Lysine acetylation targets protein complexes and co-regulates major cellular functions.

Article Details

Citation

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
NameUniProt ID
NAD(P) transhydrogenase, mitochondrialQ13423Details
Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrialP50213Details
Phenylalanine--tRNA ligase, mitochondrialO95363Details
Phenylalanine--tRNA ligase alpha subunitQ9Y285Details
TransketolaseP29401Details
Serine--tRNA ligase, cytoplasmicP49591Details
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrialP10515Details
L-lactate dehydrogenase B chainP07195Details
Acetyl-CoA acetyltransferase, mitochondrialP24752Details
Pyruvate kinase PKMP14618Details
Adenine phosphoribosyltransferaseP07741Details
Hemoglobin subunit alphaP69905Details
Tubulin beta chainP07437Details
NAD-dependent malic enzyme, mitochondrialP23368Details
Succinate-semialdehyde dehydrogenase, mitochondrialP51649Details
NADH-cytochrome b5 reductase 3P00387Details
2-oxoglutarate dehydrogenase, mitochondrialQ02218Details
Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrialP31040Details
Glutamate dehydrogenase 1, mitochondrialP00367Details
Bifunctional glutamate/proline--tRNA ligaseP07814Details
Lysine--tRNA ligaseQ15046Details
NEDD8-activating enzyme E1 regulatory subunitQ13564Details
Probable leucine--tRNA ligase, mitochondrialQ15031Details
Asparagine synthetase [glutamine-hydrolyzing]P08243Details
Valine--tRNA ligaseP26640Details
Tryptophan--tRNA ligase, cytoplasmicP23381Details
Tyrosine--tRNA ligase, cytoplasmicP54577Details
Threonine--tRNA ligase, cytoplasmicP26639Details
Trifunctional enzyme subunit alpha, mitochondrialP40939Details
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialP13995Details
Diamine acetyltransferase 2Q96F10Details
4-trimethylaminobutyraldehyde dehydrogenaseP49189Details
Serine hydroxymethyltransferase, mitochondrialP34897Details
Alanine--tRNA ligase, cytoplasmicP49588Details
S-adenosylmethionine synthase isoform type-2P31153Details
GMP synthase [glutamine-hydrolyzing]P49915Details
Ribonucleoside-diphosphate reductase large subunitP23921Details
Serine hydroxymethyltransferase, cytosolicP34896Details
Glycine amidinotransferase, mitochondrialP50440Details
Acetyl-coenzyme A synthetase, cytoplasmicQ9NR19Details
Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrialQ96I99Details
Tyrosine--tRNA ligase, mitochondrialQ9Y2Z4Details
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrialQ16836Details
Aspartate aminotransferase, mitochondrialP00505Details
Isovaleryl-CoA dehydrogenase, mitochondrialP26440Details
Peroxisomal multifunctional enzyme type 2P51659Details
CalmodulinP0DP23Details
Annexin A1P04083Details
L-lactate dehydrogenase A chainP00338Details
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5Q16718Details
Threonine synthase-like 1Q8IYQ7Details
Carnitine O-acetyltransferaseP43155Details
Glyceraldehyde-3-phosphate dehydrogenaseP04406Details
Retinal dehydrogenase 1P00352Details
Isocitrate dehydrogenase [NAD] subunit beta, mitochondrialO43837Details
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrialP08559Details
Short/branched chain specific acyl-CoA dehydrogenase, mitochondrialP45954Details
Peroxisomal bifunctional enzymeQ08426Details
Malate dehydrogenase, cytoplasmicP40925Details
ADP/ATP translocase 1P12235Details
Phosphoserine aminotransferaseQ9Y617Details
Glutamate--cysteine ligase regulatory subunitP48507Details
Asparagine--tRNA ligase, cytoplasmicO43776Details
Choline-phosphate cytidylyltransferase AP49585Details
ADP/ATP translocase 3P12236Details
Acetyl-CoA carboxylase 1Q13085Details
UMP-CMP kinaseP30085Details
UDP-glucose 6-dehydrogenaseO60701Details
Pyruvate carboxylase, mitochondrialP11498Details
Cysteine--tRNA ligase, cytoplasmicP49589Details
ADP/ATP translocase 2P05141Details
Aldehyde dehydrogenase, dimeric NADP-preferringP30838Details
Branched-chain-amino-acid aminotransferase, mitochondrialO15382Details
Inosine-5'-monophosphate dehydrogenase 2P12268Details
Aspartate--tRNA ligase, cytoplasmicP14868Details
Dihydrolipoyl dehydrogenase, mitochondrialP09622Details
Biliverdin reductase AP53004Details
Acetyl-coenzyme A synthetase 2-like, mitochondrialQ9NUB1Details
Aldose reductaseP15121Details
Farnesyl pyrophosphate synthaseP14324Details
Sphingosine-1-phosphate lyase 1O95470Details
Malate dehydrogenase, mitochondrialP40926Details
Nicotinamide N-methyltransferaseP40261Details
Glutathione S-transferase kappa 1Q9Y2Q3Details
Glutathione S-transferase PP09211Details
Glutathione S-transferase omega-1P78417Details
Maleylacetoacetate isomeraseO43708Details
Glutaminase kidney isoform, mitochondrialO94925Details
Perilipin-3O60664Details
CTP synthase 1P17812Details
Trifunctional purine biosynthetic protein adenosine-3P22102Details
Cyclin-dependent-like kinase 5Q00535Details
DNA (cytosine-5)-methyltransferase 1P26358Details
Peroxiredoxin-5, mitochondrialP30044Details
Growth factor receptor-bound protein 2P62993Details
Bifunctional epoxide hydrolase 2P34913Details
Fatty acid synthaseP49327Details
Dihydropyrimidine dehydrogenase [NADP(+)]Q12882Details
Lactoylglutathione lyaseQ04760Details
DNA topoisomerase 1P11387Details
Thiopurine S-methyltransferaseP51580Details
Glycine--tRNA ligaseP41250Details
Cytochrome b-c1 complex subunit 1, mitochondrialP31930Details
Cytochrome cP99999Details
CalnexinP27824Details
Peptidyl-prolyl cis-trans isomerase AP62937Details
Rho-associated protein kinase 1Q13464Details
Cyclin-dependent kinase 2P24941Details
Cyclin-dependent kinase 1P06493Details
Glucose-6-phosphate 1-dehydrogenaseP11413Details
Heat shock protein HSP 90-alphaP07900Details
Protein kinase C alpha typeP17252Details
14-3-3 protein zeta/deltaP63104Details
Quinone oxidoreductaseQ08257Details
Glucose-6-phosphate isomeraseP06744Details
CatalaseP04040Details
m7GpppX diphosphataseQ96C86Details
Thymidylate kinaseP23919Details
Bifunctional purine biosynthesis protein PURHP31939Details
Isocitrate dehydrogenase [NADP] cytoplasmicO75874Details
Tyrosine-protein kinase ZAP-70P43403Details
Acetyl-CoA acetyltransferase, cytosolicQ9BWD1Details
Tubulin beta-4B chainP68371Details
Tubulin beta-3 chainQ13509Details
Histidine triad nucleotide-binding protein 1P49773Details
Phosphatidylinositol transfer protein alpha isoformQ00169Details
Glucosamine-6-phosphate isomerase 1P46926Details
Leukotriene A-4 hydrolaseP09960Details
Fructose-bisphosphate aldolase AP04075Details
Poly [ADP-ribose] polymerase 1P09874Details
Medium-chain specific acyl-CoA dehydrogenase, mitochondrialP11310Details
Enoyl-CoA delta isomerase 1, mitochondrialP42126Details
Hydroxyacylglutathione hydrolase, mitochondrialQ16775Details
Kinesin-like protein KIF11P52732Details
Macrophage migration inhibitory factorP14174Details
Heat shock protein HSP 90-betaP08238Details
Fatty acid-binding protein, epidermalQ01469Details
Keratin, type II cytoskeletal 8P05787Details
CalreticulinP27797Details
Retinoblastoma-associated proteinP06400Details
Prolyl endopeptidaseP48147Details
Kynurenine--oxoglutarate transaminase 3Q6YP21Details
Cyclin-dependent kinase 6Q00534Details
Adenosine deaminaseP00813Details
Trimethyllysine dioxygenase, mitochondrialQ9NVH6Details
Multifunctional protein ADE2P22234Details
CAD proteinP27708Details
Aspartate--tRNA ligase, mitochondrialQ6PI48Details
Glutamine--tRNA ligaseP47897Details
Succinyl-CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrialP53597Details
Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrialP55809Details
Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrialQ9P2R7Details
Probable glutamate--tRNA ligase, mitochondrialQ5JPH6Details
S-formylglutathione hydrolaseP10768Details
Retinol dehydrogenase 11Q8TC12Details
Diacylglycerol kinase alphaP23743Details
Isoleucine--tRNA ligase, mitochondrialQ9NSE4Details
Probable asparagine--tRNA ligase, mitochondrialQ96I59Details
Proteasome subunit beta type-1P20618Details
Histone deacetylase 1Q13547Details
DNA-dependent protein kinase catalytic subunitP78527Details
Serine/threonine-protein kinase mTORP42345Details
Superoxide dismutase [Cu-Zn]P00441Details
DNA-(apurinic or apyrimidinic site) lyaseP27695Details
Keratin, type II cytoskeletal 7P08729Details
E3 ubiquitin-protein ligase UBR4Q5T4S7Details
Voltage-dependent anion-selective channel protein 1P21796Details
Voltage-dependent anion-selective channel protein 2P45880Details
Voltage-dependent anion-selective channel protein 3Q9Y277Details
Prostaglandin E synthase 3Q15185Details
U1 small nuclear ribonucleoprotein AP09012Details
ATP-dependent Clp protease proteolytic subunit, mitochondrialQ16740Details
Protein S100-A11P31949Details
Copper transport protein ATOX1O00244Details
Protein S100-A6P06703Details
2,4-dienoyl-CoA reductase, mitochondrialQ16698Details
Serine/threonine-protein phosphatase 5P53041Details
Nucleoside diphosphate kinase BP22392Details
Hydroxymethylglutaryl-CoA lyase, mitochondrialP35914Details
Cellular tumor antigen p53P04637Details
High mobility group protein B1P09429Details
Heat shock protein beta-1P04792Details
Transcriptional activator MybP10242Details
Histone deacetylase 5Q9UQL6Details
6-phosphogluconate dehydrogenase, decarboxylatingP52209Details
Integrin beta-1P05556Details
Deoxyguanosine kinase, mitochondrialQ16854Details
Cation-independent mannose-6-phosphate receptorP11717Details
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1Q13526Details
Nuclear receptor coactivator 2Q15596Details
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoformP30153Details
Uracil-DNA glycosylaseP13051Details
Heat shock cognate 71 kDa proteinP11142Details
60S ribosomal protein L13aP40429Details
60S ribosomal protein L37P61927Details
60S ribosomal protein L3P39023Details
60S ribosomal protein L11P62913Details
ATP synthase subunit alpha, mitochondrialP25705Details
ATP synthase subunit beta, mitochondrialP06576Details
ATP synthase subunit gamma, mitochondrialP36542Details
Triosephosphate isomeraseP60174Details
Cytosol aminopeptidaseP28838Details
Proteasome subunit alpha type-2P25787Details
Proteasome subunit alpha type-3P25788Details
Proteasome subunit alpha type-4P25789Details
Proteasome subunit alpha type-6P60900Details
Proteasome subunit alpha type-7O14818Details
Proteasome subunit beta type-3P49720Details
Casein kinase II subunit alpha'P19784Details
Cytochrome c oxidase subunit 4 isoform 1, mitochondrialP13073Details
Isopentenyl-diphosphate Delta-isomerase 1Q13907Details
Elongation factor Tu GTP-binding domain-containing protein 1Q7Z2Z2Details
Hydroxymethylglutaryl-CoA synthase, cytoplasmicQ01581Details
Profilin-1P07737Details
Peroxisomal acyl-coenzyme A oxidase 1Q15067Details
Calpain small subunit 1P04632Details
Annexin A5P08758Details
DestrinP60981Details
Cofilin-1P23528Details
Enoyl-CoA delta isomerase 2, mitochondrialO75521Details
Actin-related protein 2/3 complex subunit 1BO15143Details
Actin-related protein 2P61160Details
Actin-related protein 3P61158Details
Actin-related protein 2/3 complex subunit 2O15144Details
Actin-related protein 2/3 complex subunit 3O15145Details
Elongation factor 2P13639Details
3-hydroxyisobutyryl-CoA hydrolase, mitochondrialQ6NVY1Details
Interleukin-1 receptor-associated kinase 4Q9NWZ3Details
Protein S100-A4P26447Details
Aldo-keto reductase family 1 member B10O60218Details
CREB-binding proteinQ92793Details
Valacyclovir hydrolaseQ86WA6Details
Mediator of RNA polymerase II transcription subunit 1Q15648Details
U6 snRNA-associated Sm-like protein LSm6P62312Details
Superoxide dismutase [Mn], mitochondrialP04179Details
Phosphoglycerate kinase 1P00558Details
Thiosulfate sulfurtransferaseQ16762Details
Citrate synthase, mitochondrialO75390Details
Phosphoglucomutase-1P36871Details
VimentinP08670Details
Cytochrome b5 type BO43169Details
Acyl-CoA-binding proteinP07108Details
Galectin-1P09382Details
Enoyl-CoA hydratase, mitochondrialP30084Details
Aconitate hydratase, mitochondrialQ99798Details
Isocitrate dehydrogenase [NADP], mitochondrialP48735Details
Elongation factor Tu, mitochondrialP49411Details
T-complex protein 1 subunit gammaP49368Details
GTP-binding nuclear protein RanP62826Details
14-3-3 protein epsilonP62258Details
[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrialO14874Details
Ubiquitin-like modifier-activating enzyme 1P22314Details
Histone acetyltransferase KAT5Q92993Details
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5O60264Details
Spectrin beta chain, non-erythrocytic 1Q01082Details
Spliceosome RNA helicase DDX39BQ13838Details
Hepatocyte growth factor-regulated tyrosine kinase substrateO14964Details
Peroxiredoxin-6P30041Details
Myc proto-oncogene proteinP01106Details
Bleomycin hydrolaseQ13867Details
Proteasome subunit beta type-9P28065Details
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomeraseQ15125Details
Ras-related C3 botulinum toxin substrate 2P15153Details
Complement component 1 Q subcomponent-binding protein, mitochondrialQ07021Details
ThioredoxinP10599Details
Chloride intracellular channel protein 1O00299Details
Casein kinase II subunit betaP67870Details
Transcription factor p65Q04206Details
Ubiquitin carboxyl-terminal hydrolase isozyme L1P09936Details
Alpha-ketoglutarate-dependent dioxygenase FTOQ9C0B1Details
Alpha-enolaseP06733Details
Nucleolar and coiled-body phosphoprotein 1Q14978Details
Peroxiredoxin-1Q06830Details
Tricarboxylate transport protein, mitochondrialP53007Details
TesminQ9Y4I5Details
Calmodulin-2P0DP24Details
Calmodulin-3P0DP25Details
60 kDa heat shock protein, mitochondrialP10809Details
40S ribosomal protein S2P15880Details
Heterogeneous nuclear ribonucleoproteins A2/B1P22626Details
Heterogeneous nuclear ribonucleoprotein LP14866Details
Splicing factor, proline- and glutamine-richP23246Details
Receptor of activated protein C kinase 1P63244Details
Alpha-actinin-1P12814Details
Annexin A4P09525Details
Stress-induced-phosphoprotein 1P31948Details
Eukaryotic initiation factor 4A-IP60842Details
14-3-3 protein beta/alphaP31946Details
Hepatoma-derived growth factorP51858Details
Ran-specific GTPase-activating proteinP43487Details
Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1Q8N1G2Details
Copine-1Q99829Details
Protein RIC-3Q7Z5B4Details
Prohibitin-2Q99623Details
Flap endonuclease 1P39748Details
Eukaryotic translation initiation factor 3 subunit FO00303Details
ATP synthase subunit g, mitochondrialO75964Details
Heterogeneous nuclear ribonucleoprotein FP52597Details
Heat shock 70 kDa protein 4P34932Details
10 kDa heat shock protein, mitochondrialP61604Details
Nuclear migration protein nudCQ9Y266Details
Protein S100-A10P60903Details
Splicing factor 3A subunit 3Q12874Details
Tropomyosin alpha-1 chainP09493Details
Tropomyosin alpha-3 chainP06753Details
Tropomyosin alpha-4 chainP67936Details
Ubiquitin carboxyl-terminal hydrolase 14P54578Details
14-3-3 protein thetaP27348Details
Proliferating cell nuclear antigenP12004Details
DermcidinP81605Details
ATP synthase subunit O, mitochondrialP48047Details
Cysteine and glycine-rich protein 1P21291Details
Filamin-AP21333Details
Heterogeneous nuclear ribonucleoprotein D0Q14103Details
NucleophosminP06748Details
60S ribosomal protein L14P50914Details
60S ribosomal protein L35P42766Details
60S ribosomal protein L4P36578Details
40S ribosomal protein S13P62277Details
40S ribosomal protein S18P62269Details
40S ribosomal protein S19P39019Details
40S ribosomal protein S5P46782Details
40S ribosomal protein S6P62753Details
40S ribosomal protein S9P46781Details
Transgelin-2P37802Details
ZyxinQ15942Details
Serine/arginine-rich splicing factor 1Q07955Details
Myosin-9P35579Details
Probable ATP-dependent RNA helicase DDX5P17844Details
Splicing factor 3B subunit 1O75533Details
STE20/SPS1-related proline-alanine-rich protein kinaseQ9UEW8Details
Citron Rho-interacting kinaseO14578Details
Casein kinase I isoform alphaP48729Details
eIF-2-alpha kinase GCN2Q9P2K8Details
Mitogen-activated protein kinase kinase kinase kinase 5Q9Y4K4Details
Serine/threonine-protein kinase PAK 2Q13177Details
Phosphatidylinositol 5-phosphate 4-kinase type-2 betaP78356Details
Serine/threonine-protein kinase N1Q16512Details
Serine/threonine-protein kinase PRP4 homologQ13523Details
Exportin-1O14980Details
ProhibitinP35232Details
Voltage-gated potassium channel subunit beta-2Q13303Details
Magnesium transporter MRS2 homolog, mitochondrialQ9HD23Details
ATP-citrate synthaseP53396Details
Apolipoprotein B-100P04114Details