2.3.2.B12: ubiquitin transferase U-box E4
This is an abbreviated version!
For detailed information about ubiquitin transferase U-box E4, go to the full flat file.
Reaction
Synonyms
CHIP, CYC4, DUF1076 domain-containing protein, E4, E4 factor, E4 ligase, E4 ubiquitin ligase, E4 ubiquitin-protein ligase UFD2, MUSE3, PRP19, StoD, STY1076, Ub-conjugating E4 factor, Ube4A, UBE4B, ubiquitin chain elongation enzyme Ufd2, ubiquitin conjugation factor E4, ubiquitin fusion degradation protein 2, Ubr1-dependent E4 enzyme, UFD-2, Ufd2, Ufd2a, Ufd2b, Ufd4, Ufd4-enhancing ubiquitiylation enzyme
ECTree
Advanced search results
General Information
General Information on EC 2.3.2.B12 - ubiquitin transferase U-box E4
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
evolution
-
MUSE3 is a single copy gene encoding a ubiquitin-conjugating E4 factor with a conserved Ub-elongating factor core domain (UFD2p core domain) and a C-terminal U-box domain. Phylogenetic analysis shows that MUSE3 is a highly conserved protein in all sequenced eukaryotes
physiological function
-
E4 is an additional factor working together with ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin transferase E3, in some cases specifically required for multiubiquitin chain polymerization, a function attributed to Ufd2, the first protein designated as an E4
physiological function
-
MUSE3 functions as an E4 factor and works downstream of the E3 ligase SCFCPR1 to facilitate the polyubiquitination and degradation of Resistance proteins, including SNC1 (Supressor of NPR1, Constitutive 1) and RPS2 (Resistance to Pseudomonas syringae 2)
physiological function
-
both coactivators p300 and CREB-binding protein are required for endogenous p53 polyubiquitination and the normally rapid turnover of p53 in unstressed cells. p300/CREB-binding protein ubiquitin ligase activities are absent in nuclear extracts and exclusively cytoplasmic. Consistent with the cytoplasmic localization of its E3/E4 activity, CREB-binding protein deficiency specifically stabilizes cytoplasmic, but not nuclear p53. The N-terminal 616 aa of CREB-binding protein, which includes the conserved Zn2+-binding C/H1-TAZ1 domain, is the minimal domain sufficient to destabilize p53 in vivo, and it includes within an intrinsic E3 autoubiquitination activity and, in a two-step E4 assay, exhibits robust E4 activity for p53
physiological function
DELTANp63alpha, dominant negative isoform of the p63 family, physically interacts with U-box-type E4 ubiquitin ligase UFD2a. UFD2a stabilizes DELTANp63alpha, and ubiquitylation of DELTANp63?alpha is attenuated by UFD2a both in the presence and absence of cisplatin. Ectopic expression of UFD2a increases the half-life of DELTA?Np63alpha in association with a significant enhancement of the repressive transcriptional activity of DELTANp63alpha. Downregulation of endogenous UFD2a by RNAi results in degradation of DELTANp63alpha
physiological function
StoD is a type III secretion systems effector. In HeLa cells expressing StoD, ubiquitin is redistributed into puncta that colocalize with StoD. StoD N- and StoD C-terminus bind the same exposed surface of the beta-sheet of ubiquitin. StoD interacts with both K63- and K48-linked diubiquitin
physiological function
Ube4A is required for complete assembly of specific DNA damage repair factors at double-strand break sites and proper internal organization of double-strand break-associated protein foci. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DNA damage repair and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at double-strand break sites. The pathway is required for optimal end-resection at double-strand breaks, and its abrogation leads to up-regulation of the highly mutagenic alternative end-joining repair at the expense of error-free homologous recombination repair
physiological function
UFD-2 is a mediator of DNA-damage-induced apoptosis. After initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome. In the absence of UFD-2, RAD-51 foci persist, and DNA damage-induced apoptosis is prevented. UFD-2 foci are retained until recombination intermediates are removed by the Holliday-junction-processing enzymes GEN-1, MUS-81 or XPF-1. Formation of UFD-2 foci also requires proapoptotic CEP-1 (p53) signaling
physiological function
Ufd2 catalyses K48-linked multi-monoubiquitination on K29-linked ubiquitin chains assembled by the ubiquitin ligase Ufd4, resulting in branched ubiquitin chains. The reaction depends on the interaction of K29-linked ubiquitin chains with two N-terminal loops of Ufd2. Only following the addition of K48-linked ubiquitin to substrates modified with K29-linked ubiquitin chains, the substrates can be escorted to the proteasome for degradation. This ubiquitin chain linkage switching reaction is essential for ERAD, oleic acid and acid pH resistance in yeast