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Information on EC 3.4.17.24 - tubulin-glutamate carboxypeptidase
for references in articles please use BRENDA:EC3.4.17.24
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.17 Metallocarboxypeptidases
3.4.17.24 tubulin-glutamate carboxypeptidase
The enzyme appears in viruses and cellular organisms
- 3.4.17.24
- microtubule
- degeneration
-
polyglutamylation
-
purkinje
-
cilia
-
glutamylases
-
agtpbp1
-
deglutamylation
- pigmentosa
-
hyperglutamylation
-
ligase-like
- ciliopathies
-
detyrosination
-
infantile-onset
-
peptidomics
-
centrioles
- metallocarboxypeptidases
Reaction Schemes
showThis 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 ccp1, cytosolic carboxypeptidase 6, cytosolic carboxypeptidase-like protein 5, cytosolic carboxypeptidase 5, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AGBL5
CCP1
CCP5
CCP6
cytosolic carboxypeptidase
cytosolic carboxypeptidase 1
cytosolic carboxypeptidase 6
cytosolic carboxypeptidase-like protein 5
tubulinyl-Glu carboxypeptidase
-
-
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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.
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
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.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
beta2b-tubulin + H2O
?
Substrates: -
Products: 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
Products: 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
?
biotin-Glu-Glu + H2O
?
Substrates: Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
Products: -
Products: -
?
biotin-Glu-Glu-Glu + H2O
?
Substrates: Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
Products: -
Products: -
?
biotin-Glu-Glu-Glu-Glu + H2O
?
Substrates: Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
Products: -
Products: -
?
biotin-Glu-Glu-Glu-Glu-Glu + H2O
?
Substrates: Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
Products: -
Products: -
?
biotin-Glu-Glu-Glu-Gly-Glu-Glu + H2O
?
Substrates: Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
Products: -
Products: -
?
biotin-Glu-Glu-Gly-Glu-Glu-Glu + H2O
?
Substrates: Nna1 can metabolized substrates with two or more glutamate residues. It is more active against longer chain substrates
Products: -
Products: -
?
DATAEEEGEMYE(gamma-(E)2)-DDDEESEAQGPK + 2 H2O
DATAEEEGEMYEDDDEESEAQGPK + 2 L-Glu
Substrates: synthetic beta3-tubulin-based 24-residue C-terminal peptide with two side chain Glu residues
Products: about 30% removal of Glu side chains
Products: about 30% removal of Glu side chains
?
DATAEEEGEMYE(gamma-(E)3)-DDDEESEAQGPK + 3 H2O
DATAEEEGEMYEDDDEESEAQGPK + 3 L-Glu
Substrates: synthetic beta3-tubulin-based 24-residue C-terminal peptide with three side chain Glu residues
Products: -
Products: -
?
DATAEEEGEMYE(gamma-(E)4)-DDDEESEAQGPK + 4 H2O
DATAEEEGEMYEDDDEESEAQGPK + 4 L-Glu
Substrates: synthetic beta3-tubulin-based 24-residue C-terminal peptide with four side chain Glu residues
Products: -
Products: -
?
DATAEEEGEMYE(gamma-E)-DDDEESEAQGPK + H2O
DATAEEEGEMYEDDDEESEAQGPK + L-Glu
Substrates: synthetic beta3-tubulin-based 24-residue C-terminal peptide with one side chain Glu residue
Products: complete removal of Glu side chain
Products: complete removal of Glu side chain
?
DELTA2-tubulin + H2O
DELTA3-tubulin + L-glutamate
Substrates: i.e. tubulin lacking two C-terminal amino acids
Products: i.e. tubulin lacking two C-terminal amino acids
Products: i.e. tubulin lacking two C-terminal amino acids
?
monoglutamyl alpha-tubulin + H2O
alpha-tubulin + L-Glu
Substrates: -
Products: -
Products: -
r
monoglutamyl beta-tubulin + H2O
beta-tubulin + L-Glu
Substrates: -
Products: -
Products: -
r
monoglutamylated beta-tubulin + H2O
beta-tubulin + L-Glu
Substrates: -
Products: -
Products: -
?
polyglutamated tubulin + H2O
?
Substrates: CCP5 specifically metabolizes the gamma-carboxyl linked, branch point glutamate. It metabolized gamma-carboxyl-linked glutamate of synthetic substrates and tubulin
Products: -
Products: -
?
polyglutamylated alpha-tubulin + H2O
? + L-Glu
Substrates: -
Products: -
Products: -
?
polyglutamylated beta-tubulin + H2O
? + L-Glu
Substrates: -
Products: -
Products: -
?
polymerized microtubules + H2O
?
Substrates: 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
Products: -
Products: -
?
tubulin + H2O
?
Substrates: 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
Products: -
Products: -
?
tubulin-polyglutamate + H2O
?
Substrates: 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
Products: -
Products: -
?
[40S ribosomal protein S9]-KNAKKGQGGAGAGDDEEED + H2O
[40S ribosomal protein S9]-KNAKKGQGGAGAGDD + Glu-Glu-Glu-Asp
Substrates: -
Products: -
Products: -
?
[40S ribosomal protein S9]-KNAKKGQGGAGAGDDEEED + H2O
[40S ribosomal protein S9]-KNAKKGQGGAGAGDDE + Glu-Glu-Asp
Substrates: -
Products: -
Products: -
?
[alpha-tubulin 1A/1B]-EDMAALEKDYEEVGVDSVEGEGEEEGEE + H2O
[alpha-tubulin 1A/1B]-EDMAALEKDYEEVGVDSVEGEGEEEG + Glu-Glu
Substrates: in the case of alpha-tubulin, it is considered that CCP1 uses as substrate the pool of detyrosinated tubulin naturally present in the cell
Products: -
Products: -
?
[alpha-tubulin 1C]-EDMAALEKDYEEVGADSADGEDEGEE + H2O
[alpha-tubulin 1C]-EDMAALEKDYEEVGADSADGEDEG + Glu-Glu
Substrates: in the case of alpha-tubulin, it is considered that CCP1 uses as substrate the pool of detyrosinated tubulin naturally present in the cell
Products: -
Products: -
?
[eukaryotic translation initiation factor 4H]-EEVVQKEQE + H2O
[eukaryotic translation initiation factor 4H]-EEVVQKEQ + Glu
Substrates: -
Products: -
Products: -
?
[high mobility group protein B1]-EEEEDEEDEEDEEEEEDEEDEDEEEDDDDE + H2O
[high mobility group protein B1] + EEEEDEEDEEDEEEEEDEEDEDEEEDDDDE
Substrates: -
Products: -
Products: -
?
[high mobility group protein B2]-EDEEEEEEEEDEDEEEEDEDEE + H2O
[high mobility group protein B2] + EDEEEEEEEEDEDEEEEDEDEE
Substrates: -
Products: -
Products: -
?
[high mobility group protein B3]-KKVEEEDEEEEEEEEEEEEEEDE + H2O
[high mobility group protein B3]-KKVEEED + EEEEEEEEEEEEEEDE
Substrates: -
Products: -
Products: -
?
[high mobility group protein B3]-KKVEEEDEEEEEEEEEEEEEEDE + H2O
[high mobility group protein B3]-KKVEEEDE + EEEEEEEEEEEEEDE
Substrates: -
Products: -
Products: -
?
[myosin light chain kinase 1/telokinc]-EEEEEE + H2O
[myosin light chain kinase 1/telokinc] + EEEEEE
Substrates: -
Products: -
Products: -
?
[stathmin]-KNKESKDPADETEAD + H2O
[stathmin]-KNKESKDPADETEA + Asp
Substrates: -
Products: -
Products: -
?
[TRAF-type zinc finger domain-containing protein]-TAKAKPSKQQGAGDAEEEEEE + H2O
[TRAF-type zinc finger domain-containing protein]-TAKAKPSKQQGAGDA + Glu-Glu-Glu-Glu-Glu-Glu
Substrates: -
Products: -
Products: -
?
DELTAY-alpha-tubulin + H2O
DELTAC2 alpha-tubulin + L-Glu
Substrates: -
Products: -
Products: -
?
DELTAY-alpha-tubulin + H2O
DELTAC2 alpha-tubulin + L-Glu
-
Substrates: -
Products: -
Products: -
?
detyrosinated alpha-tubulin + H2O
DELTA2-tubulin + L-glutamate
-
Substrates: porcine brain tubulin
Products: i.e. tubulin lacking two C-terminal amino acids
Products: i.e. tubulin lacking two C-terminal amino acids
?
detyrosinated alpha-tubulin + H2O
DELTA2-tubulin + L-glutamate
Substrates: -
Products: 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
Products: 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
?
detyrosinated alpha-tubulin + H2O
DELTA2-tubulin + L-glutamate
Substrates: porcine brain tubulin
Products: i.e. tubulin lacking two C-terminal amino acids
Products: i.e. tubulin lacking two C-terminal amino acids
?
polymerized microtubules + H2O
DELTA2-tubulin + ?
-
Substrates: -
Products: i.e. tubulin lacking two C-terminal amino acids
Products: i.e. tubulin lacking two C-terminal amino acids
?
polymerized microtubules + H2O
DELTA2-tubulin + ?
Substrates: -
Products: i.e. tubulin lacking two C-terminal amino acids
Products: i.e. tubulin lacking two C-terminal amino acids
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: isoform CCP5 is a deglutamylase that specifically removes branching point glutamates. CCP5 is the only enzyme that is able to remove tubulin-tyrosine ligase-like protein TTLL4-dependent monoglutamylation. CCP5 removes glutamylation not only from tubulin but also from other substrates that are monoglutamylated by TTLL4. Active CCP5 completely removes monoglutamylation and strongly reduces polyglutamylation of tubulin by TTLL6. Only short side chains are removed, and CCP5 does not generate DELTA2-tubulin
Products: -
Products: -
?
additional information
?
-
Substrates: CCP1 processes both glutamates as well as C-terminal aspartates
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme removes both C-terminal Glu residues and the branch point Glu from both alpha- and beta-tubulin
Products: -
Products: -
-
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: CCP5 does not have detyrosinase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: CCP5 does not have detyrosinase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme removes both C-terminal Glu residues and the branch point Glu from both alpha- and beta-tubulin
Products: -
Products: -
-
additional information
?
-
Substrates: the enzyme removes both C-terminal Glu residues and the branch point Glu from both alpha- and beta-tubulin
Products: -
Products: -
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
DELTAY-alpha-tubulin + H2O
DELTAC2 alpha-tubulin + L-Glu
Substrates: -
Products: -
Products: -
?
DELTAY-alpha-tubulin + H2O
DELTAC2 alpha-tubulin + L-Glu
-
Substrates: -
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
o-phenanthroline
-
o-phenanthroline substantially inhibited CCP1 activity toward polglutamylated tubulin
1,10-phenanthroline
5 mM, the activity of the enzyme (CCP5) on branching glutamate (GT335) is inhibited
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Alstrom Syndrome
Birt-Hogg-Dubé syndrome associated with chorioretinopathy and nyctalopia: a case report and review of the literature.
Ataxia
Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of ?-Tubulin Glutamylation in Neurodegeneration.
Carcinoma
Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection.
Carcinoma, Renal Cell
Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection.
Ciliopathies
Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function.
Cysts
Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function.
Hydrocephalus
Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function.
Infertility
Lack of Cytosolic Carboxypeptidase 1 Leads to Subfertility due to the Reduced Number of Antral Follicles in pcd3J-/- Females.
Infertility, Male
Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of ?-Tubulin Glutamylation in Neurodegeneration.
Infertility, Male
Loss of the deglutamylase CCP5 perturbs multiple steps of spermatogenesis and leads to male infertility.
Retinitis Pigmentosa
Birt-Hogg-Dubé syndrome associated with chorioretinopathy and nyctalopia: a case report and review of the literature.
Retinitis Pigmentosa
Establishing the involvement of the novel gene AGBL5 in retinitis pigmentosa by whole genome sequencing.
Retinitis Pigmentosa
Exome Sequencing Reveals AGBL5 as Novel Candidate Gene and Additional Variants for Retinitis Pigmentosa in Five Turkish Families.
Retinitis Pigmentosa
Mutations in AGBL5, Encoding ?-Tubulin Deglutamylase, Are Associated With Autosomal Recessive Retinitis Pigmentosa.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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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
brenda
CCP1 and CCP5 mRNAs are predominantly expressed in tissues such as the brain, olfactory placodes, and pronephric ducts
brenda
CCP1 and CCP5 mRNAs are predominantly expressed in tissues such as the brain, olfactory placodes, and pronephric ducts
brenda
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
brenda
additional information
CCP5 mRNA is not detectable in the Purkinje cells
brenda
CCP1 and CCP5 mRNAs are predominantly expressed in tissues such as the brain, olfactory placodes, and pronephric ducts
brenda
CCP5 RNA levels are about 100times higher in testis than cerebellum or brain
brenda
CCP5 RNA levels are about 100times higher in testis than cerebellum or brain
brenda
CCP5 mRNA shows a slight enrichment in the cerebellum and olfactory bulb and in a region near the paraventricular thalamic nucleus
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the enzyme exhibits a cytosolic distribution, with a slight accumulation of CCP5 in the nucleus
brenda
the enzyme exhibits a cytosolic distribution, with a slight accumulation of CCP5 in the nucleus
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
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
malfunction
knockdown of CCP1 and CCP5 results in similar defects including severe hydrocephalus and axial curvature
malfunction
-
loss of enzyme function causes neuronal ciliary degeneration and and loss of neuronal function. Glutamylases of the tubulin tyrosine ligase-like TTLL family (ttll-4, ttll-5, and ttll-11) oppose the enzyme's deglutamylase function
malfunction
loss of isoform CCP5 leads to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells
malfunction
enzyme loss results in hyperglutamylation of beta-tubulin as well as alpha-tubulin in vivo
malfunction
-
enzyme loss results in hyperglutamylation of beta-tubulin as well as alpha-tubulin in vivo
malfunction
loss of isoform CCP6 leads to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells
malfunction
enzyme inactivation induces hyperglutamylation and neurodegeneration in the brain
malfunction
-
enzyme loss, and the resulting hyperglutamylation of microtubules, causes neurodegeneration. Enzyme knock-down increases the presence of cilia on spinal cord neurons but does not result in loss or shortening of cilia
physiological function
-
overexpression or knockdown (8090%) of isoform CCP1 in human embryonic kidney 293T cells does not affect the levels of most intracellular peptides but alters the levels of alpha-tubulin lacking two C-terminal amino acids more than 5fold, suggesting that tubulin processing is the primary function of CCP1
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
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
loss of ccpp-6 gene function, which encodes one of two cytosolic carboxypeptidases, results in elevated levels of ciliary microtubule polyglutamylation. Overexpression of this gene in ciliated cells decreases polyglutamylation signals
physiological function
isoform ccp5 knockdown increases cilia tubulin glutamylation, induces ciliopathy phenotypes, including axis curvature, hydrocephalus, and pronephric cysts, and disrupts multicilia motility. ccp5 knockdown restores tubulin glutamylation and promotes multicilia assembly in intraflagellar transport-deficient zebrafish
physiological function
CCP5 is not essential for neuronal survival in mouse. CCP5 is involved in spermatogenesis
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
CCP1 and CCP5 play important roles in zebrafish embryonic development, particularly the development and functioning of cilia. Loss of the deglutamylating enzymes causes developmental defects in zebrafish
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
CCP1-mediated shortening of acidic protein tails might regulate protein-protein and protein-DNA interactions
physiological function
the enzyme regulates the ciliary localization of the kinesin-3 KLP-6 and the polycystin PKD-2 in male-specific sensory neurons in Caenorhabditis elegans. CCPP-1 activity is required for ciliary maintenance but not ciliogenesi
physiological function
-
isoform CCP5-mediated deglutamylation is needed to maintain the ultrastructure of the photoreceptor outer segment. Deglutamylation of tubulin controlled by isoform CCP5 is important for the integrity of the photoreceptor cilia. Excessive tubulin glutamylation by the enzyme leads to the progressive loss of photoreceptors, affecting cones more severely than rods, resulting in vision loss
physiological function
isoform CCP5 inhibits cilia formation before ciliogenesis, while shorten the length of cilia after cilia formation. In addition to regulating cilia length, both isoforms also retain centriolar coiled-coil protein of 110 kDa level to suppress cilia formation in cycling cells. The inhibition of isoform CCP5 on cilia formation does not depend on its enzyme activity
physiological function
-
isoform CCP5 or CCP6 inhibits cilia formation before ciliogenesis, while shorten the length of cilia after cilia formation. In addition to regulating cilia length, both isoforms also retain Centriolar coiled-coil protein of 110 kDa level to suppress cilia formation in cycling cells. The inhibition of isoform CCP5 on cilia formation does not depend on its enzyme activity
physiological function
isoform CCP6 inhibits cilia formation before ciliogenesis, while shorten the length of cilia after cilia formation. In addition to regulating cilia length, both isoforms also retain centriolar coiled-coil protein of 110 kDa level to suppress cilia formation in cycling cells
physiological function
-
the enzyme protects spinal cord neurons from glutamate-induced excitotoxic death
Show AA Sequence and Transmembrane Helices (3978 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
high affinity Ni-charged resin column chromatography, amylose resin column chromatography, Talon resin column chromatography, Q Sepharose column chromatography, and Superdex 200 gel filtration
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Ni-charged resin chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli ArcticExpress (DE3) cells with chaperonin Cpn60 in a stoichiometric ratio of roughly 1:7 and exhibiting no enzyme activity. When coupled with a step to promote the release of the substrate protein from the chaperonins by treatment with ATP/Mg2+/K+, the recombinant isoform CCP6 with deglutamylation activity is obtained, though still partially associated with Cpn60
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CCP1 and CCP5 mRNAs are detectable between 2 h and 8 days postfertilization with highest levels 5-8 days postfertilization
enzyme levels decrease within 24 h after excitotoxic injury of spinal cord cells
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isoform CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed
isoform CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed
isoform CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kalinina, E.; Biswas, R.; Berezniuk, I.; Hermoso, A.; Aviles, F.X.; Fricker, L.D.
A novel subfamily of mouse cytosolic carboxypeptidase
FASEB J.
21
836-850
2007
Mus musculus (Q09M02)
brenda
Rogowski, K.; van Dijk, J.; Magiera, M.M.; Bosc, C.; Deloulme, J.C.; Bosson, A.; Peris, L.; Gold, N.D.; Lacroix, B.; Bosch Grau, M.; Bec, N.; Larroque, C.; Desagher, S.; Holzer, M.; Andrieux, A.; Moutin, M.J.; Janke, C.
A family of protein-deglutamylating enzymes associated with neurodegeneration
Cell
143
564-578
2010
Homo sapiens (Q8NDL9)
brenda
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
brenda
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, Mus musculus (Q09M02)
brenda
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
brenda
Pathak, N.; Austin-Tse, C.A.; Liu, Y.; Vasilyev, A.; Drummond, I.A.
Cytoplasmic carboxypeptidase 5 regulates tubulin glutamylation and zebrafish cilia formation and function
Mol. Biol. Cell
25
1836-1844
2014
Danio rerio (Q68EI3), Danio rerio
brenda
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)
brenda
Lyons, P.J.; Sapio, M.R.; Fricker, L.D.
Zebrafish cytosolic carboxypeptidases 1 and 5 are essential for embryonic development
J. Biol. Chem.
288
30454-30462
2013
Danio rerio (Q68EI3), Danio rerio (Q4U2V3)
brenda
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)
brenda
Tanco, S.; Tort, O.; Demol, H.; Aviles, F.X.; Gevaert, K.; Van Damme, P.; Lorenzo, J.
C-terminomics screen for natural substrates of cytosolic carboxypeptidase 1 reveals processing of acidic protein C termini
Mol. Cell. Proteomics
14
177-190
2015
Homo sapiens (Q9UPW5)
brenda
Wu, H.Y.; Wei, P.; Morgan, J.I.
Role of cytosolic carboxypeptidase 5 in neuronal survival and spermatogenesis
Sci. Rep.
7
41428
2017
Mus musculus (Q09M02), Mus musculus
brenda
Bodakuntla, S.; Yuan, X.; Genova, M.; Gadadhar, S.; Leboucher, S.; Birling, M.C.; Klein, D.; Martini, R.; Janke, C.; Magiera, M.M.
Distinct roles of alpha- and beta-tubulin polyglutamylation in controlling axonal transport and in neurodegeneration
EMBO J.
40
e108498
2021
Mus musculus (Q641K1), Mus musculus
brenda
Hotta, T.; Plemmons, A.; Gebbie, M.; Ziehm, T.A.; Blasius, T.L.; Johnson, C.; Verhey, K.J.; Pearring, J.N.; Ohi, R.
Mechanistic analysis of CCP1 in generating DELTAC2 alpha-tubulin in mammalian cells and photoreceptor neurons
Biomolecules
13
357
2023
Homo sapiens, Homo sapiens (Q9UPW5), Mus musculus
brenda
Wang, Y.; Zhang, Y.; Guo, X.; Zheng, Y.; Zhang, X.; Feng, S.; Wu, H.Y.
CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis
BMC Biol.
21
124
2023
Homo sapiens (Q8NDL9), Homo sapiens (Q5VU57), Mus musculus
brenda
Ramadan, Y.H.; Gu, A.; Ross, N.; McEwan, S.A.; Barr, M.M.; Firestein, B.L.; OHagan, R.
CCP1, a tubulin deglutamylase, increases survival of rodent spinal cord neurons following glutamate-induced excitotoxicity
eNeuro
8
FEHLT
2021
Rattus norvegicus
brenda
Aljammal, R.; Saravanan, T.; Guan, T.; Rhodes, S.; Robichaux, M.A.; Ramamurthy, V.
Excessive tubulin glutamylation leads to progressive cone-rod dystrophy and loss of outer segment integrity
Hum. Mol. Genet.
33
802-817
2024
Mus musculus
brenda
Power, K.M.; Akella, J.S.; Gu, A.; Walsh, J.D.; Bellotti, S.; Morash, M.; Zhang, W.; Ramadan, Y.H.; Ross, N.; Golden, A.; Smith, H.E.; Barr, M.M.; O'Hagan, R.
Mutation of NEKL-4/NEK10 and TTLL genes suppress neuronal ciliary degeneration caused by loss of CCPP-1 deglutamylase function
PLoS Genet.
16
e1009052
2020
Caenorhabditis elegans
brenda
Guo, X.; Wang, R.; Ma, R.; Fan, X.; Gao, Y.; Zhang, X.; Yuchi, Z.; Wu, H.Y.
Facile purification of active recombinant mouse cytosolic carboxypeptidase 6 from Escherichia coli
Protein Expr. Purif.
197
106112
2022
Mus musculus
brenda
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