Table 2 : Classification and characteristics of DUBs.


DUB Family   No. of members   Features   Examples   References

Ubiquitin specific proteases (USPs)   > 50   Include three subdomains – finger, thumb and palm. Finger     domain interacts with ubiquitin.
Carry cysteine and histidine boxes embedded in a region     spanning approximately 300 to 800 a.a. with a regulatory     aspartate box
May have other extra domains namely, UIM, UAD, B-Box, DUSP,     Zn finger, ULD, Exonuclease III domains.
Interaction with ubiqutin triggers a conformational change     leading to their activation
  CYLD, C19 family of papain protease   [9]

Ubiquitin C-terminal hydrolase (UCH)   4   Can process only small peptides (20 to 30 aa) from the C-     terminus of ubiquitin.
Involved in ubiquitin recycling by     targeting inappropriately     conjugated ubiquitin on nucleophiles.
Also generate monoubiquitins by processing polyubiquitin     chains and ubiquitin conjugated to ribosomal protein     precursor.
  UCHL1, UCHL3, UCHL5/UCH37 and BAP1   [9]

Ovarian Tumor domain proteases
(OTUs)
  15
Include 3 sub- families Otubains,  A20 like OTUs and OTUDs
  Have an active cysteine protease domain. The core domain has     five β-strands, situated between the helical domains.
The catalytic triad is incomplete and is stabilized by hydrogen     bonding complex.
May carry auxiliary domains like-Zn finger domain, UIMs and     UAD.
  Otubains (OTUB1 and OTUB2) A20-like OTUs (A20/TNFAIP3; Cezanne, Cezanne 2, TRABID and VCPIP1) OTUDs(OTUD1, OTUD2/ YOD1,OTUD3, OTUD4, OTUD5, OTUD6A, OTUD6B and ALG13)   [9]

Josephin family of DUBs   4   The family is named due to a pivotal role played by ATXN-3 in     spinocerebellar ataxia and Machado-Joseph disease.
In addition to the catalytic triad of one cysteine and two histidine     boxes, the members may have UIMs.
ATXN-3 has a polyubiquitin chain editing activity and ubiquitin     hydrolase activity while ATXN3L, JOSD1 and JOSD2 show DUB     activity.
  ATXN3, ATXN3L, JOSD1 and JOSD2   [9]

JAMM proteases   12   Are zinc-metalloproteases that target lys-63 linked polyubiquitin.     ;Also show isopeptidase activity for ubiquitin or ubiquitin like     proteins.
Carry a well conserved JAMM domain (Jab1/Csn5 and MPN     domain).
Involved in receptor recycling and vesicle trafficking.
  AMSH/STAMBP, STAMBPL, BRCC36. POH1/ PSMD14, MYSM1, MPND and CSN5/JAB1   [9]

MCPIP family   ~7   Anomalous cysteine protease with only cysteine and aspartate     boxes within the conserved N-terminal catalytic region.
Carry an N-terminal UAD, a conserved middle zinc-finger domain     and a proline-rich domain at its carboxy terminus.
  MCPIP1   [13]

Kumar et al.Virology Discovery  2013 1:5DOI : 10.7243/2052-6202-1-5