Histone Lysine ubiquitinases
Lysine ubiquitination is carried out by Ubiquitin ligases. The whole process requires the interplay of 3 enzymes. E1 enzyme required for activation of ubiquitin, E2 ubiquitin-conjugating enzyme for binding to ubiquitin and E3 ligase for transfer of ubiquitin from E2 to the target protein. E3 recognise the target substrate and simultaneously bind to E2 followed by the transfer of ubiquitin from E2 to substrate.
E3 are classified into 2 subclasses on the basis of the domain they harbour:
HECT (Homologous to E6-AP Carboxy Terminus) domain ubiquitinases that form an intermediate thioester bond with ubiquitin, hence participate in catalysis, and...
RING (Really Interesting New Gene) finger domain ubiquitinases that do not take part in the catalysis but only act as a scaffold to bring E2 and target substrate in close proximity.
We found, in all, 12 E3 ubiquitin ligases through literature of which except E3 ubiquitin-protein ligase HUWE1 (HECT E3) rest all are RING finger E3 ligases.
Ubiquitination machinery generally targets proteins for proteosomal degradation. However, ubiquitin marks are also shown to convey specific signals and recruit other factors. E3 ubiquitin ligases are also involved in cell cycle control, DNA damage response, base excision repair mechanisms, regulation of Hox genes, heterochromatinisation, maintainance of genome integrity and as diverse functions as VDJ recombination.
Further reading: PMID: 14998368, PMID: 10998601.
Cytogenetic map of Lysine ubiquitinases coding genes| Enzyme (UniprotKB recommended name) | Coding gene/s | Site of histone modification |
|---|---|---|
| E3 ubiquitin-protein ligase BRE1A | RNF20 | H2BK120ub |
| E3 ubiquitin-protein ligase BRE1B | RNF40 | H2BK120ub |
| E3 ubiquitin-protein ligase DTX3L | DTX3L | H4K91ub |
| E3 ubiquitin-protein ligase HUWE1 | HUWE1 | |
| E3 ubiquitin-protein ligase RBX1 | RBX1 | H2BK120ub |
| E3 ubiquitin-protein ligase RING1 | RING1 | H2AK119ub |
| E3 ubiquitin-protein ligase RING2 | RNF2 | H2AK119ub, H2AK121ub |
| E3 ubiquitin-protein ligase RNF168 | RNF168 | |
| E3 ubiquitin-protein ligase RNF8 | RNF8 | |
| E3 ubiquitin-protein ligase UBR2 | UBR2 | |
| E3 ubiquitin-protein ligase UHRF1 | UHRF1 | |
| V(D)J recombination-activating protein 1 | RAG1 |