tripeptidyl peptidase I


Gene Symbol: tripeptidyl peptidase I
Description: tripeptidyl peptidase 1
Alias: CLN2, GIG1, LPIC, SCAR7, TPP-1, tripeptidyl-peptidase 1, cell growth-inhibiting gene 1 protein, growth-inhibiting protein 1, lysosomal pepstatin insensitive protease, tripeptidyl aminopeptidase, tripeptidyl peptidase I
Species: human
Products:     tripeptidyl peptidase I

Top Publications

  1. Golabek A, Wujek P, Walus M, Bieler S, Soto C, Wisniewski K, et al. Maturation of human tripeptidyl-peptidase I in vitro. J Biol Chem. 2004;279:31058-67 pubmed
    Tripeptidyl-peptidase I (TPP I, CLN2 protein) is a lysosomal aminopeptidase that cleaves off tripeptides from the free N termini of oligopeptides and also shows minor endopeptidase activity. TPP I is synthesized as a preproenzyme...
  2. Walus M, Kida E, Wisniewski K, Golabek A. Ser475, Glu272, Asp276, Asp327, and Asp360 are involved in catalytic activity of human tripeptidyl-peptidase I. FEBS Lett. 2005;579:1383-8 pubmed
  3. Rawlings N, Barrett A. Tripeptidyl-peptidase I is apparently the CLN2 protein absent in classical late-infantile neuronal ceroid lipofuscinosis. Biochim Biophys Acta. 1999;1429:496-500 pubmed
    ..acid sequence recently described for tripeptidyl-peptidase I (TPP I) show that it is the rat homologue of the human CLN2 gene product that is deficient in classical late-infantile neuronal ceroid lipofuscinosis...
  4. Xin H, Liu D, Wan M, Safari A, Kim H, Sun W, et al. TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature. 2007;445:559-62 pubmed
  5. Wlodawer A, Durell S, Li M, Oyama H, Oda K, Dunn B. A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases. BMC Struct Biol. 2003;3:8 pubmed
    Tripeptidyl-peptidase I, also known as CLN2, is a member of the family of sedolisins (serine-carboxyl peptidases)...
  6. Lin L, Sohar I, Lackland H, Lobel P. The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. J Biol Chem. 2001;276:2249-55 pubmed
    The CLN2 gene mutated in the fatal hereditary neurodegenerative disease late infantile neuronal ceroid lipofuscinosis encodes a lysosomal protease with tripeptidyl-peptidase I activity...
  7. Nandakumar J, Bell C, Weidenfeld I, Zaug A, Leinwand L, Cech T. The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature. 2012;492:285-9 pubmed publisher
    ..Given that the interaction between telomerase and TPP1 is required for telomerase function in vivo, the TEL patch of TPP1 provides a new target for anticancer drug development...
  8. Zhang Y, Chen L, Han X, Xie W, Kim H, Yang D, et al. Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment. Proc Natl Acad Sci U S A. 2013;110:5457-62 pubmed publisher
    ..Our findings provide insight into the regulatory pathways and structural basis that control cell cycle-dependent telomerase recruitment and telomere elongation through phosphorylation of TPP1. ..
  9. Page A, Fuller K, Chambers T, Warburton M. Purification and characterization of a tripeptidyl peptidase I from human osteoclastomas: evidence for its role in bone resorption. Arch Biochem Biophys. 1993;306:354-9 pubmed
    b>Tripeptidyl peptidase I (EC, which cleaves tripeptides from the N-terminus of synthetic substrates, has been purified from human osteoclastomas (a bone tumor containing large numbers of normal osteoclasts)...

More Information


  1. Tsukamoto T, Iida J, Dobashi Y, Furukawa T, Konishi F. Overexpression in colorectal carcinoma of two lysosomal enzymes, CLN2 and CLN1, involved in neuronal ceroid lipofuscinosis. Cancer. 2006;106:1489-97 pubmed
    ..differentially expressed in metastasis, the authors isolated a clone encoding ceroid lipofuscinosis, neuronal 2 (CLN2), which is a lysosomal serine protease defective in neuronal ceroid lipofuscinosis (NCL)...
  2. Guhaniyogi J, Sohar I, Das K, Stock A, Lobel P. Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis. J Biol Chem. 2009;284:3985-97 pubmed publisher
    ..These data provide new insights into TPP1 function and represent a valuable resource for constructing improved TPP1 variants for treatment of late infantile neuronal ceroid lipofuscinosis. ..
  3. Ezaki J, Takeda Ezaki M, Oda K, Kominami E. Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis. Biochem Biophys Res Commun. 2000;268:904-8 pubmed
    Endopeptidase activities of the CLN2 gene product (Cln2p)/tripeptidyl peptidase I (TPP-I), purified from rat spleen, were studied using the synthetic fluorogenic substrates...
  4. Ezaki J, Takeda Ezaki M, Kominami E. Tripeptidyl peptidase I, the late infantile neuronal ceroid lipofuscinosis gene product, initiates the lysosomal degradation of subunit c of ATP synthase. J Biochem. 2000;128:509-16 pubmed
    ..of patients with the late infantile form of NCL (LINCL) is caused by a defect in the CLN2 gene product, tripeptidyl peptidase I (TPP-I)...
  5. Liu C, Sleat D, Donnelly R, Lobel P. Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis. Genomics. 1998;50:206-12 pubmed
    Mutations in the CLN2 gene result in classical late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal childhood neurodegenerative disease...
  6. Autefage H, Albinet V, Garcia V, Berges H, Nicolau M, Therville N, et al. Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner. J Biol Chem. 2009;284:11507-16 pubmed publisher
    ..This study investigated the role of the lysosomal serine protease CLN2 in apoptosis...
  7. Vesa J, Chin M, Oelgeschläger K, Isosomppi J, DellAngelica E, Jalanko A, et al. Neuronal ceroid lipofuscinoses are connected at molecular level: interaction of CLN5 protein with CLN2 and CLN3. Mol Biol Cell. 2002;13:2410-20 pubmed
    ..with similar tissue pathology are connected at the molecular level: CLN5 polypeptides directly interact with the CLN2 and CLN3 proteins based on coimmunoprecipitation and in vitro binding assays...
  8. Golabek A, Kida E, Walus M, Wujek P, Mehta P, Wisniewski K. Biosynthesis, glycosylation, and enzymatic processing in vivo of human tripeptidyl-peptidase I. J Biol Chem. 2003;278:7135-45 pubmed
    Human tripeptidyl-peptidase I (TPP I, CLN2 protein) is a lysosomal serine protease that removes tripeptides from the free N termini of small polypeptides and also shows a minor endoprotease activity...
  9. Golabek A, Dolzhanskaya N, Walus M, Wisniewski K, Kida E. Prosegment of tripeptidyl peptidase I is a potent, slow-binding inhibitor of its cognate enzyme. J Biol Chem. 2008;283:16497-504 pubmed publisher
    b>Tripeptidyl peptidase I (TPP I) is the first mammalian representative of a family of pepstatin-insensitive serine-carboxyl proteases, or sedolisins...
  10. Wujek P, Kida E, Walus M, Wisniewski K, Golabek A. N-glycosylation is crucial for folding, trafficking, and stability of human tripeptidyl-peptidase I. J Biol Chem. 2004;279:12827-39 pubmed
  11. Golabek A, Walus M, Wisniewski K, Kida E. Glycosaminoglycans modulate activation, activity, and stability of tripeptidyl-peptidase I in vitro and in vivo. J Biol Chem. 2005;280:7550-61 pubmed
    Tripeptidyl-peptidase I (TPP I, CLN2 protein) is a lysosomal exopeptidase that sequentially removes tripeptides from the N termini of polypeptides and shows a minor endoprotease activity...
  12. Pal A, Kraetzner R, Gruene T, Grapp M, Schreiber K, Grønborg M, et al. Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. J Biol Chem. 2009;284:3976-84 pubmed publisher
    ..28 disease-causing missense mutations are analyzed in the light of the TPP1 structure providing insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. ..
  13. Junaid M, Wu G, Pullarkat R. Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis. J Neurochem. 2000;74:287-94 pubmed
    ..CLN2p) deficiency is the underlying defect in the classical late-infantile neuronal ceroid lipofuscinosis (LINCL, CLN2)...
  14. Sleat D, Gin R, Sohar I, Wisniewski K, Sklower Brooks S, Pullarkat R, et al. Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. Am J Hum Genet. 1999;64:1511-23 pubmed
    ..The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease...
  15. Vines D, Warburton M. Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are deficient in lysosomal tripeptidyl peptidase I. FEBS Lett. 1999;443:131-5 pubmed
    b>Tripeptidyl peptidase I (TPP-I) is a lysosomal enzyme that cleaves tripeptides from the N-terminus of polypeptides...
  16. Sleat D, Donnelly R, Lackland H, Liu C, Sohar I, Pullarkat R, et al. Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science. 1997;277:1802-5 pubmed
    ..Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls. ..
  17. Kim H, Joe Y, Rah S, Kim S, Park S, Park J, et al. Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury. Cell Death Dis. 2018;9:1060 pubmed publisher
    ..Our findings describe novel mechanisms underlying CO-dependent cytoprotection in hepatocytes and liver tissue via activation of TFEB-dependent mitophagy and associated induction of both lysosomal and mitochondrial biogenesis. ..
  18. Lu J, Nelvagal H, Wang L, Birnbaum S, Cooper J, Hofmann S. Intrathecal enzyme replacement therapy improves motor function and survival in a preclinical mouse model of infantile neuronal ceroid lipofuscinosis. Mol Genet Metab. 2015;116:98-105 pubmed publisher
    ..are similar to results reported for preclinical studies involving other lysosomal storage disorders, such as CLN2/TPP1 deficiency, for which intraventricular ERT is being offered in clinical trials...
  19. Ke S, Zhou F, Yang H, Wei Y, Gong J, Mei Z, et al. Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells. Int J Oncol. 2015;46:1051-8 pubmed publisher
    ..These results suggested that HMGB1 might be a potential radiotherapy target in human breast cancer. ..
  20. Hosokawa K, Arai F. The role of telomere binding molecules for normal and abnormal hematopoiesis. Int J Hematol. 2018;107:646-655 pubmed publisher
    ..Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders. ..
  21. Kara E, Tucci A, Manzoni C, Lynch D, Elpidorou M, Bettencourt C, et al. Genetic and phenotypic characterization of complex hereditary spastic paraplegia. Brain. 2016;139:1904-18 pubmed publisher
    ..No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes. ..
  22. Machado J, Johnson W, Gilbert M, Zhang G, Jarvis E, O Brien S, et al. Bone-associated gene evolution and the origin of flight in birds. BMC Genomics. 2016;17:371 pubmed publisher
    ..Patterns of positive selection observed in bird ossification genes suggest that there was a period of intense selective pressure to improve flight efficiency that was closely linked with constraints on body size. ..
  23. Ohlmeier S, Nieminen P, Gao J, Kanerva T, Rönty M, Toljamo T, et al. Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2016;310:L1155-65 pubmed publisher
    ..Further studies in carefully characterized cohorts are required to validate the identified changes. ..
  24. Amigoni L, Colombo S, Belotti F, Alberghina L, Martegani E. The transcription factor Swi4 is target for PKA regulation of cell size at the G1 to S transition in Saccharomyces cerevisiae. Cell Cycle. 2015;14:2429-38 pubmed publisher
    ..Deletion of CLN1 gene, but not of CLN2, abolished the transient G1 phase arrest...
  25. Huber R, Mathavarajah S. Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium. Cell Signal. 2018;42:236-248 pubmed publisher
    ..g., Tpp1/Cln2, cathepsin D/Cln10, cathepsin F/Cln13) as well as proteins linked to Cln3 function in Dictyostelium (e.g...
  26. Khurana N, Laskar S, Bhattacharyya M, Bhattacharyya S. Hsp90 induces increased genomic instability toward DNA-damaging agents by tuning down RAD53 transcription. Mol Biol Cell. 2016;27:2463-78 pubmed publisher
    ..efficiency, with a drastic failure to up-regulate RAD51 expression and manifestly faster accumulation of CLN1 and CLN2 in DNA-damaged G1, cells leading to premature release from checkpoint arrest...
  27. Zhang Y, Zhang L, Tang X, Bhardwaj S, Ji J, Rong Y. MTV, an ssDNA Protecting Complex Essential for Transposon-Based Telomere Maintenance in Drosophila. PLoS Genet. 2016;12:e1006435 pubmed publisher
    ..MTV thus shares functional similarities with CST or TPP1-POT1 in protecting ssDNA, highlighting a conserved feature in end protecting mechanisms. ..
  28. Guièze R, Pages M, Véronèse L, Combes P, Lemal R, Gay Bellile M, et al. Telomere status in chronic lymphocytic leukemia with TP53 disruption. Oncotarget. 2016;7:56976-56985 pubmed publisher
    ..Thus, the telomeric profile could be tested as a biomarker in CLL patients treated with new therapeutic agents. ..
  29. Bisht K, Smith E, Tesmer V, Nandakumar J. Structural and functional consequences of a disease mutation in the telomere protein TPP1. Proc Natl Acad Sci U S A. 2016;113:13021-13026 pubmed
    ..Our studies provide mechanistic insight into telomerase-deficiency diseases and encourage the development of gene therapies to counter such diseases. ..
  30. Caballero Solares A, Hall J, Xue X, Eslamloo K, Taylor R, Parrish C, et al. The dietary replacement of marine ingredients by terrestrial animal and plant alternatives modulates the antiviral immune response of Atlantic salmon (Salmo salar). Fish Shellfish Immunol. 2017;64:24-38 pubmed publisher
    ..pIC-treated fish fed diets ABP and VEG showed higher transcript levels of tlr3, irf1b, stat1a, isg15b, and gig1 compared to those fed diet MAR...
  31. Kousi M, Siintola E, Dvorakova L, Vlaskova H, Turnbull J, Topcu M, et al. Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis. Brain. 2009;132:810-9 pubmed publisher
    ..Eight novel CLN7/MFSD8 mutations and seven novel mutations in the CLN1/PPT1, CLN2/TPP1, CLN5, CLN6 and CLN8 genes were identified in patients of various ethnic origins...
  32. Mahmood F, Fu S, Cooke J, Wilson S, Cooper J, Russell C. A zebrafish model of CLN2 disease is deficient in tripeptidyl peptidase 1 and displays progressive neurodegeneration accompanied by a reduction in proliferation. Brain. 2013;136:1488-507 pubmed publisher
    b>Tripeptidyl peptidase 1 (TPP1) deficiency causes CLN2 disease, late infantile (or classic late infantile neuronal ceroid lipofuscinosis), a paediatric neurodegenerative disease of autosomal recessive inheritance...
  33. Kalathiya U, Padariya M, Baginski M. Molecular basis and quantitative assessment of TRF1 and TRF2 protein interactions with TIN2 and Apollo peptides. Eur Biophys J. 2017;46:171-187 pubmed publisher
  34. Zhang Z, Ren P, Vashisht A, Wohlschlegel J, Quintana D, Zeng F. Cdk1-interacting protein Cip1 is regulated by the S phase checkpoint in response to genotoxic stress. Genes Cells. 2017;22:850-860 pubmed publisher
    ..Significantly, the sensitivity is increased when the dosage of the G1 cyclin CLN2 is increased, compatible to a role of Cip1 as a G1-cyclin-dependent kinase inhibitor...
  35. Zemp I, Lingner J. The shelterin component TPP1 is a binding partner and substrate for the deubiquitinating enzyme USP7. J Biol Chem. 2014;289:28595-606 pubmed publisher
    ..Altogether, our work identifies novel regulatory circuits that contribute to TPP1 stability and function. ..
  36. Geraets R, Langin L, Cain J, Parker C, Beraldi R, Kovács A, et al. A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies. PLoS ONE. 2017;12:e0176526 pubmed publisher
    ..Mutations of the CLN2 gene encoding a soluble lysosomal enzyme, tripeptidyl peptidase 1 (TPP1), cause late infantile NCL/CLN2 disease...
  37. Kibe T, Zimmermann M, de Lange T. TPP1 Blocks an ATR-Mediated Resection Mechanism at Telomeres. Mol Cell. 2016;61:236-46 pubmed publisher
    ..The data show that telomeres are protected from hyper-resection through the repression of the ATM and ATR kinases by TRF2 and TPP1-bound POT1a/b, respectively. ..
  38. Chang Y, Tseng S, Huang Y, Shen Z, Hsu P, Hsieh M, et al. Yeast Cip1 is activated by environmental stress to inhibit Cdk1-G1 cyclins via Mcm1 and Msn2/4. Nat Commun. 2017;8:56 pubmed publisher
    ..Yeast Cip1 is a Cdk1 and Cln2-associated protein. However, the function and regulation of Cip1 are still poorly understood...
  39. Katz M, Tecedor L, Chen Y, Williamson B, Lysenko E, Wininger F, et al. AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease. Sci Transl Med. 2015;7:313ra180 pubmed publisher
    ..lipofuscinosis (also called Batten disease) is caused by deficiency of the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1) resulting from mutations in the TPP1 gene...
  40. Di Giacopo R, Cianetti L, Caputo V, La Torraca I, Piemonte F, Ciolfi A, et al. Protracted late infantile ceroid lipofuscinosis due to TPP1 mutations: Clinical, molecular and biochemical characterization in three sibs. J Neurol Sci. 2015;356:65-71 pubmed publisher
    ..Our findings document that late infantile neuronal ceroid lipofuscinosis (CLN2), which is caused by TPP1 gene mutations, should be considered in the differential diagnosis of autosomal recessive ..
  41. Kohan R, Carabelos M, Xin W, Sims K, Guelbert N, Cismondi I, et al. Neuronal ceroid lipofuscinosis type CLN2: a new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America. Gene. 2013;516:114-21 pubmed publisher
    ..1 (TPP1) null or residual activity occurs in neuronal ceroid lipofuscinosis (NCL) with underlying TPP1/CLN2 mutations...
  42. Saini A, Sankhyan N, Singhi P. Chorea in Late-Infantile Neuronal Ceroid Lipofuscinosis: An Atypical Presentation. Pediatr Neurol. 2016;60:75-8 pubmed publisher
  43. Goldberg Stern H, Halevi A, Marom D, Straussberg R, Mimouni Bloch A. Late infantile neuronal ceroid lipofuscinosis: a new mutation in Arabs. Pediatr Neurol. 2009;41:297-300 pubmed publisher
    ..palmitoyl-protein thioesterase 1, encoded by the CLN1 gene, and tripeptidyl-peptidase 1, encoded by the CLN2 gene. Several mutations in CLN2 were described previously...
  44. Solé Domènech S, Rojas A, Maisuradze G, Scheraga H, Lobel P, Maxfield F. Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar A? by multiple endoproteolytic cleavages within the ?-sheet domain. Proc Natl Acad Sci U S A. 2018;115:1493-1498 pubmed publisher
    ..Cathepsin B is a lysosomal protease that has been shown to proteolyze fibrillar A?. Tripeptidyl peptidase 1 (TPP1), a lysosomal serine protease, possesses endopeptidase activity and has been shown to cleave ..
  45. Huber R. Using the social amoeba Dictyostelium to study the functions of proteins linked to neuronal ceroid lipofuscinosis. J Biomed Sci. 2016;23:83 pubmed
    ..The NCL family of proteins is comprised of lysosomal enzymes (PPT1/CLN1, TPP1/CLN2, CTSD/CLN10, CTSF/CLN13), proteins that peripherally associate with membranes (DNAJC5/CLN4, KCTD7/CLN14), a soluble ..
  46. Dimitrova M, Atanasova D, Lazarov N. Histochemical Demonstration of Tripeptidyl Aminopeptidase I. Methods Mol Biol. 2017;1560:55-68 pubmed publisher
    ..Here we describe two protocols for chromogenic and fluorogenic histochemical demonstration of tripeptidyl aminopeptidase I (TPPI), a protease that is crucial for neuronal functions...
  47. Meng Y, Wiseman J, Nemtsova Y, Moore D, Guevarra J, Reuhl K, et al. A Basic ApoE-Based Peptide Mediator to Deliver Proteins across the Blood-Brain Barrier: Long-Term Efficacy, Toxicity, and Mechanism. Mol Ther. 2017;25:1531-1543 pubmed publisher
    ..of late-infantile neuronal ceroid lipofuscinosis (LINCL), a lysosomal disease due to deficiencies in tripeptidyl peptidase 1 (TPP1)...
  48. Kumar A, Sharma P, Gomar Alba M, Shcheprova Z, Daulny A, Sanmartín T, et al. Daughter-cell-specific modulation of nuclear pore complexes controls cell cycle entry during asymmetric division. Nat Cell Biol. 2018;20:432-442 pubmed publisher
    ..of the transcriptional repressor Whi5 during anaphase and perinuclear silencing of the G1/S cyclin gene CLN2 in the following G1 phase...
  49. Breedveld G, van Wetten B, te Raa G, Brusse E, van Swieten J, Oostra B, et al. A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15. J Med Genet. 2004;41:858-66 pubmed
  50. Rajavel M, Orban T, Xu M, Hernandez Sanchez W, de la Fuente M, Palczewski K, et al. Dynamic peptides of human TPP1 fulfill diverse functions in telomere maintenance. Nucleic Acids Res. 2016;44:10467-10479 pubmed
    ..Together, these functional data combined with biophysical analyses and homology modeling provide a molecular understanding of the diverse contributions of TPP1 in telomere maintenance. ..
  51. Zhong N, Moroziewicz D, Ju W, Jurkiewicz A, Johnston L, Wisniewski K, et al. Heterogeneity of late-infantile neuronal ceroid lipofuscinosis. Genet Med. 2000;2:312-8 pubmed disorder characterized by autofluorescent inclusions and rapid progression of neurodegeneration, is due to CLN2 gene mutations...
  52. Schmidt J, Dalby A, Cech T. Identification of human TERT elements necessary for telomerase recruitment to telomeres. elife. 2014;3: pubmed publisher
    ..Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease. ..
  53. Bessa C, Teixeira C, Dias A, Alves M, Rocha S, Lacerda L, et al. CLN2/TPP1 deficiency: the novel mutation IVS7-10A>G causes intron retention and is associated with a mild disease phenotype. Mol Genet Metab. 2008;93:66-73 pubmed
    ..The underlying gene, CLN2, encodes the lysosomal soluble enzyme tripeptidyl-peptidase 1 (TPP1)...
  54. Ray S, Bandaria J, Qureshi M, Yildiz A, Balci H. G-quadruplex formation in telomeres enhances POT1/TPP1 protection against RPA binding. Proc Natl Acad Sci U S A. 2014;111:2990-5 pubmed publisher
    ..This protection is not observed at 150 mM Na(+), in which ssTEL forms only a less-stable antiparallel GQ. These results suggest that GQ formation of telomeric overhangs may contribute to suppression of DNA damage signals. ..
  55. Usmani Z, Kumar V. Characterization, partitioning, and potential ecological risk quantification of trace elements in coal fly ash. Environ Sci Pollut Res Int. 2017;24:15547-15566 pubmed publisher
    ..I geo values for metals were mostly below zero. The PERI values indicated moderate risk from TPP4 FA and low risk from TPP1, TPP2, TPP3, and TPP5 FA to the environment, according to the threshold values provided. ..
  56. Hirai Y, Tamura M, Otani J, Ishikawa F. NEK6-mediated phosphorylation of human TPP1 regulates telomere length through telomerase recruitment. Genes Cells. 2016;21:874-89 pubmed publisher
    ..Ser255 and the surrounding amino acids are conserved among vertebrates. These observations suggest that a region adjacent to the OB-fold domain of TPP1 is involved in telomere length regulation via telomerase recruitment. ..
  57. Davis Z, Verschueren E, Jang G, Kleffman K, Johnson J, Park J, et al. Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Mol Cell. 2015;57:349-60 pubmed publisher
    ..This is required for herpesviral late gene expression, a complex and poorly understood phase of the viral lifecycle. ..
  58. Tsiakas K, Steinfeld R, Storch S, Ezaki J, Lukacs Z, Kominami E, et al. Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity. Glycobiology. 2004;14:1C-5C pubmed
    ..ceroid lipofuscinosis (LINCL) is caused by the deficiency of the lysosomal tripeptidyl peptidase-I encoded by CLN2. We previously detected in two LINCL patients a homozygous missense mutation, p...
  59. Bukina A, Tsvetkova I, Semiachkina A, Il Ina E. [Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation]. Vopr Med Khim. 2002;48:594-8 pubmed
    ..diagnostics of a hereditary lisosomal storage disease, late infantile neuronal ceroid lipofuscinosis (CLN2) are presented...
  60. Sleat D, Gedvilaite E, Zhang Y, Lobel P, Xing J. Analysis of large-scale whole exome sequencing data to determine the prevalence of genetically-distinct forms of neuronal ceroid lipofuscinosis. Gene. 2016;593:284-91 pubmed publisher
    ..Based upon literature reports, such alleles may be annotated in public databases as pathogenic and this propagates errors that can have clinical consequences. ..
  61. Souweidane M, Fraser J, Arkin L, Sondhi D, Hackett N, Kaminsky S, et al. Gene therapy for late infantile neuronal ceroid lipofuscinosis: neurosurgical considerations. J Neurosurg Pediatr. 2010;6:115-22 pubmed publisher
    ..neuronal ceroid lipofuscinosis using an adenoassociated virus serotype 2 (AAV2) vector containing the deficient CLN2 gene (AAV2(CU)hCLN2). The operative technique, radiographic changes, and surgical complications are presented...
  62. Han X, Liu D, Zhang Y, Li Y, Lu W, Chen J, et al. Akt regulates TPP1 homodimerization and telomere protection. Aging Cell. 2013;12:1091-9 pubmed publisher
    ..Our findings highlight a previously unknown link between Akt signaling and telomere protection. ..
  63. Mariasina S, Efimov S, Petrova O, Rodina E, Malyavko A, Zvereva M, et al. Chemical shift assignments and the secondary structure of the Est3 telomerase subunit in the yeast Hansenula polymorpha. Biomol NMR Assign. 2018;12:57-62 pubmed publisher
    ..Structure-based sequence alignment revealed similarities in the structural organization of yeast Est3 and mammalian TPP1 proteins. ..
  64. Dawson G, Cho S. Batten's disease: clues to neuronal protein catabolism in lysosomes. J Neurosci Res. 2000;60:133-40 pubmed
    ..These include palmitoyl:protein thioesterase 1 (CLN1), tripeptidylpeptidase 1 (CLN2), cathepsin D (CLN8), and two membrane proteins of unknown function (CLN3 and CLN5)...
  65. Albrecht D, Ceschin J, Dompierre J, Gueniot F, Pinson B, Daignan Fornier B. Chemo-Genetic Interactions Between Histone Modification and the Antiproliferation Drug AICAR Are Conserved in Yeast and Humans. Genetics. 2016;204:1447-1460 pubmed
    ..on Cln3 subcellular localization and at the Cln1 protein level, while the bre1 or set1 deletion affected CLN1 and CLN2 expression...
  66. Ju W, Zhong R, Moore S, Moroziewicz D, Currie J, Parfrey P, et al. Identification of novel CLN2 mutations shows Canadian specific NCL2 alleles. J Med Genet. 2002;39:822-5 pubmed
  67. Lojewski X, Staropoli J, Biswas Legrand S, Simas A, Haliw L, Selig M, et al. Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway. Hum Mol Genet. 2014;23:2005-22 pubmed publisher
    ..pluripotent stem cells (iPSCs) for the two most common NCL subtypes: classic late-infantile NCL, caused by TPP1(CLN2) mutation, and juvenile NCL, caused by CLN3 mutation...
  68. Sexton A, Regalado S, Lai C, Cost G, O Neil C, Urnov F, et al. Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation. Genes Dev. 2014;28:1885-99 pubmed publisher
    ..These studies reveal and resolve multiple TPP1 roles in telomere elongation and stem cell telomere length homeostasis. ..
  69. Liu J, Yu C, Hu X, Kim J, Bierma J, Jun H, et al. Dissecting Fission Yeast Shelterin Interactions via MICro-MS Links Disruption of Shelterin Bridge to Tumorigenesis. Cell Rep. 2015;12:2169-80 pubmed publisher
    ..Therefore, our study reveals a connection between shelterin connectivity and tumorigenicity. ..
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    ..At least eight genes underlie the NCLs, of which four have been isolated and mutations characterised: CLN1, CLN2, CLN3, CLN5...
  71. Katz M, Johnson G, Leach S, Williamson B, Coates J, Whiting R, et al. Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression. Gene Ther. 2017;24:215-223 pubmed publisher
    b>CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1)...
  72. Mullins M, Rajavel M, Hernandez Sanchez W, de la Fuente M, Biendarra S, Harris M, et al. POT1-TPP1 Binding and Unfolding of Telomere DNA Discriminates against Structural Polymorphism. J Mol Biol. 2016;428:2695-708 pubmed publisher
    ..Together, these data indicate that binding of POT1-TPP1 unfolds telomere secondary structure to assist loading of additional heterodimers and to ensure efficient promotion of telomerase-mediated extension. ..
  73. Vuillemenot B, Katz M, Coates J, Kennedy D, Tiger P, Kanazono S, et al. Intrathecal tripeptidyl-peptidase 1 reduces lysosomal storage in a canine model of late infantile neuronal ceroid lipofuscinosis. Mol Genet Metab. 2011;104:325-37 pubmed publisher
    ..Further studies with this model will be necessary to optimize the dosing route and regimen to attenuate functional decline. ..
  74. Kuizon S, DiMaiuta K, Walus M, Jenkins E, Kuizon M, Kida E, et al. A critical tryptophan and Ca2+ in activation and catalysis of TPPI, the enzyme deficient in classic late-infantile neuronal ceroid lipofuscinosis. PLoS ONE. 2010;5:e11929 pubmed publisher
    b>Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL)...
  75. Kopan S, Sivasubramaniam U, Warburton M. The lysosomal degradation of neuromedin B is dependent on tripeptidyl peptidase-I: evidence for the impairment of neuropeptide degradation in late-infantile neuronal ceroid lipofuscinosis. Biochem Biophys Res Commun. 2004;319:58-65 pubmed
    Late-infantile neuronal ceroid lipofuscinosis (CLN2), previously known as the late-infantile form of Batten disease, is a lysosomal storage disease which results from mutations in the gene that codes for tripeptidyl peptidase-I (TPP-I)...
  76. Coppola G, Veggiotti P, del Giudice E, Bellini G, Longaretti F, Taglialatela M, et al. Mutational scanning of potassium, sodium and chloride ion channels in malignant migrating partial seizures in infancy. Brain Dev. 2006;28:76-9 pubmed
    ..The same variation has been found in 38 out of 100 control alleles. The identification of the genetic basis of this new epileptic encephalopathy requires further studies that might be enforced by familial cases. ..
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    b>Tripeptidyl peptidase I (TTP-I), also known as CLN2, a member of the family of serine-carboxyl proteinases (S53), plays a crucial role in lysosomal protein degradation and a deficiency in this enzyme leads to fatal neurodegenerative ..
  78. Sartorel E, Barrey E, Lau R, Thorner J. Plasma membrane aminoglycerolipid flippase function is required for signaling competence in the yeast mating pheromone response pathway. Mol Biol Cell. 2015;26:134-50 pubmed publisher
    ..which we could attribute to pronounced reduction in Ste5 stability resulting from an elevated rate of its Cln2⋅Cdc28-initiated degradation...
  79. Haines J, Boustany R, Alroy J, Auger K, Shook K, Terwedow H, et al. Chromosomal localization of two genes underlying late-infantile neuronal ceroid lipofuscinosis. Neurogenetics. 1998;1:217-22 pubmed
    Classical late-infantile neuronal ceroid lipofuscinosis (LINCL; CLN2) is an inherited neurodegenerative disorder of childhood characterized by seizures, loss of vision, and progressive motor and mental deterioration...
  80. Walus M, Kida E, Golabek A. Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I. Hum Mutat. 2010;31:710-21 pubmed publisher
    There are 35 missense mutations among 68 different mutations in the TPP1 gene, which encodes tripeptidyl peptidase I (TPPI), a lysosomal aminopeptidase associated with classic late-infantile neuronal ceroid lipofuscinosis (CLN2 disease)...
  81. Hu C, Rai R, Huang C, Broton C, Long J, Xu Y, et al. Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex. Cell Res. 2017;27:1485-1502 pubmed publisher
    ..Structure-based mutagenesis analyses suggest that TIN2 plays an important role in maintaining the stable shelterin complex required for proper telomere end protection. ..
  82. Lin L, Lobel P. Expression and analysis of CLN2 variants in CHO cells: Q100R represents a polymorphism, and G389E and R447H represent loss-of-function mutations. Hum Mutat. 2001;18:165 pubmed
    ..The gene underlying LINCL, CLN2, encodes a lysosomal enzyme, tripeptidyl peptidase I (TPP-I), deficiency in which leads to lysosomal accumulation of autofluorescent materials accompanied by ..