PROSITE documentation PDOC50005

TPR repeat profiles

The tetratrico peptide repeat (TPRs) [1] is a degenerate 34-amino acid repeated motif that is widespread among all organisms. In the cell, TPR containing proteins are localized in a variety of subcellular compartment, including the nucleus, the cytoplasm and mitochondria [2]. Processes involving TPR proteins include cell-cycle control, transcription repression, stress response, protein kinase inhibition, mitochondrial and peroxisomal protein transport and neurogenesis. TPR repeats mediate protein-protein interactions and the assembly of multiprotein complexes. The smallest functional unit that is widely used appears to be three tandem-TPR motifs [3].

Many 3D structures of TPR domains have been solved (see for example <PDB:1A17>) [4]. A single TPR contains two antiparallel α helices which pack into an open structure [4] such that tandem arrays of TPR motifs generate a right-handed helical structure with an amphipathic channel that might accommodate the complementary region of a target protein. An additional capping helix at the C-terminus is present in almost all TPR structures solved to date. This helix could be essential for the solubility or stability of these isolated domains. The consensus sequence of a TPR is defined by a pattern of small and large hydrophobic amino acids. Turn-positions, both between the two helices of a single TPR and between the two adjacent TPRs, show conservation of helix-breaking residues [5].

Some of the proteins containing TPR repeats are listed below:

• Eukaryotic Cdc16, Cdc23 and Cdc27 proteins, components of the anaphase-promoting complex (APC).
• Fission yeast Nuc2 protein, an homologue of Cdc27. Nuc2 interacts with spindle apparatus, chromosomes, or nuclear envelope, and interconnect nuclear and cytoskeletal functions in mitosis.
• Human Bardet-Biedl syndrome 4 protein. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation.
• Mammalian DnaJ homolog subfamily C member 7 protein (DnaJC7). TPR repeats of DnaJC7 interacts with the GAP domain of NF1.
• Eukaryotic Pex5p/Pas10p, the receptor for peroxisomal targeting signals.
• Eukaryotic translocase of outer membrane TOM70 protein, a co-receptor for mitochondrial targeting signals.
• Mammalian Ser/Thr phosphatase 5C. It interacts with CDC16 and CDC27.
• Animal O-GlcNAc transferase, p110 subunit. It adds nucleotide-activated sugars directly onto the polypeptide through O-glycosidic linkage with the hydroxyl of serine or threonine.
• Bacterial cellulose synthase protein C.
• Clostridium acetobutylicum Sol locus transcriptional repressor.
• Bacillus subtilis response regulator aspartate phosphatase F.

Two profiles were developed for this module, the first one picks up TPR repeat units while the second profile is 'circular' and will thus detects a region containing adjacent TPR repeats.