Reactome | NEDD8-UBA3:NAE1 binds a second NEDD8

NEDD8-UBA3:NAE1 binds a second NEDD8

Stable Identifier

R-HSA-8951656

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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After covalent attachment of the first NEDD8 molecule to the catalytic cysteine, a second NEDD8 binds to the now-free adenylation site on the UBA3 subunit of UBA3:NAE1. This 'doubly-loaded' E1 enzyme is primed to transfer the covalently-bound NEDD8 to the downstream E2 enzyme (Huang et al, 2005; Huang et al, 2007; reviewed in Enchev et al, 2015). Note that although not depicted here, the second NEDD8 moiety is covalently adenylated at its C-terminal glycine residue at the end of this reaction.

Literature References

PubMed ID	Title	Journal	Year
17220875	Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity Huang, DT, Ohi, MD, Hunt, HW, Schulman, BA, Holton, JM, Zhuang, M	Nature	2007
15694336	Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1 Huang, DT, Schulman, BA, Holton, JM, Paydar, A, Waddell, MB, Zhuang, M	Mol. Cell	2005
25531226	Protein neddylation: beyond cullin-RING ligases Schulman, BA, Enchev, RI, Peter, M	Nat. Rev. Mol. Cell Biol.	2015