Family T2

Family

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

Summary for family T2

Family type peptidaseT02.001 - glycosylasparaginase precursor (Homo sapiens), MEROPS Accession MER0003299 (peptidase unit: 206-346)
Content of familyPeptidase family T2 contains a set of the N-terminal nucleophile hydrolases, including the glycosylasparaginase precursor.
History Identifier created: MEROPS 5.00 (20 April 2000)
Family T2 was first recognised in MEROPS in 2000. The only peptidase reactions known to be catalysed by proteins in the family at the time were autolytic cleavage events. In these reactions, precursor proteins converted themselves into active enzymes that were not peptidases. However, the mature taspase (T02.004) is an endopeptidase (Hsieh et al., 2003).
Catalytic typeThreonine
Active site residuesT206 
Active siteProcessing of the precursor proteins exposes an N-terminal threonine residue that is the nucleophile in catalysis (Aronson, 2004). All peptidases of this family require (1) the side-chain of an N-terminal amino acid to act as a nucleophile, and (2) the free alpha amino acid group becomes the base and helps to polarize the side-chain nucleophile.
Activities and specificitiesAll the peptidases in this family are endopeptidases. Examples are found in bacteria, archaea and eukaryotes, but not in viruses. The signal peptide of the precursor is removed by intramolecular autoproteolytic cleavage, producing a two-chain heterodimer and liberating the N-terminal nucleophilic Thr responsible for hydrolytic activity. Once converted to their active forms the peptidases in family T2 vary in the reaction that they catalyse. Examples are glycosylasparaginase (EC 3.5.1.26) which hydrolyses the GlcNAcAsn (the natural linkage structure between protein and carbohydrate in Asn-linked glycoproteins) and taspase-1 which cleaves aspartyl bonds DGADD and DGVDD in the product of the Mixed-Lineage Leukaemia (MLL) gene (Hsieh et al., 2003).
InhibitorsAn inhibitor of glycosylasparaginase is 5-diazo-4-oxonorvaline (DON) which has been shown to react with the N-terminal threonine of the beta subunit (Tarentino & Maley, 1969; Kaartinen et al., 1991).
Molecular structureThe tertiary structure of the enzymes of the glycosylasparaginase precursor family is typical of the "N-terminal nucleophile" hydrolases in clan PB. It is made up of four layers. There are two anti-parallel beta sheets that lie between two layers of alpha helices, forming an alpha-beta-beta-alpha sandwich (Brannigan et al., 1995). The active-site is located in a narrow pocket between the two beta sheets.
ClanPB
SubclanPB(T)
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of archaean proteasome subunit B, the type example of clan PB.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsRoles have been identified for peptidases of this family (and in subclan PB(T) generally) in metabolism. Glycosylasparaginase is essential for the degradation of Asn-linked glycoproteins. The genetic deficiency of this peptidase leads to a lysosomal storage disease in humans (Mononenet al., 1993). Taspase (T02.004) is suggested to contribute to the initiation of leukaemia through its cleavage of the product of the MLL gene (Hsieh et al., 2003).
Statistics for family T2Sequences:4132
Identifiers:9
Identifiers with PDB entries:6
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
glycosylasparaginase precursorT02.001Yes
isoaspartyl dipeptidase (threonine type)T02.002Yes
taspase-1T02.004Yes
Chryseobacterium meningosepticum-type N4-(beta-N-acetylglucosaminyl)-L-asparaginaseT02.007Yes
At5g08100 (Arabidopsis thaliana)T02.A01Yes
At3g16150 (Arabidopsis thaliana)T02.A02-
CG10474 protein (Drosophila melanogaster)T02.A04-
K01G5.9 g.p. (Caenorhabditis elegans)T02.A05-
SPAC823.09c g.p. (Schizosaccharomyces pombe)T02.A06-
family T2 non-peptidase homologuesnon-peptidase homologue-
family T2 unassigned peptidasesunassignedYes