Abstract
We evaluated the evolutionary conservation of glycine myristoylation within eukaryotic sequences. Our large-scale cross-genome analyses, available as MYRbase, show that the functional spectrum of myristoylated proteins is currently largely underestimated. We give experimental evidence for in vitro myristoylation of selected predictions. Furthermore, we classify five membrane-attachment factors that occur most frequently in combination with, or even replacing, myristoyl anchors, as some protein family examples show.
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References
Gordon JI, Duronio RJ, Rudnick DA, Adams SP, Gokel GW: Protein N-myristoylation. J Biol Chem. 1991, 266: 8647-8650.
Boutin JA: Myristoylation. Cell Signal. 1997, 9: 15-35. 10.1016/S0898-6568(96)00100-3.
Farazi TA, Waksman G, Gordon JI: The biology and enzymology of protein n-myristoylation. J Biol Chem. 2001, 276: 39501-39504. 10.1074/jbc.R100042200.
Nimchuk Z, Marois E, Kjemtrup S, Leister RT, Katagiri F, Dangl JL: Eukaryotic fatty acylation drives plasma membrane targeting and enhances function of several type III effector proteins from Pseudomonas syringae. Cell. 2000, 101: 353-363. 10.1016/S0092-8674(00)80846-6.
McCabe JB, Berthiaume LG: N-terminal protein acylation confers localization to cholesterol, sphingolipid-enriched membranes but not to lipid rafts/caveolae. Mol Biol Cell. 2001, 12: 3601-3617.
Resh MD: Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta. 1999, 1451: 1-16. 10.1016/S0167-4889(99)00075-0.
McCabe JB, Berthiaume LG: Functional roles for fatty acylated amino-terminal domains in subcellular localization. Mol Biol Cell. 1999, 10: 3771-3786.
Hayashi N, Matsubara M, Jinbo Y, Titani K, Izumi Y, Matsushima N: Nef of HIV-1 interacts directly with calcium-bound calmodulin. Protein Sci. 2002, 11: 529-537. 10.1110/ps.23702.
Hayashi N, Izumi Y, Titani K, Matsushima N: The binding of myristoylated N-terminal nonapeptide from neuro-specific protein CAP-23/NAP-22 to calmodulin does not induce the globular structure observed for the calmodulin-nonmyristylated peptide complex. Protein Sci. 2000, 9: 1905-1913.
Ames JB, Tanaka T, Stryer L, Ikura M: Portrait of a myristoyl switch protein. Curr Opin Struct Biol. 1996, 6: 432-438. 10.1016/S0959-440X(96)80106-0.
McLaughlin S, Aderem A: The myristoyl-electrostatic switch: a modulator of reversible protein-membrane interactions. Trends Biochem Sci. 1995, 20: 272-276. 10.1016/S0968-0004(00)89042-8.
Zhou W, Resh MD: Differential membrane binding of the human immunodeficiency virus type 1 matrix protein. J Virol. 1996, 70: 8540-8548.
Hantschel O, Nagar B, Guettler S, Kretzschmar J, Dorey K, Kuriyan J, Superti-Furga G: A myristoyl/phosphotyrosine switch regulates c-Abl. Cell. 2003, 112: 845-857. 10.1016/S0092-8674(03)00191-0.
Raju RV, Datla RS, Moyana TN, Kakkar R, Carlsen SA, Sharma RK: N-myristoyltransferase. Mol Cell Biochem. 2000, 204: 135-155. 10.1023/A:1007012622030.
Maurer-Stroh S, Eisenhaber B, Eisenhaber F: N-terminal N-myristoylation of proteins: refinement of the sequence motif and its taxon-specific differences. J Mol Biol. 2002, 317: 523-540. 10.1006/jmbi.2002.5425.
Maurer-Stroh S, Eisenhaber B, Eisenhaber F: N-terminal N-myristoylation of proteins: prediction of substrate proteins from amino acid sequence. J Mol Biol. 2002, 317: 541-557. 10.1006/jmbi.2002.5426.
NMT: MyristoylCoA:Protein N-Myristoyltransferase. [http://mendel.imp.univie.ac.at/myristate]
Li W, Jaroszewski L, Godzik A: Tolerating some redundancy significantly speeds up clustering of large protein databases. Bioinformatics. 2002, 18: 77-82. 10.1093/bioinformatics/18.1.77.
Li W, Jaroszewski L, Godzik A: Clustering of highly homologous sequences to reduce the size of large protein databases. Bioinformatics. 2001, 17: 282-283. 10.1093/bioinformatics/17.3.282.
Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, Martin MJ, Michoud K, O'Donovan C, Phan I, et al: The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res. 2003, 31: 365-370. 10.1093/nar/gkg095.
Marchler-Bauer A, Anderson JB, DeWeese-Scott C, Fedorova ND, Geer LY, He S, Hurwitz DI, Jackson JD, Jacobs AR, Lanczycki CJ, et al: CDD: a curated Entrez database of conserved domain alignments. Nucleic Acids Res. 2003, 31: 383-387. 10.1093/nar/gkg087.
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25: 3389-3402. 10.1093/nar/25.17.3389.
Boisson B, Giglione C, Meinnel T: Unexpected protein families including cell defense components feature in the N-myristoylome of a higher eukaryote. J Biol Chem. 2003, 278: 43418-43429. 10.1074/jbc.M307321200.
Chen CA, Manning DR: Regulation of G proteins by covalent modification. Oncogene. 2001, 20: 1643-1652. 10.1038/sj.onc.1204185.
Ueda T, Yamaguchi M, Uchimiya H, Nakano A: Ara6, a plant-unique novel type Rab GTPase, functions in the endocytic pathway of Arabidopsis thaliana. EMBO J. 2001, 20: 4730-4741. 10.1093/emboj/20.17.4730.
Gonzalez E, Kou R, Lin AJ, Golan DE, Michel T: Subcellular targeting and agonist-induced site-specific phosphorylation of endothelial nitric-oxide synthase. J Biol Chem. 2002, 277: 39554-39560. 10.1074/jbc.M207299200.
Furuya T, Kashuba C, Docampo R, Moreno SN: A novel phosphatidylinositol-phospholipase C of Trypanosoma cruzi that is lipid modified and activated during trypomastigote to amastigote differentiation. J Biol Chem. 2000, 275: 6428-6438. 10.1074/jbc.275.9.6428.
Maroun CR, Naujokas MA, Park M: Membrane targeting of Grb2-associated Binder-1 (Gab1) scaffolding protein through Src myristoylation sequence substitutes for Gab1 pleckstrin homology domain and switches an epidermal growth factor response to an invasive morphogenic program. Mol Biol Cell. 2003, 14: 1691-1708. 10.1091/mbc.E02-06-0352.
Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000, 1: 31-39. 10.1038/35036052.
Denny PW, Gokool S, Russell DG, Field MC, Smith DF: Acylation-dependent protein export in Leishmania. J Biol Chem. 2000, 275: 11017-11025. 10.1074/jbc.275.15.11017.
Maurer-Stroh S, Washietl S, Eisenhaber F: Protein prenyltransferases. Genome Biol. 2003, 4: 212-10.1186/gb-2003-4-4-212.
Maurer-Stroh S, Washietl S, Eisenhaber F: Protein prenyltransferases: anchor size, pseudogenes and parasites. Biol Chem. 2003, 384: 977-989. 10.1515/BC.2003.110.
Chatterjee S, Mayor S: The GPI-anchor and protein sorting. Cell Mol Life Sci. 2001, 58: 1969-1987. 10.1007/PL00000831.
Eisenhaber B, Maurer-Stroh S, Novatchkova M, Schneider G, Eisenhaber F: Enzymes and auxiliary factors for GPI lipid anchor biosynthesis and post-translational transfer to proteins. BioEssays. 2003, 25: 367-385. 10.1002/bies.10254.
Murray D, Hermida-Matsumoto L, Buser CA, Tsang J, Sigal CT, Ben Tal N, Honig B, Resh MD, McLaughlin S: Electrostatics and the membrane association of Src: theory and experiment. Biochemistry. 1998, 37: 2145-2159. 10.1021/bi972012b.
McLaughlin S, Wang J, Gambhir A, Murray D: PIP(2) and proteins: interactions, organization, and information flow. Annu Rev Biophys Biomol Struct. 2002, 31: 151-175. 10.1146/annurev.biophys.31.082901.134259.
Nourry C, Grant SG, Borg JP: PDZ domain proteins: plug and play!. Science Signal Transduction Knowledge Environment. 2003, RE7-
Gallina A, Milanesi G: Transmembrane translocation of a myristylated protein amino terminus. Biochem Biophys Res Commun. 1993, 195: 637-642. 10.1006/bbrc.1993.2093.
Dawe S, Duncan R: The S4 genome segment of baboon reovirus is bicistronic and encodes a novel fusion-associated small transmembrane protein. J Virol. 2002, 76: 2131-2140. 10.1128/jvi.76.5.2131-2140.2002.
Bijlmakers MJ, Marsh M: The on-off story of protein palmitoylation. Trends Cell Biol. 2003, 13: 32-42. 10.1016/S0962-8924(02)00008-9.
Eddy SR: Profile hidden Markov models. Bioinformatics. 1998, 14: 755-763. 10.1093/bioinformatics/14.9.755.
Bateman A, Birney E, Durbin R, Eddy SR, Howe KL, Sonnhammer EL: The Pfam protein families database. Nucleic Acids Res. 2000, 28: 263-266. 10.1093/nar/28.1.263.
Hassanin A, Golub R, Lewis SM, Wu GE: Evolution of the recombination signal sequences in the Ig heavy-chain variable region locus of mammals. Proc Natl Acad Sci USA. 2000, 97: 11415-11420. 10.1073/pnas.97.21.11415.
Zha J, Weiler S, Oh KJ, Wei MC, Korsmeyer SJ: Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis. Science. 2000, 290: 1761-1765. 10.1126/science.290.5497.1761.
Nielsen H, Brunak S, von Heijne G: Machine learning approaches for the prediction of signal peptides and other protein sorting signals. Protein Eng. 1999, 12: 3-9. 10.1093/protein/12.1.3.
Ping J, Schildbach JF, Shaw SY, Quertermous T, Novotny J, Bruccoleri R, Margolies MN: Effect of heavy chain signal peptide mutations and NH2-terminal chain length on binding of anti-digoxin antibodies. J Biol Chem. 1993, 268: 23000-23007.
Pillai S, Baltimore D: Myristoylation and the post-translational acquisition of hydrophobicity by the membrane immunoglobulin heavy-chain polypeptide in B lymphocytes. Proc Natl Acad Sci USA. 1987, 84: 7654-7658.
Stevenson FT, Bursten SL, Locksley RM, Lovett DH: Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. J Exp Med. 1992, 176: 1053-1062. 10.1084/jem.176.4.1053.
Stevenson FT, Bursten SL, Fanton C, Locksley RM, Lovett DH: The 31-kDa precursor of interleukin 1 alpha is myristoylated on specific lysines within the 16-kDa N-terminal propiece. Proc Natl Acad Sci USA. 1993, 90: 7245-7249.
Meffre E, Casellas R, Nussenzweig MC: Antibody regulation of B cell development. Nat Immunol. 2000, 1: 379-385. 10.1038/80816.
Dangl JL, Jones JD: Plant pathogens and integrated defence responses to infection. Nature. 2001, 411: 826-833. 10.1038/35081161.
Collmer A, Lindeberg M, Petnicki-Ocwieja T, Schneider DJ, Alfano JR: Genomic mining type III secretion system effectors in Pseudomonas syringae yields new picks for all TTSS prospectors. Trends Microbiol. 2002, 10: 462-469. 10.1016/S0966-842X(02)02451-4.
Boehm U, Guethlein L, Klamp T, Ozbek K, Schaub A, Futterer A, Pfeffer K, Howard JC: Two families of GTPases dominate the complex cellular response to IFN-gamma. J Immunol. 1998, 161: 6715-6723.
Zerrahn J, Schaible UE, Brinkmann V, Guhlich U, Kaufmann SH: The IFN-inducible Golgi- and endoplasmic reticulum-associated 47-kDa GTPase IIGP is transiently expressed during listeriosis. J Immunol. 2002, 168: 3428-3436.
Uthaiah RC, Praefcke GJ, Howard JC, Herrmann C: IIGP1, an interferon-gamma-inducible 47-kDa GTPase of the mouse, showing cooperative enzymatic activity and GTP-dependent multimerization. J Biol Chem. 2003, 278: 29336-29343. 10.1074/jbc.M211973200.
Besse S, Rebouillat D, Marie I, Puvion-Dutilleul F, Hovanessian AG: Ultrastructural localization of interferon-inducible double-stranded RNA-activated enzymes in human cells. Exp Cell Res. 1998, 239: 379-392. 10.1006/excr.1997.3908.
Cai SY, Babbitt RW, Marchesi VT: A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division. Proc Natl Acad Sci USA. 1999, 96: 2828-2833. 10.1073/pnas.96.6.2828.
Mimnaugh EG, Kayastha G, McGovern NB, Hwang SG, Marcu MG, Trepel J, Cai SY, Marchesi VT, Neckers L: Caspase-dependent deubiquitination of monoubiquitinated nucleosomal histone H2A induced by diverse apoptogenic stimuli. Cell Death Differ. 2001, 8: 1182-1196. 10.1038/sj.cdd.4400924.
D'Andrea A, Pellman D: Deubiquitinating enzymes: a new class of biological regulators. Crit Rev Biochem Mol Biol. 1998, 33: 337-352. 10.1080/10409239891204251.
Kaitna S, Schnabel H, Schnabel R, Hyman AA, Glotzer M: A ubiquitin C-terminal hydrolase is required to maintain osmotic balance and execute actin-dependent processes in the early C. elegans embryo. J Cell Sci. 2002, 115: 2293-2302.
Kimura Y, Saeki Y, Yokosawa H, Polevoda B, Sherman F, Hirano H: N-terminal modifications of the 19S regulatory particle subunits of the yeast proteasome. Arch Biochem Biophys. 2003, 409: 341-348. 10.1016/S0003-9861(02)00639-2.
Lai EC: Protein degradation: four E3s for the Notch pathway. Curr Biol. 2002, 12: R74-R78. 10.1016/S0960-9822(01)00679-0.
Pavlopoulos E, Pitsouli C, Klueg KM, Muskavitch MA, Moschonas NK, Delidakis C: neuralized encodes a peripheral membrane protein involved in delta signaling and endocytosis. Dev Cell. 2001, 1: 807-816. 10.1016/S1534-5807(01)00093-4.
He L, Lu XY, Jolly AF, Eldridge AG, Watson SJ, Jackson PK, Barsh GS, Gunn TM: Spongiform degeneration in mahoganoid mutant mice. Science. 2003, 299: 710-712. 10.1126/science.1079694.
Kunkele KP, Heins S, Dembowski M, Nargang FE, Benz R, Thieffry M, Walz J, Lill R, Nussberger S, Neupert W: The preprotein translocation channel of the outer membrane of mitochondria. Cell. 1998, 93: 1009-1019. 10.1016/S0092-8674(00)81206-4.
Ahting U, Thieffry M, Engelhardt H, Hegerl R, Neupert W, Nussberger S: Tom40, the pore-forming component of the protein-conducting TOM channel in the outer membrane of mitochondria. J Cell Biol. 2001, 153: 1151-1160. 10.1083/jcb.153.6.1151.
Gabriel K, Egan B, Lithgow T: Tom40, the import channel of the mitochondrial outer membrane, plays an active role in sorting imported proteins. EMBO J. 2003, 22: 2380-2386. 10.1093/emboj/cdg229.
Suzuki H, Okazawa Y, Komiya T, Saeki K, Mekada E, Kitada S, Ito A, Mihara K: Characterization of rat TOM40, a central component of the preprotein translocase of the mitochondrial outer membrane. J Biol Chem. 2000, 275: 37930-37936. 10.1074/jbc.M006558200.
Steiner H, Kispal G, Zollner A, Haid A, Neupert W, Lill R: Heme binding to a conserved Cys-Pro-Val motif is crucial for the catalytic function of mitochondrial heme lyases. J Biol Chem. 1996, 271: 32605-32611. 10.1074/jbc.271.40.24458.
Dumont ME, Cardillo TS, Hayes MK, Sherman F: Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae. Mol Cell Biol. 1991, 11: 5487-5496.
Prakash SK, Cormier TA, McCall AE, Garcia JJ, Sierra R, Haupt B, Zoghbi HY, Van Den Veyver IB: Loss of holocytochrome c-type synthetase causes the male lethality of X-linked dominant microphthalmia with linear skin defects (MLS) syndrome. Hum Mol Genet. 2002, 11: 3237-3248. 10.1093/hmg/11.25.3237.
Kondo M, Ji L, Kamibayashi C, Tomizawa Y, Randle D, Sekido Y, Yokota J, Kashuba V, Zabarovsky E, Kuzmin I, et al: Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells. Oncogene. 2001, 20: 6258-6262. 10.1038/sj.onc.1204832.
Ji L, Nishizaki M, Gao B, Burbee D, Kondo M, Kamibayashi C, Xu K, Yen N, Atkinson EN, Fang B, et al: Expression of several genes in the human chromosome 3p21.3 homozygous deletion region by an adenovirus vector results in tumor suppressor activities in vitro and in vivo. Cancer Res. 2002, 62: 2715-2720.
Takai D, Jones PA: The CpG island searcher: a new WWW resource. In Silico Biol. 2003, 3: 235-240.
Melki JR, Vincent PC, Clark SJ: Cancer-specific region of hypermethylation identified within the HIC1 putative tumour suppressor gene in acute myeloid leukaemia. Leukemia. 1999, 13: 877-883. 10.1038/sj/leu/2401401.
Burgoyne RD, Weiss JL: The neuronal calcium sensor family of Ca2+-binding proteins. Biochem J. 2001, 353: 1-12. 10.1042/0264-6021:3530001.
O'Callaghan DW, Ivings L, Weiss JL, Ashby MC, Tepikin AV, Burgoyne RD: Differential use of myristoyl groups on neuronal calcium sensor proteins as a determinant of spatio-temporal aspects of Ca2+ signal transduction. J Biol Chem. 2002, 277: 14227-14237. 10.1074/jbc.M111750200.
An WF, Bowlby MR, Betty M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ: Modulation of A-type potassium channels by a family of calcium sensors. Nature. 2000, 403: 553-556. 10.1038/35000592.
Martens JR, Sakamoto N, Sullivan SA, Grobaski TD, Tamkun MM: Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J Biol Chem. 2001, 276: 8409-8414. 10.1074/jbc.M009948200.
Zacharias DA, Violin JD, Newton AC, Tsien RY: Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science. 2002, 296: 913-916. 10.1126/science.1068539.
Takimoto K, Yang EK, Conforti L: Palmitoylation of KChIP splicing variants is required for efficient cell surface expression of Kv4.3 channels. J Biol Chem. 2002, 277: 26904-26911. 10.1074/jbc.M203651200.
Delling M, Wischmeyer E, Dityatev A, Sytnyk V, Veh RW, Karschin A, Schachner M: The neural cell adhesion molecule regulates cell-surface delivery of G-protein-activated inwardly rectifying potassium channels via lipid rafts. J Neurosci. 2002, 22: 7154-7164.
Dascal N, Doupnik CA, Ivanina T, Bausch S, Wang W, Lin C, Garvey J, Chavkin C, Lester HA, Davidson N: Inhibition of function in Xenopus oocytes of the inwardly rectifying G-protein-activated atrial K channel (GIRK1) by overexpression of a membrane-attached form of the C-terminal tail. Proc Natl Acad Sci USA. 1995, 92: 6758-6762.
Ma D, Zerangue N, Lin YF, Collins A, Yu M, Jan YN, Jan LY: Role of ER export signals in controlling surface potassium channel numbers. Science. 2001, 291: 316-319. 10.1126/science.291.5502.316.
Stockklausner C, Ludwig J, Ruppersberg JP, Klocker N: A sequence motif responsible for ER export and surface expression of Kir2.0 inward rectifier K(+) channels. FEBS Lett. 2001, 493: 129-133. 10.1016/S0014-5793(01)02286-4.
Stockklausner C, Klocker N: Surface expression of inward rectifier potassium channels is controlled by selective Golgi export. J Biol Chem. 2003, 278: 17000-17005. 10.1074/jbc.M212243200.
Schulze D, Krauter T, Fritzenschaft H, Soom M, Baukrowitz T: Phosphatidylinositol 4,5-bisphosphate (PIP2) modulation of ATP and pH sensitivity in Kir channels:A tale of an active and a silent PIP2 site in the N-terminus. J Biol Chem. 2003, 278: 10500-10505. 10.1074/jbc.M208413200.
Simons K, Ikonen E: Functional rafts in cell membranes. Nature. 1997, 387: 569-572. 10.1038/42408.
Edidin M: The state of lipid rafts: from model membranes to cells. Annu Rev Biophys Biomol Struct. 2003, 32: 257-283. 10.1146/annurev.biophys.32.110601.142439.
von Haller PD, Donohoe S, Goodlett DR, Aebersold R, Watts JD: Mass spectrometric characterization of proteins extracted from Jurkat T cell detergent-resistant membrane domains. Proteomics. 2001, 1: 1010-1021. 10.1002/1615-9861(200108)1:8<1010::AID-PROT1010>3.3.CO;2-C.
Nebl T, Pestonjamasp KN, Leszyk JD, Crowley JL, Oh SW, Luna EJ: Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil plasma membranes. J Biol Chem. 2002, 277: 43399-43409. 10.1074/jbc.M205386200.
Li N, Mak A, Richards DP, Naber C, Keller BO, Li L, Shaw AR: Monocyte lipid rafts contain proteins implicated in vesicular trafficking and phagosome formation. Proteomics. 2003, 3: 536-548. 10.1002/pmic.200390067.
Bini L, Pacini S, Liberatori S, Valensin S, Pellegrini M, Raggiaschi R, Pallini V, Baldari CT: Extensive temporally regulated reorganization of the lipid raft proteome following T-cell antigen receptor triggering. Biochem J. 2003, 369: 301-309. 10.1042/BJ20020503.
Moffett S, Brown DA, Linder ME: Lipid-dependent targeting of G proteins into rafts. J Biol Chem. 2000, 275: 2191-2198. 10.1074/jbc.275.3.2191.
Kovarova M, Tolar P, Arudchandran R, Draberova L, Rivera J, Draber P: Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation. Mol Cell Biol. 2001, 21: 8318-8328. 10.1128/MCB.21.24.8318-8328.2001.
Terashita A, Funatsu N, Umeda M, Shimada Y, Ohno-Iwashita Y, Epand RM, Maekawa S: Lipid binding activity of a neuron-specific protein NAP-22 studied in vivo and in vitro. J Neurosci Res. 2002, 70: 172-179. 10.1002/jnr.10407.
Sowa G, Pypaert M, Sessa WC: Distinction between signaling mechanisms in lipid rafts vs. caveolae. Proc Natl Acad Sci USA. 2001, 98: 14072-14077. 10.1073/pnas.241409998.
Marchand S, Devillers-Thiery A, Pons S, Changeux JP, Cartaud J: Rapsyn escorts the nicotinic acetylcholine receptor along the exocytic pathway via association with lipid rafts. J Neurosci. 2002, 22: 8891-8901.
Lafont F, Lecat S, Verkade P, Simons K: Annexin XIIIb associates with lipid microdomains to function in apical delivery. J Cell Biol. 1998, 142: 1413-1427. 10.1083/jcb.142.6.1413.
Arbuzova A, Schmitz AA, Vergeres G: Cross-talk unfolded: MARCKS proteins. Biochem J. 2002, 362: 1-12. 10.1042/0264-6021:3620001.
Laux T, Fukami K, Thelen M, Golub T, Frey D, Caroni P: GAP43, MARCKS, and CAP23 modulate PI(4,5)P(2) at plasmalemmal rafts, and regulate cell cortex actin dynamics through a common mechanism. J Cell Biol. 2000, 149: 1455-1472. 10.1083/jcb.149.7.1455.
Wang JK, Kiyokawa E, Verdin E, Trono D: The Nef protein of HIV-1 associates with rafts and primes T cells for activation. Proc Natl Acad Sci USA. 2000, 97: 394-399. 10.1073/pnas.97.1.394.
Lindwasser OW, Resh MD: Multimerization of human immunodeficiency virus type 1 Gag promotes its localization to barges, raft-like membrane microdomains. J Virol. 2001, 75: 7913-7924. 10.1128/JVI.75.17.7913-7924.2001.
Dreger M, Bengtsson L, Schoneberg T, Otto H, Hucho F: Nuclear envelope proteomics: novel integral membrane proteins of the inner nuclear membrane. Proc Natl Acad Sci USA. 2001, 98: 11943-11948. 10.1073/pnas.211201898.
Takasaki A, Hayashi N, Matsubara M, Yamauchi E, Taniguchi H: Identification of the calmodulin-binding domain of neuron-specific protein kinase C substrate protein CAP-22/NAP-22. Direct involvement of protein myristoylation in calmodulin-target protein interaction. J Biol Chem. 1999, 274: 11848-11853. 10.1074/jbc.274.17.11848.
Gunaratne RS, Sajid M, Ling IT, Tripathi R, Pachebat JA, Holder AA: Characterization of N-myristoyltransferase from Plasmodium falciparum. Biochem J. 2000, 348: 459-463. 10.1042/0264-6021:3480459.
Guex N, Peitsch MC: SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 1997, 18: 2714-2723. 10.1002/elps.1150181505.
Randazzo PA, Nie Z, Miura K, Hsu VW: Molecular aspects of the cellular activities of ADP-ribosylation factors. Science Signal Transduction Knowledge Environment. 2000, RE1-
Lin CY, Li CC, Huang PH, Lee FJ: A developmentally regulated ARF-like 5 protein (ARL5), localized to nuclei and nucleoli, interacts with heterochromatin protein 1. J Cell Sci. 2002, 115: 4433-4445. 10.1242/jcs.00123.
Lu SX, Hrabak EM: An Arabidopsis calcium-dependent protein kinase is associated with the endoplasmic reticulum. Plant Physiol. 2002, 128: 1008-1021. 10.1104/pp.010770.
Martin GB, Bogdanove AJ, Sessa G: Understanding the functions of plant disease resistance proteins. Annu Rev Plant Biol. 2003, 54: 23-61. 10.1146/annurev.arplant.54.031902.135035.
Pepperkok R, Hotz-Wagenblatt A, Konig N, Girod A, Bossemeyer D, Kinzel V: Intracellular distribution of mammalian protein kinase A catalytic subunit altered by conserved Asn2 deamidation. J Cell Biol. 2000, 148: 715-726. 10.1083/jcb.148.4.715.
Fraser ID, Tavalin SJ, Lester LB, Langeberg LK, Westphal AM, Dean RA, Marrion NV, Scott JD: A novel lipid-anchored A-kinase anchoring protein facilitates cAMP-responsive membrane events. EMBO J. 1998, 17: 2261-2272. 10.1093/emboj/17.8.2261.
Vaandrager AB, Smolenski A, Tilly BC, Houtsmuller AB, Ehlert EM, Bot AG, Edixhoven M, Boomaars WE, Lohmann SM, de Jonge HR: Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl-channel activation. Proc Natl Acad Sci USA. 1998, 95: 1466-1471. 10.1073/pnas.95.4.1466.
Spilker C, Dresbach T, Braunewell KH: Reversible translocation and activity-dependent localization of the calcium-myristoyl switch protein VILIP-1 to different membrane compartments in living hippocampal neurons. J Neurosci. 2002, 22: 7331-7339.
Perrino BA, Martin BA: Ca(2+)- and myristoylation-dependent association of calcineurin with phosphatidylserine. J Biochem (Tokyo). 2001, 129: 835-841.
Timm S, Titus B, Bernd K, Barroso M: The EF-hand Ca(2+)-binding protein p22 associates with microtubules in an N-myristoylation-dependent manner. Mol Biol Cell. 1999, 10: 3473-3488.
Hwang JY, Koch KW: Calcium- and myristoyl-dependent properties of guanylate cyclase-activating protein-1 and protein-2. Biochemistry. 2002, 41: 13021-13028. 10.1021/bi026618y.
Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ: A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein. J Cell Biol. 1999, 145: 1277-1292. 10.1083/jcb.145.6.1277.
Naik UP, Naik MU: Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Blood. 2003, 102: 1355-1362. 10.1182/blood-2003-02-0591.
Resh MD: Myristylation and palmitylation of Src family members: the fats of the matter. Cell. 1994, 76: 411-413. 10.1016/0092-8674(94)90104-X.
Lang ML, Chen YW, Shen L, Gao H, Lang GA, Wade TK, Wade WF: IgA Fc receptor (FcalphaR) cross-linking recruits tyrosine kinases, phosphoinositide kinases and serine/threonine kinases to glycolipid rafts. Biochem J. 2002, 364: 517-525. 10.1042/BJ20011696.
Utsumi T, Sakurai N, Nakano K, Ishisaka R: C-terminal 15 kDa fragment of cytoskeletal actin is posttranslationally N-myristoylated upon caspase-mediated cleavage and targeted to mitochondria. FEBS Lett. 2003, 539: 37-44. 10.1016/S0014-5793(03)00180-7.
Brooks P, Fuertes G, Murray RZ, Bose S, Knecht E, Rechsteiner MC, Hendil KB, Tanaka K, Dyson J, Rivett J: Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. Biochem J. 2000, 346: 155-161. 10.1042/0264-6021:3460155.
Liu J, Hughes TE, Sessa WC: The first 35 amino acids and fatty acylation sites determine the molecular targeting of endothelial nitric oxide synthase into the Golgi region of cells: a green fluorescent protein study. J Cell Biol. 1997, 137: 1525-1535. 10.1083/jcb.137.7.1525.
Michel T: Targeting and translocation of endothelial nitric oxide synthase. Braz J Med Biol Res. 1999, 32: 1361-1366. 10.1590/S0100-879X1999001100006.
Barr FA, Puype M, Vandekerckhove J, Warren G: GRASP65, a protein involved in the stacking of Golgi cisternae. Cell. 1997, 91: 253-262. 10.1016/S0092-8674(00)80407-9.
Kuo A, Zhong C, Lane WS, Derynck R: Transmembrane transforming growth factor-alpha tethers to the PDZ domain-containing, Golgi membrane-associated protein p59/GRASP55. EMBO J. 2000, 19: 6427-6439. 10.1093/emboj/19.23.6427.
Godsel LM, Engman DM: Flagellar protein localization mediated by a calcium-myristoyl/palmitoyl switch mechanism. EMBO J. 1999, 18: 2057-2065. 10.1093/emboj/18.8.2057.
Borgese N, Aggujaro D, Carrera P, Pietrini G, Bassetti M: A role for N-myristoylation in protein targeting: NADH-cytochrome b5 reductase requires myristic acid for association with outer mitochondrial but not ER membranes. J Cell Biol. 1996, 135: 1501-1513. 10.1083/jcb.135.6.1501.
Ramulu P, Nathans J: Cellular and subcellular localization, N-terminal acylation, and calcium binding of Caenorhabditis elegans protein phosphatase with EF-hands. J Biol Chem. 2001, 276: 25127-25135. 10.1074/jbc.M011712200.
Risinger MA, Korsgren C, Cohen CM: Role of N-myristylation in targeting of band 4.2 (pallidin) in nonerythroid cells. Exp Cell Res. 1996, 229: 421-431. 10.1006/excr.1996.0387.
Stack JH, Herman PK, Schu PV, Emr SD: A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole. EMBO J. 1993, 12: 2195-2204.
Gelman IH, Lee K, Tombler E, Gordon R, Lin X: Control of cytoskeletal architecture by the src-suppressed C kinase substrate, SSeCKS. Cell Motil Cytoskeleton. 1998, 41: 1-17. 10.1002/(SICI)1097-0169(1998)41:1<1::AID-CM1>3.3.CO;2-W.
Lin SS, Manchester JK, Gordon JI: Sip2, an N-myristoylated beta subunit of Snf1 kinase, regulates aging in Saccharomyces cerevisiae by affecting cellular histone kinase activity, recombination at rDNA loci, and silencing. J Biol Chem. 2003, 278: 13390-13397. 10.1074/jbc.M212818200.
Michiels F, Stam JC, Hordijk PL, van der Kammen RA, Ruuls-Van Stalle L, Feltkamp CA, Collard JG: Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation. J Cell Biol. 1997, 137: 387-398. 10.1083/jcb.137.2.387.
Konno D, Ko JA, Usui S, Hori K, Maruoka H, Inui M, Fujikado T, Tano Y, Suzuki T, Tohyama K, Sobue K: The postsynaptic density and dendritic raft localization of PSD-Zip70, which contains an N-myristoylation sequence and leucine-zipper motifs. J Cell Sci. 2002, 115: 4695-4706. 10.1242/jcs.00127.
Clotet J, Posas F, de Nadal E, Arino J: The NH2-terminal extension of protein phosphatase PPZ1 has an essential functional role. J Biol Chem. 1996, 271: 26349-26355. 10.1074/jbc.271.42.26349.
Sullivan A, Uff CR, Isacke CM, Thorne RF: PACE-1, a novel protein that interacts with the C-terminal domain of ezrin. Exp Cell Res. 2003, 284: 224-238. 10.1016/S0014-4827(02)00054-X.
Li S, Goldberg E: A novel N-terminal domain directs membrane localization of mouse testis-specific calpastatin. Biol Reprod. 2000, 63: 1594-1600. 10.1095/biolreprod63.6.1594.
Rossi EA, Li Z, Feng H, Rubin CS: Characterization of the targeting, binding, and phosphorylation site domains of an A kinase anchor protein and a myristoylated alanine-rich C kinase substrate-like analog that are encoded by a single gene. J Biol Chem. 1999, 274: 27201-27210. 10.1074/jbc.274.38.27201.
Eberle HB, Serrano RL, Fullekrug J, Schlosser A, Lehmann WD, Lottspeich F, Kaloyanova D, Wieland FT, Helms JB: Identification and characterization of a novel human plant pathogenesis-related protein that localizes to lipid-enriched microdomains in the Golgi complex. J Cell Sci. 2002, 115: 827-838.
Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD: Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell. 2002, 3: 271-282. 10.1016/S1534-5807(02)00220-4.
Collavin L, Lazarevic D, Utrera R, Marzinotto S, Monte M, Schneider C: wt p53 dependent expression of a membrane-associated isoform of adenylate kinase. Oncogene. 1999, 18: 5879-5888. 10.1038/sj.onc.1202970.
Walker JE, Arizmendi JM, Dupuis A, Fearnley IM, Finel M, Medd SM, Pilkington SJ, Runswick MJ, Skehel JM: Sequences of 20 subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Application of a novel strategy for sequencing proteins using the polymerase chain reaction. J Mol Biol. 1992, 226: 1051-1072. 10.1016/0022-2836(92)91052-Q.
Hanakam F, Albrecht R, Eckerskorn C, Matzner M, Gerisch G: Myristoylated and non-myristoylated forms of the pH sensor protein hisactophilin II: intracellular shuttling to plasma membrane and nucleus monitored in real time by a fusion with green fluorescent protein. EMBO J. 1996, 15: 2935-2943.
Hunter C, Sung P, Schejter ED, Wieschaus E: Conserved domains of the Nullo protein required for cell-surface localization and formation of adherens junctions. Mol Biol Cell. 2002, 13: 146-157. 10.1091/mbc.01-08-0418.
Neel VA, Young MW: Igloo, a GAP-43-related gene expressed in the developing nervous system of Drosophila. Development. 1994, 120: 2235-2243.
Quest AF, Harvey DJ, McIlhinney RA: Myristoylated and nonmyristoylated pools of sea urchin sperm flagellar creatine kinase exist side-by-side: myristoylation is necessary for efficient lipid association. Biochemistry. 1997, 36: 6993-7002. 10.1021/bi9629337.
Cserzo M, Eisenhaber F, Eisenhaber B, Simon I: On filtering false positive transmembrane protein predictions. Protein Eng. 2002, 15: 745-752. 10.1093/protein/15.9.745.
Ashrafi K, Farazi TA, Gordon JI: A role for Saccharomyces cerevisiae fatty acid activation protein 4 in regulating protein N-myristoylation during entry into stationary phase. J Biol Chem. 1998, 273: 25864-25874. 10.1074/jbc.273.40.25864.
Robertson SE, Dockendorff TC, Leatherman JL, Faulkner DL, Jongens TA: germ cell-less is required only during the establishment of the germ cell lineage of Drosophila and has activities which are dependent and independent of its localization to the nuclear envelope. Dev Biol. 1999, 215: 288-297. 10.1006/dbio.1999.9453.
Acknowledgements
The authors are grateful for support from Boehringer Ingelheim. This project was partly funded by the Fonds zur Förderung der wissenschaftlichen Forschung Österreichs (FWF grant P15037), by the Austrian National Bank (OeNB - Österreichische Nationalbank), by the Austrian Gen-AU bioinformatics integration network (BIN) sponsored by BM-BWK, by the bioinformatics contract study 2002-2004 for BM-WA, by the Asahi Glass Foundation, Japan (to N.H.), by grants-in-aid for Scientific Research on Priority Areas 'Genome Information Science' (14015231 and 15014230) (to N.H.) and Scientific Research (C) (to N.H.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant-in-aid for the Fujita Health University High-tech Research Center from the Ministry of Education, Science, Sports and Culture of Japan.
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Maurer-Stroh, S., Gouda, M., Novatchkova, M. et al. MYRbase: analysis of genome-wide glycine myristoylation enlarges the functional spectrum of eukaryotic myristoylated proteins. Genome Biol 5, R21 (2004). https://doi.org/10.1186/gb-2004-5-3-r21
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DOI: https://doi.org/10.1186/gb-2004-5-3-r21