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61  structures 5348  species 5  interactions 20197  sequences 235  architectures

Family: Anticodon_1 (PF08264)

Summary: Anticodon-binding domain of tRNA

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Aminoacyl tRNA synthetase". More...

Aminoacyl tRNA synthetase Edit Wikipedia article

Anticodon-binding domain of tRNA
PDB 1obc EBI.jpg
leucyl-tRNA synthetase from Thermus thermophilus complexed with a post-transfer editing substrate analogue
Symbol Anticodon_2
Pfam PF08264
InterPro IPR013155
SCOP 1ivs
DALR anticodon binding domain 1
PDB 1iq0 EBI.jpg
Thermus thermophilus arginyl-trna synthetase
Symbol DALR_1
Pfam PF05746
Pfam clan CL0258
InterPro IPR008909
SCOP 1bs2
DALR anticodon binding domain 2
PDB 1u0b EBI.jpg
crystal structure of cysteinyl-tRNA synthetase binary complex with tRNACys
Symbol DALR_2
Pfam PF09190
Pfam clan CL0258
InterPro IPR015273

An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its tRNA. It does so by catalyzing the esterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code.

This is sometimes called "charging" or "loading" the tRNA with the amino acid. Once the tRNA is charged, a ribosome can transfer the amino acid from the tRNA onto a growing peptide, according to the genetic code. Aminoacyl tRNA therefore plays an important role in RNA translation, the expression of genes to create proteins.

As genetic efficiency evolved in higher organisms, 13 new domains with no obvious association with the catalytic activity of aaRSs genes have been added.


The synthetase first binds ATP and the corresponding amino acid (or its precursor) to form an aminoacyl-adenylate, releasing inorganic pyrophosphate (PPi). The adenylate-aaRS complex then binds the appropriate tRNA molecule's D arm, and the amino acid is transferred from the aa-AMP to either the 2'- or the 3'-OH of the last tRNA nucleotide (A76) at the 3'-end.

The mechanism can be summarized in the following reaction series:

  1. Amino Acid + ATP → Aminoacyl-AMP + PPi
  2. Aminoacyl-AMP + tRNA → Aminoacyl-tRNA + AMP

Summing the reactions, the highly exergonic overall reaction is as follows:

  • Amino Acid + tRNA + ATP → Aminoacyl-tRNA + AMP + PPi

Some synthetases also mediate a editing reaction to ensure high fidelity of tRNA charging. If the incorrect tRNA is added (aka. the tRNA is found to be improperly charged), the aminoacyl-tRNA bond is hydrolyzed. This can happen when two amino acids have different properties even if they have similar shapes—as is the case with Valine and Threonine.


There are two classes of aminoacyl tRNA synthetase:[1]

  • Class I has two highly conserved sequence motifs. It aminoacylates at the 2'-OH of a terminal adenosine nucleotide on tRNA, and it is usually monomeric or dimeric (one or two subunits, respectively).
  • Class II has three highly conserved sequence motifs. It aminoacylates at the 3'-OH of a terminal adenosine on tRNA, and is usually dimeric or tetrameric (two or four subunits, respectively). Although phenylalanine-tRNA synthetase is class II, it aminoacylates at the 2'-OH.

The amino acids are attached to the hydroxyl (-OH) group of the adenosine via the carboxyl (-COOH) group.

Regardless of where the aminoacyl is initially attached to the nucleotide, the 2'-O-aminoacyl-tRNA will ultimately migrate to the 3' position via transesterification.


Both classes of aminoacyl-tRNA synthetases are multidomain proteins. In a typical scenario, an aaRS consists of a catalytic domain (where both the above reactions take place) and an anticodon binding domain (which interacts mostly with the anticodon region of the tRNA and ensures binding of the correct tRNA to the amino acid). In addition, some aaRSs have additional RNA binding domains and editing domains[2] that cleave incorrectly paired aminoacyl-tRNA molecules.

The catalytic domains of all the aaRSs of a given class are found to be homologous to one another, whereas class I and class II aaRSs are unrelated to one another. The class I aaRSs have the ubiquitous Rossmann fold and have the parallel beta-strands architecture, whereas the class II aaRSs have a unique fold made up of antiparallel beta-strands.

The alpha helical anticodon binding domain of Arginyl, Glycyl and Cysteinyl-tRNA synthetases is known as the DALR domain after characteristic conserved amino acids.[3]


Most of the aaRSs of a given specificity are evolutionarily closer to one another than to aaRSs of another specificity. However, AsnRS and GlnRS group within AspRS and GluRS, respectively. Most of the aaRSs of a given specificity also belong to a single class. However, there are two distinct versions of the LysRS - one belonging to the class I family and the other belonging to the class II family.

The molecular phylogenies of aaRSs are often not consistent with accepted organismal phylogenies. That is, they violate the so-called canonical phylogenetic pattern shown by most other enzymes for the three domains of life - Archaea, Bacteria, and Eukarya. Furthermore, the phylogenies inferred for aaRSs of different amino acids often do not agree with one another. In addition, aaRS paralogs within the same species show a high degree of divergence between them. These are clear indications that horizontal transfer has occurred several times during the evolutionary history of aaRSs.[4][5]

A widespread belief in the evolutionary stability of this superfamily, meaning that every organism has all the aaRSs for their corresponding aminoacids is misconceived. A large-scale genomic analysis on ~2500 prokaryotic genomes showed that many of them miss one or more aaRS genes whereas many genomes have 1 or more paralogs.[5] AlaRS, GlyRS, LeuRS, IleRS and ValRS are the most evolutionarily stable members of the family. GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent from many genomes.

Application in biotechnology

In some of the aminoacyl tRNA synthetases, the cavity that holds the amino acid can be mutated and modified to carry unnatural amino acids synthesized in the lab, and to attach them to specific tRNAs. This expands the genetic code, beyond the twenty canonical amino acids found in nature, to include an unnatural amino acid as well. The unnatural amino acid is coded by a nonsense (TAG, TGA, TAA) triplet, a quadruplet codon, or in some cases a redundant rare codon. The organism that expresses the mutant synthetase can then be genetically programmed to incorporate the unnatural amino acid into any desired position in any protein of interest, allowing biochemists or structural biologists to probe or change the protein's function. For instance, one can start with the gene for a protein that binds a certain sequence of DNA, and, by directing an unnatural amino acid with a reactive side-chain into the binding site, create a new protein that cuts the DNA at the target-sequence, rather than binding it.

By mutating aminoacyl tRNA synthetases, chemists have expanded the genetic codes of various organisms to include lab-synthesized amino acids with all kinds of useful properties: photoreactive, metal-chelating, xenon-chelating, crosslinking, spin-resonant, fluorescent, biotinylated, and redox-active amino acids.[6] Another use is introducing amino acids bearing reactive functional groups for chemically modifying the target protein.

Noncatalytic domains

The novel domain additions to aaRS genes are accretive and progressive up the Tree of Life.[7][8][9] The strong evolutionary pressure for these small non-catalytic protein domains suggested their importance.[10] Findings beginning in 1999 and later revealed a previously unrecognized layer of biology: these proteins control gene expression within the cell of origin, and when released exert homeostatic and developmental control in specific human cell types, tissues and organs during adult or fetal development or both, including pathways associated with angiogenesis, inflammation, the immune response, the mechanistic target of rapamycin (mTOR) signalling, apoptosis, tumorigenesis, and interferon gamma (IFN-γ) and p53 signalling.[11][12][13][14][15][16][17][18][19]

Prediction servers

See also


  1. ^ "tRNA Synthetases". Retrieved 2007-08-18. 
  2. ^ "Molecule of the Month: Aminoacyl-tRNA Synthetases High Fidelity". Retrieved 2013-08-04. 
  3. ^ Wolf YI, Aravind L, Grishin NV, Koonin EV (August 1999). "Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events". Genome Res. 9 (8): 689–710. doi:10.1101/gr.9.8.689. PMID 10447505. 
  4. ^ Woese, CR; Olsen, GJ; Ibba, M; Söll, D (March 2000). "Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process". Microbiology and molecular biology reviews : MMBR. 64 (1): 202–36. doi:10.1128/MMBR.64.1.202-236.2000. PMC 98992Freely accessible. PMID 10704480. 
  5. ^ a b Chaliotis, Anargyros; Vlastaridis, Panayotis; Mossialos, Dimitris; Ibba, Michael; Becker, Hubert D.; Stathopoulos, Constantinos; Amoutzias, Grigorios D. (2017-02-17). "The complex evolutionary history of aminoacyl-tRNA synthetases". Nucleic Acids Research. 45 (3): 1059–1068. doi:10.1093/nar/gkw1182. ISSN 0305-1048. PMC 5388404Freely accessible. PMID 28180287. 
  6. ^ Peter G. Schultz, Expanding the genetic code
  7. ^ Ludmerer, SW; Schimmel, P (August 5, 1987). "Construction and analysis of deletions in the amino-terminal extension of glutamine tRNA synthetase of Saccharomyces cerevisiae". Journal of Biological Chemistry : JBC. 262 (22): 10807–10813. PMID 3301842. 
  8. ^ Eriani, Gilbert; Delarue, M (Sep 13, 1990). "Partition of tNRA Synthetases into Two Classes Based on Mutually Exclusive Sets of Sequence Motifs". Nature. 347 (6289): 203–206. doi:10.1038/347203a0. PMID 2203971. 
  9. ^ Cusack, S (Dec 1, 1997). "Aminoacyl-tRNA synthetases". Curr Opin Struct Biol. 7 (6): 881–889. doi:10.1016/s0959-440x(97)80161-3. PMID 9434910. 
  10. ^ Lo, Wing-Sze; Gardiner, E (July 18, 2014). "Human tRNA Synthetase Catalytic Nulls with Diverse Functions". Nature. 345 (6194): 328–332. doi:10.1126/science.1252943. 
  11. ^ Wakasugi; Schimmel, P (April 2, 1999). "Two Distinct Cytokines Released from a Human Aminoacyl-tRNA Synthetase". Science. 284 (5411): 147–151. doi:10.1126/science.284.5411.147. 
  12. ^ Lareau, LF; Green, RE (June 1, 2004). "The evolving roles of alternative splicing". Current Opinion in Structural Biology. 14 (3): 273–282. doi:10.1016/ 
  13. ^ Wakasugi, K; Slike, BM (Jan 8, 2002). "A human aminoacyl-tRNA synthetase as a regulator of angiogenesis". Proceedings of the National Academy of Sciences. 99 (1): 173–177. doi:10.1073/pnas.012602099. 
  14. ^ Tzima, E; Reader, JS (Dec 3, 2004). "VE-cadherin Links tRNA Synthetase Cytokine to Anti-angiogenic Function". Journal of Biological Chemistry. 280: 2405–2408. doi:10.1074/jbc.C400431200. 
  15. ^ Kawahara, A; Didier, YR (August 2009). "Noncanonical Activity of Seryl-Transfer RNA Synthetase and Vascular Development". Trends in Cardiovascular Medicine. 19 (6): 179–182. doi:10.1016/j.tcm.2009.11.001. 
  16. ^ Zhou, Q; Kapoor, M (Jan 2010). "Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality". Nature Structural & Molecular Biology. 17 (1): 57–61. doi:10.1038/nsmb.1706. 
  17. ^ Park, SG; Hye, JK (May 3, 2005). "Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response". PNAS. 102 (18): 6356–6361. doi:10.1073/pnas.0500226102. 
  18. ^ Arif, A; Jai, J (Jan 25, 2011). "Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control". PNAS. 108 (4): 1415–1420. doi:10.1073/pnas.1011275108. 
  19. ^ Guo, M; Schimmel , P (March 2013). "Essential nontranslational functions of tRNA synthetases". Nat Chem Biol. 9 (3): 145–153. doi:10.1038/nchembio.1158. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR015273

This article incorporates text from the public domain Pfam and InterPro IPR008909

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Anticodon-binding domain of tRNA Provide feedback

This domain is found mainly hydrophobic tRNA synthetases. The domain binds to the anticodon of the tRNA.

Literature references

  1. Fukai S, Nureki O, Sekine S, Shimada A, Tao J, Vassylyev DG, Yokoyama S; , Cell 2000;103:793-803.: Structural basis for double-sieve discrimination of L-valine from L-isoleucine and L-threonine by the complex of tRNA(Val) and valyl-tRNA synthetase. PUBMED:11114335 EPMC:11114335

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013155

The aminoacyl-tRNA synthetase (also known as aminoacyl-tRNA ligase) 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 and valine belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine 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 domain is found methionyl, valyl, leucyl and isoleucyl tRNA synthetases. It binds to the anticodon of the tRNA.

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan DALR (CL0258), which has the following description:

Members of this family are anticodon binding domains from various tRNA synthetases.

The clan contains the following 3 members:

Anticodon_1 DALR_1 DALR_2


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Curation and family details

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Seed source: Pfam-B_23 (Release 17.0)
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 162
Number in full: 20197
Average length of the domain: 144.30 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 16.12 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.1 25.1
Trusted cut-off 25.1 25.1
Noise cut-off 25.0 25.0
Model length: 152
Family (HMM) version: 12
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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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There are 5 interactions for this family. More...

Val_tRNA-synt_C tRNA-synt_1g zf-FPG_IleRS tRNA-synt_1 Anticodon_1


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 Anticodon_1 domain has been found. There are 61 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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