Family C12
Summary for family C12
| Name | Peptidase family C12 (ubiquitin C-terminal hydrolase family) |
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| Family type peptidase | C12.001 - ubiquitinyl hydrolase-L1 (Homo sapiens), MEROPS Accession MER0000832 (peptidase unit: 1-223) |
| Content of family | Peptidase family C12 contains ubiquitinyl hydrolases. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
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| Catalytic type | Cysteine |
| Active site | The spacing between Gln84 and Cys90 (numbering as in the alignment) is identical to that in families C1, C2 and C10. The other catalytic residues are His161 and Asp176. The strongest evidence for their identities comes from the tertiary structures (see below). |
| Activities and specificities | The active-site thiol is sensitive to oxidation, and reductants such as dithiothreitol or 2-mercaptoethanol are required for maximal activity. The enzymes are very selective for hydrolysis of bonds formed by the C-terminal Gly of ubiquitin, which may be alpha-peptide, isopeptide, amide or ester bonds. The binding of ubiquitin is primarily electrostatic, being prevented by high salt concentrations, and three conserved acidic residues play major roles: Glu7, Glu11 and Asp30 (Wilkinson et al., 1999). Detailed specificities have been reviewed by Wilkinson (2004). |
| Inhibitors | Like other ubiquitinyl hydrolases (e.g. those in family C19), the peptidases in family C12 are inhibited by ubiquitin aldehyde (Johnston et al., 1999) and ubiquitin vinylsulfone (Hemelaar et al., 2004). |
| Molecular structure | The tertiary structures of the yeast ubiquitinyl hydrolase YUH1 (C12.002) and human ubiquitinyl hydrolase 1 (C12.003) are very similar, and show many similarities to that of papain. The molecules are bilobed. One lobe consists mainly of helices, and the catalytic Cys is near the start of one of these. The other lobe contains a beta-barrel surrounded by helices, and the catalytic His is at the start of one of the beta-strands. A difference from papain is that the first strand of the beta-barrel precedes the helix bearing the catalytic cysteine in the sequence, whereas in papain the helix precedes all the strands of the barrel. |
| Clan | CA |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family and resembles that of papain, the type example for clan CA. |
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Distribution of family
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Bacteria |
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Archaea |
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Protozoa |
details |
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Fungi |
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Plants |
details |
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Animals |
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Viruses |
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| Biological functions | Family C12 is one of several families of ubiquitin C-terminal hydrolases. The peptidases of this family are synthesized without propeptides, and remain intracellular. Their biological function is thought to be the removal of ubiquitin from ubiquitinylated proteins and peptides. Ubiquitin is a 76-amino acid protein that is attached to other proteins, commonly as a signal for degradation by the proteasome. Ubiquitin is attached through the carboxyl group of its C-terminal glycine residue either to the N-terminus of another polypeptide or to the epsilon-amino group of a lysine residue, which forms an isopeptide bond. Ubiquitin may also be attached to another molecule of ubiquitin, and proteins targeted for degradation may be polyubiquitinated. In order for ubiquitin to be recycled there is a need for peptidases to liberate ubiquitin by hydrolysis of the C-terminal glycyl bond. Family C12 includes peptidases that can hydrolyze this glycyl bond whether it is an alpha-peptide bond or an isopeptide bond, with various specificities. The actions of these peptidases could have the effect of removing the polypeptide from the ubiquitin-directed trafficking pathway as well as recycling the ubiquitin. |
| Statistics for family C12 | Sequences: | 5233 |
| Identifiers: | 21 |
| Identifiers with PDB entries: | 5 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
