Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
acetyl-CoA + cortactin
CoA + N-acetyl-cortactin
acetyl-CoA + [alpha-TAT1]-L-lysine
CoA + [alpha-TAT1]-N6-acetyl-L-lysine
-
enzyme TAT1 acetylates itself in a regulatory mechanism that is required for effective modification of tubulin. Acetylation of multiple lysine residues on itself
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
acetyl-CoA + [alpha-tubulin]-L-lysine40
CoA + [alpha-tubulin]-N6-acetyl-L-lysine40
additional information
?
-
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
acetylation of the lysine residue at position 40
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin from calf is acetylated
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin from mouse is acetylated
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin from calf is acetylated
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin from Chlamydomonas is acetylated
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin from Chlamydomonas is acetylated
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
post-translational modification of alpha-tubulin
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin from calf is acetylated
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin from Chlamydomonas is acetylated
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
alpha-tubulin residue Ser38 is crucial for substrate recognition,whereas Asp39, Ile42, the glycine stretch (amino acid residues 4345) and Asp46 are also involved
-
?
acetyl-CoA + cortactin
CoA + N-acetyl-cortactin
-
-
-
-
?
acetyl-CoA + cortactin
CoA + N-acetyl-cortactin
-
ATAT1 acetylates, binds and colocalizes with cortactin at the adherent surface of MDA-MB-231 cells
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
K40 of alpha-tubulin is the sole site of acetylation by alphaTAT1, alphaTAT1 specifically acetylates K40 of alpha-tubulin and prefers microtubules over free tubulin, overview
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
alphaTAT1 acetylates tubulin through its GNAT domain in vitro. K40 of alpha-tubulin is the sole site of acetylation by alphaTAT1. alphaTAT1 displays a greater catalytic efficiency for taxol-stabilized microtubules than for free tubulin
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of alpha-tubulin mostly occurs on lysine residue 40, which is localized in the microtubule lumen
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40, in Tetrahymena, alpha-tubulin is the major if not the only substrate of MEC-17-dependent K acetylation
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine40
CoA + [alpha-tubulin]-N6-acetyl-L-lysine40
-
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine40
CoA + [alpha-tubulin]-N6-acetyl-L-lysine40
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine40
CoA + [alpha-tubulin]-N6-acetyl-L-lysine40
-
-
-
?
additional information
?
-
-
alphaTAT/MEC-17 is a lysine acetyltransferase for tubulin and not histones
-
-
?
additional information
?
-
-
wild-type adults have a strong signal for acetylated alpha-tubulin in the six touch receptor neurons
-
-
?
additional information
?
-
-
in vitro, MEC-17 exclusively acetylates Lys40 of alpha-tubulin
-
-
?
additional information
?
-
-
alphaTAT/MEC-17 is a lysine acetyltransferase for tubulin and not histones
-
-
?
additional information
?
-
the enzyme shows tubulin-specific acetylation activity
-
-
-
additional information
?
-
-
the enzyme shows tubulin-specific acetylation activity
-
-
-
additional information
?
-
-
recombinant GST-MEC-17 directly acetylates purified tubulin from the MEC17-KO strain in vitro
-
-
?
additional information
?
-
-
alphaTAT/MEC-17 is a lysine acetyltransferase for tubulin and not histones
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
acetyl-CoA + cortactin
CoA + N-acetyl-cortactin
-
ATAT1 acetylates, binds and colocalizes with cortactin at the adherent surface of MDA-MB-231 cells
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
acetyl-CoA + [alpha-tubulin]-L-lysine40
CoA + [alpha-tubulin]-N6-acetyl-L-lysine40
-
-
-
?
additional information
?
-
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + alpha-tubulin L-lysine
CoA + alpha-tubulin N6-acetyl-L-lysine
-
post-translational modification of alpha-tubulin
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
K40 of alpha-tubulin is the sole site of acetylation by alphaTAT1, alphaTAT1 specifically acetylates K40 of alpha-tubulin and prefers microtubules over free tubulin, overview
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of alpha-tubulin mostly occurs on lysine residue 40, which is localized in the microtubule lumen
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
acetylation of the epsilon-amino group of Lys40, in Tetrahymena, alpha-tubulin is the major if not the only substrate of MEC-17-dependent K acetylation
-
-
?
additional information
?
-
-
alphaTAT/MEC-17 is a lysine acetyltransferase for tubulin and not histones
-
-
?
additional information
?
-
-
wild-type adults have a strong signal for acetylated alpha-tubulin in the six touch receptor neurons
-
-
?
additional information
?
-
-
alphaTAT/MEC-17 is a lysine acetyltransferase for tubulin and not histones
-
-
?
additional information
?
-
-
alphaTAT/MEC-17 is a lysine acetyltransferase for tubulin and not histones
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
metabolism
-
a balance of acetylation and deaceylation by ATAT1/HDAC6, histone deacetylase 6, enzymes with opposite activities regulates the migratory and invasive capacities of breast tumor cells
evolution
-
broad phylogenetic distribution of alphaTAT1
evolution
-
distribution of alphaTAT/MEC-17 across all eukaryotic clades reveals that it was present in the last eukaryotic common ancestor, which was ciliated
evolution
-
distribution of alphaTAT/MEC-17 across all eukaryotic clades reveals that it was present in the last eukaryotic common ancestor, which was ciliated
evolution
-
distribution of alphaTAT/MEC-17 across all eukaryotic clades reveals that it was present in the last eukaryotic common ancestor, which was ciliated
evolution
-
MEC-17 is related to the Gcn5 histone acetyltransferases
evolution
-
MEC-17 is related to the Gcn5 histone acetyltransferases
evolution
-
MEC-17 is related to the Gcn5 histone acetyltransferases
evolution
-
MEC-17 is related to the Gcn5 histone acetyltransferases
malfunction
-
a delay in cilium formation for cultured human cells depleted of alphaTAT/MEC-17
malfunction
-
disrupting MEC17 in Tetrahymena abolishes tubulin acetylation, but no overt defect in cilium formation or motility occurs
malfunction
-
disruption of the Tetrahymena MEC-17 gene, resulting in a marked loss of acetyl-K40 in Tetrahymena cells, phenocopies the K40R alpha-tubulin mutation and makes microtubules more labile. Overexpression of GFP-Mec17p in Tetrahymena greatly increases acetylation of microtubules
malfunction
-
in animals lacking MEC-17, alphaTAT-2, and the sole Caenorhabditis elegans K40 alpha-tubulin MEC-12, touch sensation can be restored by expression of an acetyl-mimic MEC-12 K40Q. Transient overexpression of alphaTAT1 in PtK2 cells is sufficient to acetylate nearly all microtubules, whereas catalytically inactive alphaTAT1 D157N or the HAT Elp3 fail to detectably elevate alpha-tubulin K40 acetylation
malfunction
-
loss of Caenorhabditis elegans alphaTAT activity in the mec-17, atat-2 double mutant affects touch receptor neuron mechanosensation to a greater extent than having a nonacetylatable MEC-12 (K40R) form of tubulin in the organism
malfunction
-
MEC-12 is the only alpha-tubulin with K40, and mec-12(e1607) probable null allele worms have greatly reduced touch responses. Intergration of single transgenes encoding MEC-12 with either wild-type K40 or K40R or K40Q substitutions into the mec-12(e1607)mutant using Mos1 transposon excision repair restores the levels of touch response to 80% of wild type level,whereas animals with either MEC-12-K40R or MEC-12-K40Q show reduced touch response, overview
malfunction
-
overexpression of ATAT1 phenocopies the effect of HDAC6 inhibition by trichostatin. Random invasive migration of cells in 3D collagen I is inhibited by 40-50% upon MT1-MMP or ATAT1 knockdown
malfunction
-
touch receptor neurons in mec-17 but not atat-2 mutants exhibit morphological defects, phenotype, overview. Both mec-17(ok2109) and mec-17(u265) produced an increase in the length of the touch receptor neuron processes, effects on touch receptor neuron microtubule organization and structure, overview. Enzymatically inactive MEC-17 mutants rescue some of the mec-17 phenotypes, the function of mec-17 is protein-dependent
malfunction
-
zebrafish embryos depleted in MEC-17 show a dramatic loss of acetyl-K40 in neurons but not in cilia. Depletion of MEC-17 in zebrafish, by injection with random sequence morpholinos or 5-bp mismatched morpholinos, produces phenotypes consistent with neuromuscular defects
malfunction
the dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders
physiological function
-
elongator, a GTPase component of the hyperphosphorylated holoenzyme RNA polymerase II, is a regulator of alpha-tubulin acetylation in vivo. Elongator is important for microtubule function in correct loading and velocity of vesicles in vivo, and acetylation has a function in fine-tuning intrinsic dynamics of microtubules by modulating alpha-tubulin turnover
physiological function
-
alphaTAT1 is the major and possibly the sole alpha-tubulin K40 acetyltransferase in mammals and nematodes, and tubulin acetylation plays a conserved role in several microtubule-based processes. The worm incorporates acetylated alpha-tubulin into their microtubules. alphaTAT1 is required for the acetylation of axonemal microtubules. In Caenorhabditis elegans, microtubule acetylation is most prominent in touch receptor neurons and MEC-17, a homologue of alphaTAT1, and its paralogue alphaTAT-2 are required for alpha-tubulin acetylation and for two distinct types of touch sensation. Worm mechanosensation requires K40 alpha-tubulin acetylation
physiological function
-
dynamics and distribution of MT1-MMP-positive endosomes require regulation of acetylation levels, ATAT1 tubulin acetyltransferase binds and regulates cortactin acetylation levels. Acetylation of alpha-tubulin mostly occurs on lysine residue 40, which is localized in the microtubule lumen. ATAT1 colocalizes with cortactin at the adherent surface of the cells and it is required for 2D migration and invasive migration of MDA-MB-231 cells in collagen matrix
physiological function
-
MEC-17 and ATAT-2 are required for body touch sensation, which depends on the nonciliated, acetylated tubulin-containing touch receptor neurons. ATAT-2 is needed for acetylating tubulin in dendritic processes and cilia in those neurons. Additional role(s) for the acetyltransferase independent of tubulin acetylation
physiological function
-
MEC-17 is required for the function of touch receptor neurons in Caenorhabditis elegans and acts as a K40-specific acetyltransferase for alpha-tubulin. W06B11.1 os also required for acetylation of K40 and contribute to touch sensation
physiological function
-
the enzymatic activity of the alpha-tubulin acetyltransferase MEC-17 allows the production of 15-p microtubules in the touch receptor neurons microtubules, specific role for alpha-TAT in the formation of microtubules and in the production of higher order microtubules arrays. The alpha-TAT protein has functions that require acetyltransferase activity, such as the determination of protofilament number, and others that do not, e.g. presence of internal microtubule structures. Mec-17 and atat-2 are needed for touch sensitivity and MEC-12 acetylation
physiological function
-
the K40 residue of alpha-tubulin is important in vertebrates, acetyl-K40-carrying microtubules are abundant in the nervous system, including the brain, optical nerves, spinal cord, and axons of peripheral nerves. MEC-17 is required for K40 acetylation in zebrafish and normal embryonic development
physiological function
-
the K40 residue of alpha-tubulin is important in vertebrates, MEC-17 controls the levels of microtubule acetylation in mammalian cells
physiological function
-
the K40 residue of alpha-tubulin is not required for survival in protists, such as Chlamydomonas
physiological function
-
the K40 residue of alpha-tubulin is not required for survival in protists, such as Tetrahymena
physiological function
AcCoA and CoA each form a stable complex with human alphaTAT1 to maintain the protein integrity both in vivo and in vitro. The invariant residues Arg132 and Ser160 in alphaTAT1 participate in the stable interaction both with AcCoA and with CoA
physiological function
acetylation of alpha-tubulin is up-regulated during adipogenesis, and adipocyte development is dependent on alpha-tubulin acetylation. Acetylation of alpha-tubulin is under the control of the acetyltransferase MEC-17 and deacetylases SIRT2 and HDAC6. Adipocyte development is inhibited in MEC-17-knockdown cells, but enhanced in MEC-17-overexpressing cells. Katanin, a microtubule-severing protein with enhanced activity on acetylated alpha-tubulin, is actively involved in adipogenesis
physiological function
alphaTAT1 promotes microtubule destabilization and accelerates microtubule dynamics. This effect persists in an alphaTAT1 mutant with no acetyltransferase activity, suggesting that interaction of alphaTAT1 with microtubules is the critical factor regulating microtubule stability
physiological function
clathrin-coated pits control microtubule acetylation through a direct interaction of the alpha-tubulin acetyltransferase alphaTAT1 with the clathrin adaptor AP-2. About one-third of growing microtubule (+) ends contacts and pauses at clathrin-coated pits and loss of clathrin-coated pits decreased tubulin K40 acetylation levels. alphaTAT1 localises to clathrin-coated pits through a direct interaction with AP-2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with clathrin-coated pits accumulation at the leading edge 10, and interaction of alphaTAT1 with AP-2 is required for directional migration
physiological function
despite the confined intraluminal location of microtubule residue Lys40, TAT efficiently scans the microtubule bidirectionally and acetylates stochastically without preference for ends. TAT catalytic activity, not constrained luminal diffusion, is rate limiting for acetylation
physiological function
-
loss of MEC-17 leads to microtubule instability, a reduction in mitochondrial number, and disrupted axonal transport, with altered distribution of both mitochondria and synaptic components. MEC-17-mediated axonal degeneration occurs independently from its acetyltransferase domain, it is enhanced by mutation of coel-1, a tubulin-associated molecule; and correlates with the animals body length
physiological function
-
macrophages challenged by bacterial lipopolysaccharides undergo extensive microtubule acetylation. Suppression of lipopolysaccharide-induced microtubule acetylation by inactivating the tubulin acetyltransferase, MEC17, profoundly inhibits the induction of anti-inflammatory interlukin-10, a phenotype effectively reversed by an acetylation-mimicking alpha-tubulin mutant. Reversible microtubule acetylation is a kinase signaling modulator and a key component in the inflammatory response
physiological function
mice with a targeted deletion of Atat1 display a loss of detectable K40 alpha-tubulin acetylation across multiple tissues and in cellular structures such as cilia and axons where acetylation is normally enriched. Mice are viable and develop normally, however, the absence of Atat1 impacts upon sperm motility and male mouse fertility, and increases microtubule stability
physiological function
alpha-tubulin acetyltransferase ATAT-2 and the signaling hub RPM-1 are required presynaptically to maintain stable synapses. The acetyltransferase activity of ATAT-2 is required for synapse maintenance. RPM-1 is a hub in a genetic network composed of ATAT-2, PTRN-1 and DLK-1. ATAT-2 functions independent of the DLK-1 MAPK and likely acts downstream of RPM-1
physiological function
alphaTaT1 enters the microtubule lumen through the microtubule ends, and through bends or breaks in the lattice. Once alphaTat1 enters the microtubule lumen, the mobility of alphaTat1 within the lumen is controlled by its affinity for its acetylation sites, due to the rapid rebinding of alphaTat1 onto highly concentrated alpha-tubulin acetylation sites. Microtuble acetylation occurs at microtubule ends and is facilitated by new latice openings
physiological function
exposure of primary mouse cortical neurons to soluble chondroitin sulfate proteoglycans and myelin-associated glycoprotein substrates causes an acute and RhoA-kinase-dependent reduction in alpha-tubulin acetylation and Atat1 protein levels, without changes to either axonal histone deacetylase-6 levels or histonedeacetylase-6 activity. The chondroitin sulfate proteoglycans and myelin-associated glycoprotein-induced reduction in Atat1 occurs primarily in the distal and middle regions of neurites and reconstitution of Atat1, either by Rho-associated kinase inhibition or lentiviral-mediated Atat1 overexpression, can restore neurite growth. Chondroitin sulfate proteoglycans and myelin-associated glycoprotein signaling decreases Atat1 levels posttranscriptionally via a Rho-associated kinase-dependent increase in Atat1 protein turnover
physiological function
lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. Enzyme alphaTAT1 is involved in cell adhesion, migration, and invasion. It is the main KAT responsible for alpha-tubulin acetylation at Lys40 in higher organisms
physiological function
overexpression in ovarian cell line BmN leads to the time-dependent induction of cell cycle arrest in theG2/M phase
physiological function
overexpression of MEC-17 in A-549 cells enhances the cell spreading area, suppresses pseudopods formation in a three-dimensional culture system, and inhibits cancer cell migratory and invasive ability and tumour metastasis by orthotopic lung cancer animal model. Morphological change and migration inhibition of cancer cells are accompanied by epithelial-mesenchymal transition repression, Golgi reorientation, and polarity disruption caused by alteration of Cdc42 activity via a decrease in Rho-GAP, ARHGAP21. A reduction in endogenous MEC-17 accelerates the pseudopods formation and epithelial-mesenchymal transition, and facilitates cell migration and invasion
physiological function
protein p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. p27Kip1 stabilizes the alpha-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules. Cortical extracts isolated from P0 p27Kip1 KO mice show a reduced level of acetylated alpha-tubulin, and the protein level of Atat1 is reduced upon loss of p27Kip1
physiological function
-
treatment of cells with alpha-lipoic acid, leads to the hyperacetylation of alpha-tubulin residue K40 in the cytosol. The acetylation is blocked by pharmacological inhibition of mitochondrial citrate export, is dependent on the alpha-tubulin acetyltransferase Atat, and is coupled to a loss in function of the cytosolic histone deacetylase, HDAC6
additional information
-
MEC-17 sequences are absent from Chlamydomonas reinhardtii, an organism that has alphaTAT activity
additional information
despite having a tertiary structure similar to that of Gcn5, alphaTAT1 contains a relatively wide substrate binding pocket and unique structural elements that play an essential role in alpha-tubulin-specific acetylation, which is associated with many cellular processes connected to cancer dissemination such as cell adhesion, migration and invasion, tertiary enzyme structure in complex with acetyl-CoA (PDB ID 4gs4)
additional information
-
despite having a tertiary structure similar to that of Gcn5, alphaTAT1 contains a relatively wide substrate binding pocket and unique structural elements that play an essential role in alpha-tubulin-specific acetylation, which is associated with many cellular processes connected to cancer dissemination such as cell adhesion, migration and invasion, tertiary enzyme structure in complex with acetyl-CoA (PDB ID 4gs4)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
C120A
complete loss of activity
D157A
complete loss of activity
F186A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
F190A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
I64A
complete loss of activity
K102A
complete loss of activity
K103A
about 30% of wild-type activity
K162A
mutation in the acetyl-CoA binding pocket, mild effect on enzymatic activity
K169A
mutation in the acetyl-CoA binding pocket, mild effect on enzymatic activity
K98A
complete loss of activity
L122A
complete loss of activity
L164A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
L173A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
L60A
complete loss of activity
N181A
complete loss of activity
N182A
about 25% of wild-type activity
N73A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, discernable effect on catalytic activity
P159A
about 10% of wild-type activity
P178A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
Q131A
mutation in the acetyl-CoA binding pocket, mild effect on enzymatic activity
Q58A
complete loss of activity
R158A
about 45% of wild-type activity
R69A
about 10% of wild-type activity
S66A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, discernable effect on catalytic activity
V184A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
G134W/G136W/L139P
loss of catalytic activity
D157N
complete loss of activity
D157N
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
F105A
complete loss of activity
F105A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
F183A
complete loss of activity
F183A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
L104A
complete loss of activity
L104A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
Q179A
complete loss of activity
Q179A
mutation in highly conserved surface patches adjacent to the substrate-binding groove, pronounced effetc on catalytic activity
R132A
mutation in the acetyl-CoA binding pocket, mild effect on enzymatic activity
R132A
mutation leads to a drastic misfolding of the isolated alphaTAT1 catalytic domain in the absence of CoA and AcCoA but not in the presence of excess amounts of either cofactor. Mutant is degraded much faster than the wild-type protein
S160A
mutation in the acetyl-CoA binding pocket, mild effect on enzymatic activity
S160A
mutation leads to a drastic misfolding of the isolated alphaTAT1 catalytic domain in the absence of CoA and AcCoA but not in the presence of excess amounts of either cofactor. Mutant is degraded much faster than the wild-type protein
additional information
-
in an mec-12(e1607) background, i.e. a putative null mutant, acetylation of microtubules is absent in all developmental stages
additional information
-
overexpression of ATAT1 phenocopies the effect of HDAC6 inhibition by trichostatin
additional information
expression of truncated variants, residues 1-193 and residues 1-236. Truncation mutant 1-193 exhibits a 3 times higher Km value than 1-236
additional information
-
expression of truncated variants, residues 1-193 and residues 1-236. Truncation mutant 1-193 exhibits a 3 times higher Km value than 1-236
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MacRae, T.H.
Tubulin post-translational modifications
Eur. J. Biochem.
244
265-278
1997
Bos taurus, Chlamydomonas reinhardtii
brenda
Lloyd, R.A.; Gentleman, S.; Chader, G.J.
Assay of tubulin acetyltransferase activity in subcellular tissue fractions
Anal. Biochem.
216
42-46
1994
Bos taurus
brenda
Maruta, H.; Greer, K.; Rosenbaum, J.L.
The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules
J. Cell Biol.
103
571-579
1986
Chlamydomonas reinhardtii
brenda
Greer, K.; Maruta, H.; L'Hernault, S.W.; Rosenbaum, J.L.
Alpha-tubulin acetylase activity in isolated Chlamydomonas flagella
J. Cell Biol.
101
2081-2084
1985
Chlamydomonas reinhardtii, Chlamydomonas reinhardtii 21 gr
brenda
Solinger, J.A.; Paolinelli, R.; Kloess, H.; Scorza, F.B.; Marchesi, S.; Sauder, U.; Mitsushima, D.; Capuani, F.; Stuerzenbaum, S.R.; Cassata, G.
The Caenorhabditis elegans elongator complex regulates neuronal alpha-tubulin acetylation
PLoS Genet.
6
e1000820
2010
Caenorhabditis elegans
brenda
Topalidou, I.; Keller, C.; Kalebic, N.; Nguyen, K.C.; Somhegyi, H.; Politi, K.A.; Heppenstall, P.; Hall, D.H.; Chalfie, M.
Genetically separable functions of the MEC-17 tubulin acetyltransferase affect microtubule organization
Curr. Biol.
22
1057-1065
2012
Caenorhabditis elegans
brenda
Castro-Castro, A.; Janke, C.; Montagnac, G.; Paul-Gilloteaux, P.; Chavrier, P.
ATAT1/MEC-17 acetyltransferase and HDAC6 deacetylase control a balance of acetylation of alpha-tubulin and cortactin and regulate MT1-MMP trafficking and breast tumor cell invasion
Eur. J. Cell Biol.
91
950-960
2012
Homo sapiens
brenda
Akella, J.S.; Wloga, D.; Kim, J.; Starostina, N.G.; Lyons-Abbott, S.; Morrissette, N.S.; Dougan, S.T.; Kipreos, E.T.; Gaertig, J.
MEC-17 is an alpha-tubulin acetyltransferase
Nature
467
218-222
2010
Caenorhabditis elegans, Chlamydomonas reinhardtii, Danio rerio, Mus musculus, Tetrahymena thermophila
brenda
Leroux, M.
Tubulin acetyltransferase discovered: ciliary role in the ancestral eukaryote expanded to neurons in metazoans
Proc. Natl. Acad. Sci. USA
107
21238-21239
2010
Caenorhabditis elegans, Homo sapiens, Tetrahymena sp.
brenda
Shida, T.; Cueva, J.G.; Xu, Z.; Goodman, M.B.; Nachury, M.V.
The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation
Proc. Natl. Acad. Sci. USA
107
21517-21522
2010
Caenorhabditis elegans, no activity in Potorous tridactylis
brenda
Yang, W.; Guo, X.; Thein, S.; Xu, F.; Sugii, S.; Baas, P.; Radda, G.; Han, W.
Regulation of adipogenesis by cytoskeleton remodelling is facilitated by acetyltransferase MEC-17-dependent acetylation of alpha-tubulin
Biochem. J.
449
605-612
2013
Mus musculus (Q8K341)
brenda
Yuzawa, S.; Kamakura, S.; Hayase, J.; Sumimoto, H.
Structural basis of cofactor-mediated stabilization and substrate recognition of the alpha-tubulin acetyltransferase alphaTAT1
Biochem. J.
467
103-113
2015
Homo sapiens (Q5SQI0)
brenda
Neumann, B.; Hilliard, M.A.
Loss of MEC-17 leads to microtubule instability and axonal degeneration
Cell Rep.
6
93-103
2014
Caenorhabditis elegans
brenda
Szyk, A.; Deaconescu, A.M.; Spector, J.; Goodman, B.; Valenstein, M.L.; Ziolkowska, N.E.; Kormendi, V.; Grigorieff, N.; Roll-Mecak, A.
Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase
Cell
157
1405-1415
2014
Homo sapiens (Q5SQI0)
brenda
Davenport, A.M.; Collins, L.N.; Chiu, H.; Minor, P.J.; Sternberg, P.W.; Hoelz, A.
Structural and functional characterization of the alpha-tubulin acetyltransferase MEC-17
J. Mol. Biol.
426
2605-2616
2014
Homo sapiens (Q5SQI0), Homo sapiens
brenda
Nakakura, T.; Suzuki, T.; Nemoto, T.; Tanaka, H.; Asano-Hoshino, A.; Arisawa, K.; Nishijima, Y.; Kiuchi, Y.; Hagiwara, H.
Intracellular localization of alpha-tubulin acetyltransferase ATAT1 in rat ciliated cells
Med. Mol. Morphol.
49
133-143
2016
Rattus norvegicus
brenda
Howes, S.C.; Alushin, G.M.; Shida, T.; Nachury, M.V.; Nogales, E.
Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure
Mol. Biol. Cell
25
257-266
2014
Homo sapiens (Q5SQI0)
brenda
Kalebic, N.; Martinez, C.; Perlas, E.; Hublitz, P.; Bilbao-Cortes, D.; Fiedorczuk, K.; Andolfo, A.; Heppenstall, P.A.
Tubulin acetyltransferase alphaTAT1 destabilizes microtubules independently of its acetylation activity
Mol. Cell. Biol.
33
1114-1123
2013
Mus musculus (Q8K341)
brenda
Kalebic, N.; Sorrentino, S.; Perlas, E.; Bolasco, G.; Martinez, C.; Heppenstall, P.
alphaTAT1 is the major alpha-tubulin acetyltransferase in mice
Nat. Commun.
4
1962
2013
Mus musculus (Q8K341), Mus musculus
brenda
Wang, B.; Rao, Y.H.; Inoue, M.; Hao, R.; Lai, C.H.; Chen, D.; McDonald, S.L.; Choi, M.C.; Wang, Q.; Shinohara, M.L.; Yao, T.P.
Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production
Nat. Commun.
5
3479
2014
Mus musculus
brenda
Montagnac, G.; Meas-Yedid, V.; Irondelle, M.; Castro-Castro, A.; Franco, M.; Shida, T.; Nachury, M.V.; Benmerah, A.; Olivo-Marin, J.C.; Chavrier, P.
alphaTAT1 catalyses microtubule acetylation at clathrin-coated pits
Nature
502
567-570
2013
Homo sapiens (Q5SQI0)
brenda
Zhou, H.; Cheng, X.; Xu, X.; Jiang, T.; Zhou, H.; Sheng, Q.; Nie, Z.
Cloning, expression profiling, and acetylation identification of alpha-tubulin N-acetyltransferase 1 from Bombyx mori
Arch. Insect Biochem. Physiol.
98
e21463
2018
Bombyx mori (H9IXT4), Bombyx mori
brenda
Stoner, M.W.; Thapa, D.; Zhang, M.; Gibson, G.A.; Calderon, M.J.; St Croix, C.M.; Scott, I.
alpha-Lipoic acid promotes alpha-tubulin hyperacetylation and blocks the turnover of mitochondria through mitophagy
Biochem. J.
473
1821-1830
2016
Chlorocebus aethiops
brenda
Morelli, G.; Even, A.; Gladwyn-Ng, I.; Le Bail, R.; Shilian, M.; Godin, J.D.; Peyre, E.; Hassan, B.A.; Besson, A.; Rigo, J.M.; Weil, M.; Brone, B.; Nguyen, L.
p27Kip1 modulates axonal transport by regulating alpha-tubulin acetyltransferase 1 stability
Cell Rep.
23
2429-2442
2018
Mus musculus (Q8K341)
brenda
Borgen, M.; Giles, A.; Wang, D.; Grill, B.
Synapse maintenance is impacted by ATAT-2 tubulin acetyltransferase activity and the RPM-1 signaling hub
eLife
8
e44040
2019
Caenorhabditis elegans (Q23192)
brenda
Wong, V.; Picci, C.; Swift, M.; Levinson, M.; Willis, D.; Langley, B.
alpha-Tubulin acetyltransferase s a novel target mediating neurite growth inhibitory effects of chondroitin sulfate proteoglycans and myelin-associated glycoprotein
eNeuro
5
e0240
2018
Mus musculus (Q8K341)
brenda
Fiorentino, F.; Mai, A.; Rotili, D.
Lysine acetyltransferase inhibitors structure-activity relationships and potential therapeutic implications
Future Med. Chem.
10
1067-1091
2018
Homo sapiens (Q5SQI0), Homo sapiens
brenda
Nekooki-Machida, Y.; Nakakura, T.; Nishijima, Y.; Tanaka, H.; Arisawa, K.; Kiuchi, Y.; Miyashita, T.; Hagiwara, H.
Dynamic localization of alpha-tubulin acetyltransferase ATAT1 through the cell cycle in human fibroblastic KD cells
Med. Mol. Morphol.
51
217-226
2018
Homo sapiens (Q5SQI0), Homo sapiens
brenda
Coombes, C.; Yamamoto, A.; McClellan, M.; Reid, T.A.; Plooster, M.; Luxton, G.W.; Alper, J.; Howard, J.; Gardner, M.K.
Mechanism of microtubule lumen entry for the alpha-tubulin acetyltransferase enzyme alphaTAT1
Proc. Natl. Acad. Sci. USA
113
E7176-E7184
2016
Homo sapiens (Q5SQI0)
brenda
Lee, C.; Cheng, Y.; Chang, C.; Lin, C.; Chang, J.
Alpha-tubulin acetyltransferase/MEC-17 regulates cancer cell migration and invasion through epithelial-mesenchymal transition suppression and cell polarity disruption
Sci. Rep.
8
17477
2018
Homo sapiens (Q5SQI0)
brenda