Lysine acetylation targets protein complexes and co-regulates major cellular functions.
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Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M
Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16.
- PubMed ID
- 19608861 [ View in PubMed]
- Abstract
Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600 lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors suberoylanilide hydroxamic acid and MS-275. Lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID NAD(P) transhydrogenase, mitochondrial Q13423 Details Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial P50213 Details Phenylalanine--tRNA ligase, mitochondrial O95363 Details Phenylalanine--tRNA ligase alpha subunit Q9Y285 Details Transketolase P29401 Details Serine--tRNA ligase, cytoplasmic P49591 Details Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial P10515 Details L-lactate dehydrogenase B chain P07195 Details Acetyl-CoA acetyltransferase, mitochondrial P24752 Details Pyruvate kinase PKM P14618 Details Adenine phosphoribosyltransferase P07741 Details Hemoglobin subunit alpha P69905 Details Tubulin beta chain P07437 Details NAD-dependent malic enzyme, mitochondrial P23368 Details Succinate-semialdehyde dehydrogenase, mitochondrial P51649 Details NADH-cytochrome b5 reductase 3 P00387 Details 2-oxoglutarate dehydrogenase, mitochondrial Q02218 Details Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial P31040 Details Glutamate dehydrogenase 1, mitochondrial P00367 Details Bifunctional glutamate/proline--tRNA ligase P07814 Details Lysine--tRNA ligase Q15046 Details NEDD8-activating enzyme E1 regulatory subunit Q13564 Details Probable leucine--tRNA ligase, mitochondrial Q15031 Details Asparagine synthetase [glutamine-hydrolyzing] P08243 Details Valine--tRNA ligase P26640 Details Tryptophan--tRNA ligase, cytoplasmic P23381 Details Tyrosine--tRNA ligase, cytoplasmic P54577 Details Threonine--tRNA ligase, cytoplasmic P26639 Details Trifunctional enzyme subunit alpha, mitochondrial P40939 Details Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial P13995 Details Diamine acetyltransferase 2 Q96F10 Details 4-trimethylaminobutyraldehyde dehydrogenase P49189 Details Serine hydroxymethyltransferase, mitochondrial P34897 Details Alanine--tRNA ligase, cytoplasmic P49588 Details S-adenosylmethionine synthase isoform type-2 P31153 Details GMP synthase [glutamine-hydrolyzing] P49915 Details Ribonucleoside-diphosphate reductase large subunit P23921 Details Serine hydroxymethyltransferase, cytosolic P34896 Details Glycine amidinotransferase, mitochondrial P50440 Details Acetyl-coenzyme A synthetase, cytoplasmic Q9NR19 Details Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial Q96I99 Details Tyrosine--tRNA ligase, mitochondrial Q9Y2Z4 Details Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial Q16836 Details Aspartate aminotransferase, mitochondrial P00505 Details Isovaleryl-CoA dehydrogenase, mitochondrial P26440 Details Peroxisomal multifunctional enzyme type 2 P51659 Details Calmodulin P0DP23 Details Annexin A1 P04083 Details L-lactate dehydrogenase A chain P00338 Details NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 Q16718 Details Threonine synthase-like 1 Q8IYQ7 Details Carnitine O-acetyltransferase P43155 Details Glyceraldehyde-3-phosphate dehydrogenase P04406 Details Retinal dehydrogenase 1 P00352 Details Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial O43837 Details Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial P08559 Details Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial P45954 Details Peroxisomal bifunctional enzyme Q08426 Details Malate dehydrogenase, cytoplasmic P40925 Details ADP/ATP translocase 1 P12235 Details Phosphoserine aminotransferase Q9Y617 Details Glutamate--cysteine ligase regulatory subunit P48507 Details Asparagine--tRNA ligase, cytoplasmic O43776 Details Choline-phosphate cytidylyltransferase A P49585 Details ADP/ATP translocase 3 P12236 Details Acetyl-CoA carboxylase 1 Q13085 Details UMP-CMP kinase P30085 Details UDP-glucose 6-dehydrogenase O60701 Details Pyruvate carboxylase, mitochondrial P11498 Details Cysteine--tRNA ligase, cytoplasmic P49589 Details ADP/ATP translocase 2 P05141 Details Aldehyde dehydrogenase, dimeric NADP-preferring P30838 Details Branched-chain-amino-acid aminotransferase, mitochondrial O15382 Details Inosine-5'-monophosphate dehydrogenase 2 P12268 Details Aspartate--tRNA ligase, cytoplasmic P14868 Details Dihydrolipoyl dehydrogenase, mitochondrial P09622 Details Biliverdin reductase A P53004 Details Acetyl-coenzyme A synthetase 2-like, mitochondrial Q9NUB1 Details Aldose reductase P15121 Details Farnesyl pyrophosphate synthase P14324 Details Sphingosine-1-phosphate lyase 1 O95470 Details Malate dehydrogenase, mitochondrial P40926 Details Nicotinamide N-methyltransferase P40261 Details Glutathione S-transferase kappa 1 Q9Y2Q3 Details Glutathione S-transferase P P09211 Details Glutathione S-transferase omega-1 P78417 Details Maleylacetoacetate isomerase O43708 Details Glutaminase kidney isoform, mitochondrial O94925 Details Perilipin-3 O60664 Details CTP synthase 1 P17812 Details Trifunctional purine biosynthetic protein adenosine-3 P22102 Details Cyclin-dependent-like kinase 5 Q00535 Details DNA (cytosine-5)-methyltransferase 1 P26358 Details Peroxiredoxin-5, mitochondrial P30044 Details Growth factor receptor-bound protein 2 P62993 Details Bifunctional epoxide hydrolase 2 P34913 Details Fatty acid synthase P49327 Details Dihydropyrimidine dehydrogenase [NADP(+)] Q12882 Details Lactoylglutathione lyase Q04760 Details DNA topoisomerase 1 P11387 Details Thiopurine S-methyltransferase P51580 Details Glycine--tRNA ligase P41250 Details Cytochrome b-c1 complex subunit 1, mitochondrial P31930 Details Cytochrome c P99999 Details Calnexin P27824 Details Peptidyl-prolyl cis-trans isomerase A P62937 Details Rho-associated protein kinase 1 Q13464 Details Cyclin-dependent kinase 2 P24941 Details Cyclin-dependent kinase 1 P06493 Details Glucose-6-phosphate 1-dehydrogenase P11413 Details Heat shock protein HSP 90-alpha P07900 Details Protein kinase C alpha type P17252 Details 14-3-3 protein zeta/delta P63104 Details Quinone oxidoreductase Q08257 Details Glucose-6-phosphate isomerase P06744 Details Catalase P04040 Details m7GpppX diphosphatase Q96C86 Details Thymidylate kinase P23919 Details Bifunctional purine biosynthesis protein PURH P31939 Details Isocitrate dehydrogenase [NADP] cytoplasmic O75874 Details Tyrosine-protein kinase ZAP-70 P43403 Details Acetyl-CoA acetyltransferase, cytosolic Q9BWD1 Details Tubulin beta-4B chain P68371 Details Tubulin beta-3 chain Q13509 Details Histidine triad nucleotide-binding protein 1 P49773 Details Phosphatidylinositol transfer protein alpha isoform Q00169 Details Glucosamine-6-phosphate isomerase 1 P46926 Details Leukotriene A-4 hydrolase P09960 Details Fructose-bisphosphate aldolase A P04075 Details Poly [ADP-ribose] polymerase 1 P09874 Details Medium-chain specific acyl-CoA dehydrogenase, mitochondrial P11310 Details Enoyl-CoA delta isomerase 1, mitochondrial P42126 Details Hydroxyacylglutathione hydrolase, mitochondrial Q16775 Details Kinesin-like protein KIF11 P52732 Details Macrophage migration inhibitory factor P14174 Details Heat shock protein HSP 90-beta P08238 Details Fatty acid-binding protein, epidermal Q01469 Details Keratin, type II cytoskeletal 8 P05787 Details Calreticulin P27797 Details Retinoblastoma-associated protein P06400 Details Prolyl endopeptidase P48147 Details Kynurenine--oxoglutarate transaminase 3 Q6YP21 Details Cyclin-dependent kinase 6 Q00534 Details Adenosine deaminase P00813 Details Trimethyllysine dioxygenase, mitochondrial Q9NVH6 Details Multifunctional protein ADE2 P22234 Details CAD protein P27708 Details Aspartate--tRNA ligase, mitochondrial Q6PI48 Details Glutamine--tRNA ligase P47897 Details Succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial P53597 Details Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial P55809 Details Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrial Q9P2R7 Details Probable glutamate--tRNA ligase, mitochondrial Q5JPH6 Details S-formylglutathione hydrolase P10768 Details Retinol dehydrogenase 11 Q8TC12 Details Diacylglycerol kinase alpha P23743 Details Isoleucine--tRNA ligase, mitochondrial Q9NSE4 Details Probable asparagine--tRNA ligase, mitochondrial Q96I59 Details Proteasome subunit beta type-1 P20618 Details Histone deacetylase 1 Q13547 Details DNA-dependent protein kinase catalytic subunit P78527 Details Serine/threonine-protein kinase mTOR P42345 Details Superoxide dismutase [Cu-Zn] P00441 Details DNA-(apurinic or apyrimidinic site) lyase P27695 Details Keratin, type II cytoskeletal 7 P08729 Details E3 ubiquitin-protein ligase UBR4 Q5T4S7 Details Voltage-dependent anion-selective channel protein 1 P21796 Details Voltage-dependent anion-selective channel protein 2 P45880 Details Voltage-dependent anion-selective channel protein 3 Q9Y277 Details Prostaglandin E synthase 3 Q15185 Details U1 small nuclear ribonucleoprotein A P09012 Details ATP-dependent Clp protease proteolytic subunit, mitochondrial Q16740 Details Protein S100-A11 P31949 Details Copper transport protein ATOX1 O00244 Details Protein S100-A6 P06703 Details 2,4-dienoyl-CoA reductase, mitochondrial Q16698 Details Serine/threonine-protein phosphatase 5 P53041 Details Nucleoside diphosphate kinase B P22392 Details Hydroxymethylglutaryl-CoA lyase, mitochondrial P35914 Details Cellular tumor antigen p53 P04637 Details High mobility group protein B1 P09429 Details Heat shock protein beta-1 P04792 Details Transcriptional activator Myb P10242 Details Histone deacetylase 5 Q9UQL6 Details 6-phosphogluconate dehydrogenase, decarboxylating P52209 Details Integrin beta-1 P05556 Details Deoxyguanosine kinase, mitochondrial Q16854 Details Cation-independent mannose-6-phosphate receptor P11717 Details Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Q13526 Details Nuclear receptor coactivator 2 Q15596 Details Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform P30153 Details Uracil-DNA glycosylase P13051 Details Heat shock cognate 71 kDa protein P11142 Details 60S ribosomal protein L13a P40429 Details 60S ribosomal protein L37 P61927 Details 60S ribosomal protein L3 P39023 Details 60S ribosomal protein L11 P62913 Details ATP synthase subunit alpha, mitochondrial P25705 Details ATP synthase subunit beta, mitochondrial P06576 Details ATP synthase subunit gamma, mitochondrial P36542 Details Triosephosphate isomerase P60174 Details Cytosol aminopeptidase P28838 Details Proteasome subunit alpha type-2 P25787 Details Proteasome subunit alpha type-3 P25788 Details Proteasome subunit alpha type-4 P25789 Details Proteasome subunit alpha type-6 P60900 Details Proteasome subunit alpha type-7 O14818 Details Proteasome subunit beta type-3 P49720 Details Casein kinase II subunit alpha' P19784 Details Cytochrome c oxidase subunit 4 isoform 1, mitochondrial P13073 Details Isopentenyl-diphosphate Delta-isomerase 1 Q13907 Details Elongation factor Tu GTP-binding domain-containing protein 1 Q7Z2Z2 Details Hydroxymethylglutaryl-CoA synthase, cytoplasmic Q01581 Details Profilin-1 P07737 Details Peroxisomal acyl-coenzyme A oxidase 1 Q15067 Details Calpain small subunit 1 P04632 Details Annexin A5 P08758 Details Destrin P60981 Details Cofilin-1 P23528 Details Enoyl-CoA delta isomerase 2, mitochondrial O75521 Details Actin-related protein 2/3 complex subunit 1B O15143 Details Actin-related protein 2 P61160 Details Actin-related protein 3 P61158 Details Actin-related protein 2/3 complex subunit 2 O15144 Details Actin-related protein 2/3 complex subunit 3 O15145 Details Elongation factor 2 P13639 Details 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial Q6NVY1 Details Interleukin-1 receptor-associated kinase 4 Q9NWZ3 Details Protein S100-A4 P26447 Details Aldo-keto reductase family 1 member B10 O60218 Details CREB-binding protein Q92793 Details Valacyclovir hydrolase Q86WA6 Details Mediator of RNA polymerase II transcription subunit 1 Q15648 Details U6 snRNA-associated Sm-like protein LSm6 P62312 Details Superoxide dismutase [Mn], mitochondrial P04179 Details Phosphoglycerate kinase 1 P00558 Details Thiosulfate sulfurtransferase Q16762 Details Citrate synthase, mitochondrial O75390 Details Phosphoglucomutase-1 P36871 Details Vimentin P08670 Details Cytochrome b5 type B O43169 Details Acyl-CoA-binding protein P07108 Details Galectin-1 P09382 Details Enoyl-CoA hydratase, mitochondrial P30084 Details Aconitate hydratase, mitochondrial Q99798 Details Isocitrate dehydrogenase [NADP], mitochondrial P48735 Details Elongation factor Tu, mitochondrial P49411 Details T-complex protein 1 subunit gamma P49368 Details GTP-binding nuclear protein Ran P62826 Details 14-3-3 protein epsilon P62258 Details [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial O14874 Details Ubiquitin-like modifier-activating enzyme 1 P22314 Details Histone acetyltransferase KAT5 Q92993 Details SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 O60264 Details Spectrin beta chain, non-erythrocytic 1 Q01082 Details Spliceosome RNA helicase DDX39B Q13838 Details Hepatocyte growth factor-regulated tyrosine kinase substrate O14964 Details Peroxiredoxin-6 P30041 Details Myc proto-oncogene protein P01106 Details Bleomycin hydrolase Q13867 Details Proteasome subunit beta type-9 P28065 Details 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase Q15125 Details Ras-related C3 botulinum toxin substrate 2 P15153 Details Complement component 1 Q subcomponent-binding protein, mitochondrial Q07021 Details Thioredoxin P10599 Details Chloride intracellular channel protein 1 O00299 Details Casein kinase II subunit beta P67870 Details Transcription factor p65 Q04206 Details Ubiquitin carboxyl-terminal hydrolase isozyme L1 P09936 Details Alpha-ketoglutarate-dependent dioxygenase FTO Q9C0B1 Details Alpha-enolase P06733 Details Nucleolar and coiled-body phosphoprotein 1 Q14978 Details Peroxiredoxin-1 Q06830 Details Tricarboxylate transport protein, mitochondrial P53007 Details Tesmin Q9Y4I5 Details Calmodulin-2 P0DP24 Details Calmodulin-3 P0DP25 Details 60 kDa heat shock protein, mitochondrial P10809 Details 40S ribosomal protein S2 P15880 Details Heterogeneous nuclear ribonucleoproteins A2/B1 P22626 Details Heterogeneous nuclear ribonucleoprotein L P14866 Details Splicing factor, proline- and glutamine-rich P23246 Details Receptor of activated protein C kinase 1 P63244 Details Alpha-actinin-1 P12814 Details Annexin A4 P09525 Details Stress-induced-phosphoprotein 1 P31948 Details Eukaryotic initiation factor 4A-I P60842 Details 14-3-3 protein beta/alpha P31946 Details Hepatoma-derived growth factor P51858 Details Ran-specific GTPase-activating protein P43487 Details Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 Q8N1G2 Details Copine-1 Q99829 Details Protein RIC-3 Q7Z5B4 Details Prohibitin-2 Q99623 Details Flap endonuclease 1 P39748 Details Eukaryotic translation initiation factor 3 subunit F O00303 Details ATP synthase subunit g, mitochondrial O75964 Details Heterogeneous nuclear ribonucleoprotein F P52597 Details Heat shock 70 kDa protein 4 P34932 Details 10 kDa heat shock protein, mitochondrial P61604 Details Nuclear migration protein nudC Q9Y266 Details Protein S100-A10 P60903 Details Splicing factor 3A subunit 3 Q12874 Details Tropomyosin alpha-1 chain P09493 Details Tropomyosin alpha-3 chain P06753 Details Tropomyosin alpha-4 chain P67936 Details Ubiquitin carboxyl-terminal hydrolase 14 P54578 Details 14-3-3 protein theta P27348 Details Proliferating cell nuclear antigen P12004 Details Dermcidin P81605 Details ATP synthase subunit O, mitochondrial P48047 Details Cysteine and glycine-rich protein 1 P21291 Details Filamin-A P21333 Details Heterogeneous nuclear ribonucleoprotein D0 Q14103 Details Nucleophosmin P06748 Details 60S ribosomal protein L14 P50914 Details 60S ribosomal protein L35 P42766 Details 60S ribosomal protein L4 P36578 Details 40S ribosomal protein S13 P62277 Details 40S ribosomal protein S18 P62269 Details 40S ribosomal protein S19 P39019 Details 40S ribosomal protein S5 P46782 Details 40S ribosomal protein S6 P62753 Details 40S ribosomal protein S9 P46781 Details Transgelin-2 P37802 Details Zyxin Q15942 Details Serine/arginine-rich splicing factor 1 Q07955 Details Myosin-9 P35579 Details Probable ATP-dependent RNA helicase DDX5 P17844 Details Splicing factor 3B subunit 1 O75533 Details STE20/SPS1-related proline-alanine-rich protein kinase Q9UEW8 Details Citron Rho-interacting kinase O14578 Details Casein kinase I isoform alpha P48729 Details eIF-2-alpha kinase GCN2 Q9P2K8 Details Mitogen-activated protein kinase kinase kinase kinase 5 Q9Y4K4 Details Serine/threonine-protein kinase PAK 2 Q13177 Details Phosphatidylinositol 5-phosphate 4-kinase type-2 beta P78356 Details Serine/threonine-protein kinase N1 Q16512 Details Serine/threonine-protein kinase PRP4 homolog Q13523 Details Exportin-1 O14980 Details Prohibitin P35232 Details Voltage-gated potassium channel subunit beta-2 Q13303 Details Magnesium transporter MRS2 homolog, mitochondrial Q9HD23 Details ATP-citrate synthase P53396 Details Apolipoprotein B-100 P04114 Details Proliferation marker protein Ki-67 P46013 Details Histone acetyltransferase p300 Q09472 Details