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145  structures 1448  species 0  interactions 9568  sequences 185  architectures

Family: TTL (PF03133)

Summary: Tubulin-tyrosine ligase family

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The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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


Internal 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 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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

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Pfam Clan

This family is a member of clan ATP-grasp (CL0179), which has the following description:

The ATP-grasp domain is found in a wide variety of carboxylate-amine/thiol ligases [1]. It is composed of two subdomains, with ATP being bound in the cleft between the two.

The clan contains the following 26 members:

ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATP-grasp_6 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_TupA ATPgrasp_YheCD CP_ATPgrasp_1 CP_ATPgrasp_2 CPSase_L_D2 D123 Dala_Dala_lig_C DUF1297 GARS_A GSH-S_ATP GSP_synth Ins134_P3_kin PPDK_N R2K_2 R2K_3 RimK Synapsin_C TTL

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

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
(20)
Full
(9568)
Representative proteomes UniProt
(21678)
RP15
(3027)
RP35
(5043)
RP55
(8421)
RP75
(10724)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(20)
Full
(9568)
Representative proteomes UniProt
(21678)
RP15
(3027)
RP35
(5043)
RP55
(8421)
RP75
(10724)
Alignment:
Format:
Order:
Sequence:
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Download options

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
(20)
Full
(9568)
Representative proteomes UniProt
(21678)
RP15
(3027)
RP35
(5043)
RP55
(8421)
RP75
(10724)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 20
Number in full: 9568
Average length of the domain: 264.80 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 42.43 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -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: 295
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 145 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2K2F9 View 3D Structure Click here
A0A0R0IDU6 View 3D Structure Click here
A0A140LH35 View 3D Structure Click here
A0A1D6PJ00 View 3D Structure Click here
A0A1D8PLC3 View 3D Structure Click here
A0A2R8QCY3 View 3D Structure Click here
A1ZBN5 View 3D Structure Click here
A2APC3 View 3D Structure Click here
A4HUV1 View 3D Structure Click here
A4HWT7 View 3D Structure Click here
A4HWT7 View 3D Structure Click here
A4HXR2 View 3D Structure Click here
A4HYN9 View 3D Structure Click here
A4I351 View 3D Structure Click here
A4I479 View 3D Structure Click here
A4I479 View 3D Structure Click here
A4I479 View 3D Structure Click here
A4I5Q6 View 3D Structure Click here
A4I5Q6 View 3D Structure Click here
A4I8B4 View 3D Structure Click here
A4I8B4 View 3D Structure Click here
A4IC28 View 3D Structure Click here
A4Q9E4 View 3D Structure Click here
A4Q9E5 View 3D Structure Click here
A4Q9E8 View 3D Structure Click here
A4Q9F0 View 3D Structure Click here
A4Q9F1 View 3D Structure Click here
A4Q9F3 View 3D Structure Click here
A4Q9F4 View 3D Structure Click here
A4Q9F6 View 3D Structure Click here
A5PM86 View 3D Structure Click here
A6NNM8 View 3D Structure Click here
A6PVC2 View 3D Structure Click here
A8CVX7 View 3D Structure Click here
B5DFD2 View 3D Structure Click here
B5DFG3 View 3D Structure Click here
C0H4D8 View 3D Structure Click here
D3ZAA1 View 3D Structure Click here
D3ZE22 View 3D Structure Click here
D3ZF82 View 3D Structure Click here
D3ZJ17 View 3D Structure Click here
D4A1Q9 View 3D Structure Click here
D4A331 View 3D Structure Click here
E7F887 View 3D Structure Click here
E9P886 View 3D Structure Click here
E9QED8 View 3D Structure Click here
F1Q6C4 View 3D Structure Click here
F1QA49 View 3D Structure Click here
F1QT18 View 3D Structure Click here
F8W385 View 3D Structure Click here
H2KZM9 View 3D Structure Click here
I1MHF8 View 3D Structure Click here
M0RBT9 View 3D Structure Click here
O95922 View 3D Structure Click here
P38254 View 3D Structure Click here
P38585 View 3D Structure Click here
Q08CA4 View 3D Structure Click here
Q09512 View 3D Structure Click here
Q09647 View 3D Structure Click here
Q10438 View 3D Structure Click here
Q10QY3 View 3D Structure Click here
Q14166 View 3D Structure Click here
Q14679 View 3D Structure Click here
Q1ECV4 View 3D Structure Click here
Q21279 View 3D Structure Click here
Q3SXZ7 View 3D Structure Click here
Q3UDE2 View 3D Structure Click here
Q4CNS0 View 3D Structure Click here
Q4CQJ9 View 3D Structure Click here
Q4CQJ9 View 3D Structure Click here
Q4CV57 View 3D Structure Click here
Q4CX38 View 3D Structure Click here
Q4D5R1 View 3D Structure Click here
Q4D9R2 View 3D Structure Click here
Q4DPL9 View 3D Structure Click here
Q4DPN4 View 3D Structure Click here
Q4DRI1 View 3D Structure Click here
Q4DT74 View 3D Structure Click here
Q4DT74 View 3D Structure Click here
Q4DWS9 View 3D Structure Click here
Q4DWS9 View 3D Structure Click here
Q4DWW9 View 3D Structure Click here
Q4DXI7 View 3D Structure Click here
Q4DXI7 View 3D Structure Click here
Q4E2S4 View 3D Structure Click here
Q4E4H6 View 3D Structure Click here
Q4E5F1 View 3D Structure Click here
Q54TU1 View 3D Structure Click here
Q54XJ2 View 3D Structure Click here
Q564U4 View 3D Structure Click here
Q5PPI9 View 3D Structure Click here
Q5XI57 View 3D Structure Click here
Q641W7 View 3D Structure Click here
Q6EMB2 View 3D Structure Click here
Q6IDC7 View 3D Structure Click here
Q6ZT98 View 3D Structure Click here
Q6ZVT0 View 3D Structure Click here
Q7JVG6 View 3D Structure Click here
Q80UG8 View 3D Structure Click here
Q8CHB8 View 3D Structure Click here
Q8IJU8 View 3D Structure Click here
Q8IPB2 View 3D Structure Click here
Q8N841 View 3D Structure Click here
Q8NG68 View 3D Structure Click here
Q8NHH1 View 3D Structure Click here
Q91V51 View 3D Structure Click here
Q9BWV7 View 3D Structure Click here
Q9QXJ0 View 3D Structure Click here
Q9VB58 View 3D Structure Click here
Q9VBX5 View 3D Structure Click here
Q9VGW2 View 3D Structure Click here
Q9VM91 View 3D Structure Click here
Q9VM92 View 3D Structure Click here
Q9VQV6 View 3D Structure Click here
Q9VX74 View 3D Structure Click here
Q9VZ97 View 3D Structure Click here
Q9Y4R7 View 3D Structure Click here