KEGG   PATHWAY: hsa04120Help
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
BRITE hierarchy
Pathway map
Ubiquitin mediated proteolysis
hsa04120

All organismsOrtholog table
Module
SCF-BTRC complex [PATH:hsa04120]
SCF-SKP2 complex [PATH:hsa04120]
SCF-FBS complex [PATH:hsa04120]
ECV complex [PATH:hsa04120]
Cul3-SPOP complex [PATH:hsa04120]
Cul4-DDB1-DDB2 complex [PATH:hsa04120]
Cul4-DDB1-CSA complex [PATH:hsa04120]
SCF-FBW7 complex [PATH:hsa04120]
ECS complex [PATH:hsa04120]
APC/C complex [PATH:hsa04120]
Disease
H00478  
Prader-Willi and Angelman syndromes
H00509  
3M syndrome
H00559  
von Hippel-Lindau syndrome
H00583  
Opitz-GBBB syndrome
H00593  
Limb-girdle muscular dystrophy (LGMD)
H00658  
Syndromic X-linked mental retardation
H00810  
Progressive myoclonic epilepsy (PME/ EPM)
H01232  
Syndromic multisystem autoimmune disease
H01289  
Mulibrey nanism
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
7317  
UBA1; ubiquitin-like modifier activating enzyme 1 [KO:K03178] [EC:6.3.2.19]
10055  
SAE1; SUMO1 activating enzyme subunit 1 [KO:K10684] [EC:6.3.2.19]
10054  
UBA2; ubiquitin-like modifier activating enzyme 2 [KO:K10685] [EC:6.3.2.19]
9039  
UBA3; ubiquitin-like modifier activating enzyme 3 [KO:K10686] [EC:6.3.2.19]
7318  
UBA7; ubiquitin-like modifier activating enzyme 7 [KO:K10698] [EC:6.3.2.19]
55236  
UBA6; ubiquitin-like modifier activating enzyme 6 [KO:K10699] [EC:6.3.2.19]
7319  
UBE2A; ubiquitin-conjugating enzyme E2A [KO:K10573] [EC:6.3.2.19]
7320  
UBE2B; ubiquitin-conjugating enzyme E2B [KO:K10574] [EC:6.3.2.19]
11065  
UBE2C; ubiquitin-conjugating enzyme E2C [KO:K06688] [EC:6.3.2.19]
10477  
UBE2E3; ubiquitin-conjugating enzyme E2E 3 [KO:K06689] [EC:6.3.2.19]
51619  
UBE2D4; ubiquitin-conjugating enzyme E2D 4 (putative) [KO:K06689] [EC:6.3.2.19]
7321  
UBE2D1; ubiquitin-conjugating enzyme E2D 1 [KO:K06689] [EC:6.3.2.19]
7322  
UBE2D2; ubiquitin-conjugating enzyme E2D 2 [KO:K06689] [EC:6.3.2.19]
7323  
UBE2D3; ubiquitin-conjugating enzyme E2D 3 [KO:K06689] [EC:6.3.2.19]
7324  
UBE2E1; ubiquitin-conjugating enzyme E2E 1 [KO:K06689] [EC:6.3.2.19]
7325  
UBE2E2; ubiquitin-conjugating enzyme E2E 2 [KO:K06689] [EC:6.3.2.19]
140739  
UBE2F; ubiquitin-conjugating enzyme E2F (putative) [KO:K10687] [EC:6.3.2.19]
7326  
UBE2G1; ubiquitin-conjugating enzyme E2G 1 [KO:K10575] [EC:6.3.2.19]
7327  
UBE2G2; ubiquitin-conjugating enzyme E2G 2 [KO:K04555] [EC:6.3.2.19]
7328  
UBE2H; ubiquitin-conjugating enzyme E2H [KO:K10576] [EC:6.3.2.19]
7329  
UBE2I; ubiquitin-conjugating enzyme E2I [KO:K10577] [EC:6.3.2.19]
51465  
UBE2J1; ubiquitin-conjugating enzyme E2, J1 [KO:K10578] [EC:6.3.2.19]
118424  
UBE2J2; ubiquitin-conjugating enzyme E2, J2 [KO:K04554] [EC:6.3.2.19]
7332  
UBE2L3; ubiquitin-conjugating enzyme E2L 3 [KO:K04552] [EC:6.3.2.19]
9246  
UBE2L6; ubiquitin-conjugating enzyme E2L 6 [KO:K04553] [EC:6.3.2.19]
9040  
UBE2M; ubiquitin-conjugating enzyme E2M [KO:K10579] [EC:6.3.2.19]
389898  
UBE2NL; ubiquitin-conjugating enzyme E2N-like [KO:K10580] [EC:6.3.2.19]
7334  
UBE2N; ubiquitin-conjugating enzyme E2N [KO:K10580] [EC:6.3.2.19]
63893  
UBE2O; ubiquitin-conjugating enzyme E2O [KO:K10581] [EC:6.3.2.19]
55585  
UBE2Q1; ubiquitin-conjugating enzyme E2Q family member 1 [KO:K10582] [EC:6.3.2.19]
92912  
UBE2Q2; ubiquitin-conjugating enzyme E2Q family member 2 [KO:K10582] [EC:6.3.2.19]
134111  
UBE2QL1; ubiquitin-conjugating enzyme E2Q family-like 1 [KO:K10582] [EC:6.3.2.19]
54926  
UBE2R2; ubiquitin-conjugating enzyme E2R 2 [KO:K02207] [EC:6.3.2.19]
997  
CDC34; cell division cycle 34 [KO:K02207] [EC:6.3.2.19]
27338  
UBE2S; ubiquitin-conjugating enzyme E2S [KO:K10583] [EC:6.3.2.19]
148581  
UBE2U; ubiquitin-conjugating enzyme E2U (putative) [KO:K10584] [EC:6.3.2.19]
55284  
UBE2W; ubiquitin-conjugating enzyme E2W (putative) [KO:K10688] [EC:6.3.2.19]
65264  
UBE2Z; ubiquitin-conjugating enzyme E2Z [KO:K10585] [EC:6.3.2.19]
3093  
UBE2K; ubiquitin-conjugating enzyme E2K [KO:K04649] [EC:6.3.2.19]
57448  
BIRC6; baculoviral IAP repeat containing 6 [KO:K10586] [EC:6.3.2.19]
7337  
UBE3A; ubiquitin protein ligase E3A [KO:K10587] [EC:6.3.2.19]
89910  
UBE3B; ubiquitin protein ligase E3B [KO:K10588] [EC:6.3.2.19]
9690  
UBE3C; ubiquitin protein ligase E3C [KO:K10589] [EC:6.3.2.19]
57154  
SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:6.3.2.19]
64750  
SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:6.3.2.19]
83737  
ITCH; itchy E3 ubiquitin protein ligase [KO:K05632] [EC:6.3.2.19]
11059  
WWP1; WW domain containing E3 ubiquitin protein ligase 1 [KO:K05633] [EC:6.3.2.19]
11060  
WWP2; WW domain containing E3 ubiquitin protein ligase 2 [KO:K05630] [EC:6.3.2.19]
9320  
TRIP12; thyroid hormone receptor interactor 12 [KO:K10590] [EC:6.3.2.19]
4734  
NEDD4; neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase [KO:K10591] [EC:6.3.2.19]
23327  
NEDD4L; neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase [KO:K13305] [EC:6.3.2.19]
10075  
HUWE1; HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase [KO:K10592] [EC:6.3.2.19]
51366  
UBR5; ubiquitin protein ligase E3 component n-recognin 5 [KO:K10593] [EC:6.3.2.19]
8925  
HERC1; HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 [KO:K10594] [EC:6.3.2.19]
8924  
HERC2; HECT and RLD domain containing E3 ubiquitin protein ligase 2 [KO:K10595] [EC:6.3.2.19]
8916  
HERC3; HECT and RLD domain containing E3 ubiquitin protein ligase 3 [KO:K10614] [EC:6.3.2.19]
26091  
HERC4; HECT and RLD domain containing E3 ubiquitin protein ligase 4 [KO:K10615] [EC:6.3.2.19]
9354  
UBE4A; ubiquitination factor E4A [KO:K10596] [EC:6.3.2.19]
10277  
UBE4B; ubiquitination factor E4B [KO:K10597] [EC:6.3.2.19]
10273  
STUB1; STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase [KO:K09561] [EC:6.3.2.19]
23759  
PPIL2; peptidylprolyl isomerase (cyclophilin)-like 2 [KO:K10598] [EC:5.2.1.8]
27339  
PRPF19; pre-mRNA processing factor 19 [KO:K10599] [EC:6.3.2.19]
22888  
UBOX5; U-box domain containing 5 [KO:K10600]
4193  
MDM2; MDM2 proto-oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
23624  
CBLC; Cbl proto-oncogene C, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
867  
CBL; Cbl proto-oncogene, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
868  
CBLB; Cbl proto-oncogene B, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
5071  
PARK2; parkin RBR E3 ubiquitin protein ligase [KO:K04556] [EC:6.3.2.19]
6477  
SIAH1; siah E3 ubiquitin protein ligase 1 [KO:K04506] [EC:6.3.2.19]
5371  
PML; promyelocytic leukemia [KO:K10054]
7189  
TRAF6; TNF receptor-associated factor 6, E3 ubiquitin protein ligase [KO:K03175]
4214  
MAP3K1; mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase [KO:K04416] [EC:2.7.11.25]
64326  
RFWD2; ring finger and WD repeat domain 2, E3 ubiquitin protein ligase [KO:K10143] [EC:6.3.2.19]
25898  
RCHY1; ring finger and CHY zinc finger domain containing 1, E3 ubiquitin protein ligase [KO:K10144] [EC:6.3.2.19]
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]
79444  
BIRC7; baculoviral IAP repeat containing 7 [KO:K16061]
112401  
BIRC8; baculoviral IAP repeat containing 8 [KO:K16061]
8554  
PIAS1; protein inhibitor of activated STAT, 1 [KO:K04706] [EC:6.3.2.-]
9063  
PIAS2; protein inhibitor of activated STAT, 2 [KO:K16063] [EC:6.3.2.-]
10401  
PIAS3; protein inhibitor of activated STAT, 3 [KO:K16064] [EC:6.3.2.-]
51588  
PIAS4; protein inhibitor of activated STAT, 4 [KO:K16065] [EC:6.3.2.-]
84447  
SYVN1; synovial apoptosis inhibitor 1, synoviolin [KO:K10601] [EC:6.3.2.19]
378884  
NHLRC1; NHL repeat containing E3 ubiquitin protein ligase 1 [KO:K10602] [EC:6.3.2.19]
326  
AIRE; autoimmune regulator [KO:K10603]
23295  
MGRN1; mahogunin ring finger 1, E3 ubiquitin protein ligase [KO:K10604] [EC:6.3.2.19]
672  
BRCA1; breast cancer 1, early onset [KO:K10605]
55120  
FANCL; Fanconi anemia, complementation group L [KO:K10606] [EC:6.3.2.19]
4281  
MID1; midline 1 [KO:K08285] [EC:6.3.2.19]
22954  
TRIM32; tripartite motif containing 32 [KO:K10607] [EC:6.3.2.19]
4591  
TRIM37; tripartite motif containing 37 [KO:K10608] [EC:6.3.2.19]
9978  
RBX1; ring-box 1, E3 ubiquitin protein ligase [KO:K03868]
8454  
CUL1; cullin 1 [KO:K03347]
6500  
SKP1; S-phase kinase-associated protein 1 [KO:K03094]
8945  
BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
23291  
FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
6502  
SKP2; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase [KO:K03875]
55294  
FBXW7; F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase [KO:K10260]
26232  
FBXO2; F-box protein 2 [KO:K10099]
26272  
FBXO4; F-box protein 4 [KO:K10291]
8453  
CUL2; cullin 2 [KO:K03870]
6921  
TCEB1; transcription elongation factor B (SIII), polypeptide 1 (15kDa, elongin C) [KO:K03872]
6923  
TCEB2; transcription elongation factor B (SIII), polypeptide 2 (18kDa, elongin B) [KO:K03873]
7428  
VHL; von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase [KO:K03871]
8452  
CUL3; cullin 3 [KO:K03869]
9817  
KEAP1; kelch-like ECH-associated protein 1 [KO:K10456]
55958  
KLHL9; kelch-like family member 9 [KO:K10447]
90293  
KLHL13; kelch-like family member 13 [KO:K10447]
23221  
RHOBTB2; Rho-related BTB domain containing 2 [KO:K07868]
9886  
RHOBTB1; Rho-related BTB domain containing 1 [KO:K07868]
8450  
CUL4B; cullin 4B [KO:K10609]
8451  
CUL4A; cullin 4A [KO:K10609]
1642  
DDB1; damage-specific DNA binding protein 1, 127kDa [KO:K10610]
1643  
DDB2; damage-specific DNA binding protein 2, 48kDa [KO:K10140]
1161  
ERCC8; excision repair cross-complementation group 8 [KO:K10570]
55070  
DET1; de-etiolated homolog 1 (Arabidopsis) [KO:K10571]
9616  
RNF7; ring finger protein 7 [KO:K10611]
8065  
CUL5; cullin 5 [KO:K10612]
8651  
SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
9021  
SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
9820  
CUL7; cullin 7 [KO:K10613]
26259  
FBXW8; F-box and WD repeat domain containing 8 [KO:K10264]
51529  
ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
29882  
ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
991  
CDC20; cell division cycle 20 [KO:K03363]
51343  
FZR1; fizzy/cell division cycle 20 related 1 (Drosophila) [KO:K03364]
64682  
ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
996  
CDC27; cell division cycle 27 [KO:K03350]
29945  
ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
51433  
ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
8881  
CDC16; cell division cycle 16 [KO:K03353]
51434  
ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
8697  
CDC23; cell division cycle 23 [KO:K03355]
10393  
ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
246184  
CDC26; cell division cycle 26 [KO:K03359]
25847  
ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
Reference
PMID:16922370 (Japanese)
  Authors
Kamura T.
  Title
[Cullin-based E3 family] Japanese
  Journal
Tanpakushitsu Kakusan Koso 51:1167-72 (2006)
Reference
PMID:16922408 (Japanese)
  Authors
Matsuda N.
  Title
[Overview: hereditary disorders caused by dysfunction of ubiquitylation]
  Journal
Tanpakushitsu Kakusan Koso 51:1402-7 (2006)
Reference
PMID:16922367 (Japanese)
  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
Nat Rev Drug Discov 5:596-613 (2006)
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
J Biochem 134:1-8 (2003)
Reference
  Authors
Lee J, Zhou P.
  Title
DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase.
  Journal
Mol Cell 26:775-80 (2007)
KO pathway
 

DBGET integrated database retrieval system