N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

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Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R

N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18.

PubMed ID
22814378 [ View in PubMed
]
Abstract

Protein N-terminal acetylation (Nt-acetylation) is an important mediator of protein function, stability, sorting, and localization. Although the responsible enzymes are thought to be fairly well characterized, the lack of identified in vivo substrates, the occurrence of Nt-acetylation substrates displaying yet uncharacterized N-terminal acetyltransferase (NAT) specificities, and emerging evidence of posttranslational Nt-acetylation, necessitate the use of genetic models and quantitative proteomics. NatB, which targets Met-Glu-, Met-Asp-, and Met-Asn-starting protein N termini, is presumed to Nt-acetylate 15% of all yeast and 18% of all human proteins. We here report on the evolutionary traits of NatB from yeast to human and demonstrate that ectopically expressed hNatB in a yNatB-Delta yeast strain partially complements the natB-Delta phenotypes and partially restores the yNatB Nt-acetylome. Overall, combining quantitative N-terminomics with yeast studies and knockdown of hNatB in human cell lines, led to the unambiguous identification of 180 human and 110 yeast NatB substrates. Interestingly, these substrates included Met-Gln- N-termini, which are thus now classified as in vivo NatB substrates. We also demonstrate the requirement of hNatB activity for maintaining the structure and function of actomyosin fibers and for proper cellular migration. In addition, expression of tropomyosin-1 restored the altered focal adhesions and cellular migration defects observed in hNatB-depleted HeLa cells, indicative for the conserved link between NatB, tropomyosin, and actin cable function from yeast to human.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Glycogen phosphorylase, liver formP06737Details
7-dehydrocholesterol reductaseQ9UBM7Details
Phenylalanine--tRNA ligase alpha subunitQ9Y285Details
TransketolaseP29401Details
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylatingQ15738Details
Serine--tRNA ligase, cytoplasmicP49591Details
NADH dehydrogenase [ubiquinone] iron-sulfur protein 5O43920Details
Sterol O-acyltransferase 1P35610Details
Adenine phosphoribosyltransferaseP07741Details
Potassium channel subfamily K member 1O00180Details
Lysine--tRNA ligaseQ15046Details
NEDD8-activating enzyme E1 regulatory subunitQ13564Details
Valine--tRNA ligaseP26640Details
Tryptophan--tRNA ligase, cytoplasmicP23381Details
Calcium-binding mitochondrial carrier protein Aralar1O75746Details
Neutral amino acid transporter B(0)Q15758Details
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialP13995Details
Calcium-binding mitochondrial carrier protein Aralar2Q9UJS0Details
4-trimethylaminobutyraldehyde dehydrogenaseP49189Details
Alanine--tRNA ligase, cytoplasmicP49588Details
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4O95168Details
Spermidine synthaseP19623Details
Thymidylate synthaseP04818Details
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1O75438Details
Peroxisomal carnitine O-octanoyltransferaseQ9UKG9Details
AmidophosphoribosyltransferaseQ06203Details
KynureninaseQ16719Details
Ferritin heavy chainP02794Details
Intermediate conductance calcium-activated potassium channel protein 4O15554Details
CalmodulinP0DP23Details
Aldehyde dehydrogenase family 3 member B1P43353Details
4-hydroxyphenylpyruvate dioxygenaseP32754Details
Neutral amino acid transporter AP43007Details
3-oxo-5-alpha-steroid 4-dehydrogenase 1P18405Details
Dihydropteridine reductaseP09417Details
Glyceraldehyde-3-phosphate dehydrogenaseP04406Details
Phenylalanine--tRNA ligase beta subunitQ9NSD9Details
Aldehyde dehydrogenase family 1 member A3P47895Details
Asparagine--tRNA ligase, cytoplasmicO43776Details
Choline-phosphate cytidylyltransferase AP49585Details
C-1-tetrahydrofolate synthase, cytoplasmicP11586Details
Folylpolyglutamate synthase, mitochondrialQ05932Details
Cysteine--tRNA ligase, cytoplasmicP49589Details
Aldehyde dehydrogenase, dimeric NADP-preferringP30838Details
DNA topoisomerase 2-alphaP11388Details
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12Q9UI09Details
Chloride channel protein 2P51788Details
Farnesyl pyrophosphate synthaseP14324Details
Glucocorticoid receptorP04150Details
Glutathione S-transferase PP09211Details
Maleylacetoacetate isomeraseO43708Details
Perilipin-3O60664Details
L-xylulose reductaseQ7Z4W1Details
Fatty acid desaturase 1O60427Details
Growth factor receptor-bound protein 2P62993Details
Mitogen-activated protein kinase 1P28482Details
Phosphatidylinositol 3-kinase regulatory subunit alphaP27986Details
Dihydropyrimidine dehydrogenase [NADP(+)]Q12882Details
Catenin beta-1P35222Details
Peptidyl-prolyl cis-trans isomerase AP62937Details
Rho-associated protein kinase 1Q13464Details
Protein-glutamine gamma-glutamyltransferase 2P21980Details
Proton-coupled folate transporterQ96NT5Details
Solute carrier family 2, facilitated glucose transporter member 1P11166Details
Mitogen-activated protein kinase 3P27361Details
Cyclin-dependent kinase 2P24941Details
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2P59768Details
Cyclin-dependent kinase 1P06493Details
Glucose-6-phosphate 1-dehydrogenaseP11413Details
Excitatory amino acid transporter 1P43003Details
Protein kinase C alpha typeP17252Details
14-3-3 protein zeta/deltaP63104Details
Quinone oxidoreductaseQ08257Details
m7GpppX diphosphataseQ96C86Details
Bifunctional purine biosynthesis protein PURHP31939Details
Isocitrate dehydrogenase [NADP] cytoplasmicO75874Details
Thymidine kinase, cytosolicP04183Details
Acetyl-CoA acetyltransferase, cytosolicQ9BWD1Details
Serine/threonine-protein phosphatase PP1-gamma catalytic subunitP36873Details
Lanosterol synthaseP48449Details
Histidine triad nucleotide-binding protein 1P49773Details
Phosphatidylinositol transfer protein alpha isoformQ00169Details
Uroporphyrinogen decarboxylaseP06132Details
Leukotriene A-4 hydrolaseP09960Details
Fructose-bisphosphate aldolase AP04075Details
Ras-related protein Rab-9AP51151Details
Poly [ADP-ribose] polymerase 1P09874Details
Macrophage migration inhibitory factorP14174Details
Cyclin-dependent kinase 7P50613Details
Fatty acid-binding protein, epidermalQ01469Details
Prolyl endopeptidaseP48147Details
Glycogen phosphorylase, brain formP11216Details
Kynurenine--oxoglutarate transaminase 3Q6YP21Details
Cyclin-dependent kinase 6Q00534Details
Egl nine homolog 1Q9GZT9Details
CAD proteinP27708Details
Glutamine--tRNA ligaseP47897Details
Fatty acid desaturase 2O95864Details
N-acetyl-D-glucosamine kinaseQ9UJ70Details
Aspartyl aminopeptidaseQ9ULA0Details
Probable glutathione peroxidase 8Q8TED1Details
Vitamin K epoxide reductase complex subunit 1-like protein 1Q8N0U8Details
Peptidyl-prolyl cis-trans isomerase HO43447Details
Proteasome subunit beta type-1P20618Details
Proteasome subunit beta type-2P49721Details
Serine/threonine-protein kinase mTORP42345Details
DNA repair protein RAD51 homolog 1Q06609Details
NAD-dependent protein deacetylase sirtuin-1Q96EB6Details
Voltage-dependent anion-selective channel protein 1P21796Details
Oxidoreductase HTATIP2Q9BUP3Details
Prostaglandin E synthase 3Q15185Details
Hypoxia-inducible factor 1-alpha inhibitorQ9NWT6Details
Protein S100-A11P31949Details
Calpain-1 catalytic subunitP07384Details
Bcl2-associated agonist of cell deathQ92934Details
cAMP-dependent protein kinase type I-alpha regulatory subunitP10644Details
G-protein coupled estrogen receptor 1Q99527Details
Signal transducer and activator of transcription 3P40763Details
Microtubule-associated protein 4P27816Details
Transmembrane anterior posterior transformation protein 1 homologQ6NXT6Details
Thiamine transporter 1O60779Details
Adenosine kinaseP55263Details
V-type proton ATPase catalytic subunit AP38606Details
Geranylgeranyl pyrophosphate synthaseO95749Details
Arylamine N-acetyltransferase 1P18440Details
DNA polymerase epsilon subunit 4Q9NR33Details
Solute carrier family 22 member 3O75751Details
Solute carrier organic anion transporter family member 2A1Q92959Details
Multidrug and toxin extrusion protein 1Q96FL8Details
Solute carrier organic anion transporter family member 3A1Q9UIG8Details
Aryl hydrocarbon receptorP35869Details
Cyclin-A2P20248Details
Serine/threonine-protein kinase PLK1P53350Details
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoformQ13362Details
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoformP30153Details
cAMP-dependent protein kinase inhibitor alphaP61925Details
BAG family molecular chaperone regulator 1Q99933Details
Heat shock cognate 71 kDa proteinP11142Details
Dual specificity protein kinase TTKP33981Details
Serine/threonine-protein phosphatase PP1-alpha catalytic subunitP62136Details
60S ribosomal protein L13aP40429Details
60S ribosomal protein L37P61927Details
60S ribosomal protein L11P62913Details
Proteasome subunit alpha type-3P25788Details
Proteasome subunit beta type-4P28070Details
Proteasome subunit beta type-6P28072Details
Casein kinase I isoform gamma-3Q9Y6M4Details
Cytochrome c oxidase subunit 6CP09669Details
Cytochrome c oxidase subunit 6B1P14854Details
Elongation factor Tu GTP-binding domain-containing protein 1Q7Z2Z2Details
MAP kinase-activated protein kinase 3Q16644Details
Platelet-activating factor acetylhydrolase IB subunit gammaQ15102Details
DestrinP60981Details
Cofilin-1P23528Details
Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoformQ08209Details
Actin-related protein 2/3 complex subunit 2O15144Details
Actin-related protein 2/3 complex subunit 5O15511Details
Elongation factor 2P13639Details
Glycylpeptide N-tetradecanoyltransferase 1P30419Details
Interleukin-1 receptor-associated kinase 4Q9NWZ3Details
CREB-binding proteinQ92793Details
Acyl-coenzyme A thioesterase 13Q9NPJ3Details
NmrA-like family domain-containing protein 1Q9HBL8Details
Mothers against decapentaplegic homolog 2Q15796Details
Protein arginine N-methyltransferase 3O60678Details
Phosphoglycerate kinase 1P00558Details
Beta-enolaseP13929Details
Phosphoglucomutase-1P36871Details
VimentinP08670Details
Cytochrome b5 type BO43169Details
Acyl-CoA-binding proteinP07108Details
Adenylate kinase 2, mitochondrialP54819Details
Galectin-1P09382Details
Signal recognition particle 14 kDa proteinP37108Details
Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1Q9GZU7Details
Cyclin-dependent kinases regulatory subunit 1P61024Details
GTP-binding nuclear protein RanP62826Details
N-acylneuraminate cytidylyltransferaseQ8NFW8Details
Acylphosphatase-2P14621Details
Ubiquitin-like modifier-activating enzyme 1P22314Details
Histone acetyltransferase KAT2AQ92830Details
Spectrin beta chain, non-erythrocytic 1Q01082Details
Selenocysteine lyaseQ96I15Details
Ribosomal protein S6 kinase alpha-4O75676Details
Pyrroline-5-carboxylate reductase 3Q53H96Details
Kinesin-like protein KIF2CQ99661Details
Peroxiredoxin-6P30041Details
Folic acid synthesis protein FOL1P53848Details
Folate transporter 1P41440Details
Proteasome subunit beta type-10P40306Details
Actin, cytoplasmic 1P60709Details
Actin, cytoplasmic 2P63261Details
Actin, aortic smooth muscleP62736Details
Histone H1.4P10412Details
Solute carrier family 2, facilitated glucose transporter member 5P22732Details
Solute carrier family 2, facilitated glucose transporter member 6Q9UGQ3Details
Chloride intracellular channel protein 1O00299Details
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENP60484Details
Transcription factor p65Q04206Details
Protein O-GlcNAcaseO60502Details
Calmodulin-2P0DP24Details
Calmodulin-3P0DP25Details
40S ribosomal protein S2P15880Details
Heterogeneous nuclear ribonucleoproteins A2/B1P22626Details
Heterogeneous nuclear ribonucleoprotein HP31943Details
Heterogeneous nuclear ribonucleoprotein LP14866Details
Receptor of activated protein C kinase 1P63244Details
Annexin A4P09525Details
14-3-3 protein beta/alphaP31946Details
Serpin B9P50453Details
Prohibitin-2Q99623Details
Cyclin-dependent kinase inhibitor 1P38936Details
Flap endonuclease 1P39748Details
Beclin-1Q14457Details
RuvB-like 2Q9Y230Details
Splicing factor 3B subunit 3Q15393Details
ATP synthase subunit e, mitochondrialP56385Details
Heterogeneous nuclear ribonucleoprotein FP52597Details
Heterogeneous nuclear ribonucleoprotein KP61978Details
26S protease regulatory subunit 6AP17980Details
Splicing factor 3A subunit 3Q12874Details
Tumor protein D54O43399Details
Tropomyosin alpha-4 chainP67936Details
14-3-3 protein thetaP27348Details
Chromobox protein homolog 5P45973Details
Far upstream element-binding protein 2Q92945Details
Ras GTPase-activating-like protein IQGAP1P46940Details
40S ribosomal protein S19P39019Details
40S ribosomal protein S6P62753Details
Splicing factor 1Q15637Details
Small nuclear ribonucleoprotein Sm D2P62316Details
ZyxinQ15942Details
Survival motor neuron proteinB4DP61Details
N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase DQ6IQ20Details
TransgelinQ01995Details
Myosin-9P35579Details
Serine/threonine-protein kinase tousled-like 1Q9UKI8Details
AP2-associated protein kinase 1Q2M2I8Details
Calcium/calmodulin-dependent protein kinase type 1Q14012Details
Calcium/calmodulin-dependent protein kinase kinase 1Q8N5S9Details
Calcium/calmodulin-dependent protein kinase kinase 2Q96RR4Details
Citron Rho-interacting kinaseO14578Details
Casein kinase I isoform alphaP48729Details
Interferon-induced, double-stranded RNA-activated protein kinaseP19525Details
Dual specificity mitogen-activated protein kinase kinase 3P46734Details
Mitogen-activated protein kinase kinase kinase kinase 3Q8IVH8Details
Mitogen-activated protein kinase kinase kinase kinase 4O95819Details
Myosin light chain kinase, smooth muscleQ15746Details
Serine/threonine-protein kinase Nek3P51956Details
NUAK family SNF1-like kinase 2Q9H093Details
Serine/threonine-protein kinase PAK 1Q13153Details
Serine/threonine-protein kinase PAK 2Q13177Details
Serine/threonine-protein kinase N1Q16512Details
Serine/threonine-protein kinase PRP4 homologQ13523Details
Serine/threonine-protein kinase RIO2Q9BVS4Details
Ribulose-phosphate 3-epimeraseQ96AT9Details
Voltage-gated potassium channel subunit beta-2Q13303Details
Sodium-coupled neutral amino acid transporter 2Q96QD8Details
Thiamine-triphosphataseQ9BU02Details
Zinc transporter 5Q8TAD4Details
Tyrosine-protein phosphatase non-receptor type 12Q05209Details
Caspase-4P49662Details
Leucyl-cystinyl aminopeptidaseQ9UIQ6Details
GTP-binding protein RHO1P06780Details
Eukaryotic translation initiation factor 4E-binding protein 1Q13541Details
G1/S-specific cyclin-D3P30281Details
Dual specificity mitogen-activated protein kinase kinase 7O14733Details
3-oxoacyl-[acyl-carrier-protein] reductaseQ8N4T8Details
CD70 antigenP32970Details