PPT1

Palmitoyl-protein thioesterase 1
PDB rendering based on 1eh5.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3GRO​
Identifiers
Symbols	PPT1 ; CLN1; INCL; PPT
External IDs	OMIM: 600722 MGI: 1298204 HomoloGene: 7488 GeneCards: PPT1 Gene
EC number	3.1.2.22
Gene ontology Molecular function • palmitoyl-(protein) hydrolase activity • palmitoyl-CoA hydrolase activity Cellular component • extracellular region • extracellular space • nucleus • lysosome • Golgi apparatus • cytosol • synaptic vesicle • membrane • axon • dendrite • neuronal cell body • membrane raft • extracellular exosome Biological process • protein depalmitoylation • receptor-mediated endocytosis • pinocytosis • lysosomal lumen acidification • neurotransmitter secretion • nervous system development • brain development • visual perception • grooming behavior • associative learning • adult locomotory behavior • protein transport • lipid catabolic process • sphingolipid catabolic process • protein catabolic process • negative regulation of cell growth • membrane raft organization • regulation of phospholipase A2 activity • negative regulation of apoptotic process • negative regulation of neuron apoptotic process • cellular protein catabolic process • positive regulation of receptor-mediated endocytosis • positive regulation of pinocytosis • neuron development • regulation of synapse structure or activity • response to stimulus • cofactor transport • cofactor metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5538	19063
Ensembl	ENSG00000131238	ENSMUSG00000028657
UniProt	P50897	O88531
RefSeq (mRNA)	NM_000310	NM_008917
RefSeq (protein)	NP_000301	NP_032943
Location (UCSC)	Chr 1: 40.07 – 40.1 Mb	Chr 4: 122.84 – 122.86 Mb
PubMed search

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 infantile neuronal ceroid lipofuscinosis 1 (CLN1, or INCL) and neuronal ceroid lipofuscinosis 4 (CLN4).^[1]

References

1. "Entrez Gene: palmitoyl-protein thioesterase 1".
2. Hellsten E, Vesa J, Speer MC, Mäkelä TP, Järvelä I, Alitalo K, Ott J, Peltonen L (June 1993). "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. doi:10.1006/geno.1993.1253. PMID 8325646.
3. Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L (August 1995). "Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis". Nature 376 (6541): 584–7. doi:10.1038/376584a0. PMID 7637805.

Further reading

• Tsukamoto T, Iida J, Dobashi Y, et al. (2006). "Overexpression in colorectal carcinoma of two lysosomal enzymes, CLN2 and CLN1, involved in neuronal ceroid lipofuscinosis.". Cancer 106 (7): 1489–97. doi:10.1002/cncr.21764. PMID 16518810.
• Simonati A, Tessa A, Bernardina BD, et al. (2009). "Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations.". Pediatr. Neurol. 40 (4): 271–6. doi:10.1016/j.pediatrneurol.2008.10.018. PMID 19302939.
• Hofmann SL, Atashband A, Cho SK, et al. (2002). "Neuronal ceroid lipofuscinoses caused by defects in soluble lysosomal enzymes (CLN1 and CLN2).". Curr. Mol. Med. 2 (5): 423–37. doi:10.2174/1566524023362294. PMID 12125808.
• Kousi M, Siintola E, Dvorakova L, et al. (2009). "Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis.". Brain 132 (Pt 3): 810–9. doi:10.1093/brain/awn366. PMID 19201763.
• Weimer JM, Kriscenski-Perry E, Elshatory Y, Pearce DA (2002). "The neuronal ceroid lipofuscinoses: mutations in different proteins result in similar disease.". Neuromolecular Med. 1 (2): 111–24. doi:10.1385/NMM:1:2:111. PMID 12025857.
• Martins-de-Souza D, Gattaz WF, Schmitt A, et al. (2009). "Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.". Eur Arch Psychiatry Clin Neurosci 259 (3): 151–63. doi:10.1007/s00406-008-0847-2. PMID 19165527.
• Otsuki T, Ota T, Nishikawa T, et al. (2005). "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. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Zhang H, Li XJ, Martin DB, Aebersold R (2003). "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry". Nat. Biotechnol. 21 (6): 660–6. doi:10.1038/nbt827. PMID 12754519.
• Calero G, Gupta P, Nonato MC, et al. (2003). "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. doi:10.1074/jbc.M301225200. PMID 12855696.
• Kim SJ, Zhang Z, Sarkar C, et al. (2008). "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. doi:10.1172/JCI33482. PMC 2515381. PMID 18704195.
• Ramadan H, Al-Din AS, Ismail A, et al. (2007). "Adult neuronal ceroid lipofuscinosis caused by deficiency in palmitoyl protein thioesterase 1". Neurology 68 (5): 387–8. doi:10.1212/01.wnl.0000252825.85947.2f. PMID 17261688.
• Ahtiainen L, Van Diggelen OP, Jalanko A, Kopra O (2003). "Palmitoyl protein thioesterase 1 is targeted to the axons in neurons". J. Comp. Neurol. 455 (3): 368–77. doi:10.1002/cne.10492. PMID 12483688.
• Gregório SP, Sallet PC, Do KA; et al. (2009). "Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence". Psychiatry Res 165 (1–2): 1–9. doi:10.1016/j.psychres.2007.08.011. PMID 19054571.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Dawson G, Cho S (2000). "Batten's disease: clues to neuronal protein catabolism in lysosomes". J. Neurosci. Res. 60 (2): 133–40. doi:10.1002/(SICI)1097-4547(20000415)60:2<133::AID-JNR1>3.0.CO;2-3. PMID 10740217.
• Goswami R, Ahmed M, Kilkus J, et al. (2005). "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. doi:10.1002/jnr.20549. PMID 15929065.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Kim SJ, Zhang Z, Lee YC, Mukherjee AB (2006). "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. doi:10.1093/hmg/ddl078. PMID 16571600.
• Ahtiainen L, Luiro K, Kauppi M, et al. (2006). "Palmitoyl protein thioesterase 1 (PPT1) deficiency causes endocytic defects connected to abnormal saposin processing". Exp. Cell Res. 312 (9): 1540–53. doi:10.1016/j.yexcr.2006.01.034. PMID 16542649.

External links

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

This article incorporates text from the United States National Library of Medicine, which is in the public domain.