Histone Lysine deubiquitinases

Ubiquitin moieties attached to the core histones are cleaved using a group of proteases called 'deubiquitinases'. These are divided into 5 major classes:

Class I: Ubiquitin carboxy-terminal hydrolases (UCHs),

Class II: Ubiquitin-specific proteases (USPs)/ubiquitin-specific processing proteases,

Class III: Ovarian tumour proteases,

Class IV: Josephin or Machado-Joseph disease protein domain proteases, and

Class V: Jab1/MPN domain-associated metalloisopeptidase domain proteins.

Class I to IV are cysteine peptidases and V is a zinc metalloisopeptidase. We found 5 different deubiquitinases reported to be present in humans that recognise histones as substrates. While MYSM1 and BRCC36 belong to Class V, all other members belong to Class II deubiquitinases.

Deubiquitinases significantly affect transcriptional regulation, DNA damage response, cytokinesis, telomere maintainance. USP22 is an important enzyme as it has been designated as the signature molecule of Cancer stem cells. It is also known to regulate myc protein that is heavily involved in oncogenesis.

Further reading: PMID: 20974139.

Cytogenetic map of Lysine deubiquitinases coding genes
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Different histone Lysine deubiquitinases
Enzyme (UniprotKB recommended name) Coding gene/s Site of histone modification
Histone H2A deubiquitinase MYSM1MYSM1H2AK119ub
Lys-63-specific deubiquitinase BRCC36BRCC3
Ubiquitin carboxyl-terminal hydrolase 16USP16
Ubiquitin carboxyl-terminal hydrolase 22USP22
Ubiquitin carboxyl-terminal hydrolase 3USP3