Ailuropoda melanoleuca

    Members of JAMM family are found in proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors (1). This family is also known as the MPN domain and PAD-1-like domain JABP1 domain or JAMM domain, while the JAMM motif is critical for the activity (1-2). These are metalloenzymes that function as the ubiquitin isopeptidase/ deubiquitinase in the ubiquitin-based signaling and protein turnover pathways in eukaryotes. Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are predicted to have a similar role (3).

1. http://pfam.sanger.ac.uk/family/PF01398

2. Verma, R., Aravind, L., Oania, R., McDonald, W.H., Yates, J.R., 3rd, Koonin, E.V. and Deshaies, R.J. (2002) Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science, 298, 611-615. PMID: 12183636

3. Cope, G.A., Suh, G.S., Aravind, L., Schwarz, S.E., Zipursky, S.L., Koonin, E.V. and Deshaies, R.J. (2002) Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science, 298, 608-611. PMID: 12183637

    Josephin family represents DUBs with a papain-like cysteine protease catalytic domain. As a well studied Josephin family protein of Ataxin-3, the structure of the Josephin domain was solved by NMR which resembles that of UCH domain deubiquitinating enzymes. Furthermore, the active site residues of Ataxin-3 are positioned in a catalytically competent conformation which has been reported to edit K63-linked chains specifically (1).

1. Reyes-Turcu, F.E., Ventii, K.H. and Wilkinson, K.D. (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu. Rev. Biochem., 78, 363-397. PMID: 19489724

    MINDY deubiquitinase domain represents the catalytic domain of a group of deubiquitinating (DUB) enzymes known as the MINDY family (MIU-containing novel DUB) (1). Members of the MINDY family of DUBs contain an MIU (motif interacting with Ub) motif, which is a helical motif that binds mono-Ub (2).

1. http://www.ebi.ac.uk/interpro/entry/IPR033979

2. Abdul Rehman SA, Kristariyanto YA, Choi SY, Nkosi PJ, Weidlich S, Labib K, Hofmann K, Kulathu Y. (2016). MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes. Mol Cell., 63(1):146-55.PMID: 27292798

    OTU family is comprised of a group of predicted cysteine proteases, homologous to the Ovarian Tumour (OTU) gene in Drosophila. Members include proteins from eukaryotes, viruses and pathogenic bacterium. The conserved cysteine and histidine, and possibly the aspartate, represent the catalytic residues in this putative group of proteases (1).

1. http://pfam.xfam.org/family/PF02338

    DUB/Other family is a small single protein family of DUBs that consist of miscellaneous unconventional domain containing proteins, such as human ZC3H12A, TRIM44 and yeast WSS1.

    Ubiquitin C-terminal hydrolase (UCH-L1), also called neuronal-specific protein gene product (PGP9.3), is highly abundant in neurons. Generally, UCH enzymes are small, since there is only a proteolytic core domain that functions to cleave small molecular weight adducts from the ubiquitin C terminus (1). There are at least three mammalian isozymes which are tissue specific and developmentally regulated (UCH-L1, L2, L3). A handful of studies suggest that UCH-L1 could serve as a novel biomarker, which has the potential to determine injury severity in TBI patients (2). Four UCH active site residues, Gln84, Cys90, His166 and Asp181 (Yuh1) were identified previously through mutagenesis of UCH-L1 and determination of the crystal structure of UCH-L3 (3).

1. Larsen, C.N., Krantz, B.A. and Wilkinson, K.D. (1998). Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry, 37, 3358-3368. PMID: 9521656

2. Papa, L., Akinyi, L., Liu, M.C., Pineda, J.A., Tepas, J.J., 3rd, Oli, M.W., Zheng, W., Robinson, G., Robicsek, S.A., Gabrielli, A., Heaton, S. C., Hannay, H. J., Demery, J. A., Brophy, G. M., Layon, J., Robertson, C. S., Hayes, R. L., Wang, K. K. (2010). Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit. Care. Med., 38, 138-144. PMID: 19726976

3. Johnston, S.C., Riddle, S.M., Cohen, R.E. and Hill, C.P. (1999). Structural basis for the specificity of ubiquitin C-terminal hydrolases. EMBO J., 18, 3877-3887. PMID: 10406793

    Members of ULP family contain a catalytic domain about 220 amino acids which usually locate in C terminus. The N-terminal regions are always involved in determining the substrate specificity or localization of these enzymes. Seven members have been found in human and they contain eight blocks of highly conserved sequence in the catalytic domain. Two ULPs exist in yeast and both can hydrolyze SUMO-1 and SUMO-2/3 derivatives, although with different apparent specificity and nuclear localization (1).

1. Gan-Erdene, T., Nagamalleswari, K., Yin, L., Wu, K., Pan, Z.Q. and Wilkinson, K.D. (2003). Identification and characterization of DEN1, a deneddylase of the ULP family. J. Biol. Chem., 278, 28892-28900. PMID: 12759362

    USP is a family of cysteine peptidases, which belongs to the MEROPS peptidase family C19 (ubiquitin-specific protease family, clan CA). Families within the CA clan are loosely termed papain-like as protein fold of the peptidase unit resembles that of papain, the type example for clan CA. Predicted active site residues for members of this family and family C1 occur in the same order in the sequence: N/Q, C, H. The type example is human ubiquitin-specific protease 14 (1).

1. http://www.ebi.ac.uk/interpro/entry/IPR001394