Tripeptidyl peptidase I
Tripeptidyl-peptidase 1 is an enzyme that in humans is encoded by the TPP1 gene.[1][2]
Genomics
Molecular biology
This gene encodes a member of the sedolisin family of serine proteases. The protease functions in the lysosome to cleave N-terminal tripeptides from substrates and has weaker endopeptidase activity. It is synthesized as a catalytically inactive enzyme which is activated and autoproteolyzed upon acidification.[2]
Clinical
Mutations in this gene result in late-infantile neuronal ceroid lipofuscinosis which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome.
References
External links
Further reading
- Mole SE, Mitchison HM, Munroe PB (1999). "Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5.". Hum. Mutat. 14 (3): 199–215. doi:10.1002/(SICI)1098-1004(1999)14:3<199::AID-HUMU3>3.0.CO;2-A. PMID 10477428.
- Dawson G, Cho S (2000). "Batten's disease: clues to neuronal protein catabolism in lysosomes.". J. Neurosci. Res. 60 (2): 133–40. doi:10.1002/(SICI)1097-4547(20000415)60:2<133::AID-JNR1>3.0.CO;2-3. PMID 10740217.
- Hofmann SL, Atashband A, Cho SK, et al. (2003). "Neuronal ceroid lipofuscinoses caused by defects in soluble lysosomal enzymes (CLN1 and CLN2).". Curr. Mol. Med. 2 (5): 423–37. doi:10.2174/1566524023362294. PMID 12125808.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Page AE, Fuller K, Chambers TJ, Warburton MJ (1993). "Purification and characterization of a tripeptidyl peptidase I from human osteoclastomas: evidence for its role in bone resorption". Arch. Biochem. Biophys. 306 (2): 354–9. doi:10.1006/abbi.1993.1523. PMID 8215436.
- Sleat DE, Donnelly RJ, Lackland H, et al. (1997). "Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis". Science 277 (5333): 1802–5. doi:10.1126/science.277.5333.1802. PMID 9295267.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Rawlings ND, Barrett AJ (1999). "Tripeptidyl-peptidase I is apparently the CLN2 protein absent in classical late-infantile neuronal ceroid lipofuscinosis". Biochim. Biophys. Acta 1429 (2): 496–500. doi:10.1016/S0167-4838(98)00238-6. PMID 9989235.
- Vines DJ, Warburton MJ (1999). "Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are deficient in lysosomal tripeptidyl peptidase I". FEBS Lett. 443 (2): 131–5. doi:10.1016/S0014-5793(98)01683-4. PMID 9989590.
- Sleat DE, Gin RM, Sohar I, et al. (1999). "Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder". Am. J. Hum. Genet. 64 (6): 1511–23. doi:10.1086/302427. PMC 1377895. PMID 10330339. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1377895.
- Junaid MA, Wu G, Pullarkat RK (2000). "Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis". J. Neurochem. 74 (1): 287–94. doi:10.1046/j.1471-4159.2000.0740287.x. PMID 10617131.
- Ezaki J, Takeda-Ezaki M, Oda K, Kominami E (2000). "Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis". Biochem. Biophys. Res. Commun. 268 (3): 904–8. doi:10.1006/bbrc.2000.2207. PMID 10679303.
- Haines JL, Boustany RM, Alroy J, et al. (2000). "Chromosomal localization of two genes underlying late-infantile neuronal ceroid lipofuscinosis". Neurogenetics 1 (3): 217–22. doi:10.1007/s100480050032. PMID 10737126.
- Ezaki J, Takeda-Ezaki M, Kominami E (2000). "Tripeptidyl peptidase I, the late infantile neuronal ceroid lipofuscinosis gene product, initiates the lysosomal degradation of subunit c of ATP synthase". J. Biochem. 128 (3): 509–16. PMID 10965052.
- Lin L, Sohar I, Lackland H, Lobel P (2001). "The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH". J. Biol. Chem. 276 (3): 2249–55. doi:10.1074/jbc.M008562200. PMID 11054422.
- Lam CW, Poon PM, Tong SF, Ko CH (2001). "Two novel CLN2 gene mutations in a Chinese patient with classical late-infantile neuronal ceroid lipofuscinosis". Am. J. Med. Genet. 99 (2): 161–3. doi:10.1002/1096-8628(2001)9999:9999<::AID-AJMG1145>3.0.CO;2-Z. PMID 11241479.
- Zhong N, Moroziewicz DN, Ju W, et al. (2001). "Heterogeneity of late-infantile neuronal ceroid lipofuscinosis". Genet. Med. 2 (6): 312–8. PMID 11339651.
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| 3.4.11-19: Exopeptidase |
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| 3.4.21-24: Endopeptidase |
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| 3.4.99: Unknown |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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| Sphingolipid |
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| NCL |
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| Ceramide synthesis |
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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