PPT1 explained

Palmitoyl-protein thioesterase 1 (PPT-1), also known as palmitoyl-protein hydrolase 1, is an enzyme that in humans is encoded by the PPT1 gene.^{[1] [2] [3]}

Function

PPT-1 a member of the palmitoyl protein thioesterase family. PPT-1 is a small glycoprotein involved in the catabolism of lipid-modified proteins during lysosomal degradation. This enzyme removes thioester-linked fatty acyl groups such as palmitate from cysteine residues.^[1]

Clinical significance

Defects in this gene are a cause of neuronal ceroid lipofuscinosis type 1 (CLN1).^[4]

Further reading

• Acyl-protein thioesterase

• Tsukamoto T, Iida J, Dobashi Y, etal . Overexpression in colorectal carcinoma of two lysosomal enzymes, CLN2 and CLN1, involved in neuronal ceroid lipofuscinosis. . Cancer . 106 . 7 . 1489–97 . 2006 . 16518810 . 10.1002/cncr.21764 . 26004924 . free .
• Simonati A, Tessa A, Bernardina BD, etal . Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations. . Pediatr. Neurol. . 40 . 4 . 271–6 . 2009 . 19302939 . 10.1016/j.pediatrneurol.2008.10.018 .
• Hofmann SL, Atashband A, Cho SK, etal . Neuronal ceroid lipofuscinoses caused by defects in soluble lysosomal enzymes (CLN1 and CLN2). . Curr. Mol. Med. . 2 . 5 . 423–37 . 2002 . 12125808 . 10.2174/1566524023362294.
• Kousi M, Siintola E, Dvorakova L, etal . Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis. . Brain . 132 . Pt 3 . 810–9 . 2009 . 19201763 . 10.1093/brain/awn366 . free .
• Weimer JM, Kriscenski-Perry E, Elshatory Y, Pearce DA . The neuronal ceroid lipofuscinoses: mutations in different proteins result in similar disease. . Neuromolecular Med. . 1 . 2 . 111–24 . 2002 . 12025857 . 10.1385/NMM:1:2:111 . 33921126 .
• Martins-de-Souza D, Gattaz WF, Schmitt A, etal . Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia. . Eur Arch Psychiatry Clin Neurosci . 259 . 3 . 151–63 . 2009 . 19165527 . 10.1007/s00406-008-0847-2 . 33815571 .
• Otsuki T, Ota T, Nishikawa T, etal . Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. . DNA Res. . 12 . 2 . 117–26 . 2005 . 16303743 . 10.1093/dnares/12.2.117 . free .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Zhang H, Li XJ, Martin DB, Aebersold R . Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry . Nat. Biotechnol. . 21 . 6 . 660–6 . 2003 . 12754519 . 10.1038/nbt827 . 581283 .
• Calero G, Gupta P, Nonato MC, etal . The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2 . J. Biol. Chem. . 278 . 39 . 37957–64 . 2003 . 12855696 . 10.1074/jbc.M301225200 . free .
• Kim SJ, Zhang Z, Sarkar C, etal . Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice . J. Clin. Invest. . 118 . 9 . 3075–86 . 2008 . 18704195 . 2515381 . 10.1172/JCI33482 .
• Ramadan H, Al-Din AS, Ismail A, etal . Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1 . Neurology . 68 . 5 . 387–8 . 2007 . 17261688 . 10.1212/01.wnl.0000252825.85947.2f . 44887575 .
• Ahtiainen L, Van Diggelen OP, Jalanko A, Kopra O . Palmitoyl protein thioesterase 1 is targeted to the axons in neurons . J. Comp. Neurol. . 455 . 3 . 368–77 . 2003 . 12483688 . 10.1002/cne.10492 . 37821662 .
• Gregório SP, Sallet PC, Do KA . Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence . Psychiatry Res . 165 . 1–2 . 1–9 . 2009 . 19054571 . 10.1016/j.psychres.2007.08.011 . 43548414 . etal.
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Dawson G, Cho S . Batten's disease: clues to neuronal protein catabolism in lysosomes . J. Neurosci. Res. . 60 . 2 . 133–40 . 2000 . 10740217 . 10.1002/(SICI)1097-4547(20000415)60:2<133::AID-JNR1>3.0.CO;2-3. 28786470 .
• Goswami R, Ahmed M, Kilkus J, etal . Differential regulation of ceramide in lipid-rich microdomains (rafts): antagonistic role of palmitoyl:protein thioesterase and neutral sphingomyelinase 2 . J. Neurosci. Res. . 81 . 2 . 208–17 . 2005 . 15929065 . 10.1002/jnr.20549 . 21060010 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Kim SJ, Zhang Z, Lee YC, Mukherjee AB . Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL . Hum. Mol. Genet. . 15 . 10 . 1580–6 . 2006 . 16571600 . 10.1093/hmg/ddl078 . free .
• Ahtiainen L, Luiro K, Kauppi M, etal . Palmitoyl protein thioesterase 1 (PPT1) deficiency causes endocytic defects connected to abnormal saposin processing . Exp. Cell Res. . 312 . 9 . 1540–53 . 2006 . 16542649 . 10.1016/j.yexcr.2006.01.034 .

External links

• GeneReviews/NCBI/NIH/UW entry on Neuronal Ceroid-Lipofuscinosis

Notes and References

1. Web site: Entrez Gene: palmitoyl-protein thioesterase 1.
2. Hellsten E, Vesa J, Speer MC, Mäkelä TP, Järvelä I, Alitalo K, Ott J, Peltonen L . Refined assignment of the infantile neuronal ceroid lipofuscinosis (INCL, CLN1) locus at 1p32: incorporation of linkage disequilibrium in multipoint analysis . Genomics . 16 . 3 . 720–5 . June 1993 . 8325646 . 10.1006/geno.1993.1253 .
3. Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L . Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis . Nature . 376 . 6541 . 584–7 . August 1995 . 7637805 . 10.1038/376584a0 . 1995Natur.376..584V . 4322423 .
4. Genetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses. [Review]

   Warrier V; Vieira M; Mole SE.

   Biochimica et Biophysica Acta. 1832(11):1827-30, 2013