3ee6

Structural highlights

Disease

[TPP1_HUMAN] Defects in TPP1 are the cause of neuronal ceroid lipofuscinosis type 2 (CLN2) [MIM:204500]. A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]}

Function

[TPP1_HUMAN] Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires substrates with an unsubstituted N-terminus (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Tripeptidyl peptidase

References

1. ↑ Sleat DE, Donnelly RJ, Lackland H, Liu CG, Sohar I, Pullarkat RK, Lobel P. Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science. 1997 Sep 19;277(5333):1802-5. PMID:9295267
2. ↑ Sleat DE, Gin RM, Sohar I, Wisniewski K, Sklower-Brooks S, Pullarkat RK, Palmer DN, Lerner TJ, Boustany RM, Uldall P, Siakotos AN, Donnelly RJ, Lobel P. Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. Am J Hum Genet. 1999 Jun;64(6):1511-23. PMID:10330339 doi:10.1086/302427
3. ↑ Berry-Kravis E, Sleat DE, Sohar I, Meyer P, Donnelly R, Lobel P. Prenatal testing for late infantile neuronal ceroid lipofuscinosis. Ann Neurol. 2000 Feb;47(2):254-7. PMID:10665500
4. ↑ Zhong N, Moroziewicz DN, Ju W, Jurkiewicz A, Johnston L, Wisniewski KE, Brown WT. Heterogeneity of late-infantile neuronal ceroid lipofuscinosis. Genet Med. 2000 Nov-Dec;2(6):312-8. PMID:11339651
5. ↑ Lam CW, Poon PM, Tong SF, Ko CH. Two novel CLN2 gene mutations in a Chinese patient with classical late-infantile neuronal ceroid lipofuscinosis. Am J Med Genet. 2001 Mar 1;99(2):161-3. PMID:11241479
6. ↑ Mole SE, Zhong NA, Sarpong A, Logan WP, Hofmann S, Yi W, Franken PF, van Diggelen OP, Breuning MH, Moroziewicz D, Ju W, Salonen T, Holmberg V, Jarvela I, Taschner PE. New mutations in the neuronal ceroid lipofuscinosis genes. Eur J Paediatr Neurol. 2001;5 Suppl A:7-10. PMID:11589012
7. ↑ Steinfeld R, Heim P, von Gregory H, Meyer K, Ullrich K, Goebel HH, Kohlschutter A. Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. Am J Med Genet. 2002 Nov 1;112(4):347-54. PMID:12376936 doi:10.1002/ajmg.10660
8. ↑ Ju W, Zhong R, Moore S, Moroziewicz D, Currie JR, Parfrey P, Brown WT, Zhong N. Identification of novel CLN2 mutations shows Canadian specific NCL2 alleles. J Med Genet. 2002 Nov;39(11):822-5. PMID:12414822
9. ↑ Bukina AM, Tsvetkova IV, Semiachkina AN, Il'ina ES. [Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation]. Vopr Med Khim. 2002 Nov-Dec;48(6):594-8. PMID:12698559
10. ↑ Tsiakas K, Steinfeld R, Storch S, Ezaki J, Lukacs Z, Kominami E, Kohlschutter A, Ullrich K, Braulke T. Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity. Glycobiology. 2004 Apr;14(4):1C-5C. Epub 2004 Jan 21. PMID:14736728 doi:10.1093/glycob/cwh054
11. ↑ Kousi M, Siintola E, Dvorakova L, Vlaskova H, Turnbull J, Topcu M, Yuksel D, Gokben S, Minassian BA, Elleder M, Mole SE, Lehesjoki AE. Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis. Brain. 2009 Mar;132(Pt 3):810-9. doi: 10.1093/brain/awn366. Epub 2009 Feb 5. PMID:19201763 doi:10.1093/brain/awn366
12. ↑ Walus M, Kida E, Golabek AA. Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I. Hum Mutat. 2010 Jun;31(6):710-21. doi: 10.1002/humu.21251. PMID:20340139 doi:10.1002/humu.21251
13. ↑ Kousi M, Lehesjoki AE, Mole SE. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. PMID:21990111 doi:10.1002/humu.21624
14. ↑ Pal A, Kraetzner R, Gruene T, Grapp M, Schreiber K, Gronborg M, Urlaub H, Becker S, Asif AR, Gartner J, Sheldrick GM, Steinfeld R. Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. J Biol Chem. 2009 Feb 6;284(6):3976-84. Epub 2008 Nov 26. PMID:19038966 doi:10.1074/jbc.M806947200