ID PPGB_HUMAN Reviewed; 480 AA. AC P10619; B2R798; Q561W6; Q5JZH1; Q96KJ2; Q9BR08; Q9BW68; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 27-MAR-2024, entry version 249. DE RecName: Full=Lysosomal protective protein; DE EC=3.4.16.5; DE AltName: Full=Carboxypeptidase C; DE AltName: Full=Carboxypeptidase L; DE AltName: Full=Cathepsin A; DE AltName: Full=Protective protein cathepsin A; DE Short=PPCA; DE AltName: Full=Protective protein for beta-galactosidase; DE Contains: DE RecName: Full=Lysosomal protective protein 32 kDa chain; DE Contains: DE RecName: Full=Lysosomal protective protein 20 kDa chain; DE Flags: Precursor; GN Name=CTSA; Synonyms=PPGB; 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), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3136930; DOI=10.1016/s0092-8674(88)90999-3; RA Galjart N.J., Gillemans N., Harris A., van de Horst G.T.J., Verheijen F.W., RA Galjaard H., D'Azzo A.; RT "Expression of cDNA encoding the human 'protective protein' associated with RT lysosomal beta-galactosidase and neuraminidase: homology to yeast RT proteases."; RL Cell 54:755-764(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta, and Skin; 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 [5] RP PROTEIN SEQUENCE OF 29-53 AND 327-351. RC TISSUE=Platelet; RX PubMed=1694176; DOI=10.1016/s0021-9258(19)38586-2; RA Jackman H.L., Tan F., Tamei H., Beurling-Harbury C., Li X.-Y., RA Skidgel R.A., Erdoes E.G.; RT "A peptidase in human platelets that deamidates tachykinins. Probable RT identity with the lysosomal 'protective protein'."; RL J. Biol. Chem. 265:11265-11272(1990). RN [6] RP PROTEIN SEQUENCE OF 29-37. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [7] RP FUNCTION, AND MUTAGENESIS. RX PubMed=1907282; DOI=10.1016/s0021-9258(18)98751-x; RA Galjart N.J., Morreau H., Willemsen R., Gillemans N., Bonten E.J., RA D'Azzo A.; RT "Human lysosomal protective protein has cathepsin A-like activity distinct RT from its protective function."; RL J. Biol. Chem. 266:14754-14762(1991). RN [8] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-145. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-145 AND ASN-333. 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 [10] 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 [11] RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-28, 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 [12] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=8591035; DOI=10.1016/s0969-2126(01)00260-x; RA Rudenko G., Bonten E., D'Azzo A., Hol W.G.J.; RT "Three-dimensional structure of the human 'protective protein': structure RT of the precursor form suggests a complex activation mechanism."; RL Structure 3:1249-1259(1995). RN [13] RP VARIANT GSL VAL-440. RX PubMed=1756715; DOI=10.1002/j.1460-2075.1991.tb04980.x; RA Zhou X.Y., Galjart N.J., Willemsen R., Gillemans N., Galjaard H., RA D'Azzo A.; RT "A mutation in a mild form of galactosialidosis impairs dimerization of the RT protective protein and renders it unstable."; RL EMBO J. 10:4041-4048(1991). RN [14] RP VARIANTS GSL ARG-49; ARG-65; LEU-90; ASN-249 AND CYS-395. RX PubMed=8514852; DOI=10.1172/jci116472; RA Shimmoto M., Fukuhara Y., Itoh K., Oshima A., Sakuraba H., Suzuki Y.; RT "Protective protein gene mutations in galactosialidosis."; RL J. Clin. Invest. 91:2393-2398(1993). RN [15] RP VARIANTS GSL TYR-51; MET-132; PRO-236; ASN-249; THR-406; SER-439 AND RP VAL-440. RX PubMed=8968752; DOI=10.1093/hmg/5.12.1977; RA Zhou X.Y., van der Spoel A., Rottier R., Hale G., Willemsen R., Berry G.T., RA Strisciuglio P., Morrone A., Zammarchi E., Andria G., d'Azzo A.; RT "Molecular and biochemical analysis of protective protein/cathepsin A RT mutations: correlation with clinical severity in galactosialidosis."; RL Hum. Mol. Genet. 5:1977-1987(1996). RN [16] RP VARIANT GSL GLU-453. RX PubMed=10944848; DOI=10.1007/s100380070027; RA Takiguchi K., Itoh K., Shimmoto M., Ozand P.T., Doi H., Sakuraba H.; RT "Structural and functional study of K453E mutant protective RT protein/cathepsin A causing the late infantile form of galactosialidosis."; RL J. Hum. Genet. 45:200-206(2000). CC -!- FUNCTION: Protective protein appears to be essential for both the CC activity of beta-galactosidase and neuraminidase, it associates with CC these enzymes and exerts a protective function necessary for their CC stability and activity. This protein is also a carboxypeptidase and can CC deamidate tachykinins. {ECO:0000269|PubMed:1907282}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of a C-terminal amino acid with broad specificity.; CC EC=3.4.16.5; Evidence={ECO:0000255|PROSITE-ProRule:PRU10074, CC ECO:0000255|PROSITE-ProRule:PRU10075}; CC -!- SUBUNIT: Heterodimer of a 32 kDa chain and a 20 kDa chain; disulfide- CC linked. CC -!- SUBCELLULAR LOCATION: Lysosome. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P10619-1; Sequence=Displayed; CC Name=2; CC IsoId=P10619-2; Sequence=VSP_054832; CC -!- DISEASE: Galactosialidosis (GSL) [MIM:256540]: A lysosomal storage CC disease associated with a combined deficiency of beta-galactosidase and CC neuraminidase, secondary to a defect in cathepsin A. All patients have CC clinical manifestations typical of a lysosomal disorder, such as coarse CC facies, cherry red spots, vertebral changes, foam cells in the bone CC marrow, and vacuolated lymphocytes. Three phenotypic subtypes are CC recognized. The early infantile form is associated with fetal hydrops, CC edema, ascites, visceromegaly, skeletal dysplasia, and early death. The CC late infantile type is characterized by hepatosplenomegaly, growth CC retardation, cardiac involvement, and a normal or mildly affected CC mental state. The juvenile/adult form is characterized by myoclonus, CC ataxia, angiokeratoma, intellectual disability, neurologic CC deterioration, absence of visceromegaly, and long survival. CC {ECO:0000269|PubMed:10944848, ECO:0000269|PubMed:1756715, CC ECO:0000269|PubMed:8514852, ECO:0000269|PubMed:8968752}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the peptidase S10 family. {ECO:0000305}. 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; M22960; AAA36476.1; -; mRNA. DR EMBL; AK312898; BAG35745.1; -; mRNA. DR EMBL; AL008726; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000597; AAH00597.1; -; mRNA. DR EMBL; BC093009; AAH93009.1; -; mRNA. DR CCDS; CCDS46609.1; -. [P10619-1] DR CCDS; CCDS54467.1; -. [P10619-2] DR PIR; A31589; A31589. DR RefSeq; NP_000299.2; NM_000308.3. [P10619-1] DR RefSeq; NP_001121167.1; NM_001127695.2. [P10619-1] DR RefSeq; NP_001161066.1; NM_001167594.2. [P10619-2] DR PDB; 1IVY; X-ray; 2.20 A; A/B=29-480. DR PDB; 3BP4; X-ray; 1.85 A; C=2-10. DR PDB; 3BP7; X-ray; 1.80 A; C=2-10. DR PDB; 3BXN; X-ray; 1.86 A; C=2-10. DR PDB; 4AZ0; X-ray; 2.17 A; A=29-326, B=327-480. DR PDB; 4AZ3; X-ray; 2.04 A; A=29-326, B=327-480. DR PDB; 4CI9; X-ray; 1.58 A; A=29-480. DR PDB; 4CIA; X-ray; 1.98 A; A=29-480. DR PDB; 4CIB; X-ray; 1.89 A; A=29-480. DR PDB; 4MWS; X-ray; 2.80 A; A/B=29-480. DR PDB; 4MWT; X-ray; 3.85 A; A/B=29-480. DR PDB; 6WIA; X-ray; 2.21 A; A=29-480. DR PDBsum; 1IVY; -. DR PDBsum; 3BP4; -. DR PDBsum; 3BP7; -. DR PDBsum; 3BXN; -. DR PDBsum; 4AZ0; -. DR PDBsum; 4AZ3; -. DR PDBsum; 4CI9; -. DR PDBsum; 4CIA; -. DR PDBsum; 4CIB; -. DR PDBsum; 4MWS; -. DR PDBsum; 4MWT; -. DR PDBsum; 6WIA; -. DR AlphaFoldDB; P10619; -. DR SMR; P10619; -. DR BioGRID; 111472; 112. DR CORUM; P10619; -. DR IntAct; P10619; 27. DR MINT; P10619; -. DR STRING; 9606.ENSP00000361562; -. DR BindingDB; P10619; -. DR ChEMBL; CHEMBL6115; -. DR DrugBank; DB14761; Remdesivir. DR DrugBank; DB08934; Sofosbuvir. DR DrugBank; DB09299; Tenofovir alafenamide. DR DrugCentral; P10619; -. DR GuidetoPHARMACOLOGY; 1581; -. DR ESTHER; human-CTSA; Carboxypeptidase_S10. DR MEROPS; S10.002; -. DR GlyConnect; 1477; 6 N-Linked glycans (2 sites). DR GlyCosmos; P10619; 2 sites, 6 glycans. DR GlyGen; P10619; 6 sites, 6 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P10619; -. DR PhosphoSitePlus; P10619; -. DR SwissPalm; P10619; -. DR BioMuta; CTSA; -. DR DMDM; 20178316; -. DR OGP; P10619; -. DR EPD; P10619; -. DR jPOST; P10619; -. DR MassIVE; P10619; -. DR MaxQB; P10619; -. DR PaxDb; 9606-ENSP00000361562; -. DR PeptideAtlas; P10619; -. DR ProteomicsDB; 52619; -. [P10619-1] DR Pumba; P10619; -. DR TopDownProteomics; P10619-1; -. [P10619-1] DR TopDownProteomics; P10619-2; -. [P10619-2] DR Antibodypedia; 27832; 521 antibodies from 36 providers. DR DNASU; 5476; -. DR Ensembl; ENST00000191018.9; ENSP00000191018.5; ENSG00000064601.21. [P10619-1] DR Ensembl; ENST00000354880.9; ENSP00000346952.5; ENSG00000064601.21. [P10619-2] DR Ensembl; ENST00000372459.7; ENSP00000361537.2; ENSG00000064601.21. [P10619-1] DR Ensembl; ENST00000607482.6; ENSP00000475524.2; ENSG00000064601.21. [P10619-1] DR Ensembl; ENST00000646241.3; ENSP00000493613.2; ENSG00000064601.21. [P10619-1] DR GeneID; 5476; -. DR KEGG; hsa:5476; -. DR MANE-Select; ENST00000646241.3; ENSP00000493613.2; NM_000308.4; NP_000299.3. DR UCSC; uc002xqj.5; human. [P10619-1] DR AGR; HGNC:9251; -. DR CTD; 5476; -. DR DisGeNET; 5476; -. DR GeneCards; CTSA; -. DR HGNC; HGNC:9251; CTSA. DR HPA; ENSG00000064601; Tissue enhanced (adrenal). DR MalaCards; CTSA; -. DR MIM; 256540; phenotype. DR MIM; 613111; gene. DR neXtProt; NX_P10619; -. DR OpenTargets; ENSG00000064601; -. DR Orphanet; 575553; Cathepsin A-related arteriopathy-strokes-leukoencephalopathy. DR Orphanet; 351; Galactosialidosis. DR PharmGKB; PA33572; -. DR VEuPathDB; HostDB:ENSG00000064601; -. DR eggNOG; KOG1282; Eukaryota. DR GeneTree; ENSGT00880000138014; -. DR HOGENOM; CLU_008523_13_3_1; -. DR InParanoid; P10619; -. DR OMA; GDWMKPF; -. DR OrthoDB; 1647009at2759; -. DR PhylomeDB; P10619; -. DR TreeFam; TF323769; -. DR BRENDA; 3.4.16.5; 2681. DR PathwayCommons; P10619; -. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR Reactome; R-HSA-4085001; Sialic acid metabolism. DR Reactome; R-HSA-4341670; Defective NEU1 causes sialidosis. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism. DR SABIO-RK; P10619; -. DR SignaLink; P10619; -. DR BioGRID-ORCS; 5476; 19 hits in 1157 CRISPR screens. DR ChiTaRS; CTSA; human. DR EvolutionaryTrace; P10619; -. DR GeneWiki; Cathepsin_A; -. DR GenomeRNAi; 5476; -. DR Pharos; P10619; Tchem. DR PRO; PR:P10619; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P10619; Protein. DR Bgee; ENSG00000064601; Expressed in right adrenal gland and 207 other cell types or tissues. DR ExpressionAtlas; P10619; baseline and differential. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005764; C:lysosome; NAS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0004180; F:carboxypeptidase activity; TAS:ProtInc. DR GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc. DR GO; GO:0004185; F:serine-type carboxypeptidase activity; IMP:UniProtKB. DR GO; GO:0006886; P:intracellular protein transport; TAS:ProtInc. DR GO; GO:1904715; P:negative regulation of chaperone-mediated autophagy; IGI:ParkinsonsUK-UCL. DR GO; GO:0006508; P:proteolysis; IDA:ParkinsonsUK-UCL. DR GO; GO:1904714; P:regulation of chaperone-mediated autophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0031647; P:regulation of protein stability; IMP:ParkinsonsUK-UCL. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR001563; Peptidase_S10. DR InterPro; IPR033124; Ser_caboxypep_his_AS. DR InterPro; IPR018202; Ser_caboxypep_ser_AS. DR PANTHER; PTHR11802:SF497; LYSOSOMAL PROTECTIVE PROTEIN; 1. DR PANTHER; PTHR11802; SERINE PROTEASE FAMILY S10 SERINE CARBOXYPEPTIDASE; 1. DR Pfam; PF00450; Peptidase_S10; 1. DR PRINTS; PR00724; CRBOXYPTASEC. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS00560; CARBOXYPEPT_SER_HIS; 1. DR PROSITE; PS00131; CARBOXYPEPT_SER_SER; 1. DR Genevisible; P10619; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Carboxypeptidase; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Hydrolase; Lysosome; Protease; Reference proteome; Signal; Zymogen. FT SIGNAL 1..28 FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0000269|PubMed:1694176, ECO:0007744|PubMed:25944712" FT CHAIN 29..480 FT /note="Lysosomal protective protein" FT /id="PRO_0000004274" FT CHAIN 29..326 FT /note="Lysosomal protective protein 32 kDa chain" FT /id="PRO_0000004275" FT CHAIN 327..480 FT /note="Lysosomal protective protein 20 kDa chain" FT /id="PRO_0000004276" FT ACT_SITE 178 FT ACT_SITE 400 FT /evidence="ECO:0000250" FT ACT_SITE 457 FT CARBOHYD 145 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:19159218" FT CARBOHYD 333 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT DISULFID 88..362 FT DISULFID 240..256 FT DISULFID 241..246 FT DISULFID 281..331 FT VAR_SEQ 102..118 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_054832" FT VARIANT 49 FT /note="Q -> R (in GSL; dbSNP:rs137854541)" FT /evidence="ECO:0000269|PubMed:8514852" FT /id="VAR_001385" FT VARIANT 51 FT /note="S -> Y (in GSL; dbSNP:rs538562022)" FT /evidence="ECO:0000269|PubMed:8968752" FT /id="VAR_063018" FT VARIANT 65 FT /note="W -> R (in GSL; dbSNP:rs28934603)" FT /evidence="ECO:0000269|PubMed:8514852" FT /id="VAR_001386" FT VARIANT 90 FT /note="S -> L (in GSL; dbSNP:rs137854542)" FT /evidence="ECO:0000269|PubMed:8514852" FT /id="VAR_001387" FT VARIANT 132 FT /note="V -> M (in GSL; dbSNP:rs137854545)" FT /evidence="ECO:0000269|PubMed:8968752" FT /id="VAR_063019" FT VARIANT 236 FT /note="L -> P (in GSL; dbSNP:rs137854546)" FT /evidence="ECO:0000269|PubMed:8968752" FT /id="VAR_063020" FT VARIANT 249 FT /note="Y -> N (in GSL; small amount of activity; FT dbSNP:rs137854544)" FT /evidence="ECO:0000269|PubMed:8514852, FT ECO:0000269|PubMed:8968752" FT /id="VAR_001388" FT VARIANT 395 FT /note="Y -> C (in GSL; loss of activity; FT dbSNP:rs137854543)" FT /evidence="ECO:0000269|PubMed:8514852" FT /id="VAR_001389" FT VARIANT 406 FT /note="M -> T (in GSL; dbSNP:rs137854548)" FT /evidence="ECO:0000269|PubMed:8968752" FT /id="VAR_063021" FT VARIANT 439 FT /note="G -> S (in GSL; dbSNP:rs137854547)" FT /evidence="ECO:0000269|PubMed:8968752" FT /id="VAR_063022" FT VARIANT 440 FT /note="F -> V (in GSL; dbSNP:rs137854540)" FT /evidence="ECO:0000269|PubMed:1756715, FT ECO:0000269|PubMed:8968752" FT /id="VAR_001390" FT VARIANT 453 FT /note="K -> E (in GSL; dbSNP:rs137854549)" FT /evidence="ECO:0000269|PubMed:10944848" FT /id="VAR_063023" FT MUTAGEN 178 FT /note="S->A: Inactivates the enzyme." FT /evidence="ECO:0000269|PubMed:1907282" FT MUTAGEN 457 FT /note="H->Q: Inactivates the enzyme." FT /evidence="ECO:0000269|PubMed:1907282" FT CONFLICT 19 FT /note="Missing (in Ref. 4; AAH00597)" FT /evidence="ECO:0000305" FT CONFLICT 56 FT /note="G -> S (in Ref. 1; AAA36476)" FT /evidence="ECO:0000305" FT HELIX 31..33 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:4CIA" FT STRAND 49..55 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 60..67 FT /evidence="ECO:0007829|PDB:4CI9" FT TURN 73..75 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 78..82 FT /evidence="ECO:0007829|PDB:4CI9" FT TURN 85..87 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 91..96 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 99..103 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 110..112 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 117..119 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 120..126 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 136..139 FT /evidence="ECO:0007829|PDB:1IVY" FT HELIX 146..163 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:6WIA" FT STRAND 172..177 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 180..192 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 199..206 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 211..224 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 230..240 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 254..268 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 286..292 FT /evidence="ECO:0007829|PDB:1IVY" FT STRAND 295..298 FT /evidence="ECO:0007829|PDB:1IVY" FT HELIX 315..317 FT /evidence="ECO:0007829|PDB:1IVY" FT HELIX 318..321 FT /evidence="ECO:0007829|PDB:1IVY" FT STRAND 324..327 FT /evidence="ECO:0007829|PDB:1IVY" FT HELIX 335..341 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 344..349 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 364..369 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 375..377 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 378..386 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 391..397 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 401..403 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 405..414 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 424..429 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 431..433 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 435..444 FT /evidence="ECO:0007829|PDB:4CI9" FT STRAND 447..452 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 459..462 FT /evidence="ECO:0007829|PDB:4CI9" FT HELIX 464..475 FT /evidence="ECO:0007829|PDB:4CI9" SQ SEQUENCE 480 AA; 54466 MW; 46B737DEE775C508 CRC64; MIRAAPPPLF LLLLLLLLLV SWASRGEAAP DQDEIQRLPG LAKQPSFRQY SGYLKGSGSK HLHYWFVESQ KDPENSPVVL WLNGGPGCSS LDGLLTEHGP FLVQPDGVTL EYNPYSWNLI ANVLYLESPA GVGFSYSDDK FYATNDTEVA QSNFEALQDF FRLFPEYKNN KLFLTGESYA GIYIPTLAVL VMQDPSMNLQ GLAVGNGLSS YEQNDNSLVY FAYYHGLLGN RLWSSLQTHC CSQNKCNFYD NKDLECVTNL QEVARIVGNS GLNIYNLYAP CAGGVPSHFR YEKDTVVVQD LGNIFTRLPL KRMWHQALLR SGDKVRMDPP CTNTTAASTY LNNPYVRKAL NIPEQLPQWD MCNFLVNLQY RRLYRSMNSQ YLKLLSSQKY QILLYNGDVD MACNFMGDEW FVDSLNQKME VQRRPWLVKY GDSGEQIAGF VKEFSHIAFL TIKGAGHMVP TDKPLAAFTM FSRFLNKQPY //