Protein Engineering vol. 4 no. 1 pp. 33-37, 1990
© 1990 Oxford University Press
OTHER |
Cleavage-site motifs in mitochondrial targeting peptides
Research Group for Theoretical Biophysics. Department of Theoretical Physics, Royal Institute of Technology S-l00 44 Stockholm 1Department of Molecular Biology, Karolinska institute Center for Biotechnology, NOVUM S-14l 52 Huddinge, Sweden
2To whom correspondence should be addressed
Although mitochondrial targeting peptides lack a common consensus sequence, a certain bias in the positional distribution of amino acids has recently been found. These patterns seem to be associated with cleavage of the precursor proteins by matrix processing proteases. We have extended the previous studies and found new sequence motifs that are conserved within subgroups of mitochondrial targeting peptides. These motifs have certain common themes, indicating that they are associated with cleavage by one single protease. Two of the conserved patterns have a high predictive value, but even for sequences that do not possess these patterns, a fairly accurate prediction of the cleavage site is shown to be possible. We also suggest that a well-conserved RXY 
(S/A) pattern may be used to engineer efficiently recognized cleavage sites into uncleaved or artificial mitochondrial targeting peptides.
Keywords: cleavage site/matrix processing proteases/mitochondrial targeting peptides/precursor proteins/sequence motifs
Received April 27, 1990; accepted July 17, 1990.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Yabu, A. Shimuzu, and M. Yamashita A Novel Mitochondrial Sphingomyelinase in Zebrafish Cells J. Biol. Chem., July 24, 2009; 284(30): 20349 - 20363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, M. Johansson, and A. Karlsson Human UMP-CMP Kinase 2, a Novel Nucleoside Monophosphate Kinase Localized in Mitochondria J. Biol. Chem., January 18, 2008; 283(3): 1563 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Yasuda, K. Fukuo, X. Sun, M. Nishitani, T. Yotsui, M. Higuchi, T. Suzuki, H. Rakugi, O. Smithies, N. Maeda, et al. Apop-1, a Novel Protein Inducing Cyclophilin D-dependent but Bax/Bak-related Channel-independent Apoptosis J. Biol. Chem., August 18, 2006; 281(33): 23899 - 23907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. T. Struewing, A. Toborek, and C. D. Mao Mitochondrial and Nuclear Forms of Wnt13 Are Generated via Alternative Promoters, Alternative RNA Splicing, and Alternative Translation Start Sites J. Biol. Chem., March 17, 2006; 281(11): 7282 - 7293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ensenauer, M. He, J.-M. Willard, E. S. Goetzman, T. J. Corydon, B. B. Vandahl, A.-W. Mohsen, G. Isaya, and J. Vockley Human Acyl-CoA Dehydrogenase-9 Plays a Novel Role in the Mitochondrial {beta}-Oxidation of Unsaturated Fatty Acids J. Biol. Chem., September 16, 2005; 280(37): 32309 - 32316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Xie, H. Li, Q. Wang, S. Xie, A. Rahmeh, W. Dai, and M. Y. W. T. Lee Further Characterization of Human DNA Polymerase {delta} Interacting Protein 38 J. Biol. Chem., June 10, 2005; 280(23): 22375 - 22384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Zhang, M. Brock, and N. P. Keller Connection of Propionyl-CoA Metabolism to Polyketide Biosynthesis in Aspergillus nidulans Genetics, October 1, 2004; 168(2): 785 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-H. Tong, G. N. L. Jameson, B. H. Huynh, and T. A. Rouault Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its ability to assemble a [4Fe-4S] cluster PNAS, August 19, 2003; 100(17): 9762 - 9767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Goggin, R. Lipscombe, E. Fedorova, A. H. Millar, A. Mann, C. A. Atkins, and P. M. C. Smith Dual Intracellular Localization and Targeting of Aminoimidazole Ribonucleotide Synthetase in Cowpea Plant Physiology, March 1, 2003; 131(3): 1033 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Luo, X. Chen, H. Fang, and N. Green Factors Governing Nonoverlapping Substrate Specificity by Mitochondrial Inner Membrane Peptidase J. Biol. Chem., February 7, 2003; 278(7): 4943 - 4948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, Y. L. Lyu, and J. C. Wang Dual localization of human DNA topoisomerase IIIalpha to mitochondria and nucleus PNAS, September 17, 2002; 99(19): 12114 - 12119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Schwer, B. J. North, R. A. Frye, M. Ott, and E. Verdin The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase J. Cell Biol., August 19, 2002; 158(4): 647 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Qiao, F. C. Mei, V. L. Popov, L. A. Vergara, and X. Cheng Cell Cycle-dependent Subcellular Localization of Exchange Factor Directly Activated by cAMP J. Biol. Chem., July 12, 2002; 277(29): 26581 - 26586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Moran, Z. Sun, G. Sarath, R. Arredondo-Peter, E. K. James, M. Becana, and R. V. Klucas Molecular Cloning, Functional Characterization, and Subcellular Localization of Soybean Nodule Dihydrolipoamide Reductase Plant Physiology, January 1, 2002; 128(1): 300 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Klanner, H. Prokisch, and T. Langer MAP-1 and IAP-1, Two Novel AAA Proteases with Catalytic Sites on Opposite Membrane Surfaces in Mitochondrial Inner Membrane of Neurospora crassa Mol. Biol. Cell, September 1, 2001; 12(9): 2858 - 2869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Holzinger, W. Roschinger, F. Lagler, P. U. Mayerhofer, P. Lichtner, T. Kattenfeld, L. P. Thuy, W. L. Nyhan, H. G. Koch, A. C. Muntau, et al. Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency Hum. Mol. Genet., June 1, 2001; 10(12): 1299 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, R. K. Sunahara, A. Krumins, G. Perkins, M. L. Crochiere, M. Mackey, S. Bell, M. H. Ellisman, and S. S. Taylor Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein PNAS, March 13, 2001; 98(6): 3220 - 3225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. H. Luttik, P. Kötter, F. A. Salomons, I. J. van der Klei, J. P. van Dijken, and J. T. Pronk The Saccharomyces cerevisiae ICL2 Gene Encodes a Mitochondrial 2-Methylisocitrate Lyase Involved in Propionyl-Coenzyme A Metabolism J. Bacteriol., December 15, 2000; 182(24): 7007 - 7013. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. R. Kirby An Ancient Transpecific Polymorphism Shows Extreme Divergence in a Multitrait Cline in an Intertidal Snail (Nucella lapillus (L.)) Mol. Biol. Evol., December 1, 2000; 17(12): 1816 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Amery, M. Fransen, K. De Nys, G. P. Mannaerts, and P. P. Van Veldhoven Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans J. Lipid Res., November 1, 2000; 41(11): 1752 - 1759. [Abstract] [Full Text]
|
|
|
|
|
|
S. Ferdinandusse, S. Denis, L. IJlst, G. Dacremont, H. R. Waterham, and R. J. A. Wanders Subcellular localization and physiological role of {alpha}-methylacyl-CoA racemase J. Lipid Res., November 1, 2000; 41(11): 1890 - 1896. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Oxelmark, A. Marchini, I. Malanchi, F. Magherini, L. Jaquet, M. A. N. Hajibagheri, K. J. Blight, J.-C. Jauniaux, and M. Tommasino Mmf1p, a Novel Yeast Mitochondrial Protein Conserved throughout Evolution and Involved in Maintenance of the Mitochondrial Genome Mol. Cell. Biol., October 15, 2000; 20(20): 7784 - 7797. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Ueda, K. K. Wentz–Hunter, E. L. Cheng, T. Fukuchi, H. Abe, and B. Y.J.T. Yue Ultrastructural Localization of Myocilin in Human Trabecular Meshwork Cells and Tissues J. Histochem. Cytochem., October 1, 2000; 48(10): 1321 - 1330. [Abstract] [Full Text]
|
|
|
|
|
|
K. B. Busch and H. Fromm Plant Succinic Semialdehyde Dehydrogenase. Cloning, Purification, Localization in Mitochondria, and Regulation by Adenine Nucleotides Plant Physiology, October 1, 1999; 121(2): 589 - 598. [Abstract] [Full Text]
|
|
|
|
|
|
S. S. Branda, P. Cavadini, J. Adamec, F. Kalousek, F. Taroni, and G. Isaya Yeast and Human Frataxin Are Processed to Mature Form in Two Sequential Steps by the Mitochondrial Processing Peptidase J. Biol. Chem., August 6, 1999; 274(32): 22763 - 22769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fujikawa-Adachi, I. Nishimori, T. Taguchi, and S. Onishi Human Mitochondrial Carbonic Anhydrase VB. cDNA CLONING, mRNA EXPRESSION, SUBCELLULAR LOCALIZATION, AND MAPPING TO CHROMOSOME X J. Biol. Chem., July 23, 1999; 274(30): 21228 - 21233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Syken, T. De-Medina, and K. Munger TID1, a human homolog of the Drosophila tumor suppressor l(2)tid, encodes two mitochondrial modulators of apoptosis with opposing functions PNAS, July 20, 1999; 96(15): 8499 - 8504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-K. Huh and S.-O. Kang Molecular Cloning and Functional Expression of Alternative Oxidase from Candida albicans J. Bacteriol., July 1, 1999; 181(13): 4098 - 4102. [Abstract] [Full Text]
|
|
|
|
|
|
S. Santagata, D. Bhattacharyya, F.-H. Wang, N. Singha, A. Hodtsev, and E. Spanopoulou Molecular Cloning and Characterization of a Mouse Homolog of Bacterial ClpX, a Novel Mammalian Class II Member of the Hsp100/Clp Chaperone Family J. Biol. Chem., June 4, 1999; 274(23): 16311 - 16319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tanudji, S. Sjoling, E. Glaser, and J. Whelan Signals Required for the Import and Processing of the Alternative Oxidase into Mitochondria J. Biol. Chem., January 15, 1999; 274(3): 1286 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Pelloquin, P Belenguer, Y Menon, N Gas, and B Ducommun Fission yeast Msp1 is a mitochondrial dynamin-related protein J. Cell Sci., January 11, 1999; 112(22): 4151 - 4161. [Abstract] [PDF]
|
|
|
|
|
|
K. Kojima, S. Kitada, K. Shimokata, T. Ogishima, and A. Ito Cooperative Formation of a Substrate Binding Pocket by alpha - and beta -Subunits of Mitochondrial Processing Peptidase J. Biol. Chem., December 4, 1998; 273(49): 32542 - 32546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Knox, E. Sass, W. Neupert, and O. Pines Import into Mitochondria, Folding and Retrograde Movement of Fumarase in Yeast J. Biol. Chem., October 2, 1998; 273(40): 25587 - 25593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Nett, H. Schagger, and B. L. Trumpower Processing of the Presequence of the Schizosaccharomyces pombe Rieske Iron-Sulfur Protein Occurs in a Single Step and Can Be Converted to Two-step Processing by Mutation of a Single Proline to Serine in the Presequence J. Biol. Chem., April 10, 1998; 273(15): 8652 - 8658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Parra-Gessert, K. Koo, J. Fajardo, and R. L. Weiss Processing and Function of a Polyprotein Precursor of Two Mitochondrial Proteins in Neurospora crassa J. Biol. Chem., April 3, 1998; 273(14): 7972 - 7980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Guy and Q.-B. Li The Organization and Evolution of the Spinach Stress 70 Molecular Chaperone Gene Family PLANT CELL, April 1, 1998; 10(4): 539 - 556. [Abstract] [Full Text]
|
|
|
|
|
|
B. Lain, A. Yanez, A. Iriarte, and M. Martinez-Carrion Aminotransferase Variants as Probes for the Role of the N-terminal Region of a Mature Protein in Mitochondrial Precursor Import and Processing J. Biol. Chem., February 20, 1998; 273(8): 4406 - 4415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, C. J. Mann, Y. Bai, L. Ni, and H. Weiner Molecular Cloning, Characterization, and Potential Roles of Cytosolic and Mitochondrial Aldehyde Dehydrogenases in Ethanol Metabolism in Saccharomyces cerevisiae J. Bacteriol., February 15, 1998; 180(4): 822 - 830. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. H. Sjöberg, L. Wang, and S. Eriksson Substrate Specificity of Human Recombinant Mitochondrial Deoxyguanosine Kinase with Cytostatic and Antiviral Purine and Pyrimidine Analogs Mol. Pharmacol., February 1, 1998; 53(2): 270 - 273. [Abstract] [Full Text]
|
|
|
|
|
|
J. Ostergaard, G. Persiau, M. W. Davey, G. Bauw, and M. Van Montagu Isolation of a cDNA Coding for L-Galactono-gamma -Lactone Dehydrogenase, an Enzyme involved in the Biosynthesis of Ascorbic Acid in Plants. PURIFICATION, CHARACTERIZATION, cDNA CLONING, AND EXPRESSION IN YEAST J. Biol. Chem., November 28, 1997; 272(48): 30009 - 30016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bito, M. Haider, I. Hadler, and M. Breitenbach Identification and Phenotypic Analysis of Two Glyoxalase II Encoding Genes from Saccharomyces cerevisiae, GLO2 and GLO4, and Intracellular Localization of the Corresponding Proteins J. Biol. Chem., August 22, 1997; 272(34): 21509 - 21519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Arakane, T. Sugawara, H. Nishino, Z. Liu, J. A. Holt, D. Pain, D. M. Stocco, W. L. Miller, and J. F. Strauss III Steroidogenic acute regulatory protein (StAR) retains activity in the absence of its mitochondrial import sequence: Implications for the mechanism of StAR action PNAS, November 26, 1996; 93(24): 13731 - 13736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Hammen, M. Waltner, B. Hahnemann, T. S. Heard, and H. Weiner The Role of Positive Charges and Structural Segments in the Presequence of Rat Liver Aldehyde Dehydrogenase in Import into Mitochondria J. Biol. Chem., August 30, 1996; 271(35): 21041 - 21048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Eden, G. Simchen, and N. Benvenisty Two Yeast Homologs of ECA39, a Target for c-Myc Regulation, Code for Cytosolic and Mitochondrial Branched-chain Amino Acid Aminotransferases J. Biol. Chem., August 23, 1996; 271(34): 20242 - 20245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Church, C. Chapon, and R. O. Poyton Cloning and Characterization of PET100, a Gene Required for the Assembly of Yeast Cytochrome c Oxidase J. Biol. Chem., August 2, 1996; 271(31): 18499 - 18507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Marty and P. Fort A Delayed-early Response Nuclear Gene Encoding MRPL12, the Mitochondrial Homologue to the Bacterial Translational Regulator L7/L12 Protein J. Biol. Chem., May 10, 1996; 271(19): 11468 - 11476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-Y. Lin, S. B. Moss, and C. S. Rubin Characterization of S-AKAP84, a Novel Developmentally Regulated A Kinase Anchor Protein of Male Germ Cells J. Biol. Chem., November 17, 1995; 270(46): 27804 - 27811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Branda and G. Isaya Prediction and Identification of New Natural Substrates of the Yeast Mitochondrial Intermediate Peptidase J. Biol. Chem., November 10, 1995; 270(45): 27366 - 27373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Waltner and H. Weiner Conversion of a Nonprocessed Mitochondrial Precursor Protein into One That Is Processed by the Mitochondrial Processing Peptidase J. Biol. Chem., November 3, 1995; 270(44): 26311 - 26317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Sidhu, G. B. Kalmar, and T. J. Borgford Protease Evolution in Streptomyces griseus J. Biol. Chem., March 31, 1995; 270(13): 7594 - 7600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Nguyen, J. P. Erzberger, J. Root, and D. M. Wilson III The Human Homolog of Escherichia coli Orn Degrades Small Single-stranded RNA and DNA Oligomers J. Biol. Chem., August 18, 2000; 275(34): 25900 - 25906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Cavadini, J. Adamec, F. Taroni, O. Gakh, and G. Isaya Two-step Processing of Human Frataxin by Mitochondrial Processing Peptidase. PRECURSOR AND INTERMEDIATE FORMS ARE CLEAVED AT DIFFERENT RATES J. Biol. Chem., December 22, 2000; 275(52): 41469 - 41475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Trentin, X. Yin, S. Tahir, S. Lhotak, J. Farhang-Fallah, Y. Li, and M. Rozakis-Adcock A Mouse Homologue of the Drosophila Tumor Suppressor l(2)tid Gene Defines a Novel Ras GTPase-activating Protein (RasGAP)-binding Protein J. Biol. Chem., April 13, 2001; 276(16): 13087 - 13095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.-B. Kayser, P. G. Morgan, C. L. Hoppel, and M. M. Sedensky Mitochondrial Expression and Function of GAS-1 in Caenorhabditis elegans J. Biol. Chem., June 1, 2001; 276(23): 20551 - 20558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Szewczyk, A. Andrianopoulos, M. A. Davis, and M. J. Hynes A Single Gene Produces Mitochondrial, Cytoplasmic, and Peroxisomal NADP-dependent Isocitrate Dehydrogenase in Aspergillus nidulans J. Biol. Chem., September 28, 2001; 276(40): 37722 - 37729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Perez-Jannotti, S. M. Klein, and D. F. Bogenhagen Two Forms of Mitochondrial DNA Ligase III Are Produced in Xenopus laevis Oocytes J. Biol. Chem., December 21, 2001; 276(52): 48978 - 48987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yokogawa, N. Shimada, N. Takeuchi, L. Benkowski, T. Suzuki, A. Omori, T. Ueda, K. Nishikawa, L. L. Spremulli, and K. Watanabe Characterization and tRNA Recognition of Mammalian Mitochondrial Seryl-tRNA Synthetase J. Biol. Chem., June 23, 2000; 275(26): 19913 - 19920. [Abstract] [Full Text] [PDF]
|
|