Summary: Tubulin-tyrosine ligase family
Tubulin-tyrosine ligase family Provide feedback
Tubulins and microtubules are subjected to several post-translational modifications of which the reversible detyrosination/tyrosination of the carboxy-terminal end of most alpha-tubulins has been extensively analysed. This modification cycle involves a specific carboxypeptidase and the activity of the tubulin-tyrosine ligase (TTL) . The true physiological function of TTL has so far not been established. Tubulin-tyrosine ligase (TTL) catalyses the ATP-dependent post-translational addition of a tyrosine to the carboxy terminal end of detyrosinated alpha-tubulin. In normally cycling cells, the tyrosinated form of tubulin predominates. However, in breast cancer cells, the detyrosinated form frequently predominates, with a correlation to tumour aggressiveness . On the other hand, 3-nitrotyrosine has been shown to be incorporated, by TTL, into the carboxy terminal end of detyrosinated alpha-tubulin. This reaction is not reversible by the carboxypeptidase enzyme. Cells cultured in 3-nitrotyrosine rich medium showed evidence of altered microtubule structure and function, including altered cell morphology, epithelial barrier dysfunction, and apoptosis . Bacterial homologs of TTL are predicted to form peptide tags. Some of these are fused to a 2-oxoglutarate Fe(II)-dependent dioxygenase domain .
Mialhe A, Lafanechere L, Treilleux I, Peloux N, Dumontet C, Bremond A, Panh MH, Payan R, Wehland J, Margolis RL, Job D; , Cancer Res 2001;61:5024-5027.: Tubulin detyrosination is a frequent occurrence in breast cancers of poor prognosis. PUBMED:11431336 EPMC:11431336
Eiserich JP, Estevez AG, Bamberg TV, Ye YZ, Chumley PH, Beckman JS, Freeman BA; , Proc Natl Acad Sci U S A 1999;96:6365-6370.: Microtubule dysfunction by posttranslational nitrotyrosination of alpha-tubulin: a nitric oxide-dependent mechanism of cellular injury. PUBMED:10339593 EPMC:10339593
Iyer LM, Abhiman S, Maxwell Burroughs A, Aravind L;, Mol Biosyst. 2009;5:1636-1660.: Amidoligases with ATP-grasp, glutamine synthetase-like and acetyltransferase-like domains: synthesis of novel metabolites and peptide modifications of proteins. PUBMED:20023723 EPMC:20023723
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR004344
Tubulins and microtubules are subjected to several post-translational modifications of the carboxy-terminal end of most major forms of tubulins has been extensively analysed. This modification cycle involves a specific carboxypeptidase and the activity of the tubulin-tyrosine ligase (TTL) and the tubulin polyglutamylase (TTLL) [PUBMED:10685598, PUBMED:19524510]. Tubulin-tyrosine ligase (TTL) catalyses the ATP-dependent post-translational addition of a tyrosine to the carboxy terminal end of detyrosinated alpha-tubulin. Tubulin polyglutamylase (such as TTLL10) can modify both tubulin and non-tubulin proteins, generating side chains of glycine on the gamma-carboxyl groups of specific glutamate residues of target proteins [PUBMED:19524510]. Tubulin polyglutamylation may be involved in the organisation of the neuronal microtubule network, in centriole stability, axoneme motility and mitosis [PUBMED:15890843].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||cellular protein modification process (GO:0006464)|
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The ATP-grasp domain is found in a wide variety of carboxylate-amine/thiol ligases . It is composed of two subdomains, with ATP being bound in the cleft between the two.
The clan contains the following 21 members:ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_TupA ATPgrasp_YheCD CP_ATPgrasp_1 CP_ATPgrasp_2 CPSase_L_D2 Dala_Dala_lig_C DUF1297 GARS_A GSH-S_ATP GSP_synth Ins134_P3_kin RimK Synapsin_C TTL
We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Pfam-B_682 (release 6.5)|
|Number in seed:||20|
|Number in full:||3670|
|Average length of the domain:||266.30 aa|
|Average identity of full alignment:||23 %|
|Average coverage of the sequence by the domain:||44.06 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||11|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TTL domain has been found. There are 19 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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