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25  structures 2332  species 6  interactions 5760  sequences 1721  architectures

Family: TPR_6 (PF13174)

Summary: Tetratricopeptide repeat

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This is the Wikipedia entry entitled "Tetratricopeptide". More...

Tetratricopeptide Edit Wikipedia article

Tetratricopeptide repeat
Symbol TPR_1
Pfam PF00515
Pfam clan CL0020
InterPro IPR001440
SCOP 1a17
CDD cd00189

The tetratricopeptide repeat (TPR) is a structural motif. It consists of 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 a concave and a convex face, 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


The Hop 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]


The PEX5 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

Neutrophil cytosolic factor 2 is an 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 (Nov 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 (Mar 1998). "The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions". The EMBO Journal. 17 (5): 1192–9. doi:10.1093/emboj/17.5.1192. PMC 1170467Freely accessible. PMID 9482716. 
  3. ^ Wilson CG, Kajander T, Regan L (Jan 2005). "The crystal structure of NlpI. A prokaryotic tetratricopeptide repeat protein with a globular fold". The FEBS Journal. 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 (Apr 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, Geisbrecht BV, Gould SJ, Berg JM (Dec 2000). "Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5". Nature Structural Biology. 7 (12): 1091–5. doi:10.1038/81930. PMID 11101887. 
  6. ^ Lapouge K, Smith SJ, Walker PA, Gamblin SJ, Smerdon SJ, Rittinger K (Oct 2000). "Structure of the TPR domain of p67phox in complex with Rac.GTP". Molecular Cell. 6 (4): 899–907. doi:10.1016/S1097-2765(05)00091-2. PMID 11090627. 

Further reading

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Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR019734

The tetratrico peptide repeat region (TPR) is a structural motif present in a wide range of proteins [PUBMED:7667876, PUBMED:9482716, PUBMED:1882418]. It mediates protein-protein interactions and the assembly of multiprotein complexes [PUBMED:14659697]. The TPR motif consists of 3-16 tandem-repeats of 34 amino acids residues, although individual TPR motifs can be dispersed in the protein sequence. Sequence alignment of the TPR domains reveals a consensus sequence defined by a pattern of small and large amino acids. TPR motifs have been identified in various different organisms, ranging from bacteria to humans. Proteins containing TPRs are involved in a variety of biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The X-ray structure of a domain containing three TPRs from protein phosphatase 5 revealed that TPR adopts a helix-turn-helix arrangement, with adjacent TPR motifs packing in a parallel fashion, resulting in a spiral of repeating anti-parallel alpha-helices [PUBMED:14659697]. The two helices are denoted helix A and helix B. The packing angle between helix A and helix B is ~24 degrees within a single TPR and generates a right-handed superhelical shape. Helix A interacts with helix B and with helix A' of the next TPR. Two protein surfaces are generated: the inner concave surface is contributed to mainly by residue on helices A, and the other surface presents residues from both helices A and B.

Gene Ontology

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Domain organisation

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Seed source: Jackhmmer:O25749
Previous IDs: none
Type: Repeat
Author: Bateman A
Number in seed: 275
Number in full: 5760
Average length of the domain: 32.10 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 6.50 %

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 26.3 12.2
Trusted cut-off 26.3 12.2
Noise cut-off 26.2 12.1
Model length: 33
Family (HMM) version: 5
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Species distribution

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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 6 interactions for this family. More...

TPR_1 TPR_1 TPR_2 TPR_16 TPR_6 TPR_11


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_6 domain has been found. There are 25 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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