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
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Different histone Lysine ubiquitinases
Enzyme (UniprotKB recommended name) Coding gene/s Site of histone modification
E3 ubiquitin-protein ligase BRE1ARNF20H2BK120ub
E3 ubiquitin-protein ligase BRE1BRNF40H2BK120ub
E3 ubiquitin-protein ligase DTX3LDTX3LH4K91ub
E3 ubiquitin-protein ligase HUWE1HUWE1
E3 ubiquitin-protein ligase RBX1RBX1H2BK120ub
E3 ubiquitin-protein ligase RING1RING1H2AK119ub
E3 ubiquitin-protein ligase RING2RNF2H2AK119ub, H2AK121ub
E3 ubiquitin-protein ligase RNF168RNF168
E3 ubiquitin-protein ligase RNF8RNF8
E3 ubiquitin-protein ligase UBR2UBR2
E3 ubiquitin-protein ligase UHRF1UHRF1
V(D)J recombination-activating protein 1RAG1