Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
9  structures 1524  species 4  interactions 8494  sequences 1930  architectures

Family: TPR_10 (PF13374)

Summary: Tetratricopeptide repeat

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 "Tetratricopeptide". More...

Tetratricopeptide Edit Wikipedia article

Tetratricopeptide repeat
Pymol rendering of protein phosphatase 5, with 3 helix-pair TPR repeats in pink, lime, and purple. PDB ID 1A17.
Symbol TPR_1
Pfam PF00515
Pfam clan CL0020
InterPro IPR001440
SCOP 1a17
CDD cd00189

The tetratricopeptide repeat (TPR) is a structural motif. It consists in a degenerate 34 amino acid sequence motif identified in a wide variety of proteins. It is found in tandem arrays of 3–16 motifs,[1] which form scaffolds to mediate protein–protein interactions and often the assembly of multiprotein complexes. These alpha-helix pair repeats usually fold together to produce a single, linear solenoid domain called a TPR domain. Proteins with such domains include the anaphase-promoting complex (APC) subunits cdc16, cdc23 and cdc27, the NADPH oxidase subunit p67-phox, hsp90-binding immunophilins, transcription factors, the PKR protein kinase inhibitor, the major receptor for peroxisomal matrix protein import PEX5 and mitochondrial import proteins.

Depiction of TPR repeat. Image rendered with King Software. PDB ID: 1NA0.


The structure of the PP5 protein was the first structure to be determined. The structure solved by X-ray crystallography by Das and colleagues showed that the TPR sequence motif was composed of a pair of antiparallel alpha helices.[2] The PP5 structure contained 3 tandem TPR repeats which showed the sequential TPR repeats formed an alpha-helical solenoid structure.

A typical TPR structure is characterized by interactions between helices A and B of the first motif and helix A’ of the next TPR. Although the nature of such interactions may vary, the first two helices of the TPR motif typically have a packing angle of ~24 degrees within a single motif. Repeats of more than three TPR motifs generate a right handed superhelix characterized by both concave and a convex faces of which the concave face is usually involved in ligand binding. [1] [3]

This image shows signature residues commonly found in TPR motifs. The image was rendered using the KING Software starting from the PDB 1NA3.

In terms of sequence, a TPR possesses a mixture of small and large hydrophobic residues, nonetheless, no positions are fully invariant. There are however certain residues that are usually conserved including Tryptophan 4, Leucine 7, Glycine 8, Tyrosine 11, Alanine 20, Phenylalanine 24, Alanine 27 and Proline 32. Among those 8, Alanine at positions 8, 20 and 27 tend to be more conserved. The other positions have a stronger preference for either small, large or aromatic amino acids rather than a specific residue. In between helices, residue conservation plays more of a structural role with helix breaking residues present. Between adjacent TPR, residues have roles with both structural and functional implications.[1]

TPR containing peptides

Hop (protein)

This adaptor protein mediates the association of the molecular chaperones Hsp70 and Hsp90. It contains three 3-TPR repeats each with its own peptide-binding specificity. Its TPR1 domain is known to recognize the C-terminal of Hsp70 while TPR2 binds to the C-terminal of Hsp90. Both C-terminal sequences end with an EEVD motif and the nature of the interaction is both electrostatic and hydrophobic.[1] [4]


This protein is a receptor for PTS1 (peroxisomal targeting signal tripeptide which directs proteins into peroxisomes). It interacts with the signal via TPR motifs. Most of its contacts with the C-terminal tripeptide PTS1 are in the concave face of TPRs 1, 2 and 3. [5]

Neutrophil cytosolic factor 2

It is essential to NADPH oxidase complex which in turn produces superoxides in return to microbial infection. The binding of the Rac GTPase is a key step into the assembly of the complex and the TPRs in the phox unit mediate the assembly of the multiprotein complex by acting a binding scaffold.[6]


Human genes encoding proteins containing this motif include:


  1. ^ a b c d Blatch GL, Lässle M (November 1999). "The tetratricopeptide repeat: a structural motif mediating protein-protein interactions". BioEssays 21 (11): 932–9. doi:10.1002/(SICI)1521-1878(199911)21:11<932::AID-BIES5>3.0.CO;2-N. PMID 10517866. 
  2. ^ Das AK, Cohen PW, Barford D (March 1998). "The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions". EMBO J. 17 (5): 1192–9. doi:10.1093/emboj/17.5.1192. PMC 1170467. PMID 9482716. 
  3. ^ Wilson CG, Kajander T, Regan L. (January 2005). "The crystal structure of NlpI. A prokaryotic tetratricopeptide repeat protein with a globular fold". FEBS J. 272 (1): 166–79. doi:10.1111/j.1432-1033.2004.04397.x. PMID 15634341. 
  4. ^ Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I. (April 2000). "Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine". Cell 101 (2): 199–210. doi:10.1016/S0092-8674(00)80830-2. PMID 10786835. 
  5. ^ Gatto GJ Jr, Geisbrecht BV, Gould SJ, Berg JM. (December 2000). "Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5". Nat Struct Biol. 7 (12): 1091–5. doi:10.1038/81930. PMID 11101887. 
  6. ^ Lapouge K, Smith SJ, Walker PA, Gamblin SJ, Smerdon SJ, Rittinger K. (October 2000). "Structure of the TPR domain of p67phox in complex with Rac.GTP". Mol Cell 6 (4): 899–907. doi:10.1016/S1097-2765(05)00091-2. PMID 11090627. 

External links

Further reading

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.

Tetratricopeptide repeat Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

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

Loading domain graphics...


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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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.

Representative proteomes NCBI
Jalview View  View  View  View  View  View  View  View 
HTML View    View  View  View  View     
PP/heatmap 1   View  View  View  View     
Pfam viewer View  View             

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

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

Format an alignment

Representative proteomes NCBI

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.

Representative proteomes NCBI
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.

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.

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: Jackhmmer:Q7P422
Previous IDs: none
Type: Repeat
Author: Bateman A
Number in seed: 287
Number in full: 8494
Average length of the domain: 39.20 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 7.81 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.5 13.6
Trusted cut-off 27.5 13.6
Noise cut-off 27.4 13.5
Model length: 42
Family (HMM) version: 2
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

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


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

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...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


There are 4 interactions for this family. More...

TPR_1 TPR_10 TPR_12 TPR_12


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 TPR_10 domain has been found. There are 9 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.

Loading structure mapping...