Lysosomal protective protein

Details

Name
Lysosomal protective protein
Synonyms
  • 3.4.16.5
  • Carboxypeptidase C
  • Carboxypeptidase L
  • Cathepsin A
  • PPCA
  • PPGB
  • Protective protein cathepsin A
  • Protective protein for beta-galactosidase
Gene Name
CTSA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0050157|Lysosomal protective protein
MIRAAPPPLFLLLLLLLLLVSWASRGEAAPDQDEIQRLPGLAKQPSFRQYSGYLKGSGSK
HLHYWFVESQKDPENSPVVLWLNGGPGCSSLDGLLTEHGPFLVQPDGVTLEYNPYSWNLI
ANVLYLESPAGVGFSYSDDKFYATNDTEVAQSNFEALQDFFRLFPEYKNNKLFLTGESYA
GIYIPTLAVLVMQDPSMNLQGLAVGNGLSSYEQNDNSLVYFAYYHGLLGNRLWSSLQTHC
CSQNKCNFYDNKDLECVTNLQEVARIVGNSGLNIYNLYAPCAGGVPSHFRYEKDTVVVQD
LGNIFTRLPLKRMWHQALLRSGDKVRMDPPCTNTTAASTYLNNPYVRKALNIPEQLPQWD
MCNFLVNLQYRRLYRSMNSQYLKLLSSQKYQILLYNGDVDMACNFMGDEWFVDSLNQKME
VQRRPWLVKYGDSGEQIAGFVKEFSHIAFLTIKGAGHMVPTDKPLAAFTMFSRFLNKQPY
Number of residues
480
Molecular Weight
54465.655
Theoretical pI
Not Available
GO Classification
Functions
carboxypeptidase activity / enzyme activator activity / exo-alpha-sialidase activity / serine-type carboxypeptidase activity
Processes
glycosphingolipid metabolic process / intracellular protein transport / negative regulation of chaperone-mediated autophagy / neutrophil degranulation / proteolysis / proteolysis involved in cellular protein catabolic process / regulation of chaperone-mediated autophagy / regulation of protein stability
Components
azurophil granule lumen / endoplasmic reticulum / extracellular exosome / extracellular region / intracellular membrane-bounded organelle / lysosomal lumen / lysosome / membrane / nucleoplasm
General Function
Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.
Specific Function
Carboxypeptidase activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Lysosome
Gene sequence
>lcl|BSEQ0050158|Lysosomal protective protein (CTSA)
ATGATCCGAGCCGCGCCGCCGCCGCTGTTCCTGCTGCTGCTGCTGCTGCTGCTGCTAGTG
TCCTGGGCGTCCCGAGGCGAGGCAGCCCCCGACCAGGACGAGATCCAGCGCCTCCCCGGG
CTGGCCAAGCAGCCGTCTTTCCGCCAGTACTCCGGCTACCTCAAAGGCTCCGGCTCCAAG
CACCTCCACTACTGGTTTGTGGAGTCCCAGAAGGATCCCGAGAACAGCCCTGTGGTGCTT
TGGCTCAATGGGGGTCCCGGCTGCAGCTCACTAGATGGGCTCCTCACAGAGCATGGCCCC
TTCCTGGTCCAGCCAGATGGTGTCACCCTGGAGTACAACCCCTATTCTTGGAATCTGATT
GCCAATGTGTTATACCTGGAGTCCCCAGCTGGGGTGGGCTTCTCCTACTCCGATGACAAG
TTTTATGCAACTAATGACACTGAGGTCGCCCAGAGCAATTTTGAGGCCCTTCAAGATTTC
TTCCGCCTCTTTCCGGAGTACAAGAACAACAAACTTTTCCTGACCGGGGAGAGCTATGCT
GGCATCTACATCCCCACCCTGGCCGTGCTGGTCATGCAGGATCCCAGCATGAACCTTCAG
GGGCTGGCTGTGGGCAATGGACTCTCCTCCTATGAGCAGAATGACAACTCCCTGGTCTAC
TTTGCCTACTACCATGGCCTTCTGGGGAACAGGCTTTGGTCTTCTCTCCAGACCCACTGC
TGCTCTCAAAACAAGTGTAACTTCTATGACAACAAAGACCTGGAATGCGTGACCAATCTT
CAGGAAGTGGCCCGCATCGTGGGCAACTCTGGCCTCAACATCTACAATCTCTATGCCCCG
TGTGCTGGAGGGGTGCCCAGCCATTTTAGGTATGAGAAGGACACTGTTGTGGTCCAGGAT
TTGGGCAACATCTTCACTCGCCTGCCACTCAAGCGGATGTGGCATCAGGCACTGCTGCGC
TCAGGGGATAAAGTGCGCATGGACCCCCCCTGCACCAACACAACAGCTGCTTCCACCTAC
CTCAACAACCCGTACGTGCGGAAGGCCCTCAACATCCCGGAGCAGCTGCCACAATGGGAC
ATGTGCAACTTTCTGGTAAACTTACAGTACCGCCGTCTCTACCGAAGCATGAACTCCCAG
TATCTGAAGCTGCTTAGCTCACAGAAATACCAGATCCTATTATATAATGGAGATGTAGAC
ATGGCCTGCAATTTCATGGGGGATGAGTGGTTTGTGGATTCCCTCAACCAGAAGATGGAG
GTGCAGCGCCGGCCCTGGTTAGTGAAGTACGGGGACAGCGGGGAGCAGATTGCCGGCTTC
GTGAAGGAGTTCTCCCACATCGCCTTTCTCACGATCAAGGGCGCCGGCCACATGGTTCCC
ACCGACAAGCCCCTCGCTGCCTTCACCATGTTCTCCCGCTTCCTGAACAAGCAGCCATAC
TGA
Chromosome Location
20
Locus
20q13.12
External Identifiers
ResourceLink
UniProtKB IDP10619
UniProtKB Entry NamePPGB_HUMAN
HGNC IDHGNC:9251
General References
  1. Galjart NJ, Gillemans N, Harris A, van der Horst GT, Verheijen FW, Galjaard H, d'Azzo A: Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases. Cell. 1988 Sep 9;54(6):755-64. [PubMed:3136930]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
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  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. Jackman HL, Tan FL, Tamei H, Beurling-Harbury C, Li XY, Skidgel RA, Erdos EG: A peptidase in human platelets that deamidates tachykinins. Probable identity with the lysosomal "protective protein". J Biol Chem. 1990 Jul 5;265(19):11265-72. [PubMed:1694176]
  6. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed:12665801]
  7. Galjart NJ, Morreau H, Willemsen R, Gillemans N, Bonten EJ, d'Azzo A: Human lysosomal protective protein has cathepsin A-like activity distinct from its protective function. J Biol Chem. 1991 Aug 5;266(22):14754-62. [PubMed:1907282]
  8. Lewandrowski U, Moebius J, Walter U, Sickmann A: Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach. Mol Cell Proteomics. 2006 Feb;5(2):226-33. Epub 2005 Oct 31. [PubMed:16263699]
  9. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  10. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  11. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  12. Rudenko G, Bonten E, d'Azzo A, Hol WG: Three-dimensional structure of the human 'protective protein': structure of the precursor form suggests a complex activation mechanism. Structure. 1995 Nov 15;3(11):1249-59. [PubMed:8591035]
  13. Zhou XY, Galjart NJ, Willemsen R, Gillemans N, Galjaard H, d'Azzo A: A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable. EMBO J. 1991 Dec;10(13):4041-8. [PubMed:1756715]
  14. Shimmoto M, Fukuhara Y, Itoh K, Oshima A, Sakuraba H, Suzuki Y: Protective protein gene mutations in galactosialidosis. J Clin Invest. 1993 Jun;91(6):2393-8. [PubMed:8514852]
  15. Zhou XY, van der Spoel A, Rottier R, Hale G, Willemsen R, Berry GT, Strisciuglio P, Morrone A, Zammarchi E, Andria G, d'Azzo A: Molecular and biochemical analysis of protective protein/cathepsin A mutations: correlation with clinical severity in galactosialidosis. Hum Mol Genet. 1996 Dec;5(12):1977-87. [PubMed:8968752]
  16. Takiguchi K, Itoh K, Shimmoto M, Ozand PT, Doi H, Sakuraba H: Structural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis. J Hum Genet. 2000;45(4):200-6. [PubMed:10944848]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08934SofosbuvirapprovedunknownsubstrateDetails
DB09299Tenofovir alafenamideapprovednosubstrateDetails