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4  structures 3358  species 0  interactions 3709  sequences 10  architectures

Family: TilS_C (PF11734)

Summary: TilS substrate C-terminal domain

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TilS substrate C-terminal domain Provide feedback

This domain is found in the tRNA(Ile) lysidine synthetase (TilS) protein.

Literature references

  1. Kuratani M, Yoshikawa Y, Bessho Y, Higashijima K, Ishii T, Shibata R, Takahashi S, Yutani K, Yokoyama S; , Structure. 2007;15:1642-1653.: Structural basis of the initial binding of tRNA(Ile) lysidine synthetase TilS with ATP and L-lysine. PUBMED:18073113 EPMC:18073113

  2. Nakanishi K, Fukai S, Ikeuchi Y, Soma A, Sekine Y, Suzuki T, Nureki O; , Proc Natl Acad Sci U S A. 2005;102:7487-7492.: Structural basis for lysidine formation by ATP pyrophosphatase accompanied by a lysine-specific loop and a tRNA-recognition domain. PUBMED:15894617 EPMC:15894617

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR012796

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [ PUBMED:10704480 , PUBMED:12458790 ]. These proteins differ widely in size and oligomeric state, and have limited sequence homology [ PUBMED:2203971 ]. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric [ PUBMED:10673435 ]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [ PUBMED:8364025 ], and are mostly dimeric or multimeric, containing at least three conserved regions [ PUBMED:8274143 , PUBMED:2053131 , PUBMED:1852601 ]. However, tRNA binding involves an alpha-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [ PUBMED:10447505 ].

This entry represents the C-terminal domain of lysidine-tRNA(Ile) synthetase, which ligates lysine onto the cytidine present at position 34 of the AUA codon-specific tRNA(Ile) that contains the anticodon CAU, in an ATP-dependent manner. Cytidine is converted to lysidine, thus changing the amino acid specificity of the tRNA from methionine to isoleucine. The N-terminal region contains the highly conserved SGGXDS motif, predicted to be a PP-loop motif involved in ATP binding.

The only examples in which the wobble position of a tRNA must discriminate between G and A of mRNA are AUA (Ile) versus AUG (Met) and UGA (stop) versus UGG (Trp). In all bacteria, the wobble position of the tRNA(Ile) recognizing AUA is lysidine, a lysine derivative of cytidine. This domain is found, apparently, in all bacteria in a single copy. Eukaryotic sequences appear to be organellar. The domain architecture of this protein is variable; some, including characterised proteins of Escherichia coli and Bacillus subtilis known to be tRNA(Ile)-lysidine synthetase, include a conserved 50-residue domain that many other members lack. This protein belongs to the ATP-binding PP-loop family. It appears in the literature and protein databases as TilS, YacA, and putative cell cycle protein MesJ (a misnomer).

The PP-loop motif appears to be a modified version of the P-loop of nucleotide binding domain that is involved in phosphate binding [ PUBMED:7731953 ]. Named PP-motif, since it appears to be a part of a previously uncharacterised ATP pyrophophatase domain. ATP sulfurylases, E. coli NtrL, and B. subtilis OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain. The HUP domain class (after HIGH-signature proteins, UspA, and PP-ATPase) groups together PP-loop ATPases, the nucleotide-binding domains of class I aminoacyl-tRNA synthetases, UspA protein (USPA domains), photolyases, and electron transport flavoproteins (ETFP). The HUP domain is a distinct class of alpha/beta domain[ PUBMED:12012333 ].

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 PheT-TilS (CL0383), which has the following description:

Families here are thought to contain a putative tRNA-binding structural motif. The families are the C-terminal domains of tRNA-Ile-lysidine and the phenylalanine-tRNA synthetases.

The clan contains the following 2 members:

B3_4 TilS_C


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...

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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.

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

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

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Representative proteomes UniProt

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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.

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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...


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.

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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: pdb_1ni5
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Sammut SJ , Bateman A
Number in seed: 59
Number in full: 3709
Average length of the domain: 72.70 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 16.09 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.0 22.0
Trusted cut-off 22.0 22.0
Noise cut-off 21.9 21.9
Model length: 74
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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 TilS_C 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 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
A1K3X8 View 3D Structure Click here
A2SIL9 View 3D Structure Click here
A3CJX7 View 3D Structure Click here
A3N2I9 View 3D Structure Click here
A6LBU3 View 3D Structure Click here
A6VNE4 View 3D Structure Click here
A8F7F8 View 3D Structure Click here
B0UUD3 View 3D Structure Click here
B1KNS7 View 3D Structure Click here
B1YGQ4 View 3D Structure Click here
B4F252 View 3D Structure Click here
B7IFR8 View 3D Structure Click here
B7VIQ1 View 3D Structure Click here
C0QU23 View 3D Structure Click here
C1A873 View 3D Structure Click here
C1D1Q9 View 3D Structure Click here
C4K338 View 3D Structure Click here
C5B7T0 View 3D Structure Click here
P37563 View 3D Structure Click here
P44689 View 3D Structure Click here
P52097 View 3D Structure Click here
P57211 View 3D Structure Click here
Q01QT2 View 3D Structure Click here
Q0A7K1 View 3D Structure Click here
Q181G3 View 3D Structure Click here
Q2G0R2 View 3D Structure Click here
Q31G65 View 3D Structure Click here
Q5HRP5 View 3D Structure Click here
Q5L3T3 View 3D Structure Click here
Q5NFK3 View 3D Structure Click here
Q5P2I9 View 3D Structure Click here
Q5R0Q7 View 3D Structure Click here
Q5WAE0 View 3D Structure Click here
Q5ZXE5 View 3D Structure Click here
Q607F5 View 3D Structure Click here
Q63ST1 View 3D Structure Click here
Q65PF4 View 3D Structure Click here
Q67JG9 View 3D Structure Click here
Q6AJ19 View 3D Structure Click here
Q6D8C5 View 3D Structure Click here