PPGB_HUMAN
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 03-AUG-2022, entry version 240.
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}.
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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; CCDS13385.2; -. [P10619-1]
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.
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; 100.
DR CORUM; P10619; -.
DR IntAct; P10619; 26.
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 GlyGen; P10619; 5 sites, 6 N-linked glycans (2 sites).
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; P10619; -.
DR PeptideAtlas; P10619; -.
DR PRIDE; P10619; -.
DR ProteomicsDB; 52619; -. [P10619-1]
DR TopDownProteomics; P10619-1; -. [P10619-1]
DR TopDownProteomics; P10619-2; -. [P10619-2]
DR Antibodypedia; 27832; 486 antibodies from 36 providers.
DR DNASU; 5476; -.
DR Ensembl; ENST00000191018.9; ENSP00000191018.5; ENSG00000064601.21. [P10619-1]
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 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; 607679at2759; -.
DR PhylomeDB; P10619; -.
DR TreeFam; TF323769; -.
DR BRENDA; 3.4.16.5; 2681.
DR PathwayCommons; P10619; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
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 SABIO-RK; P10619; -.
DR SignaLink; P10619; -.
DR BioGRID-ORCS; 5476; 16 hits in 1079 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 205 other tissues.
DR ExpressionAtlas; P10619; baseline and differential.
DR Genevisible; P10619; HS.
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; -; 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; PTHR11802; 1.
DR Pfam; PF00450; Peptidase_S10; 1.
DR PRINTS; PR00724; CRBOXYPTASEC.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00560; CARBOXYPEPT_SER_HIS; 1.
DR PROSITE; PS00131; CARBOXYPEPT_SER_SER; 1.
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
