p(HGNC:UBA3)

Entity

Name

UBA3

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

It appears that E3s play a key role in the ubiquitin-mediated proteolytic cascade since they serve as the specific substrate recognition factors of the system PubMed:14556719

E3s catalyze the last step in the conjugation process: covalent attachment of ubiquitin to the substrate. PubMed:14556719

In some other cases, the first ubiquitin moiety is conjugated to the substrate by one E3, while chain elongation is catalyzed by a different ligase, often termed E4 PubMed:14556719

It appears that E3s play a key role in the ubiquitin-mediated proteolytic cascade since they serve as the specific substrate recognition factors of the system PubMed:14556719

However, earlier biochemical investigations on the SCF (Skp, Cullin, F-box containing) ubiquitin ligase complex, the archetypal member of the cullin–RING ligases, indicated that E3s can also positively influence the rate of ubiquitin transfer from the E2 to the protein substrate [17,18]. PubMed:24457024

These studies demonstrated that both E2s and E3s can affect the conformation of the ubiquitin on the E2 surface to promote its transfer to the substrate PubMed:24457024

Some E3s can also stabilize the conformation between ubiquitin and the E2, thereby accelerating further the rate of conjugation of ubiquitin to proteins PubMed:24457024

Indeed, recent studies have provided insight into the mechanism of E3-mediated activation of E2s by trapping and either co-crystallizing or characterizing by nuclear magnetic resonance (NMR) the unstable and transient complexes between E2~ubiquitin and E3. PubMed:24457024

Some E3s can also stabilize the conformation between ubiquitin and the E2, thereby accelerating further the rate of conjugation of ubiquitin to proteins PubMed:24457024

One key take-home message is that many E3 ligases likely evolved to be processive, meaning that they can conjugate multiple ubiquitins onto a substrate before it is released from enzyme PubMed:24457024

Third, there is ligation of Ub with an epsilon-amino group of lysine in the target protein by an E3 ligase. E3 ligase binds both the target protein and the E2–Ub complex; thousands of substrate- specific E3s ensure selective protein tagging and degradation. PubMed:22908190