ID TPP1_HUMAN Reviewed; 563 AA. AC O14773; Q53HT1; Q5JAK6; Q6UX56; Q71JP6; Q96C37; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2006, sequence version 2. DT 24-JAN-2024, entry version 223. DE RecName: Full=Tripeptidyl-peptidase 1; DE Short=TPP-1; DE EC=3.4.14.9 {ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}; DE AltName: Full=Cell growth-inhibiting gene 1 protein; DE AltName: Full=Lysosomal pepstatin-insensitive protease; DE Short=LPIC; DE AltName: Full=Tripeptidyl aminopeptidase; DE AltName: Full=Tripeptidyl-peptidase I; DE Short=TPP-I; DE Flags: Precursor; GN Name=TPP1; Synonyms=CLN2; ORFNames=GIG1, UNQ267/PRO304; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANTS RP CLN2 ARG-365 AND TYR-365, AND VARIANT HIS-175. RC TISSUE=Placenta; RX PubMed=9295267; DOI=10.1126/science.277.5333.1802; RA Sleat D.E., Donnelly R.J., Lackland H., Liu C.-G., Sohar I., RA Pullarkat R.K., Lobel P.; RT "Association of mutations in a lysosomal protein with classical late- RT infantile neuronal ceroid lipofuscinosis."; RL Science 277:1802-1805(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=9653647; DOI=10.1006/geno.1998.5328; RA Liu C.-G., Sleat D.E., Donnelly R.J., Lobel P.; RT "Structural organization and sequence of CLN2, the defective gene in RT classical late infantile neuronal ceroid lipofuscinosis."; RL Genomics 50:206-212(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain cortex; RA Junaid M.A., Barua M., Pullarkat R.K.; RT "Bovine brain homolog of the tripeptidyl peptidase I which is deficient in RT the human classic late-infantile neuronal ceroid lipofuscinosis."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kim J.W.; RT "Identification of a human growth inhibition gene 1 (GIG1)."; RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Adipose tissue; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 20-24; 196-200 AND 466-492, FUNCTION, CATALYTIC RP ACTIVITY, ACTIVITY REGULATION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF RP HIS-236; ASP-360; SER-475 AND ASP-517. RX PubMed=11054422; DOI=10.1074/jbc.m008562200; RA Lin L., Sohar I., Lackland H., Lobel P.; RT "The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that RT autoactivates at acidic pH."; RL J. Biol. Chem. 276:2249-2255(2001). RN [9] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=12643545; DOI=10.1021/pr025562r; RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., RA Appella E.; RT "Proteomic analysis of early melanosomes: identification of novel RT melanosomal proteins."; RL J. Proteome Res. 2:69-79(2003). RN [10] RP GLYCOSYLATION AT ASN-443. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [11] RP REVIEW ON VARIANTS. RX PubMed=10477428; RX DOI=10.1002/(sici)1098-1004(1999)14:3<199::aid-humu3>3.0.co;2-a; RA Mole S.E., Mitchison H.M., Munroe P.B.; RT "Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, RT CLN2, CLN3, and CLN5."; RL Hum. Mutat. 14:199-215(1999). RN [12] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [13] RP INTERACTION WITH CLN3. RX PubMed=17237713; DOI=10.1203/pdr.0b013e31802d8a4a; RA Persaud-Sawin D.A., Mousallem T., Wang C., Zucker A., Kominami E., RA Boustany R.M.; RT "Neuronal ceroid lipofuscinosis: a common pathway?"; RL Pediatr. Res. 61:146-152(2007). RN [14] RP INTERACTION WITH CLN5, AND SUBCELLULAR LOCATION. RX PubMed=19941651; DOI=10.1186/1471-2121-10-83; RA Lyly A., von Schantz C., Heine C., Schmiedt M.L., Sipilae T., Jalanko A., RA Kyttaelae A.; RT "Novel interactions of CLN5 support molecular networking between neuronal RT ceroid lipofuscinosis proteins."; RL BMC Cell Biol. 10:83-83(2009). RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-210; ASN-222; ASN-313 AND RP ASN-443. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP CLEAVAGE OF PROPEPTIDE [LARGE SCALE ANALYSIS] AFTER GLY-195, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, RP PROTEOLYTIC CLEAVAGE, ACTIVE SITE, CALCIUM-BINDING SITES, DISULFIDE BONDS, RP AND GLYCOSYLATION AT ASN-210; ASN-286; ASN-313 AND ASN-443. RX PubMed=19038966; DOI=10.1074/jbc.m806947200; RA Pal A., Kraetzner R., Gruene T., Grapp M., Schreiber K., Gronborg M., RA Urlaub H., Becker S., Asif A.R., Gartner J., Sheldrick G.M., Steinfeld R.; RT "Structure of tripeptidyl-peptidase I provides insight into the molecular RT basis of late infantile neuronal ceroid lipofuscinosis."; RL J. Biol. Chem. 284:3976-3984(2009). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 20-563, FUNCTION, CATALYTIC RP ACTIVITY, ACTIVE SITE, DISULFIDE BONDS, CALCIUM-BINDING SITES, SUBUNIT, RP AUTOPROTEOLYTIC CLEAVAGE, AND GLYCOSYLATION AT ASN-210; ASN-286; ASN-313 RP AND ASN-443. RX PubMed=19038967; DOI=10.1074/jbc.m806943200; RA Guhaniyogi J., Sohar I., Das K., Stock A.M., Lobel P.; RT "Crystal structure and autoactivation pathway of the precursor form of RT human tripeptidyl-peptidase 1, the enzyme deficient in late infantile RT ceroid lipofuscinosis."; RL J. Biol. Chem. 284:3985-3997(2009). RN [21] RP VARIANTS CLN2 ARG-77; ASN-287; LYS-343; ARG-365; TYR-365; ASP-385; GLU-389; RP HIS-422; HIS-447; GLU-454 AND LEU-475, AND VARIANT ARG-100. RX PubMed=10330339; DOI=10.1086/302427; RA Sleat D.E., Gin R.M., Sohar I., Wisniewski K., Sklower-Brooks S., RA Pullarkat R.K., Palmer D.N., Lerner T.J., Boustany R.-M.N., Uldall P., RA Siakotos A.N., Donnelly R.J., Lobel P.; RT "Mutational analysis of the defective protease in classic late-infantile RT neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage RT disorder."; RL Am. J. Hum. Genet. 64:1511-1523(1999). RN [22] RP VARIANT CLN2 CYS-206. RX PubMed=10665500; RX DOI=10.1002/1531-8249(200002)47:2<254::aid-ana19>3.3.co;2-z; RA Berry-Kravis E., Sleat D.E., Sohar I., Meyer P., Donnelly R., Lobel P.; RT "Prenatal testing for late infantile neuronal ceroid lipofuscinosis."; RL Ann. Neurol. 47:254-257(2000). RN [23] RP VARIANTS CLN2 GLN-127; VAL-284; ASN-428 AND ARG-473. RX PubMed=11339651; DOI=10.1097/00125817-200011000-00002; RA Zhong N., Moroziewicz D.N., Ju W., Jurkiewicz A., Johnston L., RA Wisniewski K.E., Brown W.T.; RT "Heterogeneity of late-infantile neuronal ceroid lipofuscinosis."; RL Genet. Med. 2:312-318(2000). RN [24] RP VARIANT CLN2 ARG-473. RX PubMed=11241479; RX DOI=10.1002/1096-8628(2001)9999:9999<::aid-ajmg1145>3.0.co;2-z; RA Lam C.W., Poon P.M., Tong S.F., Ko C.H.; RT "Two novel CLN2 gene mutations in a Chinese patient with classical late- RT infantile neuronal ceroid lipofuscinosis."; RL Am. J. Med. Genet. 99:161-163(2001). RN [25] RP VARIANT CLN2 LEU-202. RX PubMed=11589012; DOI=10.1053/ejpn.2000.0427; RA Mole S.E., Zhong N.A., Sarpong A., Logan W.P., Hofmann S., Yi W., RA Franken P.F., van Diggelen O.P., Breuning M.H., Moroziewicz D., Ju W., RA Salonen T., Holmberg V., Jaervelae I., Taschner P.E.M.; RT "New mutations in the neuronal ceroid lipofuscinosis genes."; RL Eur. J. Paediatr. Neurol. 5:7-10(2001). RN [26] RP CHARACTERIZATION OF VARIANTS ARG-100; GLU-389 AND HIS-447. RX PubMed=11462245; DOI=10.1002/humu.1170; RA Lin L., Lobel P.; RT "Expression and analysis of CLN2 variants in CHO cells: Q100R represents a RT polymorphism, and G389E and R447H represent loss-of-function mutations."; RL Hum. Mutat. 18:165-165(2001). RN [27] RP VARIANTS CLN2 GLN-127; SER-286 AND PRO-353. RX PubMed=12376936; DOI=10.1002/ajmg.10660; RA Steinfeld R., Heim P., von Gregory H., Meyer K., Ullrich K., Goebel H.H., RA Kohlschutter A.; RT "Late infantile neuronal ceroid lipofuscinosis: quantitative description of RT the clinical course in patients with CLN2 mutations."; RL Am. J. Med. Genet. 112:347-354(2002). RN [28] RP VARIANTS CLN2 MET-277; PRO-278; VAL-284 AND CYS-481. RX PubMed=12414822; DOI=10.1136/jmg.39.11.822; RA Ju W., Zhong R., Moore S., Moroziewicz D., Currie J.R., Parfrey P., RA Brown W.T., Zhong N.; RT "Identification of novel CLN2 mutations shows Canadian specific NCL2 RT alleles."; RL J. Med. Genet. 39:822-825(2002). RN [29] RP VARIANT CLN2 HIS-206. RX PubMed=12698559; RA Bukina A.M., Tsvetkova I.V., Semiachkina A.N., Il'ina E.S.; RT "Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A RT novel mutation."; RL Vopr. Med. Khim. 48:594-598(2002). RN [30] RP CHARACTERIZATION OF VARIANT CLN2 SER-286. RX PubMed=14736728; DOI=10.1093/glycob/cwh054; RA Tsiakas K., Steinfeld R., Storch S., Ezaki J., Lukacs Z., Kominami E., RA Kohlschuetter A., Ullrich K., Braulke T.; RT "Mutation of the glycosylated asparagine residue 286 in human CLN2 protein RT results in loss of enzymatic activity."; RL Glycobiology 14:1C-5C(2004). RN [31] RP VARIANT CLN2 ARG-482. RX PubMed=19201763; DOI=10.1093/brain/awn366; RA Kousi M., Siintola E., Dvorakova L., Vlaskova H., Turnbull J., Topcu M., RA Yuksel D., Gokben S., Minassian B.A., Elleder M., Mole S.E., RA Lehesjoki A.-E.; RT "Mutations in CLN7/MFSD8 are a common cause of variant late-infantile RT neuronal ceroid lipofuscinosis."; RL Brain 132:810-819(2009). RN [32] RP VARIANT CLN2 SER-544, AND CHARACTERIZATION OF VARIANTS CLN2 ARG-77; RP GLN-127; LEU-202; CYS-206; MET-277; VAL-284; SER-286; ASN-287; LYS-343; RP ARG-365; HIS-422; HIS-447; LEU-475 AND SER-544. RX PubMed=20340139; DOI=10.1002/humu.21251; RA Walus M., Kida E., Golabek A.A.; RT "Functional consequences and rescue potential of pathogenic missense RT mutations in tripeptidyl peptidase I."; RL Hum. Mutat. 31:710-721(2010). RN [33] RP VARIANTS CLN2 ARG-278 AND HIS-422. RX PubMed=22612257; DOI=10.1111/j.1528-1167.2012.03516.x; RA Lemke J.R., Riesch E., Scheurenbrand T., Schubach M., Wilhelm C., RA Steiner I., Hansen J., Courage C., Gallati S., Buerki S., Strozzi S., RA Simonetti B.G., Grunt S., Steinlin M., Alber M., Wolff M., Klopstock T., RA Prott E.C., Lorenz R., Spaich C., Rona S., Lakshminarasimhan M., Kroell J., RA Dorn T., Kraemer G., Synofzik M., Becker F., Weber Y.G., Lerche H., RA Boehm D., Biskup S.; RT "Targeted next generation sequencing as a diagnostic tool in epileptic RT disorders."; RL Epilepsia 53:1387-1398(2012). RN [34] RP VARIANTS CLN2 THR-62; HIS-209; GLN-266; GLN-339; ARG-382; VAL-448; CYS-501; RP TYR-504 AND ARG-548. RX PubMed=21990111; DOI=10.1002/humu.21624; RA Kousi M., Lehesjoki A.E., Mole S.E.; RT "Update of the mutation spectrum and clinical correlations of over 360 RT mutations in eight genes that underlie the neuronal ceroid RT lipofuscinoses."; RL Hum. Mutat. 33:42-63(2012). RN [35] RP VARIANT SCAR7 GLY-466. RX PubMed=23418007; DOI=10.1002/humu.22292; RA Sun Y., Almomani R., Breedveld G.J., Santen G.W., Aten E., Lefeber D.J., RA Hoff J.I., Brusse E., Verheijen F.W., Verdijk R.M., Kriek M., Oostra B., RA Breuning M.H., Losekoot M., den Dunnen J.T., van de Warrenburg B.P., RA Maat-Kievit A.J.; RT "Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants RT in TPP1, the gene involved in classic late-infantile neuronal ceroid RT lipofuscinosis 2 disease (CLN2 disease)."; RL Hum. Mutat. 34:706-713(2013). CC -!- FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I CC activity (PubMed:11054422, PubMed:19038966, PubMed:19038967). May act CC as a non-specific lysosomal peptidase which generates tripeptides from CC the breakdown products produced by lysosomal proteinases CC (PubMed:11054422, PubMed:19038966, PubMed:19038967). Requires CC substrates with an unsubstituted N-terminus (PubMed:19038966). CC {ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, CC ECO:0000269|PubMed:19038967}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of an N-terminal tripeptide from a polypeptide, but CC also has endopeptidase activity.; EC=3.4.14.9; CC Evidence={ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, CC ECO:0000269|PubMed:19038967}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}; CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:19038966, CC ECO:0000269|PubMed:19038967}; CC -!- ACTIVITY REGULATION: Inhibited by diisopropyl fluorophosphate (DFP). CC {ECO:0000269|PubMed:11054422}. CC -!- SUBUNIT: Monomer (PubMed:19038967). Interacts with CLN5 CC (PubMed:19941651). Interacts with CLN3 (PubMed:17237713). CC {ECO:0000269|PubMed:17237713, ECO:0000269|PubMed:19038967, CC ECO:0000269|PubMed:19941651}. CC -!- INTERACTION: CC O14773; Q9NWX5-2: ASB6; NbExp=3; IntAct=EBI-2800203, EBI-25838672; CC O14773; Q53EZ4: CEP55; NbExp=3; IntAct=EBI-2800203, EBI-747776; CC O14773; Q9NSE2: CISH; NbExp=3; IntAct=EBI-2800203, EBI-617866; CC O14773; Q9UKA2: FBXL4; NbExp=3; IntAct=EBI-2800203, EBI-2869903; CC O14773; Q6P3S6: FBXO42; NbExp=3; IntAct=EBI-2800203, EBI-2506081; CC O14773; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-2800203, EBI-1058491; CC O14773; Q96D59: RNF183; NbExp=3; IntAct=EBI-2800203, EBI-743938; CC O14773; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-2800203, EBI-3650647; CC O14773; P45974-2: USP5; NbExp=3; IntAct=EBI-2800203, EBI-12072186; CC O14773; O00308: WWP2; NbExp=3; IntAct=EBI-2800203, EBI-743923; CC O14773; Q8NAP3: ZBTB38; NbExp=3; IntAct=EBI-2800203, EBI-5235984; CC O14773; E5LBV4: ORF31; Xeno; NbExp=2; IntAct=EBI-2800203, EBI-14033503; CC O14773-1; Q2NKJ3-1: CTC1; NbExp=3; IntAct=EBI-15619703, EBI-15994382; CC O14773-1; Q9H668: STN1; NbExp=2; IntAct=EBI-15619703, EBI-746930; CC O14773-1; O14746: TERT; NbExp=2; IntAct=EBI-15619703, EBI-1772203; CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:19941651}. CC Melanosome {ECO:0000269|PubMed:12643545}. Note=Identified by mass CC spectrometry in melanosome fractions from stage I to stage IV. CC {ECO:0000269|PubMed:12643545}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O14773-1; Sequence=Displayed; CC Name=2; CC IsoId=O14773-2; Sequence=VSP_013118; CC -!- TISSUE SPECIFICITY: Detected in all tissues examined with highest CC levels in heart and placenta and relatively similar levels in other CC tissues. CC -!- PTM: Activated by autocatalytic proteolytical processing upon CC acidification (PubMed:11054422, PubMed:19038966, PubMed:19038967). N- CC glycosylation is required for processing and activity (PubMed:19038966, CC PubMed:19038967). {ECO:0000269|PubMed:11054422, CC ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}. CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 2 (CLN2) [MIM:204500]: A form CC of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are CC progressive neurodegenerative, lysosomal storage diseases characterized CC by intracellular accumulation of autofluorescent liposomal material, CC and clinically by seizures, dementia, visual loss, and/or cerebral CC atrophy. The lipopigment pattern seen most often in CLN2 consists of CC curvilinear profiles. {ECO:0000269|PubMed:10330339, CC ECO:0000269|PubMed:10665500, ECO:0000269|PubMed:11241479, CC ECO:0000269|PubMed:11339651, ECO:0000269|PubMed:11589012, CC ECO:0000269|PubMed:12376936, ECO:0000269|PubMed:12414822, CC ECO:0000269|PubMed:12698559, ECO:0000269|PubMed:14736728, CC ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:20340139, CC ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:22612257, CC ECO:0000269|PubMed:9295267}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 7 (SCAR7) CC [MIM:609270]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders. Patients show CC progressive incoordination of gait and often poor coordination of CC hands, speech and eye movements, due to degeneration of the cerebellum CC with variable involvement of the brainstem and spinal cord. SCAR7 CC patients show difficulty walking and writing, dysarthria, limb ataxia, CC and cerebellar atrophy. {ECO:0000269|PubMed:23418007}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAM08412.1; Type=Miscellaneous discrepancy; Note=Incorrectly indicated as originating from bovine.; Evidence={ECO:0000305}; CC Sequence=AAQ88866.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NCL CLN2; Note=Neural Ceroid Lipofuscinoses mutation CC db; CC URL="https://www.ucl.ac.uk/ncl/cln2.shtml"; CC -!- WEB RESOURCE: Name=Mendelian genes trieptidyl peptidase I (TPP1); CC Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/TPP1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF017456; AAB80725.1; -; mRNA. DR EMBL; AF039704; AAC98480.1; -; Genomic_DNA. DR EMBL; AF491290; AAM08412.1; ALT_SEQ; mRNA. DR EMBL; AY268890; AAQ72732.1; -; mRNA. DR EMBL; AY358502; AAQ88866.1; ALT_FRAME; mRNA. DR EMBL; AK222499; BAD96219.1; -; mRNA. DR EMBL; BC014863; AAH14863.1; -; mRNA. DR CCDS; CCDS7770.1; -. [O14773-1] DR RefSeq; NP_000382.3; NM_000391.3. [O14773-1] DR PDB; 3EDY; X-ray; 1.85 A; A=20-563. DR PDB; 3EE6; X-ray; 2.35 A; A/B=1-563. DR PDBsum; 3EDY; -. DR PDBsum; 3EE6; -. DR AlphaFoldDB; O14773; -. DR SMR; O14773; -. DR BioGRID; 107611; 169. DR DIP; DIP-47434N; -. DR IntAct; O14773; 65. DR MINT; O14773; -. DR STRING; 9606.ENSP00000299427; -. DR MEROPS; S53.003; -. DR GlyConnect; 1858; 8 N-Linked glycans (3 sites). DR GlyCosmos; O14773; 5 sites, 9 glycans. DR GlyGen; O14773; 8 sites, 9 N-linked glycans (3 sites), 2 O-linked glycans (2 sites). DR iPTMnet; O14773; -. DR PhosphoSitePlus; O14773; -. DR BioMuta; TPP1; -. DR EPD; O14773; -. DR jPOST; O14773; -. DR MassIVE; O14773; -. DR MaxQB; O14773; -. DR PaxDb; 9606-ENSP00000299427; -. DR PeptideAtlas; O14773; -. DR ProteomicsDB; 48224; -. [O14773-1] DR ProteomicsDB; 48225; -. [O14773-2] DR Pumba; O14773; -. DR Antibodypedia; 23932; 463 antibodies from 39 providers. DR DNASU; 1200; -. DR Ensembl; ENST00000299427.12; ENSP00000299427.6; ENSG00000166340.18. [O14773-1] DR Ensembl; ENST00000533371.6; ENSP00000437066.1; ENSG00000166340.18. [O14773-2] DR Ensembl; ENST00000642892.1; ENSP00000494165.1; ENSG00000166340.18. [O14773-2] DR Ensembl; ENST00000645620.1; ENSP00000493657.1; ENSG00000166340.18. [O14773-2] DR Ensembl; ENST00000647152.1; ENSP00000495893.1; ENSG00000166340.18. [O14773-2] DR GeneID; 1200; -. DR KEGG; hsa:1200; -. DR MANE-Select; ENST00000299427.12; ENSP00000299427.6; NM_000391.4; NP_000382.3. DR UCSC; uc001mek.2; human. [O14773-1] DR AGR; HGNC:2073; -. DR CTD; 1200; -. DR DisGeNET; 1200; -. DR GeneCards; TPP1; -. DR HGNC; HGNC:2073; TPP1. DR HPA; ENSG00000166340; Low tissue specificity. DR MalaCards; TPP1; -. DR MIM; 204500; phenotype. DR MIM; 607998; gene. DR MIM; 609270; phenotype. DR neXtProt; NX_O14773; -. DR OpenTargets; ENSG00000166340; -. DR Orphanet; 79262; Adult neuronal ceroid lipofuscinosis. DR Orphanet; 284324; Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia. DR Orphanet; 168486; Congenital neuronal ceroid lipofuscinosis. DR Orphanet; 79263; Infantile neuronal ceroid lipofuscinosis. DR Orphanet; 79264; Juvenile neuronal ceroid lipofuscinosis. DR Orphanet; 168491; Late infantile neuronal ceroid lipofuscinosis. DR PharmGKB; PA26600; -. DR VEuPathDB; HostDB:ENSG00000166340; -. DR eggNOG; ENOG502QR6D; Eukaryota. DR GeneTree; ENSGT00390000008684; -. DR HOGENOM; CLU_013783_5_1_1; -. DR InParanoid; O14773; -. DR OMA; YARSVCN; -. DR OrthoDB; 1405251at2759; -. DR PhylomeDB; O14773; -. DR TreeFam; TF333497; -. DR BRENDA; 3.4.14.9; 2681. DR PathwayCommons; O14773; -. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR SABIO-RK; O14773; -. DR SignaLink; O14773; -. DR SIGNOR; O14773; -. DR BioGRID-ORCS; 1200; 15 hits in 1161 CRISPR screens. DR ChiTaRS; TPP1; human. DR EvolutionaryTrace; O14773; -. DR GeneWiki; Tripeptidyl_peptidase_I; -. DR GenomeRNAi; 1200; -. DR Pharos; O14773; Tbio. DR PRO; PR:O14773; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O14773; Protein. DR Bgee; ENSG00000166340; Expressed in pigmented layer of retina and 205 other cell types or tissues. DR ExpressionAtlas; O14773; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:0035727; F:lysophosphatidic acid binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008233; F:peptidase activity; IMP:UniProtKB. DR GO; GO:0042277; F:peptide binding; ISS:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0008236; F:serine-type peptidase activity; IMP:UniProtKB. DR GO; GO:0120146; F:sulfatide binding; IDA:UniProtKB. DR GO; GO:0008240; F:tripeptidyl-peptidase activity; IDA:UniProtKB. DR GO; GO:0045453; P:bone resorption; IMP:UniProtKB. DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central. DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc. DR GO; GO:1905146; P:lysosomal protein catabolic process; IEA:Ensembl. DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB. DR GO; GO:0050885; P:neuromuscular process controlling balance; ISS:UniProtKB. DR GO; GO:0043171; P:peptide catabolic process; IMP:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; NAS:UniProtKB. DR GO; GO:0070198; P:protein localization to chromosome, telomeric region; IMP:CACAO. DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB. DR CDD; cd04056; Peptidases_S53; 1. DR CDD; cd11377; Pro-peptidase_S53; 1. DR Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1. DR InterPro; IPR000209; Peptidase_S8/S53_dom. DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf. DR InterPro; IPR015366; S53_propep. DR InterPro; IPR030400; Sedolisin_dom. DR PANTHER; PTHR14218; PROTEASE S8 TRIPEPTIDYL PEPTIDASE I CLN2; 1. DR PANTHER; PTHR14218:SF15; TRIPEPTIDYL-PEPTIDASE 1; 1. DR Pfam; PF00082; Peptidase_S8; 1. DR Pfam; PF09286; Pro-kuma_activ; 1. DR SMART; SM00944; Pro-kuma_activ; 1. DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1. DR SUPFAM; SSF52743; Subtilisin-like; 1. DR PROSITE; PS51695; SEDOLISIN; 1. DR Genevisible; O14773; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autocatalytic cleavage; Calcium; KW Direct protein sequencing; Disease variant; Disulfide bond; Epilepsy; KW Glycoprotein; Hydrolase; Lysosome; Metal-binding; Neurodegeneration; KW Neuronal ceroid lipofuscinosis; Protease; Reference proteome; KW Serine protease; Signal; Spinocerebellar ataxia; Zymogen. FT SIGNAL 1..19 FT /evidence="ECO:0000269|PubMed:11054422" FT PROPEP 20..195 FT /note="Removed in mature form" FT /evidence="ECO:0000269|PubMed:11054422, FT ECO:0007744|PubMed:25944712" FT /id="PRO_0000027374" FT CHAIN 196..563 FT /note="Tripeptidyl-peptidase 1" FT /id="PRO_0000027375" FT DOMAIN 199..563 FT /note="Peptidase S53" FT ACT_SITE 272 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT ACT_SITE 276 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT ACT_SITE 475 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967, ECO:0000305|PubMed:11054422" FT BINDING 517 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT BINDING 518 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT BINDING 539 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT BINDING 541 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT BINDING 543 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT CARBOHYD 210 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967, ECO:0000269|PubMed:19159218" FT CARBOHYD 222 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 286 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT CARBOHYD 313 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967, ECO:0000269|PubMed:19159218" FT CARBOHYD 443 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967, FT ECO:0000269|PubMed:19159218" FT DISULFID 111..122 FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT DISULFID 365..526 FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT DISULFID 522..537 FT /evidence="ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967" FT VAR_SEQ 1..243 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_013118" FT VARIANT 62 FT /note="S -> L (in dbSNP:rs2734715)" FT /id="VAR_037572" FT VARIANT 62 FT /note="S -> T (in CLN2)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066883" FT VARIANT 77 FT /note="G -> R (in CLN2; displays very low residual enzyme FT activity; altered intracellular trafficking; FT dbSNP:rs121908195)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139" FT /id="VAR_009603" FT VARIANT 100 FT /note="Q -> R (in dbSNP:rs1800746)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:11462245" FT /id="VAR_009604" FT VARIANT 127 FT /note="R -> Q (in CLN2; displays residual enzyme activity; FT effectively transported to the lysosome; FT dbSNP:rs121908204)" FT /evidence="ECO:0000269|PubMed:11339651, FT ECO:0000269|PubMed:12376936, ECO:0000269|PubMed:20340139" FT /id="VAR_016790" FT VARIANT 153 FT /note="S -> P (in CLN2; dbSNP:rs1554902028)" FT /id="VAR_016791" FT VARIANT 175 FT /note="R -> H (in dbSNP:rs764922748)" FT /evidence="ECO:0000269|PubMed:9295267" FT /id="VAR_005642" FT VARIANT 185 FT /note="R -> C (in dbSNP:rs34758634)" FT /id="VAR_037573" FT VARIANT 202 FT /note="P -> L (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking; FT dbSNP:rs121908205)" FT /evidence="ECO:0000269|PubMed:11589012, FT ECO:0000269|PubMed:20340139" FT /id="VAR_063640" FT VARIANT 206 FT /note="R -> C (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking; FT dbSNP:rs28940573)" FT /evidence="ECO:0000269|PubMed:10665500, FT ECO:0000269|PubMed:20340139" FT /id="VAR_009605" FT VARIANT 206 FT /note="R -> H (in CLN2; dbSNP:rs121908209)" FT /evidence="ECO:0000269|PubMed:12698559" FT /id="VAR_016792" FT VARIANT 209 FT /note="Y -> H (in CLN2; dbSNP:rs1218678626)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066884" FT VARIANT 266 FT /note="R -> Q (in CLN2; dbSNP:rs757953998)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066885" FT VARIANT 277 FT /note="V -> M (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking; demonstrates FT enhanced processing in response to folding improvement FT treatment; dbSNP:rs121908207)" FT /evidence="ECO:0000269|PubMed:12414822, FT ECO:0000269|PubMed:20340139" FT /id="VAR_016793" FT VARIANT 278 FT /note="Q -> P (in CLN2; dbSNP:rs796053439)" FT /evidence="ECO:0000269|PubMed:12414822" FT /id="VAR_016794" FT VARIANT 278 FT /note="Q -> R (in CLN2; dbSNP:rs796053439)" FT /evidence="ECO:0000269|PubMed:22612257" FT /id="VAR_072749" FT VARIANT 284 FT /note="G -> V (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking; FT dbSNP:rs119455957)" FT /evidence="ECO:0000269|PubMed:11339651, FT ECO:0000269|PubMed:12414822, ECO:0000269|PubMed:20340139" FT /id="VAR_016795" FT VARIANT 286 FT /note="N -> S (in CLN2; enzymatically inactive; lacks one FT oligosaccharide chain resulting in enzymatic inactivation FT and possibly prelysosomal protein degradation; altered FT intracellular trafficking; dbSNP:rs119455958)" FT /evidence="ECO:0000269|PubMed:12376936, FT ECO:0000269|PubMed:14736728, ECO:0000269|PubMed:20340139" FT /id="VAR_016796" FT VARIANT 287 FT /note="I -> N (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking; FT dbSNP:rs121908196)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139" FT /id="VAR_009606" FT VARIANT 339 FT /note="R -> Q (in CLN2; dbSNP:rs765380155)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066886" FT VARIANT 343 FT /note="E -> K (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking; FT dbSNP:rs121908197)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139" FT /id="VAR_009607" FT VARIANT 353 FT /note="T -> P (in CLN2; dbSNP:rs121908206)" FT /evidence="ECO:0000269|PubMed:12376936" FT /id="VAR_016797" FT VARIANT 365 FT /note="C -> R (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking; FT dbSNP:rs119455953)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139, ECO:0000269|PubMed:9295267" FT /id="VAR_005643" FT VARIANT 365 FT /note="C -> Y (in CLN2; dbSNP:rs119455954)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:9295267" FT /id="VAR_005644" FT VARIANT 382 FT /note="S -> R (in CLN2)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066887" FT VARIANT 385 FT /note="V -> D (in CLN2; dbSNP:rs121908198)" FT /evidence="ECO:0000269|PubMed:10330339" FT /id="VAR_009608" FT VARIANT 389 FT /note="G -> E (in CLN2; dbSNP:rs121908199)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:11462245" FT /id="VAR_009609" FT VARIANT 422 FT /note="Q -> H (in CLN2; displays no residual enzyme FT activity; altered intracellular trafficking;; FT dbSNP:rs121908200)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139, ECO:0000269|PubMed:22612257" FT /id="VAR_009610" FT VARIANT 428 FT /note="K -> N (in CLN2)" FT /evidence="ECO:0000269|PubMed:11339651" FT /id="VAR_016798" FT VARIANT 447 FT /note="R -> H (in CLN2; displays very low residual enzyme FT activity; altered intracellular trafficking; demonstrates FT enhanced processing in response to folding improvement FT treatment; shows a five fold increase under permissive FT temperature conditions; dbSNP:rs119455956)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:11462245, ECO:0000269|PubMed:20340139" FT /id="VAR_005645" FT VARIANT 448 FT /note="A -> V (in CLN2)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066888" FT VARIANT 454 FT /note="A -> E (in CLN2; dbSNP:rs121908201)" FT /evidence="ECO:0000269|PubMed:10330339" FT /id="VAR_009611" FT VARIANT 466 FT /note="V -> G (in SCAR7; dbSNP:rs398122959)" FT /evidence="ECO:0000269|PubMed:23418007" FT /id="VAR_070917" FT VARIANT 473 FT /note="G -> R (in CLN2; dbSNP:rs121908203)" FT /evidence="ECO:0000269|PubMed:11241479, FT ECO:0000269|PubMed:11339651" FT /id="VAR_016799" FT VARIANT 475 FT /note="S -> L (in CLN2; displays no residual enzyme FT activity; effectively transported to the lysosome; FT dbSNP:rs121908202)" FT /evidence="ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139" FT /id="VAR_009612" FT VARIANT 481 FT /note="F -> C (in CLN2)" FT /evidence="ECO:0000269|PubMed:12414822" FT /id="VAR_016800" FT VARIANT 482 FT /note="G -> R (in CLN2; dbSNP:rs121908208)" FT /evidence="ECO:0000269|PubMed:19201763" FT /id="VAR_058435" FT VARIANT 501 FT /note="G -> C (in CLN2)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066889" FT VARIANT 504 FT /note="N -> Y (in CLN2)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066890" FT VARIANT 544 FT /note="P -> S (in CLN2; displays residual enzyme activity; FT effectively transported to the lysosome; FT dbSNP:rs121908210)" FT /evidence="ECO:0000269|PubMed:20340139" FT /id="VAR_063641" FT VARIANT 548 FT /note="W -> R (in CLN2; dbSNP:rs1348967263)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066891" FT MUTAGEN 236 FT /note="H->A: No effect." FT /evidence="ECO:0000269|PubMed:11054422" FT MUTAGEN 360 FT /note="D->A: Inactive. Impaired processing." FT /evidence="ECO:0000269|PubMed:11054422" FT MUTAGEN 475 FT /note="S->A: Inactive. Impaired processing." FT /evidence="ECO:0000269|PubMed:11054422" FT MUTAGEN 517 FT /note="D->A: Inactive. Impaired processing." FT /evidence="ECO:0000269|PubMed:11054422" FT CONFLICT 115 FT /note="I -> N (in Ref. 6; BAD96219)" FT /evidence="ECO:0000305" FT CONFLICT 373 FT /note="Q -> E (in Ref. 7; AAH14863)" FT /evidence="ECO:0000305" FT STRAND 35..40 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 46..53 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 58..69 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 74..77 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 82..89 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 93..106 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 109..113 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 119..125 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 126..132 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 139..143 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 144..147 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 148..152 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 161..163 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 164..166 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 167..170 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 202..208 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 219..221 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 224..229 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 237..247 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 258..262 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 271..283 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 284..286 FT /evidence="ECO:0007829|PDB:3EE6" FT STRAND 287..292 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 295..300 FT /evidence="ECO:0007829|PDB:3EE6" FT HELIX 303..311 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 319..324 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 329..331 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 334..349 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 353..357 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 366..368 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 371..373 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 379..381 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 385..397 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 402..404 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 411..417 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 420..422 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 423..432 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 439..441 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 446..449 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 451..455 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 457..463 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 466..471 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 474..494 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 504..509 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 510..514 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 522..525 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 529..533 FT /evidence="ECO:0007829|PDB:3EDY" FT STRAND 534..537 FT /evidence="ECO:0007829|PDB:3EDY" FT TURN 544..546 FT /evidence="ECO:0007829|PDB:3EDY" FT HELIX 553..558 FT /evidence="ECO:0007829|PDB:3EDY" SQ SEQUENCE 563 AA; 61248 MW; 7299D902F6AE8555 CRC64; MGLQACLLGL FALILSGKCS YSPEPDQRRT LPPGWVSLGR ADPEEELSLT FALRQQNVER LSELVQAVSD PSSPQYGKYL TLENVADLVR PSPLTLHTVQ KWLLAAGAQK CHSVITQDFL TCWLSIRQAE LLLPGAEFHH YVGGPTETHV VRSPHPYQLP QALAPHVDFV GGLHRFPPTS SLRQRPEPQV TGTVGLHLGV TPSVIRKRYN LTSQDVGSGT SNNSQACAQF LEQYFHDSDL AQFMRLFGGN FAHQASVARV VGQQGRGRAG IEASLDVQYL MSAGANISTW VYSSPGRHEG QEPFLQWLML LSNESALPHV HTVSYGDDED SLSSAYIQRV NTELMKAAAR GLTLLFASGD SGAGCWSVSG RHQFRPTFPA SSPYVTTVGG TSFQEPFLIT NEIVDYISGG GFSNVFPRPS YQEEAVTKFL SSSPHLPPSS YFNASGRAYP DVAALSDGYW VVSNRVPIPW VSGTSASTPV FGGILSLINE HRILSGRPPL GFLNPRLYQQ HGAGLFDVTR GCHESCLDEE VEGQGFCSGP GWDPVTGWGT PNFPALLKTL LNP //