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Information on EC 3.4.17.24 - tubulin-glutamate carboxypeptidase and Organism(s) Mus musculus and UniProt Accession Q641K1
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3.4.17.24 tubulin-glutamate carboxypeptidaseSpecify your search results
Word Map
- 3.4.17.24
- microtubule
- degeneration
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polyglutamylation
-
purkinje
-
cilia
-
glutamylases
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agtpbp1
-
deglutamylation
- pigmentosa
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hyperglutamylation
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ligase-like
- ciliopathies
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detyrosination
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infantile-onset
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peptidomics
-
centrioles
- metallocarboxypeptidases
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
This is a subfamily of enzymes that cleave C-terminal and/or side chain amino acids from tubulins. The dual-specificity enzymes can cleave both alpha- and gamma-linked L-glutamate from tubulins, removing the posttranslationally added polyglutamyl side chains from the C-terminal regions. In addition, the enzyme removes two glutamate residues from the C-terminus of beta-tubulin and detyrosinated alpha-tubulin (from which the C-terminal L-tyrosine has been removed by EC 3.4.17.17, tubulinyl-Tyr carboxypeptidase). The latter is cleaved to delta2-tubulin and further to delta3-tubulin.
Synonyms
deglutamylase, ccpp-1, agbl5, cytosolic carboxypeptidase 1, ccpp-6, cytosolic carboxypeptidase 6, cytosolic carboxypeptidase ccp1, cytosolic carboxypeptidase 5, cytosolic carboxypeptidase-like protein 5, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
tubulinyl-Glu carboxypeptidase
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-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
This is a subfamily of enzymes that cleave C-terminal and/or side chain amino acids from tubulins. The dual-specificity enzymes can cleave both alpha- and gamma-linked L-glutamate from tubulins, removing the posttranslationally added polyglutamyl side chains from the C-terminal regions. In addition, the enzyme removes two glutamate residues from the C-terminus of beta-tubulin and detyrosinated alpha-tubulin (from which the C-terminal L-tyrosine has been removed by EC 3.4.17.17, tubulinyl-Tyr carboxypeptidase). The latter is cleaved to delta2-tubulin and further to delta3-tubulin.
enzyme additionally cleaves alpha-linked Glu from the C-terminus of alpha-tubulin and alpha-linked Glu residues from the side chain of alpha- and beta-tubulin
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
biotin-Glu-Glu + H2O
?
Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
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-
?
biotin-Glu-Glu-Glu + H2O
?
Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
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-
?
biotin-Glu-Glu-Glu-Glu + H2O
?
Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
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-
?
biotin-Glu-Glu-Glu-Glu-Glu + H2O
?
Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
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-
?
biotin-Glu-Glu-Glu-Gly-Glu-Glu + H2O
?
Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
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-
?
biotin-Glu-Glu-Gly-Glu-Glu-Glu + H2O
?
Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
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-
?
tubulin-polyglutamate + H2O
?
the enzyme (Nna1) metabolizes the polyglutamate side chain of tubulin. It removes the C-terminal glutamate from substrates with two or more glutamates. The enzyme exhibits a monoglutamase activity when aspartic acid precedes a single glutamate
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-
?
beta2b-tubulin + H2O
?
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incubation with isoform CCP5 causes decreases of the peaks corresponding to multi- and monoglutamylated beta2b-tubulin and a dramatic increase of the peak corresponding to beta2b-tubulin without Glu on the side chain
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?
DATAEEEGEMYE(gamma-(E)2)-DDDEESEAQGPK + 2 H2O
DATAEEEGEMYEDDDEESEAQGPK + 2 L-Glu
synthetic beta3-tubulin-based 24-residue C-terminal peptide with two side chain Glu residues
about 30% removal of Glu side chains
-
?
DATAEEEGEMYE(gamma-(E)3)-DDDEESEAQGPK + 3 H2O
DATAEEEGEMYEDDDEESEAQGPK + 3 L-Glu
synthetic beta3-tubulin-based 24-residue C-terminal peptide with three side chain Glu residues
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-
?
DATAEEEGEMYE(gamma-(E)4)-DDDEESEAQGPK + 4 H2O
DATAEEEGEMYEDDDEESEAQGPK + 4 L-Glu
synthetic beta3-tubulin-based 24-residue C-terminal peptide with four side chain Glu residues
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-
?
DATAEEEGEMYE(gamma-E)-DDDEESEAQGPK + H2O
DATAEEEGEMYEDDDEESEAQGPK + L-Glu
synthetic beta3-tubulin-based 24-residue C-terminal peptide with one side chain Glu residue
complete removal of Glu side chain
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?
DELTA2-tubulin + H2O
DELTA3-tubulin + L-glutamate
i.e. tubulin lacking two C-terminal amino acids
i.e. tubulin lacking two C-terminal amino acids
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?
polyglutamated tubulin + H2O
?
CCP5 specifically metabolizes the gamma-carboxyl linked, branch point glutamate. It metabolized gamma-carboxyl-linked glutamate of synthetic substrates and tubulin
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-
?
polymerized microtubules + H2O
?
polymerized microtubules prepared from MDA-MB-231 cells grown on a coverslip. Isoform CCP5 eliminates GT335 signals and diminishes poly(E) signals on polymerized tubulin
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-
?
polymerized microtubules + H2O
DELTA2-tubulin + ?
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i.e. tubulin lacking two C-terminal amino acids
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?
tubulin + H2O
?
porcine brain tubulin. Isoform CCP5 can process paclitaxel-treated tubulin, and the activity of CCP5 in the presence of paclitaxel is comparable with the activity in the absence of the drug
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-
?
detyrosinated alpha-tubulin + H2O
DELTA2-tubulin + L-glutamate
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treatment with isoform CCP5 leads to a decrease in the peak intensities of the multi- as well as monoglutamylated alpha-tubulin forms and an increase in the peak intensity of the form lacking all Glu residues on the side chain
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?
detyrosinated alpha-tubulin + H2O
DELTA2-tubulin + L-glutamate
porcine brain tubulin
i.e. tubulin lacking two C-terminal amino acids
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?
additional information
?
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CCP5 does not have detyrosinase activity
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-
?
additional information
?
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isoform CCP1 removes Glu residues from the polyglutamyl side chains of porcine brain alpha- and beta-tubulin and also generates a form of alpha-tubulin with two C-terminal Glu residues removed
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?
additional information
?
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isoform CCP1 removes Glu residues from the polyglutamyl side chains of porcine brain alpha- and beta-tubulin and also generates a form of alpha-tubulin with two C-terminal Glu residues removed
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?
additional information
?
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isoform CCP5 removes multiple glutamate residues and the branch point glutamate from the side chains of porcine brain alpha- and beta-tubulin. CCP5 excises C-terminal glutamates from detyrosinated alpha-tubulin. The enzyme also removes multiple glutamate residues from side chains and C-termini of paclitaxel-stabilized microtubules. CCP5 both shortens and removes side chain glutamates from synthetic peptides corresponding to the C-terminal region of beta3-tubulin
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-
?
additional information
?
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isoform CCP5 removes multiple glutamate residues and the branch point glutamate from the side chains of porcine brain alpha- and beta-tubulin. CCP5 excises C-terminal glutamates from detyrosinated alpha-tubulin. The enzyme also removes multiple glutamate residues from side chains and C-termini of paclitaxel-stabilized microtubules. CCP5 both shortens and removes side chain glutamates from synthetic peptides corresponding to the C-terminal region of beta3-tubulin
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-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
5 mM, the activity of the enzyme (CCP5) on branching glutamate (GT335) is inhibited
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
the enzyme (Nna1) exhibits higher kcat/Km when substrates contain nearby acidic amino acids
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
CCP5 mRNA shows a slight enrichment in the cerebellum and olfactory bulb and in a region near the paraventricular thalamic nucleus
CCP5 RNA levels are about 100times higher in testis than cerebellum or brain. Expression is predominantly in spermatocytes and their descendants, but is absent in spermatogonia
CCP5 RNA levels are about 100times higher in testis than cerebellum or brain
CCP5 mRNA shows a slight enrichment in the cerebellum and olfactory bulb and in a region near the paraventricular thalamic nucleus
CCP5 RNA levels are about 100times higher in testis than cerebellum or brain
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the enzyme exhibits a cytosolic distribution, with a slight accumulation of CCP5 in the nucleus
the enzyme exhibits a cytosolic distribution, with a slight accumulation of CCP5 in the nucleus
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
loss of CCP1 in mice causes cerebellar Purkinje cell degeneration. Neuronal degeneration caused by loss of CCP1 in mammals may represent a novel ciliopathy in which cilia are formed but not maintained, depriving the cell of cilia-based signal transduction
physiological function
physiological function
physiological function
CCPP-1 acts as a tubulin deglutamylase that regulates the localization and velocity of kinesin motors, and the structural integrity of microtubules in sensory cilia of a multicellular, living animal
physiological function
the C-terminal regions of tubulins undergo multiple forms of post-translational modifications, which, in addition to polyglutamylation, include removal and addition of a C-terminal tyrosine residue, addition and trimming of polyglycine side chains, and proteolytic processing to yield DELTA2 tubulin. The enzyme (Nna1) is involved in several of these processes, as it not only removes polyglutamate chains from tubulin, but also cleaves synthetic substrates that mimic the detyrosinated and DELTA2 forms of the C terminus of alpha-tubulin the enzyme is involved in the posttranslational process of polyglutamylation, where they catalyze the removal of polyglutamate side chains
physiological function
overexpression of murine CCP5 causes a dramatic loss of microtubule polyglutamylation in cultured mammalian cells. Recombinantly expressed Myc-tagged CCP5 exhibits deglutamylase biochemical activities
physiological function
the Purkinje cell degeneration (pcd) mouse has a disruption in the gene encoding cytosolic carboxypeptidase 1. Pcd mutant mouse brain shows hyperglutamylation of both alpha- and beta-tubulin
physiological function
CCP5 is not essential for neuronal survival in mouse. CCP5 is involved in spermatogenesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CBPC1_MOUSE
1218
0
137197
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kimura, Y.; Kurabe, N.; Ikegami, K.; Tsutsumi, K.; Konishi, Y.; Kaplan, O.I.; Kunitomo, H.; Iino, Y.; Blacque, O.E.; Setou, M.
Identification of tubulin deglutamylase among Caenorhabditis elegans and mammalian cytosolic carboxypeptidases (CCPs)
J. Biol. Chem.
285
22936-22941
2010
Caenorhabditis elegans (Q09296), Caenorhabditis elegans, Mus musculus (Q09M02), Mus musculus
Berezniuk, I.; Vu, H.; Lyons, P.; Sironi, J.; Xiao, H.; Burd, B.; Setou, M.; Angeletti, R.; Ikegami, K.; Fricker, L.
Cytosolic carboxypeptidase 1 is involved in processing alpha- and beta-tubulin
J. Biol. Chem.
287
6503-6517
2012
Homo sapiens, Mus musculus (Q09M02), Mus musculus
Berezniuk, I.; Lyons, P.J.; Sironi, J.J.; Xiao, H.; Setou, M.; Angeletti, R.H.; Ikegami, K.; Fricker, L.D.
Cytosolic carboxypeptidase 5 removes alpha- and gamma-linked glutamates from tubulin
J. Biol. Chem.
288
30445-30453
2013
Mus musculus (Q09M02), Mus musculus
O'Hagan, R.; Piasecki, B.P.; Silva, M.; Phirke, P.; Nguyen, K.C.; Hall, D.H.; Swoboda, P.; Barr, M.M.
The tubulin deglutamylase CCPP-1 regulates the function and stability of sensory cilia in C. elegans
Curr. Biol.
21
1685-1694
2011
Caenorhabditis elegans (O76373), Mus musculus (Q641K1)
Kalinina, E.; Biswas, R.; Berezniuk, I.; Hermoso, A.; Aviles, F.X.; Fricker, L.D.
A novel subfamily of mouse cytosolic carboxypeptidases
FASEB J.
21
836-850
2007
Mus musculus (Q09M02)
Wu, H.Y.; Rong, Y.; Correia, K.; Min, J.; Morgan, J.I.
Comparison of the enzymatic and functional properties of three cytosolic carboxypeptidase family members
J. Biol. Chem.
290
1222-1232
2015
Mus musculus (Q641K1)
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