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 13-FEB-2019, entry version 195. DE RecName: Full=Tripeptidyl-peptidase 1; DE Short=TPP-1; DE EC=3.4.14.9; 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, RP VARIANTS 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 RT deficient in the human classic late-infantile neuronal ceroid RT 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics 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 RT project: 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, MUTAGENESIS, AND RP CHARACTERIZATION. 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 RT that 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., RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., RA Hearing V.J., Hunt D.F., 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 RT CLN1, 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., RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., RA 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 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., RA Jalanko A., Kyttaelae A.; RT "Novel interactions of CLN5 support molecular networking between RT neuronal ceroid lipofuscinosis proteins."; RL BMC Cell Biol. 10:83-83(2009). RN [14] 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 RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [15] 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., RA Buerckstuemmer T., 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 [16] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] 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., RA Ayoub D., 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 [18] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS), ACTIVE SITE, CALCIUM-BINDING RP SITES, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-210; ASN-286; ASN-313 RP 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., RA Steinfeld R.; RT "Structure of tripeptidyl-peptidase I provides insight into the RT molecular basis of late infantile neuronal ceroid lipofuscinosis."; RL J. Biol. Chem. 284:3976-3984(2009). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 20-563, ACTIVE SITE, RP DISULFIDE BONDS, CALCIUM-BINDING SITES, SUBUNIT, AUTOPROTEOLYTIC RP CLEAVAGE, AND GLYCOSYLATION AT ASN-210; ASN-286; ASN-313 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 [20] RP VARIANTS CLN2 ARG-77; ASN-287; LYS-343; ARG-365; TYR-365; ASP-385; RP GLU-389; 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- RT infantile neuronal ceroid lipofuscinosis, a neurodegenerative RT lysosomal storage disorder."; RL Am. J. Hum. Genet. 64:1511-1523(1999). RN [21] 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., RA Lobel P.; RT "Prenatal testing for late infantile neuronal ceroid lipofuscinosis."; RL Ann. Neurol. 47:254-257(2000). RN [22] 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 [23] 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 RT late-infantile neuronal ceroid lipofuscinosis."; RL Am. J. Med. Genet. 99:161-163(2001). RN [24] 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 [25] 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 RT represents a polymorphism, and G389E and R447H represent loss-of- RT function mutations."; RL Hum. Mutat. 18:165-165(2001). RN [26] 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., RA Goebel H.H., Kohlschutter A.; RT "Late infantile neuronal ceroid lipofuscinosis: quantitative RT description of the clinical course in patients with CLN2 mutations."; RL Am. J. Med. Genet. 112:347-354(2002). RN [27] 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 [28] 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. RT A novel mutation."; RL Vopr. Med. Khim. 48:594-598(2002). RN [29] 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 RT protein results in loss of enzymatic activity."; RL Glycobiology 14:1C-5C(2004). RN [30] RP VARIANT CLN2 ARG-482. RX PubMed=19201763; DOI=10.1093/brain/awn366; RA Kousi M., Siintola E., Dvorakova L., Vlaskova H., Turnbull J., RA Topcu M., 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 [31] 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; RP LYS-343; 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 [32] 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., RA Klopstock T., Prott E.C., Lorenz R., Spaich C., Rona S., RA Lakshminarasimhan M., Kroell J., Dorn T., Kraemer G., Synofzik M., RA Becker F., Weber Y.G., Lerche H., Boehm D., Biskup S.; RT "Targeted next generation sequencing as a diagnostic tool in epileptic RT disorders."; RL Epilepsia 53:1387-1398(2012). RN [33] RP VARIANTS CLN2 THR-62; HIS-209; GLN-266; GLN-339; ARG-382; VAL-448; RP CYS-501; 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 [34] 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., RA Lefeber D.J., Hoff J.I., Brusse E., Verheijen F.W., Verdijk R.M., RA Kriek M., Oostra B., Breuning M.H., Losekoot M., den Dunnen J.T., RA van de Warrenburg B.P., Maat-Kievit A.J.; RT "Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by RT variants in TPP1, the gene involved in classic late-infantile neuronal RT ceroid lipofuscinosis 2 disease (CLN2 disease)."; RL Hum. Mutat. 34:706-713(2013). CC -!- FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I CC activity. May act as a non-specific lysosomal peptidase which CC generates tripeptides from the breakdown products produced by CC lysosomal proteinases. Requires substrates with an unsubstituted CC N-terminus (By similarity). {ECO:0000250|UniProtKB:Q9EQV6}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of an N-terminal tripeptide from a polypeptide, CC but also has endopeptidase activity.; EC=3.4.14.9; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:19038966, CC ECO:0000269|PubMed:19038967}; CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:19038966, CC ECO:0000269|PubMed:19038967}; CC -!- SUBUNIT: Monomer (PubMed:19038967). Interacts with CLN5 CC (PubMed:19941651). {ECO:0000269|PubMed:19038967, CC ECO:0000269|PubMed:19941651}. CC -!- INTERACTION: CC Q2NKJ3-1:CTC1; NbExp=3; IntAct=EBI-15619703, EBI-15994382; CC E5LBV4:ORF31 (xeno); NbExp=2; IntAct=EBI-2800203, EBI-14033503; CC Q9H668:STN1; NbExp=2; IntAct=EBI-15619703, EBI-746930; CC 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 Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Detected in all tissues examined with highest CC levels in heart and placenta and relatively similar levels in CC other tissues. CC -!- PTM: Activated by autocatalytic proteolytical processing upon CC acidification. N-glycosylation is required for processing and CC activity. {ECO:0000269|PubMed:12754519, CC ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967, CC ECO:0000269|PubMed:19159218}. CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 2 (CLN2) [MIM:204500]: A CC form of neuronal ceroid lipofuscinosis. Neuronal ceroid CC lipofuscinoses are progressive neurodegenerative, lysosomal CC storage diseases characterized by intracellular accumulation of CC autofluorescent liposomal material, and clinically by seizures, CC dementia, visual loss, and/or cerebral atrophy. The lipopigment CC pattern seen most often in CLN2 consists of curvilinear profiles. CC {ECO:0000269|PubMed:10330339, ECO:0000269|PubMed:10665500, CC ECO:0000269|PubMed:11241479, ECO:0000269|PubMed:11339651, CC ECO:0000269|PubMed:11589012, ECO:0000269|PubMed:12376936, CC ECO:0000269|PubMed:12414822, ECO:0000269|PubMed:12698559, CC ECO:0000269|PubMed:14736728, ECO:0000269|PubMed:19201763, CC ECO:0000269|PubMed:20340139, ECO:0000269|PubMed:21990111, CC ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:9295267}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 7 (SCAR7) CC [MIM:609270]: Spinocerebellar ataxia defines a clinically and CC genetically heterogeneous group of cerebellar disorders. Patients CC show progressive incoordination of gait and often poor CC coordination of hands, speech and eye movements, due to CC degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCAR7 patients show difficulty walking CC and writing, dysarthria, limb ataxia, and cerebellar atrophy. CC {ECO:0000269|PubMed:23418007}. Note=The disease is caused by CC mutations 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; Positions=551; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NCL CLN2; Note=Neural Ceroid Lipofuscinoses CC mutation db; CC URL="http://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="http://www.lovd.nl/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 UniGene; Hs.523454; -. DR PDB; 1R60; Model; -; A=196-563. 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; 1R60; -. DR PDBsum; 3EDY; -. DR PDBsum; 3EE6; -. DR ProteinModelPortal; O14773; -. DR SMR; O14773; -. DR BioGrid; 107611; 25. DR DIP; DIP-47434N; -. DR IntAct; O14773; 33. DR MINT; O14773; -. DR STRING; 9606.ENSP00000299427; -. DR MEROPS; S53.003; -. DR GlyConnect; 1858; -. DR iPTMnet; O14773; -. DR PhosphoSitePlus; O14773; -. DR BioMuta; TPP1; -. DR EPD; O14773; -. DR jPOST; O14773; -. DR MaxQB; O14773; -. DR PaxDb; O14773; -. DR PeptideAtlas; O14773; -. DR PRIDE; O14773; -. DR ProteomicsDB; 48224; -. DR ProteomicsDB; 48225; -. [O14773-2] DR DNASU; 1200; -. DR Ensembl; ENST00000299427; ENSP00000299427; ENSG00000166340. [O14773-1] DR Ensembl; ENST00000533371; ENSP00000437066; ENSG00000166340. [O14773-2] DR Ensembl; ENST00000642892; ENSP00000494165; ENSG00000166340. [O14773-2] DR Ensembl; ENST00000645620; ENSP00000493657; ENSG00000166340. [O14773-2] DR Ensembl; ENST00000647152; ENSP00000495893; ENSG00000166340. [O14773-2] DR GeneID; 1200; -. DR KEGG; hsa:1200; -. DR UCSC; uc001mek.2; human. [O14773-1] DR CTD; 1200; -. DR DisGeNET; 1200; -. DR EuPathDB; HostDB:ENSG00000166340.14; -. DR GeneCards; TPP1; -. DR GeneReviews; TPP1; -. DR H-InvDB; HIX0009410; -. DR HGNC; HGNC:2073; TPP1. DR HPA; HPA037709; -. DR HPA; HPA044868; -. 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 eggNOG; ENOG410IICY; Eukaryota. DR eggNOG; COG4934; LUCA. DR GeneTree; ENSGT00390000008684; -. DR HOGENOM; HOG000171253; -. DR HOVERGEN; HBG004449; -. DR InParanoid; O14773; -. DR KO; K01279; -. DR OMA; PGRHESQ; -. DR OrthoDB; 1294880at2759; -. DR PhylomeDB; O14773; -. DR TreeFam; TF333497; -. DR BRENDA; 3.4.14.9; 2681. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR SABIO-RK; O14773; -. DR SignaLink; O14773; -. DR ChiTaRS; TPP1; human. DR EvolutionaryTrace; O14773; -. DR GeneWiki; Tripeptidyl_peptidase_I; -. DR GenomeRNAi; 1200; -. DR PMAP-CutDB; O14773; -. DR PRO; PR:O14773; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; ENSG00000166340; Expressed in 215 organ(s), highest expression level in right adrenal gland cortex. DR ExpressionAtlas; O14773; baseline and differential. DR Genevisible; O14773; HS. DR GO; GO:0070062; C:extracellular exosome; HDA: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:0004175; F:endopeptidase activity; 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: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:0036498; P:IRE1-mediated unfolded protein response; TAS:Reactome. DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc. 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: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; IPR036852; Peptidase_S8/S53_dom_sf. DR InterPro; IPR015366; S53_propep. DR InterPro; IPR030400; Sedolisin_dom. 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 Complete proteome; Direct protein sequencing; Disease mutation; KW Disulfide bond; Epilepsy; Glycoprotein; Hydrolase; Lysosome; KW Metal-binding; Neurodegeneration; Neuronal ceroid lipofuscinosis; KW Polymorphism; Protease; Reference proteome; Serine protease; Signal; KW Spinocerebellar ataxia; Zymogen. FT SIGNAL 1 19 {ECO:0000269|PubMed:11054422}. FT PROPEP 20 195 Removed in mature form. FT {ECO:0000244|PubMed:25944712, FT ECO:0000269|PubMed:11054422}. FT /FTId=PRO_0000027374. FT CHAIN 196 563 Tripeptidyl-peptidase 1. FT /FTId=PRO_0000027375. FT DOMAIN 199 563 Peptidase S53. FT ACT_SITE 272 272 Charge relay system. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT ACT_SITE 276 276 Charge relay system. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT ACT_SITE 475 475 Charge relay system. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT METAL 517 517 Calcium. {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT METAL 518 518 Calcium; via carbonyl oxygen. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT METAL 539 539 Calcium; via carbonyl oxygen. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT METAL 541 541 Calcium; via carbonyl oxygen. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT METAL 543 543 Calcium. {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT CARBOHYD 210 210 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967, FT ECO:0000269|PubMed:19159218}. FT CARBOHYD 222 222 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 286 286 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT CARBOHYD 313 313 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967, FT ECO:0000269|PubMed:19159218}. FT CARBOHYD 443 443 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967, FT ECO:0000269|PubMed:19159218}. FT DISULFID 111 122 {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT DISULFID 365 526 {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT DISULFID 522 537 {ECO:0000269|PubMed:19038966, FT ECO:0000269|PubMed:19038967}. FT VAR_SEQ 1 243 Missing (in isoform 2). FT {ECO:0000303|Ref.4}. FT /FTId=VSP_013118. FT VARIANT 62 62 S -> L (in dbSNP:rs2734715). FT /FTId=VAR_037572. FT VARIANT 62 62 S -> T (in CLN2). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066883. FT VARIANT 77 77 G -> R (in CLN2; displays very low FT residual enzyme activity; altered FT intracellular trafficking; FT dbSNP:rs121908195). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_009603. FT VARIANT 100 100 Q -> R (in dbSNP:rs1800746). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:11462245}. FT /FTId=VAR_009604. FT VARIANT 127 127 R -> Q (in CLN2; displays residual enzyme FT activity; effectively transported to the FT lysosome; dbSNP:rs121908204). FT {ECO:0000269|PubMed:11339651, FT ECO:0000269|PubMed:12376936, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_016790. FT VARIANT 153 153 S -> P (in CLN2). FT /FTId=VAR_016791. FT VARIANT 175 175 R -> H (in dbSNP:rs764922748). FT {ECO:0000269|PubMed:9295267}. FT /FTId=VAR_005642. FT VARIANT 185 185 R -> C (in dbSNP:rs34758634). FT /FTId=VAR_037573. FT VARIANT 202 202 P -> L (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking; dbSNP:rs121908205). FT {ECO:0000269|PubMed:11589012, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_063640. FT VARIANT 206 206 R -> C (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking; dbSNP:rs28940573). FT {ECO:0000269|PubMed:10665500, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_009605. FT VARIANT 206 206 R -> H (in CLN2; dbSNP:rs121908209). FT {ECO:0000269|PubMed:12698559}. FT /FTId=VAR_016792. FT VARIANT 209 209 Y -> H (in CLN2; dbSNP:rs1218678626). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066884. FT VARIANT 266 266 R -> Q (in CLN2; dbSNP:rs757953998). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066885. FT VARIANT 277 277 V -> M (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking; demonstrates enhanced FT processing in response to folding FT improvement treatment; FT dbSNP:rs121908207). FT {ECO:0000269|PubMed:12414822, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_016793. FT VARIANT 278 278 Q -> P (in CLN2; dbSNP:rs796053439). FT {ECO:0000269|PubMed:12414822}. FT /FTId=VAR_016794. FT VARIANT 278 278 Q -> R (in CLN2; dbSNP:rs796053439). FT {ECO:0000269|PubMed:22612257}. FT /FTId=VAR_072749. FT VARIANT 284 284 G -> V (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking; dbSNP:rs119455957). FT {ECO:0000269|PubMed:11339651, FT ECO:0000269|PubMed:12414822, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_016795. FT VARIANT 286 286 N -> S (in CLN2; enzymatically inactive; FT lacks one oligosaccharide chain resulting FT in enzymatic inactivation and possibly FT prelysosomal protein degradation; altered FT intracellular trafficking; FT dbSNP:rs119455958). FT {ECO:0000269|PubMed:12376936, FT ECO:0000269|PubMed:14736728, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_016796. FT VARIANT 287 287 I -> N (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking; dbSNP:rs121908196). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_009606. FT VARIANT 339 339 R -> Q (in CLN2; dbSNP:rs765380155). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066886. FT VARIANT 343 343 E -> K (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking; dbSNP:rs121908197). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_009607. FT VARIANT 353 353 T -> P (in CLN2; dbSNP:rs121908206). FT {ECO:0000269|PubMed:12376936}. FT /FTId=VAR_016797. FT VARIANT 365 365 C -> R (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking; dbSNP:rs119455953). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139, FT ECO:0000269|PubMed:9295267}. FT /FTId=VAR_005643. FT VARIANT 365 365 C -> Y (in CLN2; dbSNP:rs119455954). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:9295267}. FT /FTId=VAR_005644. FT VARIANT 382 382 S -> R (in CLN2). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066887. FT VARIANT 385 385 V -> D (in CLN2; dbSNP:rs121908198). FT {ECO:0000269|PubMed:10330339}. FT /FTId=VAR_009608. FT VARIANT 389 389 G -> E (in CLN2; dbSNP:rs121908199). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:11462245}. FT /FTId=VAR_009609. FT VARIANT 422 422 Q -> H (in CLN2; displays no residual FT enzyme activity; altered intracellular FT trafficking;; dbSNP:rs121908200). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139, FT ECO:0000269|PubMed:22612257}. FT /FTId=VAR_009610. FT VARIANT 428 428 K -> N (in CLN2). FT {ECO:0000269|PubMed:11339651}. FT /FTId=VAR_016798. FT VARIANT 447 447 R -> H (in CLN2; displays very low FT residual enzyme activity; altered FT intracellular trafficking; demonstrates FT enhanced processing in response to FT folding improvement treatment; shows a FT five fold increase under permissive FT temperature conditions; FT dbSNP:rs119455956). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:11462245, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_005645. FT VARIANT 448 448 A -> V (in CLN2). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066888. FT VARIANT 454 454 A -> E (in CLN2; dbSNP:rs121908201). FT {ECO:0000269|PubMed:10330339}. FT /FTId=VAR_009611. FT VARIANT 466 466 V -> G (in SCAR7; dbSNP:rs398122959). FT {ECO:0000269|PubMed:23418007}. FT /FTId=VAR_070917. FT VARIANT 473 473 G -> R (in CLN2; dbSNP:rs121908203). FT {ECO:0000269|PubMed:11241479, FT ECO:0000269|PubMed:11339651}. FT /FTId=VAR_016799. FT VARIANT 475 475 S -> L (in CLN2; displays no residual FT enzyme activity; effectively transported FT to the lysosome; dbSNP:rs121908202). FT {ECO:0000269|PubMed:10330339, FT ECO:0000269|PubMed:20340139}. FT /FTId=VAR_009612. FT VARIANT 481 481 F -> C (in CLN2). FT {ECO:0000269|PubMed:12414822}. FT /FTId=VAR_016800. FT VARIANT 482 482 G -> R (in CLN2; dbSNP:rs121908208). FT {ECO:0000269|PubMed:19201763}. FT /FTId=VAR_058435. FT VARIANT 501 501 G -> C (in CLN2). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066889. FT VARIANT 504 504 N -> Y (in CLN2). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066890. FT VARIANT 544 544 P -> S (in CLN2; displays residual enzyme FT activity; effectively transported to the FT lysosome; dbSNP:rs121908210). FT {ECO:0000269|PubMed:20340139}. FT /FTId=VAR_063641. FT VARIANT 548 548 W -> R (in CLN2; dbSNP:rs1348967263). FT {ECO:0000269|PubMed:21990111}. FT /FTId=VAR_066891. FT MUTAGEN 236 236 H->A: No effect. FT {ECO:0000269|PubMed:11054422}. FT MUTAGEN 360 360 D->A: Inactive. Impaired processing. FT {ECO:0000269|PubMed:11054422}. FT MUTAGEN 475 475 S->A: Inactive. Impaired processing. FT {ECO:0000269|PubMed:11054422}. FT MUTAGEN 517 517 D->A: Inactive. Impaired processing. FT {ECO:0000269|PubMed:11054422}. FT CONFLICT 115 115 I -> N (in Ref. 6; BAD96219). FT {ECO:0000305}. FT CONFLICT 373 373 Q -> E (in Ref. 7; AAH14863). FT {ECO:0000305}. FT STRAND 35 40 {ECO:0000244|PDB:3EDY}. FT STRAND 46 53 {ECO:0000244|PDB:3EDY}. FT HELIX 58 69 {ECO:0000244|PDB:3EDY}. FT TURN 74 77 {ECO:0000244|PDB:3EDY}. FT HELIX 82 89 {ECO:0000244|PDB:3EDY}. FT HELIX 93 106 {ECO:0000244|PDB:3EDY}. FT STRAND 109 113 {ECO:0000244|PDB:3EDY}. FT STRAND 119 125 {ECO:0000244|PDB:3EDY}. FT HELIX 126 132 {ECO:0000244|PDB:3EDY}. FT STRAND 139 143 {ECO:0000244|PDB:3EDY}. FT TURN 144 147 {ECO:0000244|PDB:3EDY}. FT STRAND 148 152 {ECO:0000244|PDB:3EDY}. FT HELIX 161 163 {ECO:0000244|PDB:3EDY}. FT TURN 164 166 {ECO:0000244|PDB:3EDY}. FT STRAND 167 170 {ECO:0000244|PDB:3EDY}. FT HELIX 202 208 {ECO:0000244|PDB:3EDY}. FT STRAND 219 221 {ECO:0000244|PDB:3EDY}. FT STRAND 224 229 {ECO:0000244|PDB:3EDY}. FT HELIX 237 247 {ECO:0000244|PDB:3EDY}. FT STRAND 258 262 {ECO:0000244|PDB:3EDY}. FT HELIX 271 283 {ECO:0000244|PDB:3EDY}. FT TURN 284 286 {ECO:0000244|PDB:3EE6}. FT STRAND 287 292 {ECO:0000244|PDB:3EDY}. FT TURN 295 300 {ECO:0000244|PDB:3EE6}. FT HELIX 303 311 {ECO:0000244|PDB:3EDY}. FT STRAND 319 324 {ECO:0000244|PDB:3EDY}. FT HELIX 329 331 {ECO:0000244|PDB:3EDY}. FT HELIX 334 349 {ECO:0000244|PDB:3EDY}. FT STRAND 353 357 {ECO:0000244|PDB:3EDY}. FT STRAND 366 368 {ECO:0000244|PDB:3EDY}. FT STRAND 371 373 {ECO:0000244|PDB:3EDY}. FT TURN 379 381 {ECO:0000244|PDB:3EDY}. FT STRAND 385 397 {ECO:0000244|PDB:3EDY}. FT STRAND 402 404 {ECO:0000244|PDB:3EDY}. FT STRAND 411 417 {ECO:0000244|PDB:3EDY}. FT HELIX 420 422 {ECO:0000244|PDB:3EDY}. FT HELIX 423 432 {ECO:0000244|PDB:3EDY}. FT HELIX 439 441 {ECO:0000244|PDB:3EDY}. FT STRAND 446 449 {ECO:0000244|PDB:3EDY}. FT STRAND 451 455 {ECO:0000244|PDB:3EDY}. FT STRAND 457 463 {ECO:0000244|PDB:3EDY}. FT STRAND 466 471 {ECO:0000244|PDB:3EDY}. FT HELIX 474 494 {ECO:0000244|PDB:3EDY}. FT HELIX 504 509 {ECO:0000244|PDB:3EDY}. FT TURN 510 514 {ECO:0000244|PDB:3EDY}. FT STRAND 522 525 {ECO:0000244|PDB:3EDY}. FT TURN 529 533 {ECO:0000244|PDB:3EDY}. FT STRAND 534 537 {ECO:0000244|PDB:3EDY}. FT TURN 544 546 {ECO:0000244|PDB:3EDY}. FT HELIX 553 558 {ECO:0000244|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 //