Enzyme Nomenclature. Recommendations 1992

Continued from EC to EC

EC 3.4.25

EC 3.4.25 Threonine endopeptidases


EC proteasome endopeptidase complex
EC HslU—HslV peptidase



Accepted name: proteasome endopeptidase complex

Reaction: Cleavage of peptide bonds with very broad specificity

Other names: ingensin; macropain; multicatalytic endopeptidase complex; prosome; multicatalytic proteinase (complex); MCP; proteasome; large multicatalytic protease; multicatalytic proteinase; proteasome organelle; alkaline protease; 26S protease; tricorn proteinase; tricorn protease

Comments: A 20-S protein composed of 28 subunits arranged in four rings of seven. The outer rings are composed of α subunits, but the β subunits forming the inner rings are responsible for peptidase activity. In eukaryotic organisms there are up to seven different types of β subunits, three of which may carry the N-terminal threonine residues that are the nucleophiles in catalysis, and show different specificities. The molecule is barrel-shaped, and the active sites are on the inner surfaces. Terminal apertures restrict access of substrates to the active sites. There is evidence that catalytic subunits are replaced by others under some conditions so as to alter the specificity of proteolysis, perhaps optimizing it for the formation of antigenic peptides. A complex of the 20-S proteasome endopeptidase complex with a 19-S regulatory unit is the 26-S proteasome that degrades ubiquitin-protein conjugates. Type example of peptidase family T1. Formerly EC, EC and EC

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 140879-24-9


1. Seemüller, E., Lupas, A., Stock, D., Löwe, J., Huber, R. and Baumeister, W. Proteasome from Thermoplasma acidophilum: a threonine protease. Science 268 (1995) 579-582. [PMID: 7725107]

2. Coux, O., Tanaka, K. and Goldberg, A.L. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65 (1996) 801-847. [PMID: 8811196]

3. Groll, M., Ditzel, L., Löwe, J., Stock, D., Bochtler, M., Bartunik, H.D. and Huber, R. Structure of 20S proteasome from yeast at 2.4Å resolution. Nature 386 (1997) 463-471. [PMID: 9087403]

4. Dick, T.P., Nussbaum, A.K., Deeg, M., Heinemeyer, W., Groll, M., Schirle, M., Keilholz, W., Stevanovic, S., Wolf, D.H., Huber, R., Rammensee, H.G. and Schild, H. Contribution of proteasomal β-subunits to the cleavage of peptide substrates analyzed with yeast mutants. J. Biol. Chem.386 (1998) 25637-25646. [PMID: 9748229]

[EC created 1978 as EC, part transferred 1989 to EC, transferred 1992 to EC, transferred 2000 to EC]


Accepted name: HslU—HslV peptidase

Reaction: ATP-dependent cleavage of peptide bonds with broad specificity.

Other name(s): HslUV; HslV-HslU; HslV peptidase; ATP-dependent HslV-HslU proteinase; caseinolytic protease X; caseinolytic proteinase X; ClpXP ATP-dependent protease; ClpXP protease; ClpXP serine proteinase; Escherichia coli ClpXP serine proteinase; HslUV protease; HslUV proteinase; HslVU protease; HslVU proteinase; protease HslVU; proteinase HslUV

Comments: The HslU subunit of the HslU—HslV complex functions as an ATP dependent “unfoldase”. The binding of ATP and its subsequent hydrolysis by HslU are essential for unfolding of protein substrates subsequently hydrolysed by HslV [5]. HslU recognizes the N-terminal part of its protein substrates and unfolds these before they are guided to HslV for hydrolysis [7]. In peptidase family T1.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS Metacyc, PDB, CAS registry number:


1. Wang, J., Rho, S.H., Park, H.H. and Eom, S.H. Correction of X-ray intensities from an HslV-HslU co-crystal containing lattice-translocation defects. Acta Crystallogr. D Biol. Crystallogr. 61 (2005) 932-941. [PMID: 15983416]

2. Nishii, W. and Takahashi, K. Determination of the cleavage sites in SulA, a cell division inhibitor, by the ATP-dependent HslVU protease from Escherichia coli. FEBS Lett. 553 (2003) 351-354. [PMID: 14572649]

3. Ramachandran, R., Hartmann, C., Song, H.K., Huber, R. and Bochtler, M. Functional interactions of HslV (ClpQ) with the ATPase HslU (ClpY). Proc. Natl. Acad. Sci. USA 99 (2002) 7396-7401. [PMID: 12032294]

4. Yoo, S.J., Seol, J.H., Shin, D.H., Rohrwild, M., Kang, M.S., Tanaka, K., Goldberg, A.L. and Chung, C.H. Purification and characterization of the heat shock proteins HslV and HslU that form a new ATP-dependent protease in Escherichia coli. J. Biol. Chem. 271 (1996) 14035-14040. [PMID: 8662828]

5. Yoo, S.J., Seol, J.H., Seong, I.S., Kang, M.S. and Chung, C.H. ATP binding, but not its hydrolysis, is required for assembly and proteolytic activity of the HslVU protease in Escherichia coli. Biochem. Biophys. Res. Commun. 238 (1997) 581-585. [PMID: 9299555]

6. Kanemori, M., Nishihara, K., Yanagi, H. and Yura, T. Synergistic roles of HslVU and other ATP-dependent proteases in controlling in vivo turnover of σ32 and abnormal proteins in Escherichia coli. J. Bacteriol. 179 (1997) 7219-7225. [PMID: 9393683]

7. Burton, R.E., Baker, T.A. and Sauer, R.T. Nucleotide-dependent substrate recognition by the AAA+ HslUV protease. Nat Struct Mol Biol 12 (2005) 245-251. [PMID: 15696175]

[EC created 2009, modified 2010]

Continued with EC 3.4.99
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