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4  structures 310  species 0  interactions 2286  sequences 53  architectures

Family: TTL (PF03133)

Summary: Tubulin-tyrosine ligase family

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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) [2]. 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 [3]. 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 [4]. Bacterial homologs of TTL are predicted to form peptide tags. Some of these are fused to a 2-oxoglutarate Fe(II)-dependent dioxygenase domain [6].

Literature references

  1. Ersfeld K, Wehland J, Plessmann U, Dodemont H, Gerke V, Weber K; , J Cell Biol 1993;120:725-732.: Characterization of the tubulin-tyrosine ligase. PUBMED:8093886 EPMC:8093886

  2. Erck C, Frank R, Wehland J; , Neurochem Res 2000;25:5-10.: Tubulin-tyrosine ligase, a long-lasting enigma. PUBMED:10685598 EPMC:10685598

  3. 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

  4. 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

  5. Dideberg O, Bertrand J; , Trends Biochem Sci 1998;23:57-58.: Tubulin tyrosine ligase: a shared fold with the glutathione synthetase ADP-forming family. PUBMED:9538689 EPMC:9538689

  6. 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 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) [PUBMED:10685598]. Tubulin-tyrosine ligase (TTL) catalyses the ATP-dependent post-translational addition of a tyrosine to the carboxy terminal end of detyrosinated alpha-tubulin. The true physiological function of TTL has so far not been established. 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 [PUBMED:11431336].

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 [PUBMED:10339593].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(21)
Full
(2286)
Representative proteomes NCBI
(2259)
Meta
(173)
RP15
(771)
RP35
(931)
RP55
(1276)
RP75
(1558)
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Format an alignment

  Seed
(21)
Full
(2286)
Representative proteomes NCBI
(2259)
Meta
(173)
RP15
(771)
RP35
(931)
RP55
(1276)
RP75
(1558)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(21)
Full
(2286)
Representative proteomes NCBI
(2259)
Meta
(173)
RP15
(771)
RP35
(931)
RP55
(1276)
RP75
(1558)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_682 (release 6.5)
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 21
Number in full: 2286
Average length of the domain: 263.90 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 44.99 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.1 20.1
Trusted cut-off 20.1 20.1
Noise cut-off 20.0 20.0
Model length: 294
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Structures

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 4 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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