Reactome | Ub-Cys632-UBA1 adenylates ubiquitin in the cytosol

Ub-Cys632-UBA1 adenylates ubiquitin in the cytosol

Stable Identifier

R-HSA-8852132

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Ub-Cys632-UBA1 adenylates ubiquitin in the cytosol

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Activation of ubiquitin by UBA1 proceeds through 3 steps: adenylation of ubiquitin, conjugation of ubiquitin from adenyl-ubiquitin to an internal cysteine residue of UBA1, and adenylation of a second molecule of ubiquitin. In the third step, the UBA1-ubiquitin conjugate adenylates the C-terminal glycine of a second ubiquitin molecule. This results in UBA1 loaded with 2 ubiquitin molecules, one of which is conjugated to an internal cysteine residue of UBA1 and one of which is adenylated and non-covalently bound to UBA1 (Jin et al. 2007, inferred from the rabbit homologue in Haas et al. 1982, Hershko et al. 1983, reviewed in Groettrup et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
17597759	Dual E1 activation systems for ubiquitin differentially regulate E2 enzyme charging Jin, J, Li, X, Gygi, SP, Harper, JW	Nature	2007
18353650	Activating the ubiquitin family: UBA6 challenges the field Groettrup, M, Pelzer, C, Schmidtke, G, Hofmann, K	Trends Biochem. Sci.	2008
6277905	Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation Haas, AL, Warms, JV, Hershko, A, Rose, IA	J. Biol. Chem.	1982
6305978	Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown Hershko, A, Heller, H, Elias, S, Ciechanover, A	J. Biol. Chem.	1983