|SMART accession number:||SM00028|
|Description:||Repeats present in 4 or more copies in proteins. Contain a minimum of 34 amino acids each and self-associate via a "knobs and holes" mechanism.|
|Interpro abstract (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.
|GO function:||protein binding (GO:0005515)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing TPR domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with TPR domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing TPR domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
Binding / catalysis: protein-binding
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Das AK, Cohen PW, Barford D
- The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions.
- EMBO J. 1998; 17: 1192-9
- Display abstract
The tetratricopeptide repeat (TPR) is a degenerate 34 amino acid sequence identified in a wide variety of proteins, present in tandem arrays of 3-16 motifs, which form scaffolds to mediate protein-protein interactions and often the assembly of multiprotein complexes. TPR-containing proteins 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, and peroxisomal and mitochondrial import proteins. Here, we report the crystal structure of the TPR domain of a protein phosphatase, PP5. Each of the three TPR motifs of this domain consist of a pair of antiparallel alpha-helices of equivalent length. Adjacent TPR motifs are packed together in a parallel arrangement such that a tandem TPR motif structure is composed of a regular series of antiparallel alpha-helices. The uniform angular and spatial arrangement of neighbouring alpha-helices defines a helical structure and creates an amphipathic groove. Multiple-TPR motif proteins would fold into a right-handed super-helical structure with a continuous helical groove suitable for the recognition of target proteins, hence defining a novel mechanism for protein recognition. The spatial arrangement of alpha-helices in the PP5-TPR domain is similar to those within 14-3-3 proteins.
- Lamb JR, Tugendreich S, Hieter P
- Tetratrico peptide repeat interactions: to TPR or not to TPR?
- Trends Biochem Sci. 1995; 20: 257-9
- Goebl M, Yanagida M
- The TPR snap helix: a novel protein repeat motif from mitosis to transcription.
- Trends Biochem Sci. 1991; 16: 173-7
- Display abstract
The recently discovered TPR gene family encodes a diverse group of proteins that function in mitosis, transcription, splicing, protein import and neurogenesis. These multi-domain proteins all contain tandemly arranged repeats of a 34-amino acid motif that are presumed to form helix-turn structures, each with a 'knob' and 'hole', acting as helix-associating domains.
- Sikorski RS, Boguski MS, Goebl M, Hieter P
- A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis.
- Cell. 1990; 60: 307-17
- Display abstract
We have identified and characterized a novel, repeating 34 amino acid motif (the TPR motif) that is reiterated several times within the CDC23 gene product of S. cerevisiae. Multiple copies of this motif were discovered in five other proteins, three encoded by cell division cycle genes required to complete mitosis and two involved in RNA synthesis. Quantitative sequence analyses suggest the existence of a common underlying structure in each TPR unit that consists of amphipathic alpha-helical regions punctuated by proline-induced turns. The TPR motif defines a new family of genes and an important structural unit common to several proteins whose functions are required for mitosis and RNA synthesis.
- Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the TPR domain.
Protein Disease Peroxisomal targeting signal 1 receptor (P50542) (SMART) OMIM:600414: Adrenoleukodystrophy, neonatal
Neutrophil cytosol factor 2 (P19878) (SMART) OMIM:233710: Chronic granulomatous disease due to deficiency of NCF-2
- Metabolism (metabolic pathways involving proteins which contain this domain)
Click the image to view the interactive version of the map in iPath
% proteins involved KEGG pathway ID Description 14.61 map04120 Ubiquitin mediated proteolysis 14.38 map04111 Cell cycle - yeast 13.70 map03090 Type II secretion system 13.01 map04110 Cell cycle 13.01 map04914 Progesterone-mediated oocyte maturation 3.65 map00230 Purine metabolism 3.20 map04010 MAPK signaling pathway 2.51 map04020 Calcium signaling pathway 2.28 map01030 Glycan structures - biosynthesis 1 2.28 map00632 Benzoate degradation via CoA ligation 2.28 map00512 O-Glycan biosynthesis 2.05 map00562 Inositol phosphate metabolism 2.05 map02030 Bacterial chemotaxis - General 1.60 map04670 Leukocyte transendothelial migration 1.60 map00051 Fructose and mannose metabolism 1.60 map00561 Glycerolipid metabolism 1.14 map00860 Porphyrin and chlorophyll metabolism 0.68 map00960 Alkaloid biosynthesis II 0.46 map00650 Butanoate metabolism 0.46 map00623 2,4-Dichlorobenzoate degradation 0.46 map00100 Biosynthesis of steroids 0.23 map00350 Tyrosine metabolism 0.23 map00910 Nitrogen metabolism 0.23 map00340 Histidine metabolism 0.23 map00642 Ethylbenzene degradation 0.23 map03060 Protein export 0.23 map03020 RNA polymerase 0.23 map00564 Glycerophospholipid metabolism 0.23 map00903 Limonene and pinene degradation 0.23 map00310 Lysine degradation 0.23 map00624 1- and 2-Methylnaphthalene degradation 0.23 map00360 Phenylalanine metabolism 0.23 map00500 Starch and sucrose metabolism 0.23 map00540 Lipopolysaccharide biosynthesis
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with TPR domain which could be assigned to a KEGG orthologous group, and not all proteins containing TPR domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of TPR domains in PDB
PDB code Main view Title 1a17 TETRATRICOPEPTIDE REPEATS OF PROTEIN PHOSPHATASE 5 1e96 Structure of the Rac/p67phox complex 1elr Crystal structure of the TPR2A domain of HOP in complex with the HSP90 peptide MEEVD 1elw Crystal structure of the TPR1 domain of HOP in complex with a HSC70 peptide 1fch CRYSTAL STRUCTURE OF THE PTS1 COMPLEXED TO THE TPR REGION OF HUMAN PEX5 1hh8 crystal structure of the N-terminal region of the phagocyte oxidase factor p67phox at 1.8 Ã… resolution 1ihg Bovine Cyclophilin 40, monoclinic form 1iip Bovine Cyclophilin 40, Tetragonal Form 1na0 Design of Stable alpha-Helical Arrays from an Idealized TPR Motif 1p5q Crystal Structure of FKBP52 C-terminal Domain 1qz2 Crystal Structure of FKBP52 C-terminal Domain complex with the C-terminal peptide MEEVD of Hsp90 1w3b The superhelical TPR domain of O-linked GlcNAc transferase reveals structural similarities to importin alpha. 1wao PP5 structure 1wm5 Crystal structure of the N-terminal TPR domain (1-203) of p67phox 1xnf Crystal structure of E.coli TPR-protein NlpI 2bug Solution structure of the TPR domain from Protein phosphatase 5 in complex with Hsp90 derived peptide 2c0l TPR DOMAIN OF HUMAN PEX5P IN COMPLEX WITH HUMAN MSCP2 2c0m apo form of the TPR domain of the pex5p receptor 2c2l Crystal structure of the CHIP U-box E3 ubiquitin ligase 2dba The solution structure of the tetratrico peptide repeat of human Smooth muscle cell associated protein-1, isoform 2 2fbn Plasmodium falciparum putative FK506-binding protein PFL2275c, C-terminal TPR-containing domain 2fi7 Crystal Structure of PilF : Functional implication in the type 4 pilus biogenesis in Pseudomonas aeruginosa 2fo7 Crystal structure of an 8 repeat consensus TPR superhelix (trigonal crystal form) 2gw1 Crystal Structure of the Yeast Tom70 2ho1 Functional Characterization of Pseudomonas Aeruginosa pilF 2hyz Crystal structure of an 8 repeat consensus TPR superhelix (orthorombic crystal form) 2if4 Crystal structure of a multi-domain immunophilin from Arabidopsis thaliana 2j9q A novel conformation for the TPR domain of pex5p 2jlb Xanthomonas campestris putative OGT (XCC0866), complex with UDP- GlcNAc phosphonate analogue 2lni Solution NMR Structure of Stress-induced-phosphoprotein 1 STI1 from Homo sapiens, Northeast Structural Genomics Consortium Target HR4403E 2pl2 Crystal structure of TTC0263: a thermophilic TPR protein in Thermus thermophilus HB27 2q7f Crystal structure of YrrB: a TPR protein with an unusual peptide-binding site 2vq2 Crystal structure of PilW, widely conserved type IV pilus biogenesis factor 2vsn Structure and topological arrangement of an O-GlcNAc transferase homolog: insight into molecular control of intracellular glycosylation 2vsy Xanthomonas campestris putative OGT (XCC0866), apostructure 2vyi Crystal Structure of the TPR domain of Human SGT 2wqh Crystal structure of CTPR3Y3 2xev Crystal structure of the TPR domain of Xanthomonas campestris ybgF 2xgm Substrate and product analogues as human O-GlcNAc transferase inhibitors. 2xgo XcOGT in complex with UDP-S-GlcNAc 2xgs XcOGT in complex with C-UDP 2xpi Crystal structure of APC/C hetero-tetramer Cut9-Hcn1 2y4t Crystal structure of the human co-chaperone P58(IPK) 2y4u Crystal structure of human P58(IPK) in space group P312 3as4 MamA AMB-1 C2221 3as5 MamA AMB-1 P212121 3as8 MamA MSR-1 P41212 3asd MamA R50E mutant 3asf MamA MSR-1 C2 3asg MamA D159K mutant 2 3ash MamA D159K mutant 1 3ceq The TPR domain of Human Kinesin Light Chain 2 (hKLC2) 3cv0 Structure of Peroxisomal Targeting Signal 1 (PTS1) binding domain of Trypanosoma brucei Peroxin 5 (TbPEX5)complexed to T. brucei Phosphoglucoisomerase (PGI) PTS1 peptide 3cvl Structure of Peroxisomal Targeting Signal 1 (PTS1) binding domain of Trypanosoma brucei Peroxin 5 (TbPEX5)complexed to T. brucei Phosphofructokinase (PFK) PTS1 peptide 3cvn Structure of Peroxisomal Targeting Signal 1 (PTS1) binding domain of Trypanosoma brucei Peroxin 5 (TbPEX5)complexed to T. brucei Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) PTS1 peptide 3cvp Structure of Peroxisomal Targeting Signal 1 (PTS1) binding domain of Trypanosoma brucei Peroxin 5 (TbPEX5)complexed to PTS1 peptide (10-SKL) 3cvq Structure of Peroxisomal Targeting Signal 1 (PTS1) binding domain of Trypanosoma brucei Peroxin 5 (TbPEX5)complexed to PTS1 peptide (7-SKL) 3edt Crystal structure of the mutated S328N hKLC2 TPR domain 3esk Structure of HOP TPR2A domain in complex with the non-cognate Hsc70 peptide ligand 3fp2 Crystal structure of Tom71 complexed with Hsp82 C-terminal fragment 3fp3 Crystal structure of Tom71 3fp4 Crystal structure of Tom71 complexed with Ssa1 C-terminal fragment 3fwv Crystal Structure of a Redesigned TPR Protein, T-MOD(VMY), in Complex with MEEVF Peptide 3hym Insights into Anaphase Promoting Complex TPR subdomain assembly from a CDC26-APC6 structure 3ieg Crystal Structure of P58(IPK) TPR Domain at 2.5 A 3kd7 Designed TPR module (CTPR390) in complex with its peptide-ligand (Hsp90 peptide) 3lca Structure of Tom71 complexed with Hsp70 Ssa1 C terminal tail indicating conformational plasticity 3nf1 Crystal structure of the TPR domain of kinesin light chain 1 3pe3 Structure of human O-GlcNAc transferase and its complex with a peptide substrate 3pe4 Structure of human O-GlcNAc transferase and its complex with a peptide substrate 3q15 Crystal Structure of RapH complexed with Spo0F 3q47 Crystal structure of TPR domain of CHIP complexed with pseudophosphorylated Smad1 peptide 3q49 Crystal structure of the TPR domain of CHIP complexed with Hsp70-C peptide 3q4a Crystal structure of the TPR domain of CHIP complexed with phosphorylated Smad1 peptide 3qky Crystal structure of Rhodothermus marinus BamD 3r9a Human alanine-glyoxylate aminotransferase in complex with the TPR domain of human PEX5P 3ro2 Structures of the LGN/NuMA complex 3ro3 crystal structure of LGN/mInscuteable complex 3sf4 Crystal structure of the complex between the conserved cell polarity proteins Inscuteable and LGN 3sz7 Crystal structure of the Sgt2 TPR domain from Aspergillus fumigatus 3tax A Neutral Diphosphate Mimic Crosslinks the Active Site of Human O-GlcNAc Transferase 3ulq Crystal Structure of the Anti-Activator RapF Complexed with the Response Regulator ComA DNA Binding Domain 3upv TPR2B-domain:pHsp70-complex of yeast Sti1 3uq3 TPR2AB-domain:pHSP90-complex of yeast Sti1 3vtx Crystal structure of MamA protein 3vty Crystal structure of MamA 3zfw Crystal structure of the TPR domain of kinesin light chain 2 in complex with a tryptophan-acidic cargo peptide 3zgq Crystal structure of human interferon-induced protein IFIT5 4a1s Crystallographic structure of the Pins:Insc complex 4ay5 Human O-GlcNAc transferase (OGT) in complex with UDP and glycopeptide 4ay6 Human O-GlcNAc transferase (OGT) in complex with UDP-5SGlcNAc and substrate peptide 4buj Crystal structure of the S. cerevisiae Ski2-3-8 complex 4cdr Human O-GlcNAc transferase in complex with a bisubstrate inhibitor, Goblin1 4cgv First TPR of Spaghetti (RPAP3) bound to HSP90 peptide SRMEEVD 4eqf Trip8b-1a#206-567 interacting with the carboxy-terminal seven residues of HCN2 4g1t Crystal structure of interferon-stimulated gene 54 4g2v Structure complex of LGN binding with FRMPD1 4gcn N-terminal domain of stress-induced protein-1 (STI-1) from C.elegans 4gco Central domain of stress-induced protein-1 (STI-1) from C.elegans 4gpk Crystal structure of NprR in complex with its cognate peptide NprX 4gyo Crystal Structure of Rap Protein Complexed with Competence and Sporulation Factor 4gyw Crystal structure of human O-GlcNAc Transferase in complex with UDP and a glycopeptide 4gyy Crystal structure of human O-GlcNAc Transferase with UDP-5SGlcNAc and a peptide substrate 4gz3 Crystal structure of human O-GlcNAc Transferase with UDP and a thioglycopeptide 4gz5 Crystal structure of human O-GlcNAc Transferase with UDP-GlcNAc 4gz6 Crystal structure of human O-GlcNAc Transferase with UDP-5SGlcNAc 4hoq Crystal Structure of Full-Length Human IFIT5 4hor Crystal Structure of Full-Length Human IFIT5 with 5`-triphosphate Oligocytidine 4hos Crystal Structure of Full-Length Human IFIT5 with 5`-triphosphate Oligouridine 4hot Crystal Structure of Full-Length Human IFIT5 with 5`-triphosphate Oligoadenine 4hou Crystal Structure of N-terminal Human IFIT1 4i9c Crystal structure of aspartyl phosphate phosphatase F from B.subtilis in complex with its inhibitory peptide 4i9e Crystal structure of Aspartyl phosphate phosphatase F from Bacillus subtilis 4j0u Crystal structure of IFIT5/ISG58 4j8d Middle domain of Hsc70-interacting protein, crystal form II 4j8e Middle domain of Hsc70-interacting protein, crystal form I 4j8f Crystal structure of a fusion protein containing the NBD of Hsp70 and the middle domain of Hip 4ja7 Rat PP5 co-crystallized with P5SA-2 4ja9 Rat PP5 apo 4jhr An auto-inhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs 4kvm The NatA (Naa10p/Naa15p) amino-terminal acetyltransferase complex bound to a bisubstrate analog 4kvo The NatA (Naa10p/Naa15p) amino-terminal acetyltrasferase complex bound to AcCoA 4n39 Crystal structure of human O-GlcNAc transferase bound to a peptide from HCF-1 pro-repeat 2 (11-26) 4n3a Crystal Structure of human O-GlcNAc transferase bound to a peptide from HCF-1 pro-repeat 2 (1-26)E10A 4n3b Crystal Structure of human O-GlcNAc Transferase bound to a peptide from HCF-1 pro-repeat2(1-26)E10Q and UDP-5SGlcNAc 4n3c Crystal Structure of human O-GlcNAc Transferase bound to a peptide from HCF-1 pro-repeat2(1-26) and UDP-GlcNAc
- Links (links to other resources describing this domain)
PFAM TPR INTERPRO IPR019734