|Family type peptidase||C78.001 - UfSP1 peptidase (Mus musculus), MEROPS Accession MER0041174 (peptidase unit: 1-217)|
|Content of family||Peptidase family C78 contains peptidases that cleave a glycyl bond at the C-terminus of ubiquitin-fold modifier-1 protein.|
Identifier created: MEROPS 7.8 (23 April 2007)|
Ubiquitin-fold modifier-1 (Ufm1) is a protein structurally and functionally similar to ubiquitin. Like ubiquitin, Ufm1 can be conjugated to intracellular proteins via a C-terminal glycine. Tagged proteins are not targetted for degradation, and the physiological function is unknown. Ufm1 is synthesized as a precursor and is activated by the removal of a C-terminal dipeptide by peptidases in family C78. These peptidases are also responsible for the release of Ufm1 from conjugates (Kang et al., 2007).
|Active site residues||Y41 C53 D175 H177 |
|Active site||The tertiary structure of UfSP1 (C78.001) shows the catalytic residues to be Cys53 (which has also been identified by labelling with Ufm1-vinylmethylester and by site-directed mutagenesis) and His177. Additional residues shown to be important are Tyr41, which helps form the oxyanion hole, and Asp175, which orientates the imidazolium ring of the active site histidine (Ha et al., 2008). The cysteine occurs within an Asp-Xaa-Gly-Trp-Gly-Cys-Xbb-Tyr-Arg motif where Xaa is any amino acid and Xbb is either Gly or Ala. The aspartate and histidine residues occur within a Xcc-Asp-Pro-His-Xdd-Xaa-Gly motif where Xcc is an aliphatic residue and Xdd is tyrosine or phenylalanine. This motif is very similar to that around the catalytic histidine in family C54, where the aspartate has also been proposed to be the third member of a catalytic triad.|
|Activities and specificities||UfSP1 (C78.001) has been shown to process the Ufm1 precursor and to remove Ufm1 from conjugated proteins. UfSP2 (C78.002) can also perform both reactions, but much less efficiently (Kang et al., 2007).|
|Molecular structure||The tertiary structure has been solved for UfSP1 (C78.001) and shows a papain-like structure (Ha et al., 2008). Hence family C78 is included in clan CA. However, families C54 and C78 are unusual members of the clan in that the third member (Asp in both C54 and C78) of the catalytic triad is N-terminal of the His rather than C-terminal as it is in all other families in the clan. UfSP2 has an additional N-terminal domain of unknown function.|