The domain within your query sequence starts at position 135 and ends at position 168; the E-value for the TPR domain shown below is 7.11e1.

PKINMMLANLYKKAGQERPSVTSYKEVLRQCPLA

TPR

Tetratricopeptide repeats

• 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)

There are 1309452 TPR domains in 257843 proteins in SMART's nrdb database.

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

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

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

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 OMIM:202370:
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)

% 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	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
3jcm	3JCM
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
4kbq	4KBQ
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
4kxk	4KXK
4kyo	4KYO
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
4r7s	4R7S
4rg6	4RG6
4rg7	4RG7
4rg9	4RG9
4ui9	4UI9
4wnd	4WND
4wne	4WNE
4wnf	4WNF
4wng	4WNG
4xi0	4XI0
4xi9	4XI9
4xif	4XIF
4y6c	4Y6C
4y6w	4Y6W
4ynv	4YNV
4ynw	4YNW
4zlh	4ZLH
5a01	5A01
5a31	5A31
5a6c	5A6C
5a7d	5A7D
5aem	5AEM
5aio	5AIO
5bnw	5BNW
5c1d	5C1D
5dbk	5DBK
5djs	5DJS
5dse	5DSE
5efr	5EFR
5fjy	5FJY
5fzq	5FZQ
5fzr	5FZR
5fzs	5FZS
5g04	5G04
5g05	5G05
5gan	5GAN
5gap	5GAP
5hgv	5HGV
5khr	5KHR
5khu	5KHU
5l9t	5L9T
5l9u	5L9U
5lcw	5LCW

Links (links to other resources describing this domain)

• INTERPRO: IPR019734
• PFAM: TPR