amino acid repetitive sequences


Summary: A sequential pattern of amino acids occurring more than once in the same protein sequence. There often is some sequence variation between the repeated segments. Many PROTEIN DOMAINS are constituted from repeats.

Top Publications

  1. Huntley M, Clark A. Evolutionary analysis of amino acid repeats across the genomes of 12 Drosophila species. Mol Biol Evol. 2007;24:2598-609 pubmed
    ..With additional evidence to suggest a corresponding elevation in positive selection we propose that some repeats may be inducing compensatory substitutions in their surrounding sequence. ..
  2. Simon M, Hancock J. Tandem and cryptic amino acid repeats accumulate in disordered regions of proteins. Genome Biol. 2009;10:R59 pubmed publisher
    ..However, no more than 15% of IURs contained an AAR. Their location within IURs explains many of the evolutionary properties of AARs. Further study is needed on the types of IURs containing AARs. ..
  3. Frey S, Richter R, Gorlich D. FG-rich repeats of nuclear pore proteins form a three-dimensional meshwork with hydrogel-like properties. Science. 2006;314:815-7 pubmed
    ..Furthermore, we obtained evidence that such hydrogel formation is required for viability in yeast. ..
  4. Walter E, Chattopadhyay M, Millhauser G. The affinity of copper binding to the prion protein octarepeat domain: evidence for negative cooperativity. Biochemistry. 2006;45:13083-92 pubmed
    ..Consideration of these findings, along with the demonstrated ability of the protein to quench copper redox activity at high occupancy, suggests that PrP may function to protect cells by scavenging excess copper. ..
  5. McHale L, Tan X, Koehl P, Michelmore R. Plant NBS-LRR proteins: adaptable guards. Genome Biol. 2006;7:212 pubmed
    ..Their precise role in recognition is unknown; however, they are thought to monitor the status of plant proteins that are targeted by pathogen effectors. ..
  6. Mularoni L, Guigo R, Albà M. Mutation patterns of amino acid tandem repeats in the human proteome. Genome Biol. 2006;7:R33 pubmed
    ..We show that the mutational dynamics of different amino acid repeat types are very diverse. We provide a list of loci with highly variable repeat structures, some of which may be potentially involved in disease. ..
  7. Siwach P, Pophaly S, Ganesh S. Genomic and evolutionary insights into genes encoding proteins with single amino acid repeats. Mol Biol Evol. 2006;23:1357-69 pubmed
    ..Therefore, instability associated with repeats might be driven by processes that are specific to sperm or oocyte development, and the recombination frequency might play a positive role in this process. ..
  8. Sammeth M, Heringa J. Global multiple-sequence alignment with repeats. Proteins. 2006;64:263-74 pubmed
    ..The method supports different stringency modes to adapt to various levels of detail and reliability of the repeat information available. ..
  9. Mead S, Webb T, Campbell T, Beck J, Linehan J, Rutherfoord S, et al. Inherited prion disease with 5-OPRI: phenotype modification by repeat length and codon 129. Neurology. 2007;69:730-8 pubmed

More Information


  1. El Shami M, Pontier D, Lahmy S, Braun L, Picart C, Vega D, et al. Reiterated WG/GW motifs form functionally and evolutionarily conserved ARGONAUTE-binding platforms in RNAi-related components. Genes Dev. 2007;21:2539-44 pubmed
  2. Mularoni L, Veitia R, Albà M. Highly constrained proteins contain an unexpectedly large number of amino acid tandem repeats. Genomics. 2007;89:316-25 pubmed
    ..Interestingly, polyalanine and polyglutamine repeats associated with disease show very distinctive features regarding the degree of repeat conservation and the protein sequence selective constraints. ..
  3. Faux N, Huttley G, Mahmood K, Webb G, de la Banda M, Whisstock J. RCPdb: An evolutionary classification and codon usage database for repeat-containing proteins. Genome Res. 2007;17:1118-27 pubmed
    ..Third, homopeptides that are conserved across different species lie within regions that are under stronger purifying selection in contrast to nonconserved homopeptides. ..
  4. Söding J, Remmert M, Biegert A. HHrep: de novo protein repeat detection and the origin of TIM barrels. Nucleic Acids Res. 2006;34:W137-42 pubmed
    ..This symmetry might be the trace of an ancient origin through duplication of a betaalphabetaalpha or betaalpha unit. HHrep can be accessed at ..
  5. Frey S, Gorlich D. A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes. Cell. 2007;130:512-23 pubmed
    ..Intragel diffusion of the importin beta-cargo complex occurred rapidly enough to traverse an NPC within approximately 12 ms. We extend the "selective phase model" to explain these effects. ..
  6. Behm Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P, Izaurralde E. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev. 2006;20:1885-98 pubmed
    ..Our findings indicate that GW182 links the miRNA pathway to mRNA degradation by interacting with AGO1 and promoting decay of at least a subset of miRNA targets. ..
  7. Eugster M, Roten C, Greub G. Analyses of six homologous proteins of Protochlamydia amoebophila UWE25 encoded by large GC-rich genes (lgr): a model of evolution and concatenation of leucine-rich repeats. BMC Evol Biol. 2007;7:231 pubmed
    ..Our model established on bacterial LRRs can be challenged in eucaryotic proteins carrying less conserved LRRs, such as NOD proteins and Toll-like receptors. ..
  8. Ye Z, Ting J. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family. Curr Opin Immunol. 2008;20:3-9 pubmed publisher
    ..Its role in inflammation is linked to the formation of biochemical complexes such as the inflammasome, and its roles in cell death might be linked to the proposed formation of pyroptosome and necrosome. ..
  9. Leliveld S, Stitz L, Korth C. Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein. Biochemistry. 2008;47:6267-78 pubmed publisher
    ..This idea was supported by a trial bioassay in transgenic mice overexpressing wild-type MoPrP, where intracerebral injection of recombinant MoPrP with an expanded OR domain but not wild-type MoPrP caused prion disease. ..
  10. Santiveri C, Lechtenberg B, Allen M, Sathyamurthy A, Jaulent A, Freund S, et al. The malignant brain tumor repeats of human SCML2 bind to peptides containing monomethylated lysine. J Mol Biol. 2008;382:1107-12 pubmed publisher
    ..The crystal structure of the complex between the protein and monomethyllysine reveals that the modified amino acid binds to an aromatic rich pocket at one end of the beta-barrel of the second repeat. ..
  11. Cruz F, Roux J, Robinson Rechavi M. The expansion of amino-acid repeats is not associated to adaptive evolution in mammalian genes. BMC Genomics. 2009;10:619 pubmed publisher
    ..Relaxed purifying selection or positive selection do not associate with more or more recent amino acid repeats. Their occurrence is slightly favoured by the sequence context but mainly determined by the molecular function of the gene. ..
  12. Frey S, Gorlich D. FG/FxFG as well as GLFG repeats form a selective permeability barrier with self-healing properties. EMBO J. 2009;28:2554-67 pubmed publisher
    ..NTRs not only left the barrier intact, they even tightened it against passive influx, pointing to a role for NTRs in establishing and maintaining the permeability barrier of NPCs. ..
  13. Keller L, Geimer S, Romijn E, Yates J, Zamora I, Marshall W. Molecular architecture of the centriole proteome: the conserved WD40 domain protein POC1 is required for centriole duplication and length control. Mol Biol Cell. 2009;20:1150-66 pubmed publisher
    ..Together, these data suggest that POC1 is involved in early steps of centriole duplication as well as in the later steps of centriole length control. ..
  14. Sugino E, Nishiura C, Minoura K, In Y, Sumida M, Taniguchi T, et al. Three-/four-repeat-dependent aggregation profile of tau microtubule-binding domain clarified by dynamic light scattering analysis. Biochem Biophys Res Commun. 2009;385:236-40 pubmed publisher
    ..The repeat-number-dependent aggregation model of MBD, together with the function of each repeat, reported in this paper should help to devise a method of preventing tau PHF formation. ..
  15. Matsushima N, Mikami T, Tanaka T, Miyashita H, Yamada K, Kuroki Y. Analyses of non-leucine-rich repeat (non-LRR) regions intervening between LRRs in proteins. Biochim Biophys Acta. 2009;1790:1217-37 pubmed publisher
    ..The sequence analysis of IRs offers functional similarity in some LRR@IR protein families. This study suggests that various IRs and super motifs provide a great variety of structures and functions for LRRs. ..
  16. Shivji M, Mukund S, Rajendra E, Chen S, Short J, Savill J, et al. The BRC repeats of human BRCA2 differentially regulate RAD51 binding on single- versus double-stranded DNA to stimulate strand exchange. Proc Natl Acad Sci U S A. 2009;106:13254-9 pubmed publisher
    ..Our work provides fresh insight into the mechanism of HDR in humans, and its regulation by the BRCA2 tumor suppressor. ..
  17. Oma Y, Kino Y, Toriumi K, Sasagawa N, Ishiura S. Interactions between homopolymeric amino acids (HPAAs). Protein Sci. 2007;16:2195-204 pubmed
    ..The misfolding of these tracts is thought to be a common molecular aspect underlying the pathogenesis of polyalanine-related diseases. ..
  18. Li H, Fischle W, Wang W, Duncan E, Liang L, Murakami Ishibe S, et al. Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. Mol Cell. 2007;28:677-91 pubmed
  19. Biegert A, Söding J. De novo identification of highly diverged protein repeats by probabilistic consistency. Bioinformatics. 2008;24:807-14 pubmed publisher
    ..Server:; Executables: ..
  20. Haerty W, Golding G. Genome-wide evidence for selection acting on single amino acid repeats. Genome Res. 2010;20:755-60 pubmed publisher
    ..We also observed lower codon diversity and longer homocodons, suggesting a balance between slippage and point mutations linked to the constraints imposed by selection. ..
  21. Palidwor G, Shcherbinin S, Huska M, Rasko T, Stelzl U, Arumughan A, et al. Detection of alpha-rod protein repeats using a neural network and application to huntingtin. PLoS Comput Biol. 2009;5:e1000304 pubmed publisher This can be further visualized using BiasViz, a graphic tool for representation of multiple sequence alignments. ..
  22. Mularoni L, Ledda A, Toll Riera M, Albà M. Natural selection drives the accumulation of amino acid tandem repeats in human proteins. Genome Res. 2010;20:745-54 pubmed publisher
    ..The data obtained in this study have allowed us to identify a set of 92 repeats that are postulated to play important functional roles due to their strong selective signature, including five cases with direct experimental evidence. ..
  23. Dosztanyi Z, Chen J, Dunker A, Simon I, Tompa P. Disorder and sequence repeats in hub proteins and their implications for network evolution. J Proteome Res. 2006;5:2985-95 pubmed
  24. Shivji M, Davies O, Savill J, Bates D, Pellegrini L, Venkitaraman A. A region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchange. Nucleic Acids Res. 2006;34:4000-11 pubmed
    ..Thus, the human BRC repeats, embedded within their surronding sequences as an eight-repeat unit, mediate homologous recombination independent of the BRCA2(CTD) through a previously unrecognized role in control of RAD51 activity. ..
  25. Kalita M, Ramasamy G, Duraisamy S, Chauhan V, Gupta D. ProtRepeatsDB: a database of amino acid repeats in genomes. BMC Bioinformatics. 2006;7:336 pubmed
    ..The database is useful for identification of species or organism specific repeat markers, interspecies variations and polymorphism. ..
  26. Choe J, Kelker M, Wilson I. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science. 2005;309:581-5 pubmed
  27. Ou W, Silver J. Inhibition of murine leukemia virus envelope protein (env) processing by intracellular expression of the env N-terminal heptad repeat region. J Virol. 2005;79:4782-92 pubmed
    ..The results highlight another mechanism by which the N-helix peptides can inhibit fusion. ..
  28. van der Hoorn R, Wulff B, Rivas S, Durrant M, van der Ploeg A, de Wit P, et al. Structure-function analysis of cf-9, a receptor-like protein with extracytoplasmic leucine-rich repeats. Plant Cell. 2005;17:1000-15 pubmed
    ..The glycosylation pattern and several other features are conserved in other eLRR proteins, where similar mutations show similar phenotypes. ..
  29. Faux N, Bottomley S, Lesk A, Irving J, Morrison J, de la Banda M, et al. Functional insights from the distribution and role of homopeptide repeat-containing proteins. Genome Res. 2005;15:537-51 pubmed
    ..These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling. ..
  30. Main E, Stott K, Jackson S, Regan L. Local and long-range stability in tandemly arrayed tetratricopeptide repeats. Proc Natl Acad Sci U S A. 2005;102:5721-6 pubmed
    ..The results also show the relationship between the number of tandem repeats and the overall stability and folding of the protein. ..
  31. Bocharova O, Breydo L, Salnikov V, Baskakov I. Copper(II) inhibits in vitro conversion of prion protein into amyloid fibrils. Biochemistry. 2005;44:6776-87 pubmed
  32. Gruber M, Söding J, Lupas A. REPPER--repeats and their periodicities in fibrous proteins. Nucleic Acids Res. 2005;33:W239-43 pubmed
    ..REPPER is available at ..
  33. Chapman R, Conrad M, Eick D. Role of the mammalian RNA polymerase II C-terminal domain (CTD) nonconsensus repeats in CTD stability and cell proliferation. Mol Cell Biol. 2005;25:7665-74 pubmed
    ..We conclude that all other nonconsensus CTD repeats are dispensable for the transcription and pre-mRNA processing of genes essential for proliferation. ..
  34. Tetteh K, Cavanagh D, Corran P, Musonda R, McBride J, Conway D. Extensive antigenic polymorphism within the repeat sequence of the Plasmodium falciparum merozoite surface protein 1 block 2 is incorporated in a minimal polyvalent immunogen. Infect Immun. 2005;73:5928-35 pubmed
    ..Thus, complex allelic polymorphism was deconstructed and a minimal composite polyvalent antigen was engineered, delivering a designed candidate sequence for inclusion in a malaria vaccine. ..
  35. Chattopadhyay M, Walter E, Newell D, Jackson P, Aronoff Spencer E, Peisach J, et al. The octarepeat domain of the prion protein binds Cu(II) with three distinct coordination modes at pH 7.4. J Am Chem Soc. 2005;127:12647-56 pubmed
    ..This work provides the first complete characterization of all dominant copper coordination modes at pH 7.4. ..
  36. Castilla J, Gutierrez Adan A, Brun A, Pintado B, Salguero F, Parra B, et al. Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non-transmissible, neurodegenerative disease and an expedited course of BSE infection. FEBS Lett. 2005;579:6237-46 pubmed
    ..This Tg mouse model constitutes a new way of understanding the pathobiology of bovine transmissible spongiform encephalopathy. Its potential applications include the assessment of new therapies against prion diseases. ..
  37. Isgro T, Schulten K. Binding dynamics of isolated nucleoporin repeat regions to importin-beta. Structure. 2005;13:1869-79 pubmed
  38. Wen D, Wildes C, Silvian L, Walus L, Mi S, Lee D, et al. Disulfide structure of the leucine-rich repeat C-terminal cap and C-terminal stalk region of Nogo-66 receptor. Biochemistry. 2005;44:16491-501 pubmed
    ..A structural model of the LRRCT with extended residues 311-344 from the CT stalk region is proposed, and its function in coreceptor binding is discussed. ..
  39. Moore R, Herzog C, Errett J, Kocisko D, Arnold K, Hayes S, et al. Octapeptide repeat insertions increase the rate of protease-resistant prion protein formation. Protein Sci. 2006;15:609-19 pubmed
    ..Our data from both models support the hypothesis that extra octapeptide repeats in PrP increase the rate at which protease resistant PrP is formed which in turn may affect the rate of disease onset in familial forms of CJD. ..
  40. Depledge D, Dalby A. COPASAAR--a database for proteomic analysis of single amino acid repeats. BMC Bioinformatics. 2005;6:196 pubmed
    ..The insights gained from these studies will give a better insight into the evolution of protein sequence and function. ..
  41. Janssen B, Hohenadel D, Brinkkoetter P, Peters V, Rind N, Fischer C, et al. Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1. Diabetes. 2005;54:2320-7 pubmed
    ..Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells. ..
  42. Matsushima N, Tachi N, Kuroki Y, Enkhbayar P, Osaki M, Kamiya M, et al. Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases. Cell Mol Life Sci. 2005;62:2771-91 pubmed
    ..In contrast, missense mutations at some specific positions in LRRs are very rare or are not observed at all. ..
  43. Hancock J, Simon M. Simple sequence repeats in proteins and their significance for network evolution. Gene. 2005;345:113-8 pubmed
    ..We outline a conceptualization of how protein SSRs may arise and become fixed in proteins during evolution, and suggest that emergence and change in length of protein SSRs may affect the topology of protein interaction networks. ..
  44. Sterky F, Ruzzenente B, Gustafsson C, Samuelsson T, Larsson N. LRPPRC is a mitochondrial matrix protein that is conserved in metazoans. Biochem Biophys Res Commun. 2010;398:759-64 pubmed publisher
    ..The LRPPRC protein is imported to the mitochondrial matrix and its mitochondrial targeting sequence is cleaved upon entry. ..
  45. Jorda J, Kajava A. T-REKS: identification of Tandem REpeats in sequences with a K-meanS based algorithm. Bioinformatics. 2009;25:2632-8 pubmed publisher
    ..The algorithm has been implemented in JAVA, the program is available upon request at Protein Repeat DataBase generated by using T-REKS is accessible at ..
  46. Sackett K, Nethercott M, Epand R, Epand R, Kindra D, Shai Y, et al. Comparative analysis of membrane-associated fusion peptide secondary structure and lipid mixing function of HIV gp41 constructs that model the early pre-hairpin intermediate and final hairpin conformations. J Mol Biol. 2010;397:301-15 pubmed publisher
    ..Membrane insertion of the FP may therefore be associated with the early PHI conformation and FP withdrawal with the final hairpin conformation. ..
  47. Rao J, Kim Y, Park L, Ulmer T. Effect of pseudorepeat rearrangement on alpha-synuclein misfolding, vesicle binding, and micelle binding. J Mol Biol. 2009;390:516-29 pubmed publisher
    ..By demonstrating the importance of the distribution of beta-sheet propensities and by revealing inhomogeneous aS surfactant affinities, the present study provides novel insights into two central themes of synuclein biology. ..
  48. Han D, Kim K, Kim Y, Kang Y, Lee J, Kim Y. Crystal structure of the N-terminal domain of anaphase-promoting complex subunit 7. J Biol Chem. 2009;284:15137-46 pubmed publisher
    ..This model suggests that TPR-containing subunits self-associate and bind to adaptors and substrates via an IR peptide in TPR-containing subunits of APC/C. ..
  49. Ishii K, Hirano Y, Araki N, Oda T, Kumeta M, Takeyasu K, et al. Nuclear matrix contains novel WD-repeat and disordered-region-rich proteins. FEBS Lett. 2008;582:3515-9 pubmed publisher
    ..Seven WD-repeat proteins and 16 disordered region-rich proteins, which act frequently as scaffolding proteins for macro-protein complexes, were found amongst the novel proteins. ..
  50. Holman H, MacLean A. Neurovirulent factor ICP34.5 uniquely expressed in the herpes simplex virus type 1 Delta gamma 1 34.5 mutant 1716. J Neurovirol. 2008;14:28-40 pubmed publisher
    ..5 gene and restore most (but not all) wild-type function. These findings are discussed with respect to the use of the gamma(1)34.5 deleted mutant, 1716, in oncolytic viral vector therapies and future studies for ICP34.5. ..
  51. Liang J, Pan Y, Zhang D, Guo C, Shi Y, Wang J, et al. Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS. FASEB J. 2007;21:2247-56 pubmed
  52. Ensslin M, Shur B. The EGF repeat and discoidin domain protein, SED1/MFG-E8, is required for mammary gland branching morphogenesis. Proc Natl Acad Sci U S A. 2007;104:2715-20 pubmed
    ..These results suggest that SED1 contributes, at least partly, to the intercellular signaling between luminal and myoepithelial cells that is required for branching morphogenesis. ..
  53. Rauceo J, De Armond R, Otoo H, Kahn P, Klotz S, Gaur N, et al. Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p. Eukaryot Cell. 2006;5:1664-73 pubmed
    ..Thus, the TR region of Als5p modulated the structure of the Ig-T region, augmented cell adhesion activity through increased binding to mammalian ligands, and simultaneously promoted fungal cell-cell interactions. ..