CCPs deglutamylate tubulin

Stable Identifier
Reaction [transition]
Homo sapiens
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Cytosolic carboxypeptidases (CCPs) catalyze the removal of glutamate residues from the C-terminal tails of both alpha- and beta-tubulin. These glutamate residues are either enzymatically added in the polyglutamylation reaction, or gene-encoded glutamate residues are removed from alpha-tubulin after detyrosination to generate delta2-tubulin (Kimura et al. 2010, Rogowski et al. 2010). CCPs are members of the MC clan, M14 family, subfamily M14D of metallopeptidases (Kalinina et al. 2007, Rodriguez de la Vega et al. 2007). Mouse Ccp1, 2, 3, 4, and 6 are functionally homologous and remove linearly added glutamates from tubulin (alpha-peptide bonds), while Ccp5 specifically removes branching-point glutamates (gamma-peptide bonds) which are generated as first step of the polyglutamylation reaction (Rogowski et al. 2010; Tort et al. 2014). The catalytic activities of the human proteins are inferred from the properties of their mouse homologues and limited studies of human proteins expressed in cultured cells (Rogowski et al. 2010). In this event polyglutamylation is arbitrarily shown on only one tubulin protofilament within the polyglutamylated microtubule.
Literature References
PubMed ID Title Journal Year
21074048 A family of protein-deglutamylating enzymes associated with neurodegeneration

Desagher, S, Bosson, A, Rogowski, K, van Dijk, J, Bosc, C, Larroque, C, Bosch Grau, M, Holzer, M, Lacroix, B, Magiera, MM, Bec, N, Gold, ND, Deloulme, JC, Moutin, MJ, Andrieux, A, Janke, C, Peris, L

Cell 2010
17244818 A novel subfamily of mouse cytosolic carboxypeptidases

Avilés, FX, Berezniuk, I, Biswas, R, Fricker, LD, Kalinina, E, Hermoso, A

FASEB J. 2007
17244817 Nna1-like proteins are active metallocarboxypeptidases of a new and diverse M14 subfamily

Avilés, FX, Diez, A, Bautista, JM, Sevilla, RG, Lorenzo, J, Rodriguez de la Vega, M, Fricker, LD, Tanco, S, Hermoso, A

FASEB J. 2007
20519502 Identification of tubulin deglutamylase among Caenorhabditis elegans and mammalian cytosolic carboxypeptidases (CCPs)

Setou, M, Kurabe, N, Kimura, Y, Konishi, Y, Iino, Y, Kaplan, OI, Blacque, OE, Kunitomo, H, Tsutsumi, K, Ikegami, K

J. Biol. Chem. 2010
25103237 The cytosolic carboxypeptidases CCP2 and CCP3 catalyze posttranslational removal of acidic amino acids

Avilés, FX, Rocha, C, Tort, O, Lorenzo, J, Seixas, C, Bièche, I, Moutin, MJ, Andrieux, A, Janke, C, Bosc, C, Tanco, S

Mol. Biol. Cell 2014
Event Information
Catalyst Activity

metallocarboxypeptidase activity of CCPs [cytosol]

Inferred From
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