N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
Article Details
- CitationCopy to clipboard
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
Name UniProt ID Glycogen phosphorylase, liver form P06737 Details 7-dehydrocholesterol reductase Q9UBM7 Details Phenylalanine--tRNA ligase alpha subunit Q9Y285 Details Transketolase P29401 Details Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating Q15738 Details Serine--tRNA ligase, cytoplasmic P49591 Details NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 O43920 Details Sterol O-acyltransferase 1 P35610 Details Adenine phosphoribosyltransferase P07741 Details Potassium channel subfamily K member 1 O00180 Details Lysine--tRNA ligase Q15046 Details NEDD8-activating enzyme E1 regulatory subunit Q13564 Details Valine--tRNA ligase P26640 Details Tryptophan--tRNA ligase, cytoplasmic P23381 Details Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial O75746 Details Neutral amino acid transporter B(0) Q15758 Details Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial P13995 Details Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial Q9UJS0 Details 4-trimethylaminobutyraldehyde dehydrogenase P49189 Details Alanine--tRNA ligase, cytoplasmic P49588 Details NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 O95168 Details Spermidine synthase P19623 Details Thymidylate synthase P04818 Details NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 O75438 Details Peroxisomal carnitine O-octanoyltransferase Q9UKG9 Details Amidophosphoribosyltransferase Q06203 Details Kynureninase Q16719 Details Ferritin heavy chain P02794 Details Intermediate conductance calcium-activated potassium channel protein 4 O15554 Details Aldehyde dehydrogenase family 3 member B1 P43353 Details 4-hydroxyphenylpyruvate dioxygenase P32754 Details Neutral amino acid transporter A P43007 Details 3-oxo-5-alpha-steroid 4-dehydrogenase 1 P18405 Details Dihydropteridine reductase P09417 Details Glyceraldehyde-3-phosphate dehydrogenase P04406 Details Phenylalanine--tRNA ligase beta subunit Q9NSD9 Details Retinaldehyde dehydrogenase 3 P47895 Details Asparagine--tRNA ligase, cytoplasmic O43776 Details Choline-phosphate cytidylyltransferase A P49585 Details C-1-tetrahydrofolate synthase, cytoplasmic P11586 Details Folylpolyglutamate synthase, mitochondrial Q05932 Details Cysteine--tRNA ligase, cytoplasmic P49589 Details Aldehyde dehydrogenase, dimeric NADP-preferring P30838 Details DNA topoisomerase 2-alpha P11388 Details NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 Q9UI09 Details Chloride channel protein 2 P51788 Details Farnesyl pyrophosphate synthase P14324 Details Glucocorticoid receptor P04150 Details Glutathione S-transferase P P09211 Details Maleylacetoacetate isomerase O43708 Details Perilipin-3 O60664 Details L-xylulose reductase Q7Z4W1 Details Acyl-CoA (8-3)-desaturase O60427 Details Growth factor receptor-bound protein 2 P62993 Details Mitogen-activated protein kinase 1 P28482 Details Phosphatidylinositol 3-kinase regulatory subunit alpha P27986 Details Dihydropyrimidine dehydrogenase [NADP(+)] Q12882 Details Catenin beta-1 P35222 Details Peptidyl-prolyl cis-trans isomerase A P62937 Details Rho-associated protein kinase 1 Q13464 Details Protein-glutamine gamma-glutamyltransferase 2 P21980 Details Proton-coupled folate transporter Q96NT5 Details Solute carrier family 2, facilitated glucose transporter member 1 P11166 Details Mitogen-activated protein kinase 3 P27361 Details Cyclin-dependent kinase 2 P24941 Details Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 P59768 Details Cyclin-dependent kinase 1 P06493 Details Glucose-6-phosphate 1-dehydrogenase P11413 Details Excitatory amino acid transporter 1 P43003 Details Protein kinase C alpha type P17252 Details 14-3-3 protein zeta/delta P63104 Details Quinone oxidoreductase Q08257 Details m7GpppX diphosphatase Q96C86 Details Bifunctional purine biosynthesis protein ATIC P31939 Details Isocitrate dehydrogenase [NADP] cytoplasmic O75874 Details Thymidine kinase, cytosolic P04183 Details Acetyl-CoA acetyltransferase, cytosolic Q9BWD1 Details Serine/threonine-protein phosphatase PP1-gamma catalytic subunit P36873 Details Lanosterol synthase P48449 Details Adenosine 5'-monophosphoramidase HINT1 P49773 Details Phosphatidylinositol transfer protein alpha isoform Q00169 Details Uroporphyrinogen decarboxylase P06132 Details Leukotriene A-4 hydrolase P09960 Details Fructose-bisphosphate aldolase A P04075 Details Ras-related protein Rab-9A P51151 Details Poly [ADP-ribose] polymerase 1 P09874 Details Macrophage migration inhibitory factor P14174 Details Cyclin-dependent kinase 7 P50613 Details Fatty acid-binding protein 5 Q01469 Details Prolyl endopeptidase P48147 Details Glycogen phosphorylase, brain form P11216 Details Kynurenine--oxoglutarate transaminase 3 Q6YP21 Details Cyclin-dependent kinase 6 Q00534 Details Egl nine homolog 1 Q9GZT9 Details Multifunctional protein CAD P27708 Details Glutamine--tRNA ligase P47897 Details Acyl-CoA 6-desaturase O95864 Details N-acetyl-D-glucosamine kinase Q9UJ70 Details Aspartyl aminopeptidase Q9ULA0 Details Probable glutathione peroxidase 8 Q8TED1 Details Vitamin K epoxide reductase complex subunit 1-like protein 1 Q8N0U8 Details Peptidyl-prolyl cis-trans isomerase H O43447 Details Proteasome subunit beta type-1 P20618 Details Proteasome subunit beta type-2 P49721 Details Serine/threonine-protein kinase mTOR P42345 Details DNA repair protein RAD51 homolog 1 Q06609 Details NAD-dependent protein deacetylase sirtuin-1 Q96EB6 Details Non-selective voltage-gated ion channel VDAC1 P21796 Details Oxidoreductase HTATIP2 Q9BUP3 Details Prostaglandin E synthase 3 Q15185 Details Hypoxia-inducible factor 1-alpha inhibitor Q9NWT6 Details Protein S100-A11 P31949 Details Calpain-1 catalytic subunit P07384 Details Bcl2-associated agonist of cell death Q92934 Details cAMP-dependent protein kinase type I-alpha regulatory subunit P10644 Details G-protein coupled estrogen receptor 1 Q99527 Details Signal transducer and activator of transcription 3 P40763 Details Microtubule-associated protein 4 P27816 Details Transmembrane anterior posterior transformation protein 1 homolog Q6NXT6 Details Thiamine transporter 1 O60779 Details Adenosine kinase P55263 Details V-type proton ATPase catalytic subunit A P38606 Details Geranylgeranyl pyrophosphate synthase O95749 Details Arylamine N-acetyltransferase 1 P18440 Details DNA polymerase epsilon subunit 4 Q9NR33 Details Solute carrier family 22 member 3 O75751 Details Solute carrier organic anion transporter family member 2A1 Q92959 Details Multidrug and toxin extrusion protein 1 Q96FL8 Details Solute carrier organic anion transporter family member 3A1 Q9UIG8 Details Aryl hydrocarbon receptor P35869 Details Cyclin-A2 P20248 Details Serine/threonine-protein kinase PLK1 P53350 Details Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform Q13362 Details Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform P30153 Details cAMP-dependent protein kinase inhibitor alpha P61925 Details BAG family molecular chaperone regulator 1 Q99933 Details Heat shock cognate 71 kDa protein P11142 Details Dual specificity protein kinase TTK P33981 Details Serine/threonine-protein phosphatase PP1-alpha catalytic subunit P62136 Details Large ribosomal subunit protein uL13 P40429 Details Large ribosomal subunit protein eL37 P61927 Details Large ribosomal subunit protein uL5 P62913 Details Proteasome subunit alpha type-3 P25788 Details Proteasome subunit beta type-4 P28070 Details Proteasome subunit beta type-6 P28072 Details Casein kinase I isoform gamma-3 Q9Y6M4 Details Cytochrome c oxidase subunit 6C P09669 Details Cytochrome c oxidase subunit 6B1 P14854 Details Elongation factor-like GTPase 1 Q7Z2Z2 Details MAP kinase-activated protein kinase 3 Q16644 Details Platelet-activating factor acetylhydrolase IB subunit alpha1 Q15102 Details Destrin P60981 Details Cofilin-1 P23528 Details Protein phosphatase 3 catalytic subunit alpha Q08209 Details Actin-related protein 2/3 complex subunit 2 O15144 Details Actin-related protein 2/3 complex subunit 5 O15511 Details Elongation factor 2 P13639 Details Glycylpeptide N-tetradecanoyltransferase 1 P30419 Details Interleukin-1 receptor-associated kinase 4 Q9NWZ3 Details CREB-binding protein Q92793 Details Acyl-coenzyme A thioesterase 13 Q9NPJ3 Details NmrA-like family domain-containing protein 1 Q9HBL8 Details Mothers against decapentaplegic homolog 2 Q15796 Details Protein arginine N-methyltransferase 3 O60678 Details Phosphoglycerate kinase 1 P00558 Details Beta-enolase P13929 Details Phosphoglucomutase-1 P36871 Details Vimentin P08670 Details Cytochrome b5 type B O43169 Details Acyl-CoA-binding protein P07108 Details Adenylate kinase 2, mitochondrial P54819 Details Galectin-1 P09382 Details Signal recognition particle 14 kDa protein P37108 Details Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 Q9GZU7 Details Cyclin-dependent kinases regulatory subunit 1 P61024 Details GTP-binding nuclear protein Ran P62826 Details N-acylneuraminate cytidylyltransferase Q8NFW8 Details Acylphosphatase-2 P14621 Details Ubiquitin-like modifier-activating enzyme 1 P22314 Details Histone acetyltransferase KAT2A Q92830 Details Spectrin beta chain, non-erythrocytic 1 Q01082 Details Selenocysteine lyase Q96I15 Details Ribosomal protein S6 kinase alpha-4 O75676 Details Pyrroline-5-carboxylate reductase 3 Q53H96 Details Kinesin-like protein KIF2C Q99661 Details Peroxiredoxin-6 P30041 Details Folic acid synthesis protein FOL1 P53848 Details Reduced folate transporter P41440 Details Proteasome subunit beta type-10 P40306 Details Actin, cytoplasmic 1 P60709 Details Actin, cytoplasmic 2 P63261 Details Actin, aortic smooth muscle P62736 Details Histone H1.4 P10412 Details Solute carrier family 2, facilitated glucose transporter member 5 P22732 Details Solute carrier family 2, facilitated glucose transporter member 6 Q9UGQ3 Details Chloride intracellular channel protein 1 O00299 Details Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN P60484 Details Transcription factor p65 Q04206 Details Protein O-GlcNAcase O60502 Details Calmodulin-2 P0DP24 Details Calmodulin-3 P0DP25 Details Small ribosomal subunit protein uS5 P15880 Details Heterogeneous nuclear ribonucleoproteins A2/B1 P22626 Details Heterogeneous nuclear ribonucleoprotein H P31943 Details Heterogeneous nuclear ribonucleoprotein L P14866 Details Small ribosomal subunit protein RACK1 P63244 Details Annexin A4 P09525 Details 14-3-3 protein beta/alpha P31946 Details Serpin B9 P50453 Details Prohibitin-2 Q99623 Details Cyclin-dependent kinase inhibitor 1 P38936 Details Flap endonuclease 1 P39748 Details Beclin-1 Q14457 Details RuvB-like 2 Q9Y230 Details Splicing factor 3B subunit 3 Q15393 Details ATP synthase subunit e, mitochondrial P56385 Details Heterogeneous nuclear ribonucleoprotein F P52597 Details Heterogeneous nuclear ribonucleoprotein K P61978 Details 26S proteasome regulatory subunit 6A P17980 Details Splicing factor 3A subunit 3 Q12874 Details Tumor protein D54 O43399 Details Tropomyosin alpha-4 chain P67936 Details 14-3-3 protein theta P27348 Details Chromobox protein homolog 5 P45973 Details Far upstream element-binding protein 2 Q92945 Details Ras GTPase-activating-like protein IQGAP1 P46940 Details Small ribosomal subunit protein eS19 P39019 Details Small ribosomal subunit protein eS6 P62753 Details Splicing factor 1 Q15637 Details Small nuclear ribonucleoprotein Sm D2 P62316 Details Zyxin Q15942 Details Survival motor neuron protein B4DP61 Details N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D Q6IQ20 Details Transgelin Q01995 Details Myosin-9 P35579 Details Serine/threonine-protein kinase tousled-like 1 Q9UKI8 Details AP2-associated protein kinase 1 Q2M2I8 Details Calcium/calmodulin-dependent protein kinase type 1 Q14012 Details Calcium/calmodulin-dependent protein kinase kinase 1 Q8N5S9 Details Calcium/calmodulin-dependent protein kinase kinase 2 Q96RR4 Details Citron Rho-interacting kinase O14578 Details Casein kinase I isoform alpha P48729 Details Interferon-induced, double-stranded RNA-activated protein kinase P19525 Details Dual specificity mitogen-activated protein kinase kinase 3 P46734 Details Mitogen-activated protein kinase kinase kinase kinase 3 Q8IVH8 Details Mitogen-activated protein kinase kinase kinase kinase 4 O95819 Details Myosin light chain kinase, smooth muscle Q15746 Details Serine/threonine-protein kinase Nek3 P51956 Details NUAK family SNF1-like kinase 2 Q9H093 Details Serine/threonine-protein kinase PAK 1 Q13153 Details Serine/threonine-protein kinase PAK 2 Q13177 Details Serine/threonine-protein kinase N1 Q16512 Details Serine/threonine-protein kinase PRP4 homolog Q13523 Details Serine/threonine-protein kinase RIO2 Q9BVS4 Details Ribulose-phosphate 3-epimerase Q96AT9 Details Voltage-gated potassium channel subunit beta-2 Q13303 Details Sodium-coupled neutral amino acid symporter 2 Q96QD8 Details Thiamine-triphosphatase Q9BU02 Details Proton-coupled zinc antiporter SLC30A5 Q8TAD4 Details Tyrosine-protein phosphatase non-receptor type 12 Q05209 Details Caspase-4 P49662 Details Leucyl-cystinyl aminopeptidase Q9UIQ6 Details GTP-binding protein RHO1 P06780 Details Eukaryotic translation initiation factor 4E-binding protein 1 Q13541 Details G1/S-specific cyclin-D3 P30281 Details Dual specificity mitogen-activated protein kinase kinase 7 O14733 Details 3-oxoacyl-[acyl-carrier-protein] reductase Q8N4T8 Details CD70 antigen P32970 Details