KEGG   PATHWAY: hsa04120
Entry
hsa04120                    Pathway                                
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 degradation
Pathway map
hsa04120  Ubiquitin mediated proteolysis
hsa04120

Network
nt06463  Parkinson disease
nt06466  Pathways of neurodegeneration
  Element
N01019  Parkin-mediated ubiquitination
N01021  Parkin-mediated ubiquitination
N01023  Parkin-mediated ubiquitination
N01025  Parkin-mediated ubiquitination
Drug
D11219  Idasanutlin (USAN/INN)
D12268  Subasumstat (USAN/INN)
D12378  Navtemadlin (USAN/INN)
D12417  Siremadlin (USAN/INN)
D12418  Siremadlin succinate (USAN)
D12621  Milademetan (USAN/INN)
D12622  Milademetan tosylate (USAN)
D12842  Brigimadlin (JAN/USAN/INN)
Other DBs
GO: 0016567
Organism
Homo sapiens (human) [GN:hsa]
Gene
10054  UBA2; ubiquitin like modifier activating enzyme 2 [KO:K10685] [EC:6.2.1.45]
10055  SAE1; SUMO1 activating enzyme subunit 1 [KO:K10684] [EC:6.2.1.45]
10075  HUWE1; HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1 [KO:K10592] [EC:2.3.2.26]
10273  STUB1; STIP1 homology and U-box containing protein 1 [KO:K09561] [EC:2.3.2.27]
10277  UBE4B; ubiquitination factor E4B [KO:K10597] [EC:2.3.2.27]
10393  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
10401  PIAS3; protein inhibitor of activated STAT 3 [KO:K16064] [EC:2.3.2.-]
10477  UBE2E3; ubiquitin conjugating enzyme E2 E3 [KO:K20217] [EC:2.3.2.23]
11059  WWP1; WW domain containing E3 ubiquitin protein ligase 1 [KO:K05633] [EC:2.3.2.26]
11060  WWP2; WW domain containing E3 ubiquitin protein ligase 2 [KO:K05630] [EC:2.3.2.26]
11065  UBE2C; ubiquitin conjugating enzyme E2 C [KO:K06688] [EC:2.3.2.23]
1161  ERCC8; ERCC excision repair 8, CSA ubiquitin ligase complex subunit [KO:K10570]
118424  UBE2J2; ubiquitin conjugating enzyme E2 J2 [KO:K04554] [EC:2.3.2.23]
119504  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
134111  UBE2QL1; ubiquitin conjugating enzyme E2 QL1 [KO:K10582] [EC:2.3.2.23]
140739  UBE2F; ubiquitin conjugating enzyme E2 F (putative) [KO:K10687] [EC:2.3.2.34]
148581  UBE2U; ubiquitin conjugating enzyme E2 U [KO:K10584] [EC:2.3.2.23]
1642  DDB1; damage specific DNA binding protein 1 [KO:K10610]
1643  DDB2; damage specific DNA binding protein 2 [KO:K10140]
22888  UBOX5; U-box domain containing 5 [KO:K10600]
22954  TRIM32; tripartite motif containing 32 [KO:K10607] [EC:2.3.2.27]
23221  RHOBTB2; Rho related BTB domain containing 2 [KO:K07868]
23291  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
23295  MGRN1; mahogunin ring finger 1 [KO:K10604] [EC:2.3.2.27]
23327  NEDD4L; NEDD4 like E3 ubiquitin protein ligase [KO:K13305] [EC:2.3.2.26]
23624  CBLC; Cbl proto-oncogene C [KO:K22518] [EC:2.3.2.27]
23759  PPIL2; peptidylprolyl isomerase like 2 [KO:K10598] [EC:5.2.1.8]
246184  CDC26; cell division cycle 26 [KO:K03359]
25847  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
25898  RCHY1; ring finger and CHY zinc finger domain containing 1 [KO:K10144] [EC:2.3.2.27]
25906  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
26091  HERC4; HECT and RLD domain containing E3 ubiquitin protein ligase 4 [KO:K10615] [EC:2.3.2.26]
26232  FBXO2; F-box protein 2 [KO:K10099]
26259  FBXW8; F-box and WD repeat domain containing 8 [KO:K10264]
26272  FBXO4; F-box protein 4 [KO:K10291]
27338  UBE2S; ubiquitin conjugating enzyme E2 S [KO:K10583] [EC:2.3.2.23]
27339  PRPF19; pre-mRNA processing factor 19 [KO:K10599] [EC:2.3.2.27]
29882  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
29945  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
3093  UBE2K; ubiquitin conjugating enzyme E2 K [KO:K04649] [EC:2.3.2.23]
326  AIRE; autoimmune regulator [KO:K10603]
329  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
330  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
331  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
378884  NHLRC1; NHL repeat containing E3 ubiquitin protein ligase 1 [KO:K10602] [EC:2.3.2.27]
389898  UBE2NL; ubiquitin conjugating enzyme E2 N like (gene/pseudogene) [KO:K10580] [EC:2.3.2.23]
4193  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
4214  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
4281  MID1; midline 1 [KO:K08285] [EC:2.3.2.27]
4591  TRIM37; tripartite motif containing 37 [KO:K10608] [EC:2.3.2.27]
4734  NEDD4; NEDD4 E3 ubiquitin protein ligase [KO:K10591] [EC:2.3.2.26]
5071  PRKN; parkin RBR E3 ubiquitin protein ligase [KO:K04556] [EC:2.3.2.31]
51343  FZR1; fizzy and cell division cycle 20 related 1 [KO:K03364]
51366  UBR5; ubiquitin protein ligase E3 component n-recognin 5 [KO:K10593] [EC:2.3.2.26]
51433  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
51434  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
51465  UBE2J1; ubiquitin conjugating enzyme E2 J1 [KO:K10578] [EC:2.3.2.23]
51529  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
51588  PIAS4; protein inhibitor of activated STAT 4 [KO:K16065] [EC:2.3.2.27]
51619  UBE2D4; ubiquitin conjugating enzyme E2 D4 [KO:K06689] [EC:2.3.2.23]
5371  PML; PML nuclear body scaffold [KO:K10054] [EC:2.3.2.-]
54926  UBE2R2; ubiquitin conjugating enzyme E2 R2 [KO:K02207] [EC:2.3.2.23]
55070  DET1; DET1 partner of COP1 E3 ubiquitin ligase [KO:K10571]
55120  FANCL; FA complementation group L [KO:K10606] [EC:2.3.2.27]
55236  UBA6; ubiquitin like modifier activating enzyme 6 [KO:K10699] [EC:6.2.1.45]
55284  UBE2W; ubiquitin conjugating enzyme E2 W [KO:K10688] [EC:2.3.2.23 2.3.2.25]
55294  FBXW7; F-box and WD repeat domain containing 7 [KO:K10260]
55585  UBE2Q1; ubiquitin conjugating enzyme E2 Q1 [KO:K10582] [EC:2.3.2.23]
55958  KLHL9; kelch like family member 9 [KO:K10447]
57154  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
57448  BIRC6; baculoviral IAP repeat containing 6 [KO:K10586] [EC:2.3.2.23]
6233  RPS27A; ribosomal protein S27a [KO:K02977]
63893  UBE2O; ubiquitin conjugating enzyme E2 O [KO:K10581] [EC:2.3.2.24]
64326  COP1; COP1 E3 ubiquitin ligase [KO:K10143] [EC:2.3.2.27]
64682  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
64750  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
6477  SIAH1; siah E3 ubiquitin protein ligase 1 [KO:K04506] [EC:2.3.2.27]
6500  SKP1; S-phase kinase associated protein 1 [KO:K03094]
6502  SKP2; S-phase kinase associated protein 2 [KO:K03875]
65264  UBE2Z; ubiquitin conjugating enzyme E2 Z [KO:K10585] [EC:2.3.2.23]
672  BRCA1; BRCA1 DNA repair associated [KO:K10605] [EC:2.3.2.27]
6921  ELOC; elongin C [KO:K03872]
6923  ELOB; elongin B [KO:K03873]
7189  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
7311  UBA52; ubiquitin A-52 residue ribosomal protein fusion product 1 [KO:K02927]
7314  UBB; ubiquitin B [KO:K04551]
7316  UBC; ubiquitin C [KO:K08770]
7317  UBA1; ubiquitin like modifier activating enzyme 1 [KO:K03178] [EC:6.2.1.45]
7318  UBA7; ubiquitin like modifier activating enzyme 7 [KO:K10698] [EC:6.2.1.45]
7319  UBE2A; ubiquitin conjugating enzyme E2 A [KO:K10573] [EC:2.3.2.23]
7320  UBE2B; ubiquitin conjugating enzyme E2 B [KO:K10574] [EC:2.3.2.23]
7321  UBE2D1; ubiquitin conjugating enzyme E2 D1 [KO:K06689] [EC:2.3.2.23]
7322  UBE2D2; ubiquitin conjugating enzyme E2 D2 [KO:K06689] [EC:2.3.2.23]
7323  UBE2D3; ubiquitin conjugating enzyme E2 D3 [KO:K06689] [EC:2.3.2.23]
7324  UBE2E1; ubiquitin conjugating enzyme E2 E1 [KO:K20217] [EC:2.3.2.23]
7325  UBE2E2; ubiquitin conjugating enzyme E2 E2 [KO:K20217] [EC:2.3.2.23]
7326  UBE2G1; ubiquitin conjugating enzyme E2 G1 [KO:K10575] [EC:2.3.2.23]
7327  UBE2G2; ubiquitin conjugating enzyme E2 G2 [KO:K04555] [EC:2.3.2.23]
7328  UBE2H; ubiquitin conjugating enzyme E2 H [KO:K10576] [EC:2.3.2.23]
7329  UBE2I; ubiquitin conjugating enzyme E2 I [KO:K10577]
7332  UBE2L3; ubiquitin conjugating enzyme E2 L3 [KO:K04552] [EC:2.3.2.23]
7334  UBE2N; ubiquitin conjugating enzyme E2 N [KO:K10580] [EC:2.3.2.23]
7337  UBE3A; ubiquitin protein ligase E3A [KO:K10587] [EC:2.3.2.26]
7428  VHL; von Hippel-Lindau tumor suppressor [KO:K03871]
79444  BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]
8065  CUL5; cullin 5 [KO:K10612]
83737  ITCH; itchy E3 ubiquitin protein ligase [KO:K05632] [EC:2.3.2.26]
84447  SYVN1; synoviolin 1 [KO:K10601] [EC:2.3.2.27]
8450  CUL4B; cullin 4B [KO:K10609]
8451  CUL4A; cullin 4A [KO:K10609]
8452  CUL3; cullin 3 [KO:K03869]
8453  CUL2; cullin 2 [KO:K03870]
8454  CUL1; cullin 1 [KO:K03347]
8554  PIAS1; protein inhibitor of activated STAT 1 [KO:K04706] [EC:2.3.2.-]
8651  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
867  CBL; Cbl proto-oncogene [KO:K04707] [EC:2.3.2.27]
868  CBLB; Cbl proto-oncogene B [KO:K22517] [EC:2.3.2.27]
8697  CDC23; cell division cycle 23 [KO:K03355]
8881  CDC16; cell division cycle 16 [KO:K03353]
8916  HERC3; HECT and RLD domain containing E3 ubiquitin protein ligase 3 [KO:K10614] [EC:2.3.2.26]
8924  HERC2; HECT and RLD domain containing E3 ubiquitin protein ligase 2 [KO:K10595] [EC:2.3.2.26]
8925  HERC1; HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 [KO:K10594] [EC:2.3.2.26]
8945  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
89910  UBE3B; ubiquitin protein ligase E3B [KO:K10588] [EC:2.3.2.26]
9021  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
90293  KLHL13; kelch like family member 13 [KO:K10447]
9039  UBA3; ubiquitin like modifier activating enzyme 3 [KO:K10686] [EC:6.2.1.64]
9040  UBE2M; ubiquitin conjugating enzyme E2 M [KO:K10579] [EC:2.3.2.34]
9063  PIAS2; protein inhibitor of activated STAT 2 [KO:K16063] [EC:2.3.2.-]
9246  UBE2L6; ubiquitin conjugating enzyme E2 L6 [KO:K04553] [EC:2.3.2.23]
92912  UBE2Q2; ubiquitin conjugating enzyme E2 Q2 [KO:K10582] [EC:2.3.2.23]
9320  TRIP12; thyroid hormone receptor interactor 12 [KO:K10590] [EC:2.3.2.26]
9354  UBE4A; ubiquitination factor E4A [KO:K10596] [EC:2.3.2.27]
9616  RNF7; ring finger protein 7 [KO:K10611]
9690  UBE3C; ubiquitin protein ligase E3C [KO:K10589] [EC:2.3.2.26]
9817  KEAP1; kelch like ECH associated protein 1 [KO:K10456]
9820  CUL7; cullin 7 [KO:K10613]
9886  RHOBTB1; Rho related BTB domain containing 1 [KO:K07868]
991  CDC20; cell division cycle 20 [KO:K03363]
996  CDC27; cell division cycle 27 [KO:K03350]
997  CDC34; cell division cycle 34, ubiqiutin conjugating enzyme [KO:K02207] [EC:2.3.2.23]
9978  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
Reference
PMID:16922370
  Authors
Kamura T.
  Title
[Cullin-based E3 family]
  Journal
Tanpakushitsu Kakusan Koso 51:1167-72 (2006)
Reference
PMID:16922408
  Authors
Matsuda N.
  Title
[Overview: hereditary disorders caused by dysfunction of ubiquitylation]
  Journal
Tanpakushitsu Kakusan Koso 51:1402-7 (2006)
Reference
PMID:16922367
  Authors
Tokunaga F.
  Title
[E2 ubiquitin-conjugating enzymes: structures and functions]
  Journal
Tanpakushitsu Kakusan Koso 51:1150-6 (2006)
Reference
PMID:16816840
  Authors
Nalepa G, Rolfe M, Harper JW.
  Title
Drug discovery in the ubiquitin-proteasome system.
  Journal
Nat Rev Drug Discov 5:596-613 (2006)
DOI:10.1038/nrd2056
Reference
PMID:16405856
  Authors
Hsu YJ, Goodman SR.
  Title
Spectrin and ubiquitination: a review.
  Journal
Cell Mol Biol (Noisy-le-grand) Suppl 51:OL801-7 (2005)
Reference
PMID:12944364
  Authors
Hatakeyama S, Nakayama KI.
  Title
Ubiquitylation as a quality control system for intracellular proteins.
  Journal
J Biochem 134:1-8 (2003)
DOI:10.1093/jb/mvg106
Reference
PMID:17588513
  Authors
Lee J, Zhou P.
  Title
DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase.
  Journal
Mol Cell 26:775-80 (2007)
DOI:10.1016/j.molcel.2007.06.001
Related
pathway
hsa03050  Proteasome
KO pathway
ko04120   

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