 ubiquitin-protein ligase FANCL [EC:]
K08285  midline 1 [EC:]
K10607  tripartite motif-containing protein 32 [EC:]
K10608  tripartite motif-containing protein 37 [EC:]
K03868  E3 ubiquitin-protein ligase RBX1 [EC:]
K03347  cullin 1
K03094  S-phase kinase-associated protein 1
K03362  F-box and WD-40 domain protein 1/11
K03875  F-box and leucine-rich repeat protein 1 (S-phase kinase-associated protein 2)
K10260  F-box and WD-40 domain protein 7
K10099  F-box protein 2
K10291  F-box protein 4
K03361  F-box and WD-40 domain protein CDC4
K10259  F-box and WD-40 domain protein MET30
K03360  F-box and leucine-rich repeat protein GRR1
K03870  cullin 2
K03872  elongin-C
K03873  elongin-B
K03871  von Hippel-Lindau disease tumor supressor
K03869  cullin 3
K10456  kelch-like protein 19
K10447  kelch-like protein 9/13
K07868  Rho-related BTB domain-containing protein 1/2
K03876  BTB domain ubiquitin protein ligase cofactor
K10609  cullin 4
K10610  DNA damage-binding protein 1
K10140  DNA damage-binding protein 2
K10570  DNA excision repair protein ERCC-8
K10571  de-etiolated-1
K10611  RING-box protein 2
K10612  cullin 5
K04694  suppressor of cytokine signaling 1
K04696  suppressor of cytokine signaling 3
K10613  cullin 7
K10264  F-box and WD-40 domain protein 8
K03358  anaphase-promoting complex subunit 11
K03349  anaphase-promoting complex subunit 2
K03363  cell division cycle 20, cofactor of APC complex
K03364  cell division cycle 20-like protein 1, cofactor of APC complex
K03348  anaphase-promoting complex subunit 1
K03350  anaphase-promoting complex subunit 3
K03351  anaphase-promoting complex subunit 4
K03352  anaphase-promoting complex subunit 5
K03353  anaphase-promoting complex subunit 6
K03354  anaphase-promoting complex subunit 7
K03355  anaphase-promoting complex subunit 8
K03356  anaphase-promoting complex subunit 9
K03357  anaphase-promoting complex subunit 10
K03359  anaphase-promoting complex subunit 12
K12456  anaphase-promoting complex subunit 13
K12416  anaphase-promoting complex subunit SWM1
PMID:16922370 (Japanese)
Kamura T.
[Cullin-based E3 family] Japanese
Tanpakushitsu Kakusan Koso 51:1167-72 (2006)
PMID:16922408 (Japanese)
Matsuda N.
[Overview: hereditary disorders caused by dysfunction of ubiquitylation]
Tanpakushitsu Kakusan Koso 51:1402-7 (2006)
PMID:16922367 (Japanese)
Tokunaga F.
[E2 ubiquitin-conjugating enzymes: structures and functions]
Tanpakushitsu Kakusan Koso 51:1150-6 (2006)
Nalepa G, Rolfe M, Harper JW.
Drug discovery in the ubiquitin-proteasome system.
Nat Rev Drug Discov 5:596-613 (2006)
Hsu YJ, Goodman SR.
Spectrin and ubiquitination: a review.
Cell Mol Biol (Noisy-le-grand) Suppl 51:OL801-7 (2005)
Hatakeyama S, Nakayama KI.
Ubiquitylation as a quality control system for intracellular proteins.
J Biochem 134:1-8 (2003)
Lee J, Zhou P.
DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase.
Mol Cell 26:775-80 (2007)
ko03050  Proteasome

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