TPP1_HUMAN
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 03-AUG-2022, entry version 215.
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>3.0.co;2-7;
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";
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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; 160.
DR DIP; DIP-47434N; -.
DR IntAct; O14773; 62.
DR MINT; O14773; -.
DR STRING; 9606.ENSP00000299427; -.
DR MEROPS; S53.003; -.
DR GlyConnect; 1858; 8 N-Linked glycans (3 sites).
DR GlyGen; O14773; 7 sites, 9 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR iPTMnet; O14773; -.
DR PhosphoSitePlus; O14773; -.
DR BioMuta; TPP1; -.
DR EPD; O14773; -.
DR jPOST; O14773; -.
DR MassIVE; O14773; -.
DR MaxQB; O14773; -.
DR PaxDb; O14773; -.
DR PeptideAtlas; O14773; -.
DR PRIDE; O14773; -.
DR ProteomicsDB; 48224; -. [O14773-1]
DR ProteomicsDB; 48225; -. [O14773-2]
DR Antibodypedia; 23932; 437 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 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; 284324; Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia.
DR Orphanet; 228349; CLN2 disease.
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; HDEMKRM; -.
DR OrthoDB; 1294880at2759; -.
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 BioGRID-ORCS; 1200; 15 hits in 1081 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 203 other tissues.
DR ExpressionAtlas; O14773; baseline and differential.
DR Genevisible; O14773; HS.
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; -; 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 Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF09286; Pro-kuma_activ; 1.
DR SMART; SM00944; Pro-kuma_activ; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51695; SEDOLISIN; 1.
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
