E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification.
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Full-length UBE2F is a NEDD8-conjugating E2, and UBE2F/RBX2 and UBE2M/RBX1 have different target cullin specificities.
"the previously uncharacterized E2 UBE2F is a NEDD8-conjugating enzyme in vitro
and in vivo."
Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.
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Full-length UBE2F neddylates CUL5, which is required for Vif-mediated degradation of APOBEC3G. UBE2F acts upstream of ubiquitin transfer; it is not itself a ubiquitin E2.
"conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating
enzyme UBE2F is required for HIV Vif-mediated degradation"
Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes.
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Canonical UBE2F keeps its initiator methionine, which is N-terminally acetylated. An acetylated peptide of UBE2F residues 1-25 binds the DCNL3 PONY domain. F8WDQ9 contains this whole N-terminal segment unchanged.
"LC-MS/MS analysis revealed UBE2F as retaining its N-terminal methionine and being N-terminally acetylated"
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An N-terminally acetylated UBE2F peptide competitively inhibits DCNL-stimulated NEDD8 transfer in vitro. Any fragment that keeps this segment could, in principle, do the same, but this has not been tested for F8WDQ9.
"N-terminal acetylation was absolutely required for the UBE2F peptide mediated inhibition."
Exact UBE2F product-to-reference sequence mapping
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F8WDQ9 residues 1-94 are identical to Q969M7 residues 1-94. Its residues 95-101 align only weakly to Q969M7 residues 179-185 (2 of 7 identical). It covers 70 of the 154 residues of the UBC core and does not include active-site Cys116.
"| Active site: Glycyl thioester intermediate | 116–116 | 0 / 1 | 0 |"
UniProt entry F8WDQ9
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UniProt's PROSITE rule places F8WDQ9 in the ubiquitin-conjugating enzyme family but warns that it lacks conserved residues needed to propagate the rule's feature annotation, which fits the loss of the active site.
"CAUTION: Lacks conserved residue(s) required for the propagation of"
Frozen exact-input ProtNLM output and UniProt sequence for F8WDQ9