Reactome | NEDD8-K699-CUL2:ELOB:ELOC:RBX1:KLHDC10 binds alanine-tailed nascent peptide

NEDD8-K699-CUL2:ELOB:ELOC:RBX1:KLHDC10 binds alanine-tailed nascent peptide

Stable Identifier

R-HSA-9954723

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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NEDD8-K699-CUL2:ELOB:ELOC:RBX1:KLHDC10 binds alanine-tailed nascent peptide

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The CRL2-KLHDC10 ubiquitin E3 ligase complex (NEDD8-K699-CUL2:ELOB:ELOC:RBX1:KLHDC10) binds C-terminal alanine residues that have been polymerized ("CAT-tailed") by NEMF onto a nascent peptide from a 60S ribosomal subunit that has been dissociated from a stalled 80S ribosome (Thrun et al. 2021, Patil et al. 2023). Substrates of the CRL2-KLHDC10 complex also include C-termini containing alanine-glycine, tryptophan-glycine, and proline glycine (Koren et al. 2018). The mechanism by which the nascent peptide is cleaved from the peptidyl-tRNA and extracted from the 60S ribosomal subunit is uncharacterized.

Literature References

PubMed ID	Title	Journal	Year
33909987	Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailing Thrun, A, Garzia, A, Kigoshi-Tansho, Y, Patil, PR, Umbaugh, CS, Dallinger, T, Liu, J, Kreger, S, Patrizi, A, Cox, GA, Tuschl, T, Joazeiro, CAP	Mol Cell	2021
37676773	Mechanism and evolutionary origins of alanine-tail C-degron recognition by E3 ligases Pirh2 and CRL2-KLHDC10 Patil, PR, Burroughs, AM, Misra, M, Cerullo, F, Costas-Insua, C, Hung, HC, Dikic, I, Aravind, L, Joazeiro, CAP	Cell Rep	2023