Continued from EC 3.4.26
Accepted name: intramembrane prenyl-peptidase Rce1
Reaction: Hydrolyses the peptide bond -P2-(S-farnesyl or geranylgeranyl)C-P1'-P2'-P3'-COOH where where P1' and P2' are amino acids with aliphatic sidechains and P3' is any C-terminal residue
Other name(s): CaaX prenyl protease 2; prenyl protein-specific endoprotease 2; PPSEP 2; α-factor-converting enzyme RCE1; ras converting enzyme; RACE; glutamic-type intramembrane endopeptidase Rce1; type II CAAX protease
Comments: The cleavage site motif is typically referred to as CaaX, where the letter a represents any amino acid, rather than alanine, and X represents the C-terminal amino acid of the target protein. The enzyme has been found in the yeast Saccharomyces cerevisiae and homologues exist in humans and several other species. Although the cleavage site is similar to that of the metallo-peptidase Ste24 endopeptidase (EC 3.4.24.84), there appear to be specificity differences in the proteins hydrolysed by these two enzymes, with amino-acid substitution studies indicating activity of the yeast enzyme towards substrates with a hydrophylic residue at (P1') that are not hydrolysed by EC 3.4.24.84 [4].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Otto, J.C., Kim, E., Young, S.G. and Casey, P.J. Cloning and characterization of a mammalian prenyl protein-specific protease. J. Biol. Chem. 274 (1999) 8379-8382. [PMID: 10085068]
2. Manolaridis, I., Kulkarni, K., Dodd, R.B., Ogasawara, S., Zhang, Z., Bineva, G., Reilly, N.O., Hanrahan, S.J., Thompson, A.J., Cronin, N., Iwata, S. and Barford, D. Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1. Nature 504 (2013) 301-305. [PMID: 24291792]
3. Pei, J., Mitchell, D.A., Dixon, J.E. and Grishin, N.V. Expansion of type II CAAX proteases reveals evolutionary origin of γ-secretase subunit APH-1. J. Mol. Biol. 410 (2011) 18-26. [PMID: 21570408]
4. Trueblood, C.E., Boyartchuk, V.L., Picologlou, E.A., Rozema, D., Poulter, C.D. and Rine, J. The CaaX proteases, Afc1p and Rce1p, have overlapping but distinct substrate specificities. Mol. Cell Biol. 20 (2000) 4381-4392. [PMID: 10825201]
5. Plummer, L.J., Hildebrandt, E.R., Porter, S.B., Rogers, V.A., McCracken, J. and Schmidt, W.K. Mutational analysis of the ras converting enzyme reveals a requirement for glutamate and histidine residues. J. Biol. Chem. 281 (2006) 4596-4605. [PMID: 16361710]
Accepted name: scytalidoglutamic peptidase
Reaction: Hydrolysis of proteins, with a strong preference for Phe or Tyr at position P1 and one of the smaller amino-acids at P1' in the sequence - P3 - P2 - P1 ┼P1'- P2'- P3'-. Cleaves the Tyr26-Thr27 bond in the B chain of oxidized insulin, which is not cleaved by pepsin.
Other name(s): scytalidopepsin-B; SCP-B; SGP; scytalidocarboxylpeptidase-B
Comments: The enzyme, isolated from the fungus Scytalidium lignicola and found in several other fungi, has a low pH optimum, being most active at pH 2 with casein as substrate. It differs from the pepsins (EC 3.4.23.1 and EC 3.4.23.2) in being insensitive to inhibition by pepstatin. It also differs from mammalian pepsins in showing a preference for a positively charged residue (Lys or Arg) at the P3 position. In addition to the catalytic Glu residue, a Gln residue appears to play an important role in the hydrolytic mechanism. A member of peptidase family G01, the "eqolisin" family of glutamic peptidases (G01.0001).
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, MetaCyc, CAS registry number:
References:
1. Kataoka, Y., Takada, K., Oyama, H., Tsunemi, M., James, M.N. and Oda, K. Catalytic residues and substrate specificity of scytalidoglutamic peptidase, the first member of the eqolisin in family (G1) of peptidases. FEBS Lett. 579 (2005) 2991-2994. [PMID: 15907842]
2. Fujinaga, M., Cherney, M.M., Oyama, H., Oda, K. and James, M.N. The molecular structure and catalytic mechanism of a novel carboxyl peptidase from Scytalidium lignicolum. Proc. Natl. Acad. Sci. USA 101 (2004) 3364-3369. [PMID: 14993599]
3. Pillai, B., Cherney, M.M., Hiraga, K., Takada, K., Oda, K. and James, M.N. Crystal structure of scytalidoglutamic peptidase with its first potent inhibitor provides insights into substrate specificity and catalysis. J. Mol. Biol. 365 (2007) 343-361. [PMID: 17069854]
4. Kondo, M.Y., Okamoto, D.N., Santos, J.A., Juliano, M.A., Oda, K., Pillai, B., James, M.N., Juliano, L. and Gouvea, I.E. Studies on the catalytic mechanism of a glutamic peptidase. J. Biol. Chem. 285 (2010) 21437-21445. [PMID: 20442413]