Family T1

Family

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

T1A

Summary Holotypes Alignment Tree Genomes Literature

T1B

Summary Holotypes Alignment Tree Genomes Literature

Summary for family T1

NamePeptidase family T1 (proteasome family)
Family type peptidaseT01.002 - archaean proteasome, beta component (Thermoplasma acidophilum), MEROPS Accession MER0000548 (peptidase unit: 9-211)
Content of familyPeptidase family T1 contains the component peptidases of the proteasome and related compound peptidases.
History Identifier created: Proteolysis in Cell Function, pp13-21, IOS Press, Amsterdam (1997)
The discovery of a fifth peptidase catalytic type came when the crystallographic structure of the eukaryotic proteasome (XT01-001) from Saccharomyces cerevisiae was determined (Lowe et al., 1995), showing an N-terminal threonine at the active site. The catalytic type of the proteasome had been a puzzle because of its resistence to inhibition by most standard peptidase inhibitors. The structure also revealed the number of subunits in the peptidase complex as fourteen, and the N-terminal threonine residues of some of the subunits as catalytic residues. Prokaryote homologues have a simpler structure: the bacterial proteasome (T01.005) has four different kinds of subunits, the archaean (T01.002) only two, and the bacterial HslVU (T01.006) peptidase consists of a proteasome subunit (HslV) and an ATP-binding subunit (HslU).
Catalytic typeThreonine
Active siteThe N-terminal threonine residues of some of the beta subunits are the nucleophiles in catalysis (Seemuller et al., 1995).
Activities and specificitiesThe eukaryotic proteasome has three different activities (trypsin-like, chymotrypsin-like and cleavage after glutamate). Each activity resides in a different β subunit. The archaean and bacterial proteasomes have only chymotrypsin-like activity. The catalytic subunits are synthesized as precursors that are autocatalytically activated. The synthetic substrate Suc-Leu-Leu-Val-Tyr-NHMec has been used to assay the chymotrysin-like activity, various trypsin substrates for the trypsin-like activity and Z-Leu-Leu-Glu-NHNap for the peptidylglutamate activity.
InhibitorsNo known natural protein inhibitors are known. The small, naturally occurring compounds lactacystin , epoxomycin and eponemycin from actinomycete bacteria inactivate by interaction with the catalytic threonine, blocking all three catalytic activities. Chymostatin inhibits the chymotrypsin-like activity and leupeptin the trypsin-like.
Molecular structureThe proteasome complex molecule consists of four rings of seven subunits, and takes the form of a hollow cylinder with the active sites on the walls of the inner chamber. Rings one and four contain alpha-type subunits whereas rings two and three are composed of beta-type subunits. In the eukaryotic proteasome, the only subunits with peptidase activity are three of the seven kinds of beta subunits, although in mammals three additional active subunits inducible by gamma-interferon can replace the constitutive active subunits. Each subunit is the product of a different gene. Additional kinds of subunits may be added as a cap to the proteasome (the 19S cap). The uncapped enzyme is known as the 20S proteasome (20S being its approximate sedimentation coefficient; XT01-001) whereas the capped enzyme is the 26S proteasome (XT01-002). The cap consists of several subunits, one of which is a deubiquitinating enzyme in peptidase family M67 (M67.002). In bacteria such as Rhodococcus, the proteasome consists of two different alpha subunits and two different, active beta subunits. In archaea, there is only one alpha and one beta subunit gene, though the number of components and rings in the proteasome is the same as in eukaryotes. The bacterial proteasome is different again with a single active peptidase subunit and an unrelated ATP-binding subunit. In all forms of the proteasome, the peptidase subunits are N-terminal nucleophile hydrolases, which means that in the mature protein the catalytic residue is Thr1. The N-terminal threonine possesses both the nucleophile (the hydroxyl group) and the general base (the amino group) and can be artificially replaced with serine without significant loss of activity. The tertiary structure shows an alpha/beta/beta/alpha sandwich, with each beta sheet containing four strands and with the active site at one end of the beta sheet. The structure is similar to those of other Ntn hydrolases in clan PB, such as penicillin acylase (S45.001) and glycosylasparaginase (T02.001).
ClanPB
SubclanPB(T)
Basis of clan assignmentType family of clan PB.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsThe proteasome is involved in the turnover of intracellular proteins, including proteins specifically targeted for degradation by polyubiquitination. The 20S proteasome is latent and requires activation either via the 19S cap, an 11S complex known as PA28 or SDS. The 26S proteasome is capable of cleaving proteins unfolded by the 19S cap in an ATP-dependent process. The PA28-activated proteasome is only capable of hydrolysing oligopeptides in an ATP-independent manner, however, such as peptides of viral origin in type 2 antigen processing.
Pharmaceutical and biotech relevanceInhibitors of the proteasome are under investigation for possible use against cancer and a variety of other conditions.
Statistics for family T1Sequences:17968
Identifiers:60
Identifiers with PDB entries:37
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily T1A
Name Peptidase subfamily T1A
Subfamily type peptidase T01.002 - archaean proteasome, beta component (Thermoplasma acidophilum), MEROPS Accession MER0000548 (peptidase unit: 9-211)
Active site residues T9 
Statistics Sequences: 14950
Identifiers: 51
Identifiers with PDB entries: 29
Other databases CATH 3.60.20.10
HOMSTRAD proteasome
HSSP 1pma
INTERPRO IPR000243
PFAM PF00227
PFAM PF10584
SCOP 56251
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
archaean proteasome, beta componentT01.002Yes
bacterial proteasome, beta componentT01.005Yes
proteasome subunit beta1cT01.010Yes
proteasome subunit beta2cT01.011Yes
proteasome subunit beta5cT01.012Yes
proteasome subunit beta1iT01.013Yes
proteasome subunit beta2iT01.014Yes
proteasome subunit beta5iT01.015-
proteasome subunit beta5tT01.016-
protein serine kinase c17T01.017Yes
similar to proteasome subunit beta type 6 (Rattus norvegicus)T01.019-
similar to proteasome subunit beta type 6 (Rattus norvegicus) (but not T01.019)T01.020Yes
archaean proteasome, alpha componentT01.970Yes
proteasome subunit alpha 6T01.971Yes
proteasome subunit alpha 2T01.972Yes
proteasome subunit alpha 4T01.973Yes
proteasome subunit alpha 7T01.974Yes
proteasome subunit alpha 5T01.975Yes
proteasome subunit alpha 1T01.976Yes
proteasome subunit alpha 3T01.977Yes
2410072d24rik protein (mouse)T01.978-
proteasome subunit XAPC7T01.979Yes
similar to proteasome subunit beta type 3 (Rattus norvegicus)T01.982-
proteasome subunit beta 3T01.983Yes
proteasome subunit beta 2T01.984Yes
similar to proteasome subunit beta type 3 (Rattus norvegicus) (but not T01.982)T01.985-
proteasome subunit beta 1T01.986Yes
similar to proteasome subunit beta 3 (Mus musculus)T01.989-
similar to splicing factor U2AF homolog (Mus musculus)T01.990Yes
Mername-AA230 peptidase homologue (Homo sapiens)T01.991-
Mername-AA241 peptidase homologue (Mus musculus)T01.994-
Mername-AA242 peptidase homologue (Mus musculus)T01.995-
Mername-AA243 peptidase homologueT01.996-
Mername-AA244 peptidase homologueT01.997Yes
protein similar to proteasome subunit iotaT01.998-
similar to proteasome subunit alpha type 2 (Rattus norvegicus)T01.999-
yip3 (Drosophila melanogaster)T01.A01-
proteasome subunit beta2 (Drosophila melanogaster)T01.A02Yes
CG12161 protein (Drosophila melanogaster)T01.A03-
CG18341 protein (Drosophila melanogaster)T01.A04-
CG31742 protein (Drosophila melanogaster)T01.A05-
beta5 subunit (Drosophila melanogaster)T01.A06-
CG9868 protein (Drosophila melanogaster)T01.A07-
pbs-5 g.p. (Caenorhabditis elegans)T01.A09-
PBE2 g.p. (Arabidopsis thaliana)T01.A10-
20S proteasome component beta 6T01.A12Yes
PFE0915c g.p. (Plasmodium falciparum)T01.A14Yes
PF10_0111 g.p. (Plasmodium falciparum)T01.A15Yes
proteasome subunit beta pseudogeneT01.P01-
Mername-AA231 pseudogene (Homo sapiens)T01.P02-
Mername-AA232 pseudogene (Homo sapiens)T01.P03-
subfamily T1A non-peptidase homologuesnon-peptidase homologueYes
subfamily T1A unassigned peptidasesunassignedYes
Subfamily T1B
Name Peptidase subfamily T1B
Subfamily type peptidase T01.006 - HslV component of HslUV peptidase (Escherichia coli), MEROPS Accession MER0001627 (peptidase unit: 2-176)
Active site residues S,T2 
Statistics Sequences: 1953
Identifiers: 4
Identifiers with PDB entries: 4
Other databases CATH 3.60.20.10
HOMSTRAD proteasome
HSSP 1ht2
INTERPRO IPR001353
PANTHER PTHR32194
PFAM PF00227
SCOP 56251
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
HslV component of HslUV peptidaseT01.006Yes
CodW component of CodWX peptidaseT01.007Yes
PfHslV peptidaseT01.018-
TbHslUV peptidaseT01.021Yes
subfamily T01B non-peptidase homologuesnon-peptidase homologue-
subfamily T1B unassigned peptidasesunassignedYes
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
proteasome subunit beta 4T01.987Yes
pbs-7 g.p. (Caenorhabditis elegans)T01.A08-
SPCC1442.06 g.p. (Schizosaccharomyces pombe)T01.A11-
psmB4-2 g.p. (Dictyostelium discoideum)T01.A13Yes
PF14_0716 g.p. (Plasmodium falciparum)T01.A16Yes
family T1 non-peptidase homologuesnon-peptidase homologue-
family T1 unassigned peptidasesunassignedYes