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Understanding the Functions of Peroxisomal Proteins: The Peroxisomal Proteome, Peroxisomal Import, Proteases and Other Protein Families and Their Network Organization: What Has Computational Biology Contributed?

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Molecular Machines Involved in Peroxisome Biogenesis and Maintenance

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Abstract

Computational studies based on high-throughput experimental datasets, some of which were even not generated in the context of peroxisome research, have considerably shaped the understanding of the peroxisomal proteome. Most importantly, this research revealed to a considerable extent how the total peroxisomal proteome is composed and what is its network and pathway structure. Computational prediction tools have been instrumental for finding proteins that are imported into peroxisomes via canonical import mechanisms. Based on sequence homology considerations, functions of many experimentally uncharacterized proteins have been suggested and subsequently verified experimentally. As an example, the case of peroxisomal proteases is analyzed in detail. Additionally, resources such databases or WWW servers dedicated to peroxisomal biology are reviewed.

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References

  • Akiyama H, Shii K, Yokono K, Yonezawa K, Sato S, Watanabe K, Baba S (1988) Cellular localization of insulin-degrading enzyme in rat liver using monoclonal antibodies specific for this enzyme. Biochem Biophys Res Commun 155(2):914–922

    CAS  PubMed  Google Scholar 

  • Aksam EB, Koek A, Kiel JA, Jourdan S, Veenhuis M, van dKI (2007) A peroxisomal lon protease and peroxisome degradation by autophagy play key roles in vitality of Hansenula polymorpha cells. Autophagy 3(2):96–105

    CAS  PubMed  Google Scholar 

  • Andrade-Navarro MA, Sanchez-Pulido L, McBride HM (2009) Mitochondrial vesicles: an ancient process providing new links to peroxisomes. Curr Opin Cell Biol 21(4):560–567

    CAS  PubMed  Google Scholar 

  • Authier F, Rachubinski RA, Posner BI, Bergeron JJ (1994) Endosomal proteolysis of insulin by an acidic thiol metalloprotease unrelated to insulin degrading enzyme. J Biol Chem 269(4):3010–3016

    CAS  PubMed  Google Scholar 

  • Authier F, Cameron PH, Taupin V (1996) Association of insulin-degrading enzyme with a 70 kDa cytosolic protein in hepatoma cells. Biochem J 319(Pt 1):149–158

    CAS  PubMed Central  PubMed  Google Scholar 

  • Babujee L, Wurtz V, Ma C, Lueder F, Soni P, van DA, Reumann S (2010) The proteome map of spinach leaf peroxisomes indicates partial compartmentalization of phylloquinone (vitamin K1) biosynthesis in plant peroxisomes. J Exp Bot 61(5):1441–1453

    CAS  PubMed  Google Scholar 

  • Baker A, Sparkes IA (2005) Peroxisome protein import: some answers, more questions. Curr Opin Plant Biol 8(6):640–647

    CAS  PubMed  Google Scholar 

  • Bannai H, Tamada Y, Maruyama O, Nakai K, Miyano S (2002) Extensive feature detection of N-terminal protein sorting signals. Bioinformatics 18(2):298–305

    CAS  PubMed  Google Scholar 

  • Bartoszewska M, Williams C, Kikhney A, Opalinski L, van Roermund CW, de Boer R, Veenhuis M, van der Klei IJ (2012) Peroxisomal proteostasis involves a Lon family protein that functions as protease and chaperone. J Biol Chem 287(33):27380–27395

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baumeister H, Muller D, Rehbein M, Richter D (1993) The rat insulin-degrading enzyme. Molecular cloning and characterization of tissue-specific transcripts. FEBS Lett 317(3):250–254

    CAS  PubMed  Google Scholar 

  • Bennett RG, Duckworth WC, Hamel FG (2000) Degradation of amylin by insulin-degrading enzyme. J Biol Chem 275(47):36621–36625

    CAS  PubMed  Google Scholar 

  • Blum T, Briesemeister S, Kohlbacher O (2009) MultiLoc2: integrating phylogeny and gene ontology terms improves subcellular protein localization prediction. BMC Bioinformatics 10:274

    PubMed Central  PubMed  Google Scholar 

  • Boden M, Hawkins J (2005) Prediction of subcellular localization using sequence-biased recurrent networks. Bioinformatics 21(10):2279–2286

    CAS  PubMed  Google Scholar 

  • Bonekamp NA, Volkl A, Fahimi HD, Schrader M (2009) Reactive oxygen species and peroxisomes: struggling for balance. Biofactors 35(4):346–355

    CAS  PubMed  Google Scholar 

  • Bork P, Koonin EV (1998) Predicting functions from protein sequences–where are the bottlenecks? Nat Genet 18(4):313–318

    CAS  PubMed  Google Scholar 

  • Bork P, Dandekar T, Diaz-Lazcoz Y, Eisenhaber F, Huynen M, Yuan Y (1998) Predicting function: from genes to genomes and back. J Mol Biol 283(4):707–725

    CAS  PubMed  Google Scholar 

  • Bota DA, Davies KJ (2002) Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism. Nat Cell Biol 4(9):674–680

    CAS  PubMed  Google Scholar 

  • Brady S, Shatkay H (2008) EpiLoc: a (working) text-based system for predicting protein subcellular location. Pac Symp Biocomput 604–615

    Google Scholar 

  • Braverman N, Steel G, Obie C, Moser A, Moser H, Gould SJ, Valle D (1997) Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nat Genet 15(4):369–376

    CAS  PubMed  Google Scholar 

  • Briesemeister S, Rahnenfuhrer J, Kohlbacher O (2010) YLoc--an interpretable web server for predicting subcellular localization. Nucleic Acids Res 38(Web Server Issue):W497–W502

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bulloj A, Leal MC, Xu H, Castano EM, Morelli L (2010) Insulin-degrading enzyme sorting in exosomes: a secretory pathway for a key brain amyloid-beta degrading protease. J Alzheimers Dis 19(1):79–95

    PubMed  Google Scholar 

  • Bussell JD, Behrens C, Ecke W, Eubel H (2013) Arabidopsis peroxisome proteomics". Front Plant Sci 4:101

    PubMed Central  PubMed  Google Scholar 

  • Chang CC, Warren DS, Sacksteder KA, Gould SJ (1999) PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import. J Cell Biol 147(4):761–774

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chesneau V, Perlman RK, Li W, Keller GA, Rosner MR (1997) Insulin-degrading enzyme does not require peroxisomal localization for insulin degradation. Endocrinology 138(8):3444–3451

    CAS  PubMed  Google Scholar 

  • Chiti F, Dobson CM (2006) Protein misfolding functional amyloid, and human disease. Annu Rev Biochem 75:333–366

    CAS  PubMed  Google Scholar 

  • Chou KC, Shen HB (2010a) A new method for predicting the subcellular localization of eukaryotic proteins with both single and multiple sites: Euk-mPLoc 2.0. PLoS One 5(4):e9931

    PubMed Central  PubMed  Google Scholar 

  • Chou KC, Shen HB (2010b) Plant-mPLoc: a top-down strategy to augment the power for predicting plant protein subcellular localization. PLoSOne 5(6):e11335

    PubMed Central  PubMed  Google Scholar 

  • Clastre M, Papon N, Courdavault V, Giglioli-Guivarc'h N, St-Pierre B, Simkin AJ (2011) Subcellular evidence for the involvement of peroxisomes in plant isoprenoid biosynthesis. Plant Signal Behav 6(12):2044–2046

    CAS  PubMed Central  PubMed  Google Scholar 

  • Danpure CJ, Jennings PR, Leiper JM, Lumb MJ, Oatey PB (1996) Targeting of alanine: glyoxylate aminotransferase in normal individuals and its mistargeting in patients with primary hyperoxaluria type 1. Ann N Y Acad Sci 804:477–490

    CAS  PubMed  Google Scholar 

  • De DC (1969) The peroxisome: a new cytoplasmic organelle. Proc R Soc Lond B Biol Sci 173(30):71–83

    Google Scholar 

  • Delille HK, Alves R, Schrader M (2009) Biogenesis of peroxisomes and mitochondria: linked by division. Histochem Cell Biol 131(4):441–446

    CAS  PubMed  Google Scholar 

  • Diano S, Liu ZW, Jeong JK, Dietrich MO, Ruan HB, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser JL, Belsham DD, Sarruf DA, Schwartz MW, Bennett AM, Shanabrough M, Mobbs CV, Yang X, Gao XB, Horvath TL (2011) Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nat Med 17(9):1121–1127

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dimmer EC, Huntley RP, Faruque Y, Sawford T, O'Donovan C, Martin MJ, Bely B, Browne P, Mun CW, Eberhardt R, Gardner M, Laiho K, Legge D, Magrane M, Pichler K, Poggioli D, Sehra H, Auchincloss A, Axelsen K, Blatter MC, Boutet E, Braconi-Quintaje S, Breuza L, Bridge A, Coudert E, Estreicher A, Famiglietti L, Ferro-Rojas S, Feuermann M, Gos A, Gruaz-Gumowski N, Hinz U, Hulo C, James J, Jimenez S, Jungo F, Keller G, Lemercier P, Lieberherr D, Masson P, Moinat M, Pedruzzi I, Poux S, Rivoire C, Roechert B, Schneider M, Stutz A, Sundaram S, Tognolli M, Bougueleret L, Rgoud-Puy G, Cusin I, Duek-Roggli P, Xenarios I, Apweiler R (2012) The UniProt-GO annotation database in 2011. Nucleic Acids Res 40(Database issue):D565–D570

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dische FE, Wernstedt C, Westermark GT, Westermark P, Pepys MB, Rennie JA, Gilbey SG, Watkins PJ (1988) Insulin as an amyloid-fibril protein at sites of repeated insulin injections in a diabetic patient. Diabetologia 31(3):158–161

    CAS  PubMed  Google Scholar 

  • Distel B, Veenhuis M, Tabak HF (1987) Import of alcohol oxidase into peroxisomes of Saccharomyces cerevisiae. EMBO J 6(10):3111–3116

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC (2010) Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141(4):668–681

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dodt G, Braverman N, Wong C, Moser A, Moser HW, Watkins P, Valle D, Gould SJ (1995) Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Nat Genet 9(2):115–125

    CAS  PubMed  Google Scholar 

  • Duckworth WC, Bennett RG, Hamel FG (1998) Insulin degradation: progress and potential. Endocr Rev 19(5):608–624

    CAS  PubMed  Google Scholar 

  • Dyer JM, McNew JA, Goodman JM (1996) The sorting sequence of the peroxisomal integral membrane protein PMP47 is contained within a short hydrophilic loop. J Cell Biol 133(2):269–280

    CAS  PubMed  Google Scholar 

  • Ebberink MS, Kofster J, Wanders RJ, Waterham HR (2010) Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. Hum Mutat 31(1):E1058–E1070

    PubMed  Google Scholar 

  • Eisenhaber F (2012) A decade after the first full human genome sequencing: when will we understand our own genome? J Bioinform Comput Biol 10(5):1271001

    PubMed  Google Scholar 

  • Eisenhaber B, Eisenhaber F (2007) Posttranslational modifications and subcellular localization signals: indicators of sequence regions without inherent 3D structure? Curr Protein Pept Sci 8(2):197–203

    CAS  PubMed  Google Scholar 

  • Eisenhaber B, Eisenhaber F (2010) Prediction of posttranslational modification of proteins from their amino acid sequence. Methods Mol Biol 609:365–384

    CAS  PubMed  Google Scholar 

  • Eisenhaber B, Bork P, Eisenhaber F (1998) Sequence properties of GPI-anchored proteins near the omega-site: constraints for the polypeptide binding site of the putative transamidase. Protein Eng 11(12):1155–1161

    CAS  PubMed  Google Scholar 

  • Eisenhaber F, Eisenhaber B, Kubina W, Maurer-Stroh S, Neuberger G, Schneider G, Wildpaner M (2003a) Prediction of lipid posttranslational modifications and localization signals from protein sequences: big-Pi, NMT and PTS1. Nucleic Acids Res 31(13):3631–3634

    CAS  PubMed Central  PubMed  Google Scholar 

  • Eisenhaber F, Eisenhaber B, Maurer-Stroh S (2003b) Prediction of post-translational modifications from amino acid sequence: problems, pitfalls, methodological hints. In: Andrade MM (ed) Bioinformatics and genomes: current perspectives, 1st edn. Horizon Scientific Press, Wymondham, pp 81–105

    Google Scholar 

  • Eisenhaber B, Eisenhaber F, Maurer-Stroh S, Neuberger G (2004) Prediction of sequence signals for lipid post-translational modifications: insights from case studies. Proteomics 4(6):1614–1625

    CAS  PubMed  Google Scholar 

  • Elgersma Y, Kwast L, van den Berg M, Snyder WB, Distel B, Subramani S, Tabak HF (1997) Overexpression of Pex15p, a phosphorylated peroxisomal integral membrane protein required for peroxisome assembly in S.cerevisiae, causes proliferation of the endoplasmic reticulum membrane. EMBO J 16(24):7326–7341

    CAS  PubMed Central  PubMed  Google Scholar 

  • Elgersma Y, Elgersma-Hooisma M, Wenzel T, McCaffery JM, Farquhar MG, Subramani S (1998) A mobile PTS2 receptor for peroxisomal protein import in Pichia pastoris. J Cell Biol 140(4):807–820

    CAS  PubMed Central  PubMed  Google Scholar 

  • Emanuelsson O, Elofsson A, von Heijne G, Cristobal S (2003) In silico prediction of the peroxisomal proteome in fungi, plants and animals. J Mol Biol 330(2):443–456

    CAS  PubMed  Google Scholar 

  • Emanuelsson O, Brunak S, von Heijne G, Nielsen H (2007) Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc 2(4):953–971

    CAS  PubMed  Google Scholar 

  • Erdmann R, Blobel G (1996) Identification of Pex13p a peroxisomal membrane receptor for the PTS1 recognition factor. J Cell Biol 135(1):111–121

    CAS  PubMed  Google Scholar 

  • Eubel H, Meyer EH, Taylor NL, Bussell JD, O'Toole N, Heazlewood JL, Castleden I, Small ID, Smith SM, Millar AH (2008) Novel proteins, putative membrane transporters, and an integrated metabolic network are revealed by quantitative proteomic analysis of Arabidopsis cell culture peroxisomes. Plant Physiol 148(4):1809–1829

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fang Y, Morrell JC, Jones JM, Gould SJ (2004) PEX3 functions as a PEX19 docking factor in the import of class I peroxisomal membrane proteins. J Cell Biol 164(6):863–875

    CAS  PubMed Central  PubMed  Google Scholar 

  • Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE, Selkoe DJ, Guenette S (2003) Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A 100(7):4162–4167

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fransen M, Van Veldhoven PP, Subramani S (1999) Identification of peroxisomal proteins by using M13 phage protein VI phage display: molecular evidence that mammalian peroxisomes contain a 2,4-dienoyl-CoA reductase. Biochem J 340(Pt 2):561–568

    CAS  PubMed Central  PubMed  Google Scholar 

  • Freitag J, Ast J, Bolker M (2012) Cryptic peroxisomal targeting via alternative splicing and stop codon read-through in fungi. Nature 485(7399):522–525

    CAS  PubMed  Google Scholar 

  • Fujiki Y, Matsuzono Y, Matsuzaki T, Fransen M (2006) Import of peroxisomal membrane proteins: the interplay of Pex3p- and Pex19p-mediated interactions. Biochim Biophys Acta 1763(12):1639–1646

    CAS  PubMed  Google Scholar 

  • Fujiki Y, Nashiro C, Miyata N, Tamura S, Okumoto K (2012) New insights into dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p in shuttling of PTS1-receptor Pex5p during peroxisome biogenesis. Biochim Biophys Acta 1823(1):145–149

    CAS  PubMed  Google Scholar 

  • Fujiwara T, Hori K, Ozaki K, Yokota Y, Mitsuya S, Ichiyanagi T, Hattori T, Takabe T (2008) Enzymatic characterization of peroxisomal and cytosolic betaine aldehyde dehydrogenases in barley. Physiol Plant 134(1):22–30

    CAS  PubMed  Google Scholar 

  • Fukao Y, Hayashi M, Nishimura M (2002) Proteomic analysis of leaf peroxisomal proteins in greening cotyledons of Arabidopsis thaliana. Plant Cell Physiol 43(7):689–696

    CAS  PubMed  Google Scholar 

  • Fukao Y, Hayashi M, Hara-Nishimura I, Nishimura M (2003) Novel glyoxysomal protein kinase, GPK1, identified by proteomic analysis of glyoxysomes in etiolated cotyledons of Arabidopsis thaliana. Plant Cell Physiol 44(10):1002–1012

    CAS  PubMed  Google Scholar 

  • Furuta S, Hashimoto T, Miura S, Mori M, Tatibana M (1982) Cell-free synthesis of the enzymes of peroxisomal beta-oxidation. Biochem Biophys Res Commun 105(2):639–646

    CAS  PubMed  Google Scholar 

  • Garg A, Bhasin M, Raghava GP (2005) Support vector machine-based method for subcellular localization of human proteins using amino acid compositions, their order, and similarity search. J Biol Chem 280(15):14427–14432

    CAS  PubMed  Google Scholar 

  • Gatto GJ Jr, Geisbrecht BV, Gould SJ, Berg JM (2000) Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. Nat Struct Biol 7(12):1091–1095

    CAS  PubMed  Google Scholar 

  • Girzalsky W, Platta HW, Erdmann R (2009) Protein transport across the peroxisomal membrane. Biol Chem 390(8):745–751

    CAS  PubMed  Google Scholar 

  • Glebov K, Schutze S, Walter J (2011) Functional relevance of a novel SlyX motif in non-conventional secretion of insulin-degrading enzyme. J Biol Chem 286(26):22711–22715

    CAS  PubMed Central  PubMed  Google Scholar 

  • Glover JR, Andrews DW, Subramani S, Rachubinski RA (1994) Mutagenesis of the amino targeting signal of Saccharomyces cerevisiae 3-ketoacyl-CoA thiolase reveals conserved amino acids required for import into peroxisomes in vivo. J Biol Chem 269(10):7558–7563

    CAS  PubMed  Google Scholar 

  • Gould SG, Keller GA, Subramani S (1987) Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase. J Cell Biol 105(6 Pt 2):2923–2931

    CAS  PubMed  Google Scholar 

  • Gould SJ, Keller GA, Subramani S (1988) Identification of peroxisomal targeting signals located at the carboxy terminus of four peroxisomal proteins. J Cell Biol 107(3):897–905

    CAS  PubMed  Google Scholar 

  • Gould SJ, Keller GA, Hosken N, Wilkinson J, Subramani S (1989) A conserved tripeptide sorts proteins to peroxisomes. J Cell Biol 108(5):1657–1664

    CAS  PubMed  Google Scholar 

  • Gould SJ, Kalish JE, Morrell JC, Bjorkman J, Urquhart AJ, Crane DI (1996) Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor. J Cell Biol 135(1):85–95

    CAS  PubMed  Google Scholar 

  • Goyer A, Johnson TL, Collakova E, Shachar-Hill Y, Rhodes D, Hanson AD (2004) Characterization and metabolic function of a peroxisomal sarcosine and pipecolate oxidase from Arabidopsis. J Biol Chem 279(17):16947–16953

    CAS  PubMed  Google Scholar 

  • Gur E, Sauer RT (2008) Recognition of misfolded proteins by Lon, a AAA(+) protease. Genes Dev 22(16):2267–2277

    CAS  PubMed Central  PubMed  Google Scholar 

  • Halbach A, Rucktaschel R, Rottensteiner H, Erdmann R (2009a) The N-domain of Pex22p can functionally replace the Pex3p N-domain in targeting and peroxisome formation. J Biol Chem 284(6):3906–3916

    CAS  PubMed  Google Scholar 

  • Halbach A, Rucktaschel R, Rottensteiner H, Erdmann R (2009b) The N-domain of Pex22p can functionally replace the Pex3p N-domain in targeting and peroxisome formation. J Biol Chem 284(6):3906–3916

    CAS  PubMed  Google Scholar 

  • Halbach A, Rucktaschel R, Rottensteiner H, Erdmann R (2009c) The N-domain of Pex22p can functionally replace the Pex3p N-domain in targeting and peroxisome formation. J Biol Chem 284(6):3906–3916

    CAS  PubMed  Google Scholar 

  • Hawkins J, Boden M (2006) Detecting and sorting targeting peptides with neural networks and support vector machines. J Bioinform Comput Biol 4(1):1–18

    CAS  PubMed  Google Scholar 

  • Hawkins J, Mahony D, Maetschke S, Wakabayashi M, Teasdale RD, Boden M (2007) Identifying novel peroxisomal proteins. Proteins 69(3):606–616

    CAS  PubMed  Google Scholar 

  • Hayashi M, Aoki M, Kondo M, Nishimura M (1997) Changes in targeting efficiencies of proteins to plant microbodies caused by amino acid substitutions in the carboxy-terminal tripeptide. Plant Cell Physiol 38(6):759–768

    CAS  PubMed  Google Scholar 

  • Helm M, Luck C, Prestele J, Hierl G, Huesgen PF, Frohlich T, Arnold GJ, Adamska I, Gorg A, Lottspeich F, Gietl C (2007) Dual specificities of the glyoxysomal/peroxisomal processing protease Deg15 in higher plants. Proc Natl Acad Sci U S A 104(27):11501–11506

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hoepfner S, Severin F, Cabezas A, Habermann B, Runge A, Gillooly D, Stenmark H, Zerial M (2005) Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 121(3):437–450

    CAS  PubMed  Google Scholar 

  • Hogenboom S, Tuyp JJ, Espeel M, Koster J, Wanders RJ, Waterham HR (2004a) Human mevalonate pyrophosphate decarboxylase is localized in the cytosol. Mol Genet Metab 81(3):216–224

    CAS  PubMed  Google Scholar 

  • Hogenboom S, Tuyp JJ, Espeel M, Koster J, Wanders RJ, Waterham HR (2004b) Mevalonate kinase is a cytosolic enzyme in humans. J Cell Sci 117(Pt 4):631–639

    CAS  PubMed  Google Scholar 

  • Hogenboom S, Tuyp JJ, Espeel M, Koster J, Wanders RJ, Waterham HR (2004c) Phosphomevalonate kinase is a cytosolic protein in humans. J Lipid Res 45(4):697–705

    CAS  PubMed  Google Scholar 

  • Holbrook JD, Birdsey GM, Yang Z, Bruford MW, Danpure CJ (2000) Molecular adaptation of alanine:glyoxylate aminotransferase targeting in primates. Mol Biol Evol 17(3):387–400

    CAS  PubMed  Google Scholar 

  • Honsho M, Fujiki Y (2001) Topogenesis of peroxisomal membrane protein requires a short, positively charged intervening-loop sequence and flanking hydrophobic segments. study using human membrane protein PMP34. J Biol Chem 276(12):9375–9382

    CAS  PubMed  Google Scholar 

  • Horton P, Park KJ, Obayashi T, Fujita N, Harada H, Ms-Collier CJ, Nakai K (2007) WoLF PSORT: protein localization predictor. Nucleic Acids Res 35(Web Server issue):W585–W587

    PubMed Central  PubMed  Google Scholar 

  • Imazaki A, Tanaka A, Harimoto Y, Yamamoto M, Akimitsu K, Park P, Tsuge T (2010) Contribution of peroxisomes to secondary metabolism and pathogenicity in the fungal plant pathogen Alternaria alternata. Eukaryot Cell 9(5):682–694

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jankowski A, Kim JH, Collins RF, Daneman R, Walton P, Grinstein S (2001) In situ measurements of the pH of mammalian peroxisomes using the fluorescent protein pHluorin. J Biol Chem 276(52):48748–48753

    CAS  PubMed  Google Scholar 

  • Jones JM, Morrell JC, Gould SJ (2004) PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins. J Cell Biol 164(1):57–67

    CAS  PubMed Central  PubMed  Google Scholar 

  • Joo HJ, Yim YH, Jeong PY, Jin YX, Lee JE, Kim H, Jeong SK, Chitwood DJ, Paik YK (2009) Caenorhabditis elegans utilizes dauer pheromone biosynthesis to dispose of toxic peroxisomal fatty acids for cellular homoeostasis. Biochem J 422(1):61–71

    CAS  PubMed  Google Scholar 

  • Joo HJ, Kim KY, Yim YH, Jin YX, Kim H, Kim MY, Paik YK (2010) Contribution of the peroxisomal acox gene to the dynamic balance of daumone production in Caenorhabditis elegans. J Biol Chem 285(38):29319–29325

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamada T, Nito K, Hayashi H, Mano S, Hayashi M, Nishimura M (2003) Functional differentiation of peroxisomes revealed by expression profiles of peroxisomal genes in Arabidopsis thaliana. Plant Cell Physiol 44(12):1275–1289

    CAS  PubMed  Google Scholar 

  • Kamada-Nobusada T, Hayashi M, Fukazawa M, Sakakibara H, Nishimura M (2008) A putative peroxisomal polyamine oxidase, AtPAO4, is involved in polyamine catabolism in Arabidopsis thaliana. Plant Cell Physiol 49(9):1272–1282

    CAS  PubMed  Google Scholar 

  • Kanehisa M (2013) Molecular network analysis of diseases and drugs in KEGG. Methods Mol Biol 939:263–275

    CAS  PubMed  Google Scholar 

  • Kanzawa N, Maeda Y, Ogiso H, Murakami Y, Taguchi R, Kinoshita T (2009) Peroxisome dependency of alkyl-containing GPI-anchor biosynthesis in the endoplasmic reticulum. Proc Natl Acad Sci U S A 106(42):17711–17716

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kaur N, Hu J (2011) Defining the plant peroxisomal proteome: from Arabidopsis to rice. Front Plant Sci 2:103

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kaye GC, Butler MG, Ardenne AJ, Edmondson SJ, Camm AJ, Slavin G (1986) Identification of immunoreactive atrial natriuretic peptide in atrial amyloid. J Clin Pathol 39(5):581–582

    CAS  PubMed Central  PubMed  Google Scholar 

  • Keller GA, Krisans S, Gould SJ, Sommer JM, Wang CC, Schliebs W, Kunau W, Brody S, Subramani S (1991) Evolutionary conservation of a microbody targeting signal that targets proteins to peroxisomes, glyoxysomes, and glycosomes. J Cell Biol 114(5):893–904

    CAS  PubMed  Google Scholar 

  • Kienow L, Schneider K, Bartsch M, Stuible HP, Weng H, Miersch O, Wasternack C, Kombrink E (2008) Jasmonates meet fatty acids: functional analysis of a new acyl-coenzyme A synthetase family from Arabidopsis thaliana. J Exp Bot 59(2):403–419

    CAS  PubMed  Google Scholar 

  • Kikuchi M, Hatano N, Yokota S, Shimozawa N, Imanaka T, Taniguchi H (2004) Proteomic analysis of rat liver peroxisome: presence of peroxisome-specific isozyme of Lon protease. J Biol Chem 279(1):421–428

    CAS  PubMed  Google Scholar 

  • Kovacs WJ, Tape KN, Shackelford JE, Duan X, Kasumov T, Kelleher JK, Brunengraber H, Krisans SK (2007) Localization of the pre-squalene segment of the isoprenoid biosynthetic pathway in mammalian peroxisomes. Histochem Cell Biol 127(3):273–290

    CAS  PubMed  Google Scholar 

  • Kowit JD, Goldberg AL (1977) Intermediate steps in the degradation of a specific abnormal protein in Escherichia coli. J Biol Chem 252(23):8350–8357

    CAS  PubMed  Google Scholar 

  • Kragler F, Langeder A, Raupachova J, Binder M, Hartig A (1993) Two independent peroxisomal targeting signals in catalase A of Saccharomyces cerevisiae. J Cell Biol 120(3):665–673

    CAS  PubMed  Google Scholar 

  • Kunze M, Kragler F, Binder M, Hartig A, Gurvitz A (2002) Targeting of malate synthase 1 to the peroxisomes of Saccharomyces cerevisiae cells depends on growth on oleic acid medium. Eur J Biochem 269(3):915–922

    CAS  PubMed  Google Scholar 

  • Kunze M, Neuberger G, Maurer-Stroh S, Ma J, Eck T, Braverman N, Schmid JA, Eisenhaber F, Berger J (2011) Structural requirements for interaction of peroxisomal targeting signal 2 and its receptor PEX7. J Biol Chem 286(52):45048–45062

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuo WL, Gehm BD, Rosner MR, Li W, Keller G (1994) Inducible expression and cellular localization of insulin-degrading enzyme in a stably transfected cell line. J Biol Chem 269(36):22599–22606

    CAS  PubMed  Google Scholar 

  • Kurochkin IV (1998) Amyloidogenic determinant as a substrate recognition motif of insulin-degrading enzyme. FEBS Lett 427(2):153–156

    CAS  PubMed  Google Scholar 

  • Kurochkin IV (2001) Insulin-degrading enzyme: embarking on amyloid destruction. Trends Biochem Sci 26(7):421–425

    CAS  PubMed  Google Scholar 

  • Kurochkin IV, Goto S (1994) Alzheimer's beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Lett 345(1):33–37

    CAS  PubMed  Google Scholar 

  • Kurochkin IV, Konagaya A, Nagashima T, Schonbach C, RIKEN GER Group (2003) Identification of potential peroxisomal proteins in mouse. Genome Res 13(6B):1560

    CAS  Google Scholar 

  • Kurochkin IV, Mizuno Y, Konagaya A, Sakaki Y, Schonbach C, Okazaki Y (2007) Novel peroxisomal protease Tysnd1 processes PTS1- and PTS2-containing enzymes involved in beta-oxidation of fatty acids. EMBO J 26(3):835–845

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuznetsov V, Lee HK, Maurer-Stroh S, Molnar MJ, Pongor S, Eisenhaber B, Eisenhaber F (2013) How bioinformatics influences health informatics: usage of biomolecular sequences, expression profiles and automated microscopic image analyses for clinical needs and public health. Health Inform Sci Syst 1:2

    Google Scholar 

  • Lamesch P, Berardini TZ, Li D, Swarbreck D, Wilks C, Sasidharan R, Muller R, Dreher K, Alexander DL, Garcia-Hernandez M, Karthikeyan AS, Lee CH, Nelson WD, Ploetz L, Singh S, Wensel A, Huala E (2012) The Arabidopsis Information Resource (TAIR): improved gene annotation and new tools. Nucleic Acids Res 40(Database issue):D1202–D1210

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lametschwandtner G, Brocard C, Fransen M, Van VP, Berger J, Hartig A (1998) The difference in recognition of terminal tripeptides as peroxisomal targeting signal 1 between yeast and human is due to different affinities of their receptor Pex5p to the cognate signal and to residues adjacent to it. J Biol Chem 273(50):33635–33643

    CAS  PubMed  Google Scholar 

  • Lanyon-Hogg T, Warriner SL, Baker A (2010) Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes. Biol Cell 102(4):245–263

    CAS  PubMed  Google Scholar 

  • Leal MC, Magnani N, Villordo S, Buslje CM, Evelson P, Castano EM, Morelli L (2013) Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid beta (abeta) peptide catabolism and functionality. J Biol Chem 288(18):12920–12931

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee I, Suzuki CK (2008) Functional mechanics of the ATP-dependent Lon protease- lessons from endogenous protein and synthetic peptide substrates. Biochim Biophys Acta 1784(5):727–735

    CAS  PubMed Central  PubMed  Google Scholar 

  • Leissring MA, Farris W, Chang AY, Walsh DM, Wu X, Sun X, Frosch MP, Selkoe DJ (2003) Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40(6):1087–1093

    CAS  PubMed  Google Scholar 

  • Leissring MA, Farris W, Wu X, Christodoulou DC, Haigis MC, Guarente L, Selkoe DJ (2004) Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria. Biochem J 383(Pt. 3):439–446

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lingard MJ, Bartel B (2009) Arabidopsis LON2 is necessary for peroxisomal function and sustained matrix protein import. Plant Physiol 151(3):1354–1365

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ma C, Agrawal G, Subramani S (2011) Peroxisome assembly: matrix and membrane protein biogenesis. J Cell Biol 193(1):7–16

    CAS  PubMed Central  PubMed  Google Scholar 

  • Malito E, Hulse RE, Tang WJ (2008) Amyloid beta-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin. Cell Mol Life Sci 65(16):2574–2585

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marzioch M, Erdmann R, Veenhuis M, Kunau WH (1994) PAS7 encodes a novel yeast member of the WD-40 protein family essential for import of 3-oxoacyl-CoA thiolase, a PTS2-containing protein, into peroxisomes. EMBO J 13(20):4908–4918

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mast FD, Fagarasanu A, Rachubinski R (2010) The peroxisomal protein importomer: a bunch of transients with expanding waistlines. Nat Cell Biol 12(3):203–205

    CAS  PubMed  Google Scholar 

  • Matsuda S, Vert JP, Saigo H, Ueda N, Toh H, Akutsu T (2005) A novel representation of protein sequences for prediction of subcellular location using support vector machines. Protein Sci 14(11):2804–2813

    CAS  PubMed Central  PubMed  Google Scholar 

  • Matsuzono Y, Matsuzaki T, Fujiki Y (2006) Functional domain mapping of peroxin Pex19p: interaction with Pex3p is essential for function and translocation. J Cell Sci 119(Pt 17):3539–3550

    CAS  PubMed  Google Scholar 

  • Maurer-Stroh S, Eisenhaber F (2005) Refinement and prediction of protein prenylation motifs. Genome Biol 6(6):R55

    PubMed Central  PubMed  Google Scholar 

  • Maurer-Stroh S, Eisenhaber B, Eisenhaber F (2002) N-terminal N-myristoylation of proteins: refinement of the sequence motif and its taxon-specific differences. J Mol Biol 317(4):523–540

    CAS  PubMed  Google Scholar 

  • Maynard EL, Gatto GJ Jr, Berg JM (2004) Pex5p binding affinities for canonical and noncanonical PTS1 peptides. Proteins 55(4):856–861

    CAS  PubMed  Google Scholar 

  • McCollum D, Monosov E, Subramani S (1993) The pas8 mutant of Pichia pastoris exhibits the peroxisomal protein import deficiencies of Zellweger syndrome cells–the PAS8 protein binds to the COOH-terminal tripeptide peroxisomal targeting signal, and is a member of the TPR protein family. J Cell Biol 121(4):761–774

    CAS  PubMed  Google Scholar 

  • McNew JA, Goodman JM (1996) The targeting and assembly of peroxisomal proteins: some old rules do not apply. Trends Biochem Sci 21(2):54–58

    CAS  PubMed  Google Scholar 

  • Meinecke M, Cizmowski C, Schliebs W, Kruger V, Beck S, Wagner R, Erdmann R (2010) The peroxisomal importomer constitutes a large and highly dynamic pore. Nat Cell Biol 12(3):273–277

    CAS  PubMed  Google Scholar 

  • Mirsky IA, Broh-Kahn RH (1949) The inactivation of insulin by tissue extracts; the distribution and properties of insulin inactivating extracts. Arch Biochem 20(1):1–9

    CAS  PubMed  Google Scholar 

  • Mitsuya S, Yokota Y, Fujiwara T, Mori N, Takabe T (2009) OsBADH1 is possibly involved in acetaldehyde oxidation in rice plant peroxisomes. FEBS Lett 583(22):3625–3629

    CAS  PubMed  Google Scholar 

  • Mizuno Y, Ninomiya Y, Nakachi Y, Iseki M, Iwasa H, Akita M, Tsukui T, Shimozawa N, Ito C, Toshimori K, Nishimukai M, Hara H, Maeba R, Okazaki T, Alodaib AN, Al AM, Jacob M, Alkuraya FS, Horai Y, Watanabe M, Motegi H, Wakana S, Noda T, Kurochkin IV, Mizuno Y, Schonbach C, Okazaki Y (2013) Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility. PLoS Genet 9(2):e1003286

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morelli L, Llovera RE, Alonso LG, Frangione B, de Prat-Gay G, Ghiso J, Castano EM (2005) Insulin-degrading enzyme degrades amyloid peptides associated with British and Danish familial dementia. Biochem Biophys Res Commun 332(3):808–816

    CAS  PubMed  Google Scholar 

  • Morita M, Kurochkin IV, Motojima K, Goto S, Takano T, Okamura S, Sato R, Yokota S, Imanaka T (2000) Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades oxidized proteins. Cell Struct Funct 25(5):309–315

    CAS  PubMed  Google Scholar 

  • Motley AM, Hettema EH (2007) Yeast peroxisomes multiply by growth and division. J Cell Biol 178(3):399–410

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nair DM, Purdue PE, Lazarow PB (2004) Pex7p translocates in and out of peroxisomes in Saccharomyces cerevisiae. J Cell Biol 167(4):599–604

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nakai K, Horton P (1999) PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization. Trends Biochem Sci 24(1):34–36

    CAS  PubMed  Google Scholar 

  • Neant-Fery M, Garcia-Ordonez RD, Logan TP, Selkoe DJ, Li L, Reinstatler L, Leissring MA (2008) Molecular basis for the thiol sensitivity of insulin-degrading enzyme. Proc Natl Acad Sci U S A 105(28):9582–9587

    CAS  PubMed Central  PubMed  Google Scholar 

  • Neuberger G, Maurer-Stroh S, Eisenhaber B, Hartig A, Eisenhaber F (2003a) Motif refinement of the peroxisomal targeting signal 1 and evaluation of taxon-specific differences. J Mol Biol 328(3):567–579

    CAS  PubMed  Google Scholar 

  • Neuberger G, Maurer-Stroh S, Eisenhaber B, Hartig A, Eisenhaber F (2003b) Prediction of peroxisomal targeting signal 1 containing proteins from amino acid sequence. J Mol Biol 328(3):581–592

    CAS  PubMed  Google Scholar 

  • Neuberger G, Kunze M, Eisenhaber F, Berger J, Hartig A, Brocard C (2004) Hidden localization motifs: naturally occurring peroxisomal targeting signals in non-peroxisomal proteins. Genome Biol 5(12):R97

    PubMed Central  PubMed  Google Scholar 

  • Nguyen SD, Baes M, Van Veldhoven PP (2008) Degradation of very long chain dicarboxylic polyunsaturated fatty acids in mouse hepatocytes, a peroxisomal process. Biochim Biophys Acta 1781(8):400–405

    CAS  PubMed  Google Scholar 

  • Nicolay K, Veenhuis M, Douma AC, Harder W (1987) A 31P NMR study of the internal pH of yeast peroxisomes. Arch Microbiol 147(1):37–41

    CAS  PubMed  Google Scholar 

  • Nishikawa M, Hagishita T, Yurimoto H, Kato N, Sakai Y, Hatanaka T (2000a) Primary structure and expression of peroxisomal acetylspermidine oxidase in the methylotrophic yeast Candida boidinii. FEBS Lett 476(3):150–154

    CAS  PubMed  Google Scholar 

  • Nishikawa M, Hagishita T, Yurimoto H, Kato N, Sakai Y, Hatanaka T (2000b) Primary structure and expression of peroxisomal acetylspermidine oxidase in the methylotrophic yeast Candida boidinii. FEBS Lett 476(3):150–154

    CAS  PubMed  Google Scholar 

  • Nito K, Hayashi M, Nishimura M (2002) Direct interaction and determination of binding domains among peroxisomal import factors in Arabidopsis thaliana. Plant Cell Physiol 43(4):355–366

    CAS  PubMed  Google Scholar 

  • Niu B, Jin YH, Feng KY, Lu WC, Cai YD, Li GZ (2008) Using AdaBoost for the prediction of subcellular location of prokaryotic and eukaryotic proteins. Mol Divers 12(1):41–45

    CAS  PubMed  Google Scholar 

  • Oatey PB, Lumb MJ, Danpure CJ (1996a) Molecular basis of the variable mitochondrial and peroxisomal localisation of alanine-glyoxylate aminotransferase. Eur J Biochem 241(2):374–385

    CAS  PubMed  Google Scholar 

  • Oatey PB, Lumb MJ, Jennings PR, Danpure CJ (1996b) Context dependency of the PTS1 motif in human alanine: glyoxylate aminotransferase 1. Ann Y Acad Sci 804:652–653

    CAS  Google Scholar 

  • Oda T, Uchida C, Miura S (2000) Mitochondrial targeting signal-induced conformational change and repression of the peroxisomal targeting signal of the precursor for rat liver serine:pyruvate/alanine:glyoxylate aminotransferase. J Biochem 127(4):665–671

    CAS  PubMed  Google Scholar 

  • Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, Yamanaka I, Kiyosawa H, Yagi K, Tomaru Y, Hasegawa Y, Nogami A, Schonbach C, Gojobori T, Baldarelli R, Hill DP, Bult C, Hume DA, Quackenbush J, Schriml LM, Kanapin A, Matsuda H, Batalov S, Beisel KW, Blake JA, Bradt D, Brusic V, Chothia C, Corbani LE, Cousins S, Dalla E, Dragani TA, Fletcher CF, Forrest A, Frazer KS, Gaasterland T, Gariboldi M, Gissi C, Godzik A, Gough J, Grimmond S, Gustincich S, Hirokawa N, Jackson IJ, Jarvis ED, Kanai A, Kawaji H, Kawasawa Y, Kedzierski RM, King BL, Konagaya A, Kurochkin IV, Lee Y, Lenhard B, Lyons PA, Maglott DR, Maltais L, Marchionni L, McKenzie L, Miki H, Nagashima T, Numata K, Okido T, Pavan WJ, Pertea G, Pesole G, Petrovsky N, Pillai R, Pontius JU, Qi D, Ramachandran S, Ravasi T, Reed JC, Reed DJ, Reid J, Ring BZ, Ringwald M, Sandelin A, Schneider C, Semple CA, Setou M, Shimada K, Sultana R, Takenaka Y, Taylor MS, Teasdale RD, Tomita M, Verardo R, Wagner L, Wahlestedt C, Wang Y, Watanabe Y, Wells C, Wilming LG, Wynshaw-Boris A, Yanagisawa M, Yang I, Yang L, Yuan Z, Zavolan M, Zhu Y, Zimmer A, Carninci P, Hayatsu N, Hirozane-Kishikawa T, Konno H, Nakamura M, Sakazume N, Sato K, Shiraki T, Waki K, Kawai J, Aizawa K, Arakawa T, Fukuda S, Hara A, Hashizume W, Imotani K, Ishii Y, Itoh M, Kagawa I, Miyazaki A, Sakai K, Sasaki D, Shibata K, Shinagawa A, Yasunishi A, Yoshino M, Waterston R, Lander ES, Rogers J, Birney E, Hayashizaki Y (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420(6915):563–573

    PubMed  Google Scholar 

  • Okumoto K, Kametani Y, Fujiki Y (2011) Two proteases, trypsin domain-containing 1 (Tysnd1) and peroxisomal lon protease (PsLon), cooperatively regulate fatty acid beta-oxidation in peroxisomal matrix. J Biol Chem 286(52):44367–44379

    CAS  PubMed Central  PubMed  Google Scholar 

  • Omi S, Nakata R, Okamura-Ikeda K, Konishi H, Taniguchi H (2008) Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes. J Biochem 143(5):649–660

    CAS  PubMed  Google Scholar 

  • Ono Y, Kim DW, Watanabe K, Sasaki A, Niitsu M, Berberich T, Kusano T, Takahashi Y (2012) Constitutively and highly expressed Oryza sativa polyamine oxidases localize in peroxisomes and catalyze polyamine back conversion. Amino Acids 42(2–3):867–876

    CAS  PubMed  Google Scholar 

  • Oshima Y, Kamigaki A, Nakamori C, Mano S, Hayashi M, Nishimura M, Esaka M (2008) Plant catalase is imported into peroxisomes by Pex5p but is distinct from typical PTS1 import. Plant Cell Physiol 49(4):671–677

    CAS  PubMed  Google Scholar 

  • Osinga KA, Swinkels BW, Gibson WC, Borst P, Veeneman GH, Van Boom JH, Michels PA, Opperdoes FR (1985) Topogenesis of microbody enzymes: a sequence comparison of the genes for the glycosomal (microbody) and cytosolic phosphoglycerate kinases of Trypanosoma brucei. EMBO J 4(13B):3811–3817

    CAS  PubMed Central  PubMed  Google Scholar 

  • Osumi T, Hashimoto T (1980) Purification and properties of mitochondrial and peroxisomal 3-hydroxyacyl-CoA dehydrogenase from rat liver. Arch Biochem Biophys 203(1):372–383

    CAS  PubMed  Google Scholar 

  • Osumi T, Tsukamoto T, Hata S (1992) Signal peptide for peroxisomal targeting: replacement of an essential histidine residue by certain amino acids converts the amino-terminal presequence of peroxisomal 3-ketoacyl-CoA thiolase to a mitochondrial signal peptide. Biochem Biophys Res Commun 186(2):811–818

    CAS  PubMed  Google Scholar 

  • Pan D, Nakatsu T, Kato H (2013) Crystal structure of peroxisomal targeting signal-2 bound to its receptor complex Pex7p-Pex21p. Nat Struct Mol Biol 20(8):987–93

    CAS  PubMed  Google Scholar 

  • Perry RJ, Mast FD, Rachubinski RA (2009) Endoplasmic reticulum-associated secretory proteins Sec20p, Sec39p, and Dsl1p are involved in peroxisome biogenesis. Eukaryot Cell 8(6):830–843

    CAS  PubMed Central  PubMed  Google Scholar 

  • Petriv OI, Tang L, Titorenko VI, Rachubinski RA (2004) A new definition for the consensus sequence of the peroxisome targeting signal type 2. J Mol Biol 341(1):119–134

    CAS  PubMed  Google Scholar 

  • Petsalaki EI, Bagos PG, Litou ZI, Hamodrakas SJ (2006) PredSL: a tool for the N-terminal sequence-based prediction of protein subcellular localization. Genomics Proteomics Bioinformatics 4(1):48–55

    CAS  PubMed  Google Scholar 

  • Rawlings ND, Barrett AJ, Bateman A (2012) MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res 40(Database issue):D343–D350

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rayapuram N, Subramani S (2006) The importomer–a peroxisomal membrane complex involved in protein translocation into the peroxisome matrix. Biochim Biophys Acta 1763(12):1613–1619

    CAS  PubMed  Google Scholar 

  • Rehling P, Marzioch M, Niesen F, Wittke E, Veenhuis M, Kunau WH (1996) The import receptor for the peroxisomal targeting signal 2 (PTS2) in Saccharomyces cerevisiae is encoded by the PAS7 gene. EMBO J 15(12):2901–2913

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reumann S (2004) Specification of the peroxisome targeting signals type 1 and type 2 of plant peroxisomes by bioinformatics analyses. Plant Physiol 135(2):783–800

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reumann S, Babujee L, Ma C, Wienkoop S, Siemsen T, Antonicelli GE, Rasche N, Luder F, Weckwerth W, Jahn O (2007) Proteome analysis of Arabidopsis leaf peroxisomes reveals novel targeting peptides, metabolic pathways, and defense mechanisms. Plant Cell 19(10):3170–3193

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reumann S, Quan S, Aung K, Yang P, Manandhar-Shrestha K, Holbrook D, Linka N, Switzenberg R, Wilkerson CG, Weber AP, Olsen LJ, Hu J (2009) In-depth proteome analysis of Arabidopsis leaf peroxisomes combined with in vivo subcellular targeting verification indicates novel metabolic and regulatory functions of peroxisomes. Plant Physiol 150(1):125–143

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reumann S, Buchwald D, Lingner T (2012) PredPlantPTS1: a web server for the prediction of plant peroxisomal proteins. Front Plant Sci 3:194

    PubMed Central  PubMed  Google Scholar 

  • Rucktaschel R, Girzalsky W, Erdmann R (2011a) Protein import machineries of peroxisomes. Biochim Biophys Acta 1808(3):892–900

    PubMed  Google Scholar 

  • Rucktaschel R, Girzalsky W, Erdmann R (2011b) Protein import machineries of peroxisomes. Biochim Biophys Acta 1808(3):892–900

    PubMed  Google Scholar 

  • Saikia S, Scott B (2009) Functional analysis and subcellular localization of two geranylgeranyl diphosphate synthases from Penicillium paxilli. Mol Genet Genomics 282(3):257–271

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sapir-Mir M, Mett A, Belausov E, Tal-Meshulam S, Frydman A, Gidoni D, Eyal Y (2008) Peroxisomal localization of Arabidopsis isopentenyl diphosphate isomerases suggests that part of the plant isoprenoid mevalonic acid pathway is compartmentalized to peroxisomes. Plant Physiol 148(3):1219–1228

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schluter A, Real-Chicharro A, Gabaldon T, Sanchez-Jimenez F, Pujol A (2010) PeroxisomeDB 2.0: an integrative view of the global peroxisomal metabolome. Nucleic Acids Res 38(Database issue):D800–D805

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schneider K, Kienow L, Schmelzer E, Colby T, Bartsch M, Miersch O, Wasternack C, Kombrink E, Stuible HP (2005) A new type of peroxisomal acyl-coenzyme A synthetase from Arabidopsis thaliana has the catalytic capacity to activate biosynthetic precursors of jasmonic acid. J Biol Chem 280(14):13962–13972

    CAS  PubMed  Google Scholar 

  • Schrader M, Fahimi HD (2008) The peroxisome: still a mysterious organelle. Histochem Cell Biol 129(4):421–440

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schrader M, Yoon Y (2007) Mitochondria and peroxisomes: are the 'big brother' and the 'little sister' closer than assumed? Bioessays 29(11):1105–1114

    CAS  PubMed  Google Scholar 

  • Schueller N, Holton SJ, Fodor K, Milewski M, Konarev P, Stanley WA, Wolf J, Erdmann R, Schliebs W, Song YH, Wilmanns M (2010) The peroxisomal receptor Pex19p forms a helical mPTS recognition domain. EMBO J 29(15):2491–2500

    CAS  PubMed Central  PubMed  Google Scholar 

  • Seta KA, Roth RA (1997) Overexpression of insulin degrading enzyme: cellular localization and effects on insulin signaling. Biochem Biophys Res Commun 231(1):167–171

    CAS  PubMed  Google Scholar 

  • Shen Y, Joachimiak A, Rosner MR, Tang WJ (2006) Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature 443(7113):870–874

    CAS  PubMed Central  PubMed  Google Scholar 

  • Simkin AJ, Guirimand G, Papon N, Courdavault V, Thabet I, Ginis O, Bouzid S, Giglioli-Guivarc'h N, Clastre M (2011) Peroxisomal localisation of the final steps of the mevalonic acid pathway in planta. Planta 234(5):903–914

    CAS  PubMed  Google Scholar 

  • Sirota FL, Batagov A, Schneider G, Eisenhaber B, Eisenhaber F, Maurer-Stroh S (2012) Beware of moving targets: reference proteome content fluctuates substantially over the years. J Bioinform Comput Biol 10(6):1250020

    PubMed  Google Scholar 

  • Small I, Peeters N, Legeai F, Lurin C (2004) Predotar: a tool for rapidly screening proteomes for N-terminal targeting sequences. Proteomics 4(6):1581–1590

    CAS  PubMed  Google Scholar 

  • Song ES, Juliano MA, Juliano L, Hersh LB (2003) Substrate activation of insulin-degrading enzyme (insulysin). A potential target for drug development. J Biol Chem 278(50):49789–49794

    CAS  PubMed  Google Scholar 

  • Soukupova M, Sprenger C, Gorgas K, Kunau WH, Dodt G (1999) Identification and characterization of the human peroxin PEX3. Eur J Cell Biol 78(6):357–374

    CAS  PubMed  Google Scholar 

  • Sparkes IA, Hawes C, Baker A (2005) AtPEX2 and AtPEX10 are targeted to peroxisomes independently of known endoplasmic reticulum trafficking routes. Plant Physiol 139(2):690–700

    CAS  PubMed Central  PubMed  Google Scholar 

  • Spiegel CN, Batista-Pereira LG, Bretas JA, Eiras AE, Hooper AM, Peixoto AA, Soares MJ (2011) Pheromone gland development and pheromone production in lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae). J Med Entomol 48(3):489–495

    CAS  PubMed  Google Scholar 

  • Stahlberg H, Kutejova E, Suda K, Wolpensinger B, Lustig A, Schatz G, Engel A, Suzuki CK (1999) Mitochondrial Lon of Saccharomyces cerevisiae is a ring-shaped protease with seven flexible subunits. Proc Natl Acad Sci U S A 96(12):6787–6790

    CAS  PubMed Central  PubMed  Google Scholar 

  • Steinberg SJ, Dodt G, Raymond GV, Braverman NE, Moser AB, Moser HW (2006) Peroxisome biogenesis disorders. Biochim Biophys Acta 1763(12):1733–1748

    CAS  PubMed  Google Scholar 

  • Subramani S (1992) Targeting of proteins into the peroxisomal matrix. J Membr Biol 125(2):99–106

    CAS  PubMed  Google Scholar 

  • Swinkels BW, Gould SJ, Bodnar AG, Rachubinski RA, Subramani S (1991) A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase. EMBO J 10(11):3255–3262

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tabak HF, Murk JL, Braakman I, Geuze HJ (2003) Peroxisomes start their life in the endoplasmic reticulum. Traffic 4(8):512–518

    CAS  PubMed  Google Scholar 

  • Tabak HF, van der Zand A, Braakman I (2008a) Peroxisomes: minted by the ER. Curr Opin Cell Biol 20(4):393–400

    CAS  PubMed  Google Scholar 

  • Tabak HF, van der Zand A, Braakman I (2008b) Peroxisomes: minted by the ER. Curr Opin Cell Biol 20(4):393–400

    CAS  PubMed  Google Scholar 

  • Tamboli IY, Barth E, Christian L, Siepmann M, Kumar S, Singh S, Tolksdorf K, Heneka MT, Lutjohann D, Wunderlich P, Walter J (2010) Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion. J Biol Chem 285(48):37405–37414

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tamura T, Akutsu T (2007) Subcellular location prediction of proteins using support vector machines with alignment of block sequences utilizing amino acid composition. BMC Bioinformatics 8:466

    PubMed Central  PubMed  Google Scholar 

  • Tanabe Y, Maruyama J, Yamaoka S, Yahagi D, Matsuo I, Tsutsumi N, Kitamoto K (2011) Peroxisomes are involved in biotin biosynthesis in Aspergillus and Arabidopsis. J Biol Chem 286(35):30455–30461

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tanz SK, Castleden I, Hooper CM, Vacher M, Small I, Millar HA (2013) SUBA3: a database for integrating experimentation and prediction to define the SUBcellular location of proteins in Arabidopsis. Nucleic Acids Res 41(Database issue):D1185–D1191

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thabet I, Guirimand G, Courdavault V, Papon N, Godet S, Dutilleul C, Bouzid S, Giglioli-Guivarc'h N, Clastre M, Simkin AJ (2011) "The subcellular localization of periwinkle farnesyl diphosphate synthase provides insight into the role of peroxisome in isoprenoid biosynthesis", J. Plant Physiol 168(17):2110–2116

    CAS  Google Scholar 

  • Theodoulou FL, Bernhardt K, Linka N, Baker A (2013a) Peroxisome membrane proteins: multiple trafficking routes and multiple functions? Biochem J 451(3):345–352

    CAS  PubMed  Google Scholar 

  • Theodoulou FL, Bernhardt K, Linka N, Baker A (2013b) Peroxisome membrane proteins: multiple trafficking routes and multiple functions? Biochem J 451(3):345–352

    CAS  PubMed  Google Scholar 

  • Titorenko VI, Rachubinski RA (1998) Mutants of the yeast Yarrowia lipolytica defective in protein exit from the endoplasmic reticulum are also defective in peroxisome biogenesis. Mol Cell Biol 18(5):2789–2803

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tolbert NE, Yamazaki RK (1969) Leaf peroxisomes and their relation to photorespiration and photosynthesis. Ann N Y Acad Sci 168(2):325–341

    CAS  PubMed  Google Scholar 

  • Tolbert NE, Oeser A, Kisaki T, Hageman RH, Yamazaki RK (1968) Peroxisomes from spinach leaves containing enzymes related to glycolate metabolism. J Biol Chem 243(19):5179–5184

    CAS  PubMed  Google Scholar 

  • Turnell WG, Finch JT (1992) Binding of the dye congo red to the amyloid protein pig insulin reveals a novel homology amongst amyloid-forming peptide sequences. J Mol Biol 227(4):1205–1223

    CAS  PubMed  Google Scholar 

  • Van der Leij I, Franse MM, Elgersma Y, Distel B, Tabak HF (1993) PAS10 is a tetratricopeptide-repeat protein that is essential for the import of most matrix proteins into peroxisomes of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 90(24):11782–11786

    PubMed Central  PubMed  Google Scholar 

  • van der Zand A, Braakman I, Tabak HF (2010) Peroxisomal membrane proteins insert into the endoplasmic reticulum. Mol Biol Cell 21(12):2057–2065

    PubMed Central  PubMed  Google Scholar 

  • van Roermund CW, de Jong M, IJlst L, van Marle J, Dansen TB, Wanders RJ, Waterham HR (2004) The peroxisomal lumen in Saccharomyces cerevisiae is alkaline. JCell Sci 117(no. Pt 18):4231–4237

    PubMed  Google Scholar 

  • Van AE, Fransen M (2006) Targeting signals in peroxisomal membrane proteins. Biochim Biophys Acta 1763(12):1629–1638

    Google Scholar 

  • Van DP, Maurer-Stroh S, Plasman K, Van DJ, Colaert N, Timmerman E, De Bock PJ, Goethals M, Rousseau F, Schymkowitz J, Vandekerckhove J, Gevaert K (2009) Analysis of protein processing by N-terminal proteomics reveals novel species-specific substrate determinants of granzyme B orthologs. Mol Cell Proteomics 8(2):258–272

    Google Scholar 

  • Van DP, Maurer-Stroh S, Hao H, Colaert N, Timmerman E, Eisenhaber F, Vandekerckhove J, Gevaert K (2010) The substrate specificity profile of human granzyme A. Biol Chem 391(8):983–997

    Google Scholar 

  • Venkatesh S, Lee J, Singh K, Lee I, Suzuki CK (2012) Multitasking in the mitochondrion by the ATP-dependent Lon protease. Biochim Biophys Acta 1823(1):56–66

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wagner I, Arlt H, van Dyck L, Langer T, Neupert W (1994) Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria. EMBO J 13(21):5135–5145

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wanders RJ, Waterham HR (2006) Peroxisomal disorders: the single peroxisomal enzyme deficiencies. Biochim Biophys Acta 1763(12):1707–1720

    CAS  PubMed  Google Scholar 

  • Waugh DF (1946) Reactions involved in insulin fibril formation. Fed Proc 5(1 Pt 2):111

    CAS  PubMed  Google Scholar 

  • Willemsen AM, Jansen GA, Komen JC, van Hoff S, Waterham HR, Brites PM, Wanders RJ, van Kampen AH (2008) Organization and integration of biomedical knowledge with concept maps for key peroxisomal pathways. Bioinformatics 24(16):i21–i27

    CAS  PubMed  Google Scholar 

  • Wiszniewski AA, Zhou W, Smith SM, Bussell JD (2009) Identification of two Arabidopsis genes encoding a peroxisomal oxidoreductase-like protein and an acyl-CoA synthetase-like protein that are required for responses to pro-auxins. Plant Mol Biol 69(5):503–515

    CAS  PubMed  Google Scholar 

  • Wolff SP, Dean RT (1986) Fragmentation of proteins by free radicals and its effect on their susceptibility to enzymic hydrolysis. Biochem J 234(2):399–403

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wong WC, Maurer-Stroh S, Eisenhaber F (2010) More than 1,001 problems with protein domain databases: transmembrane regions, signal peptides and the issue of sequence homology. PLoS Comput Biol 6(7):e1000867

    PubMed Central  PubMed  Google Scholar 

  • Wu T, Yankovskaya V, McIntire WS (2003) Cloning, sequencing, and heterologous expression of the murine peroxisomal flavoprotein, N1-acetylated polyamine oxidase. J Biol Chem 278(23):20514–20525

    CAS  PubMed  Google Scholar 

  • Yan M, Rachubinski DA, Joshi S, Rachubinski RA, Subramani S (2008) Dysferlin domain-containing proteins, Pex30p and Pex31p, localized to two compartments, control the number and size of oleate-induced peroxisomes in Pichia pastoris. Mol Biol Cell 19(3):885–898

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zolman BK, Yoder A, Bartel B (2000) Genetic analysis of indole-3-butyric acid responses in Arabidopsis thaliana reveals four mutant classes. Genetics 156(3):1323–1337

    CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01, Matrix, Singapore, 138671

    Poonam Singh, Sebastian Maurer-Stroh, Igor Kurochkin, Birgit Eisenhaber & Frank Eisenhaber

  2. School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore, Singapore, 637551

    Sebastian Maurer-Stroh

  3. Department of Biological Sciences (DBS), National University of Singapore (NUS), 8 Medical Drive, Singapore, Singapore, 117597

    Frank Eisenhaber

  4. School of Computer Engineering (SCE), Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore, Singapore, 637553

    Frank Eisenhaber

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  1. Poonam Singh
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  2. Sebastian Maurer-Stroh
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  3. Igor Kurochkin
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  4. Birgit Eisenhaber
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  5. Frank Eisenhaber
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Correspondence to Frank Eisenhaber .

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  1. Mauerbach, Austria

    Cecile Brocard

  2. Max F. Perutz Laboratories University of Vienna, Vienna, Austria

    Andreas Hartig

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Singh, P., Maurer-Stroh, S., Kurochkin, I., Eisenhaber, B., Eisenhaber, F. (2014). Understanding the Functions of Peroxisomal Proteins: The Peroxisomal Proteome, Peroxisomal Import, Proteases and Other Protein Families and Their Network Organization: What Has Computational Biology Contributed?. In: Brocard, C., Hartig, A. (eds) Molecular Machines Involved in Peroxisome Biogenesis and Maintenance. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1788-0_9

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