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7bol
From Proteopedia
ubiquitin-conjugating enzyme, Ube2D2
Structural highlights
FunctionUB2D2_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedThe RING domain of MUL1 (RINGMUL1 ) alone mediates ubiquitylation of the p53-transactivation domain (TADp53 ). To elucidate the mechanism underlying the simultaneous recruitment of UBE2D2 and the substrate TADp53 by RINGMUL1 , we determined the complex structure of RINGMUL1 :UBE2D2 and studied the interaction between RINGMUL1 and TADp53 in the presence of UBE2D2-UB thioester (UBE2D2~UB) mimetics. The RINGMUL1 -binding induced the closed conformation of UBE2D2(S22R/C85S) -UB(K48R) oxyester (UBE2D2(RS) -UB(R) OE ), and strongly accelerated its hydrolysis, which was suppressed by the additional N77A-mutation of UBE2D2. Interestingly, UBE2D2(S22R/N77A/C85S) -UB(K48R) oxyester (UBE2D2(RAS) -UB(R) OE ) already formed a closed conformation in the absence of RINGMUL1 . Although TADp53 exhibited weak binding for RINGMUL1 or UBE2D2 alone, its binding affinity was enhanced and even further for RINGMUL1 :UBE2D2 and RINGMUL1 :UBE2D2(RAS) -UB(R) OE , respectively. The recognition of TADp53 by RINGMUL1 as a complex with UBE2D2~UB is related to the multivalency of the binding events and underlies the ability of RINGMUL1 to ubiquitylate the intrinsically disordered protein, TADp53 . MUL1-RING recruits the substrate, p53-TAD as a complex with UBE2D2-UB conjugate.,Lee MS, Lee SO, Choi J, Ryu M, Lee MK, Kim JH, Hwang E, Lee CK, Chi SW, Ryu KS FEBS J. 2022 Jan 19. doi: 10.1111/febs.16360. PMID:35048531[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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