Family C19

Family

Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq Architecture

Summary for family C19

NamePeptidase family C19 (ubiquitin-specific protease family)
Family type peptidaseC19.015 - ubiquitin-specific peptidase 14 (Homo sapiens), MEROPS Accession MER0002667 (peptidase unit: 73-494)
Content of familyPeptidase family C19 contains ubiquitinyl hydrolases.
History Identifier created: Methods Enzymol. 244:461-486 (1994)
Catalytic typeCysteine
Active site residuesN109 C114 H435 D,N451 
Active siteThe active site residues occur in the order Asn, Cys, His and Asp. The spacing between the Asn and the Cys is one residue less than that found between the equivalent Gln and Cys residues found in several other families in clan CA. They are commonly found in the motif Asn-Leu-Gly-Asn-Tyr-Cys. The catalytic His is found within the motif Gly-His-Tyr-Xaa where Xaa is a hydrophobic residue. There is a conserved tryptophan which may correspond to Ile320 in papain, but is Trp in many members of family C1, which is part of the hydrophobic core of the molecule (Kamphuis et al., 1984). The active site Asp may be replaced by Asn, but is always found one residue N-terminal to a conserved Asp (see the Alignment).
Activities and specificitiesThe peptidases of family C19 hydrolyse bonds involving the carboxyl group of the C-terminal Gly residue of ubiquitin. These ubiquitinyl bonds can be alpha-peptide bonds to the N-terminus of another ubiquitin molecule, or isopeptide bonds to the sidechain of Lys48 in another ubiquitin molecule or to the sidechain of a Lys residue in another protein. The varied specificities of peptidases in the family have been reviewed by Amerik & Hochstrasse (2004), Baker (2004), Everett (2004) and Wilkinson (2004).
InhibitorsN-Ethylmaleimide (1mM ) is an inhibitor. More selective reagents include ubiquitin aldehyde (Hu et al., 2002) and vinyl sulfones (Hemelaar et al., 2004).
Molecular structureThe peptidases of family C19 have a more complicated structure than the ubiquitinyl hydrolases in the related family C12. Many of the proteins have multiple domains. Ubiquitin-specific protease 7 (C19.016) contains three domains and a similar active site structure to that of papain (Hu et al., 2002). The peptidase unit contains a 'fingers domain' that is a four-stranded beta sheet that interacts with the ubiquinated substrate.
ClanCA
Basis of clan assignmentPredicted active site residues for members of this family and family C1 occur in the same order in the sequence: N/Q, C, H.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsThe ubiquitinyl hydrolases of family C19 are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. The purpose of the de-ubiquitination is thought to be editing of the ubiquitin conjugates, which could rescue them from degradation, as well as recycling of the ubiquitin. The ubiquitin/proteasome system is responsible for most protein turnover in the mammalian cell, and with over 50 members, family C19 is one of the largest families of peptidases in the human genome.
Pharmaceutical and biotech relevanceA number of the peptidases of family C19 are of interest as therapeutic targets.
Statistics for family C19Sequences:24499
Identifiers:201
Identifiers with PDB entries:25
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH 3.10.20.90
INTERPRO IPR001394
PANTHER PTHR13020
PANTHER PTHR22957
PANTHER PTHR22975
PANTHER PTHR24006
PANTHER PTHR43913
PANTHER PTHR43937
PANTHER PTHR43942
PANTHER PTHR43961
PANTHER PTHR43982
PANTHER PTHR44032
PANTHER PTHR44033
PANTHER PTHR44128
PANTHER PTHR44130
PANTHER PTHR44141
PANTHER PTHR44148
PANTHER PTHR44150
PANTHER PTHR44182
PANTHER PTHR44183
PANTHER PTHR44275
PANTHER PTHR44353
PANTHER PTHR44446
PANTHER PTHR44498
PANTHER PTHR44509
PANTHER PTHR44532
PANTHER PTHR44556
PANTHER PTHR44570
PANTHER PTHR44595
PANTHER PTHR44611
PANTHER PTHR44642
PANTHER PTHR44646
PANTHER PTHR44658
PANTHER PTHR44728
PANTHER PTHR44959
PANTHER PTHR45149
PANTHER PTHR45492
PANTHER PTHR45499
PANTHER PTHR45511
PFAM PF00443
PFAM PF13423
SCOP 82568
Peptidases and Homologues MEROPS ID Structure
ubiquitin-specific peptidase 5C19.001Yes
Ubp1 ubiquitin peptidaseC19.002-
Ubp2 ubiquitin peptidaseC19.003-
Ubp3 ubiquitin peptidaseC19.004Yes
Doa4 ubiquitin peptidaseC19.005-
Ubp5 ubiquitin peptidaseC19.006-
Fat facets proteinC19.007-
Ubp3 ubiquitin peptidase (plant-type)C19.008-
ubiquitin-specific peptidase 6C19.009-
ubiquitin-specific peptidase 4C19.010Yes
ubiquitin-specific peptidase 8C19.011Yes
ubiquitin-specific peptidase 13C19.012Yes
ubiquitin-specific peptidase 2C19.013Yes
ubiquitin-specific peptidase 11C19.014Yes
ubiquitin-specific peptidase 14C19.015Yes
ubiquitin-specific peptidase 7C19.016Yes
ubiquitin-specific peptidase 9XC19.017Yes
ubiquitin-specific peptidase 10C19.018-
ubiquitin-specific peptidase 1C19.019-
ubiquitin-specific peptidase 12C19.020-
ubiquitin-specific peptidase 16C19.021-
ubiquitin-specific peptidase 15C19.022Yes
ubiquitin-specific peptidase 17C19.023-
ubiquitin-specific peptidase 19C19.024-
ubiquitin-specific peptidase 20C19.025-
ubiquitin-specific peptidase 3C19.026-
ubiquitin-specific peptidase 9YC19.028-
ubiquitin-specific peptidase 18C19.030Yes
DUB-1 ubiquitin-specific peptidaseC19.031-
DUB-2 ubiquitin-specific peptidaseC19.032-
ubiquitin-specific peptidase 21C19.034Yes
ubiquitin-specific peptidase 22C19.035-
ubiquitin-specific peptidase 33C19.037Yes
Mername-AA059 peptidaseC19.039-
ubiquitin-specific peptidase 29C19.040-
ubiquitin-specific peptidase 25C19.041Yes
ubiquitin-specific peptidase 36C19.042-
Mername-AA004 peptidaseC19.043-
ubiquitin-specific peptidase 32C19.044-
ubiquitin-specific peptidase 26 (mouse-type)C19.045-
ubiquitin-specific peptidase 26 (Homo sapiens-type)C19.046-
ubiquitin-specific peptidase 24C19.047-
ubiquitin-specific peptidase 42C19.048-
Mername-AA001 peptidaseC19.050-
Usp9y g.p. (Mus musculus)C19.051-
ubiquitin-specific peptidase 46C19.052Yes
ubiquitin-specific peptidase 37C19.053-
ubiquitin-specific peptidase 28C19.054Yes
ubiquitin-specific peptidase 47C19.055-
ubiquitin-specific peptidase 38C19.056Yes
ubiquitin-specific peptidase 44C19.057-
ubiquitin-specific peptidase 50C19.058-
ubiquitin-specific peptidase 35C19.059Yes
ubiquitin-specific peptidase 30C19.060Yes
ubiquitin-specific peptidase 45C19.064-
ubiquitin-specific peptidase 51C19.065-
ubiquitin-specific peptidase 34C19.067-
ubiquitin-specific peptidase 48C19.068-
ubiquitin-specific peptidase 40C19.069-
ubiquitin-specific peptidase 41C19.070-
ubiquitin-specific peptidase 31C19.071-
Mername-AA129 peptidaseC19.072-
ubiquitin-specific peptidase 49C19.073-
ubiquitin-specific peptidase 27XC19.075-
protein similar to high mobility group proteinC19.076-
Dub5 peptidase (Mus musculus)C19.077-
USP17-like peptidaseC19.078-
ubiquitin-specific peptidase 6 (Saccharomyces-type)C19.079Yes
ubiquitin-specific peptidase 54C19.080-
ubiquitin-specific peptidase 53C19.081-
deubiquitinating enzyme 6 (Mus musculus)C19.082-
deubiquitinating enzyme 14 (Saccharomyces cerevisiae)-like peptidaseC19.083-
deubiquitinating enzyme 14 (plant)C19.084Yes
DUB-1A peptidase (Mus musculus)C19.085-
DUB-2A peptidase (Mus musculus)C19.086-
ubiquitin-specific peptidase 8 (Saccharomyces cerevisiae)C19.087Yes
ubiquitin-specific peptidase 10 (Saccharomycetales)C19.088-
Mername-AA305 putative ubiquitin isopeptidaseC19.089Yes
AtUBP2 peptidase (Arabidopsis thaliana) and similarC19.090-
AtUBP1 peptidase (Arabidopsis thaliana)C19.091-
AtUBP4 peptidase (Arabidopsis thaliana) and similarC19.092-
AtUBP5 peptidase (Arabidopsis thaliana)-like peptidaseC19.093-
UBP6 peptidase (Arabidopsis-type)C19.094-
Nonstop peptidaseC19.095-
ubiquitin-specific peptidase 15 (Arabidopsis thaliana)-like peptidaseC19.096-
dUSP36-type peptidaseC19.097-
TssM peptidase (Burkholderia sp.)C19.098-
UBP15 peptidase (Saccharomyces cerevisiae)C19.099-
ubiquitin carboxyl-terminal hydrolase 13 (Saccharomyces cerevisiae)C19.100-
ubiquitin carboxy-terminal hydrolase 7 (Saccharomyces cerevisiae)C19.101-
putative ubiquitin carboxyl-terminal hydrolase ybl067c (Saccharomyces cerevisiae)C19.102-
putative ubiquitin carboxyl-terminal hydrolase ybr058c (Saccharomyces cerevisiae)C19.103-
ubpA (Dictyostelium discoideum)C19.104-
ubiquitin-specific peptidase 47 (Drosophila melanogaster-type)C19.105-
USP27XC19.106-
ubiquitin-specific peptidase 32C19.107-
ubiquitin-specific peptidase 43 [misleading]C19.108-
ubiquitin-specific endopeptidase 39 [misleading]C19.972Yes
Mername-AA090 non-peptidase homologueC19.974-
ubiquitin-specific peptidase 52 [misleading]C19.978-
hypothetical ubiquitin carboxyl-terminal hydrolase USP43C19.979-
LOC623640 peptidase homologue (Mus musculus)C19.981-
USP17L7C19.984-
USP17L4C19.985-
USP17L8C19.986-
USP17L23C19.987-
At5g22030 (Arabidopsis thaliana)C19.A01-
At4g10570 (Arabidopsis thaliana)C19.A02-
At4g10590 (Arabidopsis thaliana)C19.A03-
At1g32850 (Arabidopsis thaliana)C19.A04-
At3g21280 (Arabidopsis thaliana)C19.A05-
At5g65450 (Arabidopsis thaliana)C19.A06-
At4g24560 (Arabidopsis thaliana)C19.A07-
At4g31670 (Arabidopsis thaliana)C19.A08-
At2g24640 (Arabidopsis thaliana)C19.A09-
At5g10790 (Arabidopsis thaliana)C19.A11-
At5g57990 (Arabidopsis thaliana)C19.A12-
At3g14400 (Arabidopsis thaliana)-like peptidaseC19.A13-
At4g30890 (Arabidopsis thaliana)C19.A14-
At5g46740 (Arabidopsis thaliana)C19.A15-
At4g17890 (Arabidopsis thaliana)C19.A16-
ubiquitin carboxy-terminal hydrolase 16 (Saccharomyces cerevisiae)C19.A18-
ubiquitin carboxyl-terminal hydrolase 9 (Saccharomyces cerevisiae)C19.A20-
CG7023 g.p. (Drosophila melanogaster)C19.A23-
USP2 (Drosophila melanogaster)C19.A24-
CG15817 g.p. (Drosophila melanogaster)C19.A25-
CG8494 g.p. (Drosophila melanogaster)C19.A26-
CG8830 g.p. (Drosophila melanogaster)C19.A27-
CG12082 g.p. (Drosophila melanogaster)C19.A28-
USP-48 (Caenorhabditis elegans-type)C19.A29-
F37B12.4 g.p. (Caenorhabditis elegans)C19.A30-
F59E12.6 g.p. (Caenorhabditis elegans)C19.A31-
H12I13.2 g.p. (Caenorhabditis elegans)C19.A32-
H34C03.2 g.p. (Caenorhabditis elegans)C19.A33-
K02C4.3 g.p. (Caenorhabditis elegans)C19.A34-
usp-33 (Caenorhabditis elegans-type)C19.A35-
queuine tRNA-ribosyltransferase (Caenorhabditis elegans)C19.A36-
usp-46 (Caenorhabditis elegans-type)C19.A37-
USP-47 (Caenorhabditis elegans)C19.A38-
F07A11.4 g.p. (Caenorhabditis elegans)C19.A39-
T22F3.2 g.p. (Caenorhabditis elegans)C19.A40-
T27A3.2 g.p. (Caenorhabditis elegans)C19.A41-
E01B7.1 g.p. (Caenorhabditis elegans)C19.A42-
Y67D2.2 g.p. (Caenorhabditis elegans)C19.A43-
cyk-3 g.p. (Caenorhabditis elegans)C19.A44-
GH27809p (Drosophila melanogaster)C19.A45-
USP34 peptidase (Drosophila melanogaster)C19.A46-
CT18196 g.p. (Drosophila melanogaster)C19.A47-
CT24583 g.p. (Drosophila melanogaster)C19.A48-
Cg32479 g.p. (ld28815p) (Drosophila melanogaster)C19.A49-
T17F15.230 (Arabidopsis thaliana)C19.A51-
Usp7 (Drosophila melanogaster-type)C19.A52-
UBP13 (Arabidopsis thaliana-type)C19.A53-
usp-7 (Caenorhabditis elegans-type)C19.A54-
ubp1 (Schizosaccharomyces pombe-type)C19.A55-
ubp2/SPAC328.06 (Schizosaccharomyces pombe)C19.A56-
ubp3 (Schizosaccharomyces pombe-type)C19.A57-
ubp4 (Schizosaccharomyces pombe-type)C19.A58-
ubp5 (Schizosaccharomyces pombe-type)C19.A59-
ubp6 (Schizosaccharomyces pombe-type)C19.A60-
ubp8 (Schizosaccharomyces pombe-type)C19.A61-
ubp9 (Schizosaccharomyces pombe-type)C19.A62-
ubp11 (Schizosaccharomyces pombe-type)C19.A63-
ubp12 (Schizosaccharomyces pombe-type)C19.A64-
ubp14 (Schizosaccharomyces pombe)C19.A65-
ubp16 (Schizosaccharomyces pombe)C19.A66-
ubpB (Dictyostelium discoideum)C19.A68-
DDB_G0275415 (Dictyostelium discoideum)C19.A69-
usp14 (Dictyostelium discoideum-type)C19.A70-
DDB_G0274827 (Dictyostelium discoideum)C19.A71-
usp7 (Dictyostelium discoideum-type)C19.A72-
UBP12 (Arabidopsis thaliana-type)C19.A73-
PFD0680c g.p. (Plasmodium falciparum)C19.A74-
PFD0165w g.p. (Plasmodium falciparum)C19.A75-
PFA_0220w g.p. (Plasmodium falciparum)C19.A76-
PFI0225w g.p. (Plasmodium falciparum)C19.A77-
PFE1355c g.p. (Plasmodium falciparum)C19.A78-
PFE0835w g.p. (Plasmodium falciparum)C19.A79-
PF14_0145 g.p. (Plasmodium falciparum)C19.A80-
LOC100334535 g.p. (Brachydanio rerio)C19.A81-
USP17L11C19.A82-
USP17L2C19.A83-
USP17L1C19.A84-
USP17L3C19.A85-
USP17L5C19.A86-
USP17L6PC19.A87-
USP17L10C19.A88-
USP17L12C19.A89-
USP17L13C19.A90-
USP17L15C19.A91-
USP17L17C19.A92-
USP17L18C19.A93-
USP17L19C19.A94-
USP17L20C19.A95-
USP17L21C19.A96-
USP17L22C19.A97-
NEK2 pseudogeneC19.P01-
C19 pseudogene (Homo sapiens: chromosome 5)C19.P02-
Dub5-related pseudogene (Mus musculus)C19.P03-
LOC269980 pseudogene (Mus musculus chromosome 7)C19.P04-
Mername-AA088 peptidaseC19.P05-
Family C19 non-peptidase homologuesnon-peptidase homologue-
Family C19 unassigned peptidasesunassigned-