Reactome | E3 ubiquitin ligases ubiquitinate target proteins

E3 ubiquitin ligases ubiquitinate target proteins

Stable Identifier

R-HSA-8866654

DOI

10.3180/R-HSA-8866654.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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E3 ubiquitin ligases ubiquitinate target proteins

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E3 ubiquitin ligases catalyze the transfer of an ubiquitin from an E2-ubiquitin conjugate to a target protein. Generally, ubiquitin is transferred via formation of an amide bond to a particular lysine residue of the target protein, but ubiquitylation of cysteine, serine and threonine residues in a few targeted proteins has also been demonstrated (reviewed in McDowell and Philpott 2013, Berndsen and Wolberger 2014). Based on protein homologies, families of E3 ubiquitin ligases have been identified that include RING-type ligases (reviewed in Deshaies et al. 2009, Metzger et al. 2012, Metzger et al. 2014), HECT-type ligases (reviewed in Rotin et al. 2009, Metzger et al. 2012), and RBR-type ligases (reviewed in Dove et al. 2016). A subset of the RING-type ligases participate in CULLIN-RING ligase complexes (CRLs which include SCF complexes, reviewed in Lee and Zhou 2007, Genschik et al. 2013, Skaar et al. 2013, Lee et al. 2014).
Some E3-E2 combinations catalyze mono-ubiquitination of the target protein (reviewed in Nakagawa and Nakayama 2015). Other E3-E2 combinations catalyze conjugation of further ubiquitin monomers to the initial ubiquitin, forming polyubiquitin chains. (It may also be possible for some E3-E2 combinations to preassemble polyubiquitin and transfer it as a unit to the target protein.) Ubiquitin contains several lysine (K) residues and a free alpha amino group to which further ubiquitin can be conjugated. Thus different types of polyubiquitin are possible: K11 linked polyubiquitin is observed in endoplasmic reticulum-associated degradation (ERAD), K29 linked polyubiquitin is observed in lysosomal degradation, K48 linked polyubiquitin directs target proteins to the proteasome for degradation, whereas K63 linked polyubiquitin generally acts as a scaffold to recruit other proteins in several cellular processes, notably DNA repair (reviewed in Komander et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
17588513	DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase Lee, J, Zhou, P	Mol Cell	2007
23912815	The emerging family of CULLIN3-RING ubiquitin ligases (CRL3s): cellular functions and disease implications Lechner, E, Sumara, I, Genschik, P	EMBO J.	2013
27312108	Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms Klevit, RE, Rittinger, K, Dove, KK, Stieglitz, B, Duncan, ED	EMBO Rep.	2016
24699078	New insights into ubiquitin E3 ligase mechanism Wolberger, C, Berndsen, CE	Nat. Struct. Mol. Biol.	2014
19754430	The emerging complexity of protein ubiquitination Komander, D	Biochem. Soc. Trans.	2009
26085183	Protein monoubiquitylation: targets and diverse functions Nakagawa, T, Nakayama, K	Genes Cells	2015
23732108	Non-canonical ubiquitylation: mechanisms and consequences McDowell, GS, Philpott, A	Int. J. Biochem. Cell Biol.	2013
23657496	Mechanisms and function of substrate recruitment by F-box proteins Pagan, JK, Skaar, JR, Pagano, M	Nat. Rev. Mol. Cell Biol.	2013
23747565	RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination Klevit, RE, Metzger, MB, Weissman, AM, Pruneda, JN	Biochim. Biophys. Acta	2014
19489725	RING domain E3 ubiquitin ligases Deshaies, RJ, Joazeiro, CA	Annu Rev Biochem	2009
22389392	HECT and RING finger families of E3 ubiquitin ligases at a glance Hristova, VA, Metzger, MB, Weissman, AM	J. Cell. Sci.	2012
19436320	Physiological functions of the HECT family of ubiquitin ligases Kumar, S, Rotin, D	Nat. Rev. Mol. Cell Biol.	2009
23624913	SCFs in the new millennium Lee, EK, Diehl, JA	Oncogene	2014