N-alpha-acetyltransferase 10

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N(alpha)-acetyltransferase 10, NatA catalytic subunit
PDB rendering based on 4KVM: Crystal structure of S. pombe Naa10 bound to bisubstrate analog.[1]
Symbols NAA10 ; ARD1; ARD1A; ARD1P; DXS707; MCOPS1; NATD; TE2
External IDs OMIM300013 MGI1915255 HomoloGene2608 GeneCards: NAA10 Gene
EC number
RNA expression pattern
PBB GE ARD1A 203025 at tn.png
More reference expression data
Species Human Mouse
Entrez 8260 56292
Ensembl ENSG00000102030 ENSMUSG00000031388
UniProt P41227 Q9QY36
RefSeq (mRNA) NM_001256119 NM_001177965
RefSeq (protein) NP_001243048 NP_001171436
Location (UCSC) Chr HG1497_PATCH:
153.1 – 153.1 Mb
Chr X:
73.92 – 73.92 Mb
PubMed search [1] [2]

N-alpha-acetyltransferase 10 (NAA10) also known as NatA catalytic subunit Naa10 and arrest-defective protein 1 homolog A (ARD1A) is an enzyme that in humans is encoded NAA10 gene.[2][3] Together with its auxiliary subunit Naa15, Naa10 constitutes the NatA (Nα-acetyltransferase A) complex that specifically catalyzes the transfer of an acetyl group from acetyl-CoA to the N-terminal primary amino group of certain proteins. In higher eukaryotes, 5 other N-acetyltransferase (NAT) complexes, NatB-NatF, have been described that differ both in substrate specificity and subunit composition.[4]

Gene and transcripts[edit]

The human NAA10 is located on chromosome Xq28 and is encoded by 8 exons 2 encoding three different isoforms derived from alternate splicing.[5] Additionally, a processed NAA10 gene duplication NAA11 (ARD2) has been identified that is expressed in several human cell lines;[6] however, later studies indicate that Naa11 is not expressed in the human cell lines HeLa and HEK293 or in cancerous tissues, and NAA11 transcripts were only detected in testicular and placental tissues.[7] Naa11 has also been found in mouse, where it is mainly expressed in the testis.[8] NAA11 is located on chromosome 4q21.21 in human and 5 E3 in mouse, and only contains two exons.

In mouse, NAA10 is located on chromosome X A7.3 and contains 9 exons. Two alternative splicing products of mouse Naa10, mNaa10235 and mNaa10225, were reported in NIH-3T3 and JB6 cells that may have different activities and function in different subcellular compartments.[9]

Homologues for Naa10 have been identified in almost all kingdoms of life analyzed, including plants,[10][11][12] fungi,[10][13] amoebozoa,[10] archaeabacteria[10][14][15][16] and protozoa.[17][18] In eubacteria, 3 Nα-acetyltransferases, RimI, RimJ and RimL, have been identified[19][20][21] but according to their low sequence identity with the NATs, it is likely that the RIM proteins do not have a common ancestor and evolved independently.[22][23]


To date, no X-ray crystal structure of the human Naa10 has been reported. However, size-exclusion chromatography and circular dichroism indicated that human Naa10 consists of a compact globular region comprising two thirds of the protein and a flexible unstructured C-terminus.[24] Furthermore, the recent X-ray crystal structure of the 100 kD holo-NatA (Naa10/Naa15) complex from S. pombe showed that Naa10 adopts a typical GNAT fold containing a N-terminal α1–loop–α2 segment that features one large hydrophobic interface and exhibits interactions with its auxiliary subunit Naa15, a central acetyl CoA-binding region, and C-terminal segments that are similar to the corresponding regions in Naa50, another Nα-acetyltransferase.[25] The X-ray crystal structure of archaeal T. volcanium Naa10 has also been reported, revealing multiple distinct modes of acetyl-Co binding involving the loops between β4 and α3, including the P-loop.[16] Interestingly, non-complexed (Naa15 unbound) Naa10 adopts a different fold: Leu22 and Tyr26 shift out of the active site of Naa10, and Glu24 (important for substrate binding and catalysis of NatA) is repositioned by ~5 Å, resulting in a conformation that allows for the acetylation of a different subset of substrates.[25]

A functional nuclear localization signal in the C-terminus of hNaa10 between residues 78 and 83 (KRSHRR) has been described.[26][27]


Naa10, as part of the NatA complex, is bound to the ribosome and co-translationally acetylates proteins starting with small side chains such as Ser, Ala, Thr, Gly, Val and Cys, after the initiator methionine (iMet) has been cleaved by methionine aminopeptidases (MetAP).[28] Furthermore, post-translational acetylation by non-ribosome-associated Naa10 might occur. About 40-50 % of all proteins are potential NatA substrates.[4][29] Additionally, in a monomeric state, structural rearrangements of the substrate binding pocket Naa10 allow acetylation of N-termini with acidic side chains.[25][30] Furthermore, Nε-acetyltransferase activity[31][32][33][34][35][36][37] and N-terminal propionyltransferase activity [38] have been reported.

Despite the fact that Nα-terminal acetylation of proteins has been known for many years, the functional consequences of this modification are not well understood. However, accumulating evidence have linked Naa10 to various signaling pathways, including Wnt/β-catenin,[33][34][39][40] MAPK,[39] JAK/STAT,[41] and NF-κB,[42][43][44][45] thereby regulating various cellular processes, including cell migration,[46][47] cell cycle control,[48][49][50] DNA damage control,[44][51] caspase-dependent cell death,[51][52] p53 dependent apoptosis,[49] cell proliferation and autophagy [53] as well as hypoxia,[34][35][37][54][55] although there are some major discrepancies regarding hypoxia[56][57][58][59][60] and even isoform specific effects of Naa10 functions have been reported in mouse.[9][61]

Naa10 is essential in D. melanogaster,[62] C. elegans[63] and T. brucei.[17] In S. cerevisiae, Naa10 function is not essential but yNAA10Δ cells display severe defects including de-repression of the silent mating type locus (HML), failure to enter Go phase, temperature sensitivity, and impaired growth.[13][64] Naa10-knockout mice have very recently been reported to be viable, displaying a defect in bone development.[45]


Recently, a c.109T>C (p.Ser37Pro) variant in NAA10 was identified in two unrelated families with Ogden Syndrome, a X-linked disorder involving a distinct combination of an aged appearance, craniofacial anomalies, hypotonia, global developmental delays, cryptorchidism, and cardiac arrhythmias.[65] Patient fibroblasts displayed altered morphology, growth and migration characteristics and molecular studies indicate that this S37P mutation disrupts the NatA complex and decreases Naa10 enzymatic activity in vitro and in vivo.[65][66][67]

Furthermore, two other mutations in Naa10 (R116W mutation in a boy and a V107F mutation in a girl) have been described in two unrelated families with sporadic cases of non-syndromic intellectual disabilities, postnatal growth failure, and skeletal anomalies.[68][69] The girl was reported as having delayed closure of the fontanels, delayed bone age, broad great toes, mild pectus carinatum, pulmonary artery stenosis, atrial septal defect, prolonged QT interval. The boy was reported as having small hands/feet, high arched palate, and wide interdental spaces.

Additionally, a splice mutation in the intron 7 splice donor site (c.471+2T→A) of NAA10 was reported in a single family with Lenz microphthalmia syndrome (LMS), a very rare, genetically heterogeneous X-linked recessive disorder characterized by microphthalmia or anophthalmia, developmental delay, intellectual disability, skeletal abnormalities and malformations of teeth, fingers and toes.[70] Patient fibroblasts displayed cell proliferation defects, dysregulation of genes involved in retinoic acid signaling pathway, such as STRA6, and deficiencies in retinol uptake.[70]

Accumulating evidence suggests Naa10 function might regulate co-translational protein folding through the modulation of chaperone function, thereby affecting pathological formation of toxic amyloid aggregates in Alzheimer's disease or prion [PSI+] propagation in yeast.[71][72][73][74]


  1. ^ Liszczak G, Goldberg JM, Foyn H, Petersson EJ, Arnesen T, Marmorstein R (2013). "Molecular basis for N-terminal acetylation by the heterodimeric NatA complex". Nat. Struct. Mol. Biol. 20 (9): 1098–105. doi:10.1038/nsmb.2636. PMC 3766382. PMID 23912279. 
  2. ^ Tribioli C, Mancini M, Plassart E, Bione S, Rivella S, Sala C et al. (Jan 1995). "Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae". Hum Mol Genet 3 (7): 1061–7. doi:10.1093/hmg/3.7.1061. PMID 7981673. 
  3. ^ "Entrez Gene: ARD1A ARD1 homolog A, N-acetyltransferase (S. cerevisiae)". 
  4. ^ a b Starheim KK, Gevaert K, Arnesen T (April 2012). "Protein N-terminal acetyltransferases: when the start matters.". Trends in Biochemical Sciences 37 (4): 152–61. doi:10.1016/j.tibs.2012.02.003. PMID 22405572. 
  5. ^ Pruitt KD, Tatusova T, Maglott DR (January 2007). "NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins.". Nucleic Acids Research 35 (Database issue): D61–5. doi:10.1093/nar/gkl842. PMC 1716718. PMID 17130148. 
  6. ^ Arnesen T, Betts MJ, Pendino F, Liberles DA, Anderson D, Caro J et al. (25 April 2006). "Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-alpha-acetyltransferase.". BMC biochemistry 7: 13. doi:10.1186/1471-2091-7-13. PMID 16638120. 
  7. ^ Pang AL, Clark J, Chan WY, Rennert OM (November 2011). "Expression of human NAA11 (ARD1B) gene is tissue-specific and is regulated by DNA methylation.". Epigenetics : official journal of the DNA Methylation Society 6 (11): 1391–9. doi:10.4161/epi.6.11.18125. PMID 22048246. 
  8. ^ Pang AL, Peacock S, Johnson W, Bear DH, Rennert OM, Chan WY (August 2009). "Cloning, characterization, and expression analysis of the novel acetyltransferase retrogene Ard1b in the mouse.". Biology of Reproduction 81 (2): 302–9. doi:10.1095/biolreprod.108.073221. PMID 19246321. 
  9. ^ a b Chun KH, Cho SJ, Choi JS, Kim SH, Kim KW, Lee SK (2 February 2007). "Differential regulation of splicing, localization and stability of mammalian ARD1235 and ARD1225 isoforms.". Biochemical and Biophysical Research Communications 353 (1): 18–25. doi:10.1016/j.bbrc.2006.11.131. PMID 17161380. 
  10. ^ a b c d Polevoda B, Sherman F (24 January 2003). "N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins.". Journal of Molecular Biology 325 (4): 595–622. doi:10.1016/s0022-2836(02)01269-x. PMID 12507466. 
  11. ^ Liu CC, Zhu HY, Dong XM, Ning DL, Wang HX, Li WH et al. (2013). "Identification and analysis of the acetylated status of poplar proteins reveals analogous N-terminal protein processing mechanisms with other eukaryotes.". PLOS ONE 8 (3): e58681. doi:10.1371/journal.pone.0058681. PMID 23536812. 
  12. ^ Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T et al. (June 2012). "Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-α-acetylation features.". Molecular & cellular proteomics : MCP 11 (6): M111.015131. doi:10.1074/mcp.m111.015131. PMID 22223895. 
  13. ^ a b Whiteway M, Szostak JW (December 1985). "The ARD1 gene of yeast functions in the switch between the mitotic cell cycle and alternative developmental pathways.". Cell 43 (2 Pt 1): 483–92. doi:10.1016/0092-8674(85)90178-3. PMID 3907857. 
  14. ^ Mackay DT, Botting CH, Taylor GL, White MF (June 2007). "An acetylase with relaxed specificity catalyses protein N-terminal acetylation in Sulfolobus solfataricus.". Molecular microbiology 64 (6): 1540–8. doi:10.1111/j.1365-2958.2007.05752.x. PMID 17511810. 
  15. ^ Han SH, Ha JY, Kim KH, Oh SJ, Kim do J, Kang JY et al. (1 November 2006). "Expression, crystallization and preliminary X-ray crystallographic analyses of two N-terminal acetyltransferase-related proteins from Thermoplasma acidophilum.". Acta crystallographica. Section F, Structural biology and crystallization communications 62 (Pt 11): 1127–30. doi:10.1107/s1744309106040267. PMID 17077495. 
  16. ^ a b Ma C, Pathak C, Jang S, Lee SJ, Nam M, Kim SJ et al. (October 2014). "Structure of Thermoplasma volcanium Ard1 belongs to N-acetyltransferase family member suggesting multiple ligand binding modes with acetyl coenzyme A and coenzyme A.". Biochimica et Biophysica Acta 1844 (10): 1790–7. doi:10.1016/j.bbapap.2014.07.011. PMID 25062911. 
  17. ^ a b Ingram AK, Cross GA, Horn D (December 2000). "Genetic manipulation indicates that ARD1 is an essential N(alpha)-acetyltransferase in Trypanosoma brucei.". Molecular and biochemical parasitology 111 (2): 309–17. doi:10.1016/s0166-6851(00)00322-4. PMID 11163439. 
  18. ^ Chang HH, Falick AM, Carlton PM, Sedat JW, DeRisi JL, Marletta MA (August 2008). "N-terminal processing of proteins exported by malaria parasites.". Molecular and biochemical parasitology 160 (2): 107–15. doi:10.1016/j.molbiopara.2008.04.011. PMID 18534695. 
  19. ^ Isono K, Isono S (1980). "Ribosomal protein modification in Escherichia coli. II. Studies of a mutant lacking the N-terminal acetylation of protein S18.". Molecular & general genetics : MGG 177 (4): 645–51. doi:10.1007/bf00272675. PMID 6991870. 
  20. ^ Cumberlidge AG, Isono K (25 June 1979). "Ribosomal protein modification in Escherichia coli. I. A mutant lacking the N-terminal acetylation of protein S5 exhibits thermosensitivity.". Journal of Molecular Biology 131 (2): 169–89. doi:10.1016/0022-2836(79)90072-X. PMID 385889. 
  21. ^ Isono S, Isono K (1981). "Ribosomal protein modification in Escherichia coli. III. Studies of mutants lacking an acetylase activity specific for protein L12.". Molecular & general genetics : MGG 183 (3): 473–7. doi:10.1007/bf00268767. PMID 7038378. 
  22. ^ Vetting MW, Bareich DC, Yu M, Blanchard JS (October 2008). "Crystal structure of RimI from Salmonella typhimurium LT2, the GNAT responsible for N(alpha)-acetylation of ribosomal protein S18.". Protein science : a publication of the Protein Society 17 (10): 1781–90. doi:10.1110/ps.035899.108. PMID 18596200. 
  23. ^ Polevoda B, Sherman F (15 August 2003). "Composition and function of the eukaryotic N-terminal acetyltransferase subunits.". Biochemical and Biophysical Research Communications 308 (1): 1–11. doi:10.1016/s0006-291x(03)01316-0. PMID 12890471. 
  24. ^ Sánchez-Puig N, Fersht AR (August 2006). "Characterization of the native and fibrillar conformation of the human Nalpha-acetyltransferase ARD1.". Protein science : a publication of the Protein Society 15 (8): 1968–76. doi:10.1110/ps.062264006. PMID 16823041. 
  25. ^ a b c Liszczak G, Goldberg JM, Foyn H, Petersson EJ, Arnesen T, Marmorstein R (September 2013). "Molecular basis for N-terminal acetylation by the heterodimeric NatA complex.". Nature structural & molecular biology 20 (9): 1098–105. doi:10.1038/nsmb.2636. PMID 23912279. 
  26. ^ Arnesen T, Anderson D, Baldersheim C, Lanotte M, Varhaug JE, Lillehaug JR (15 March 2005). "Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.". The Biochemical journal 386 (Pt 3): 433–43. doi:10.1042/bj20041071. PMID 15496142. 
  27. ^ Park JH, Seo JH, Wee HJ, Vo TT, Lee EJ, Choi H et al. (2014). "Nuclear translocation of hARD1 contributes to proper cell cycle progression.". PLOS ONE 9 (8): e105185. doi:10.1371/journal.pone.0105185. PMID 25133627. 
  28. ^ Arnesen T, Gromyko D, Kagabo D, Betts MJ, Starheim KK, Varhaug JE et al. (29 May 2009). "A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1).". BMC biochemistry 10: 15. doi:10.1186/1471-2091-10-15. PMID 19480662. 
  29. ^ Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG et al. (July 2011). "NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation.". PLoS genetics 7 (7): e1002169. doi:10.1371/journal.pgen.1002169. PMID 21750686. 
  30. ^ Van Damme P, Evjenth R, Foyn H, Demeyer K, De Bock PJ, Lillehaug JR et al. (May 2011). "Proteome-derived peptide libraries allow detailed analysis of the substrate specificities of N(alpha)-acetyltransferases and point to hNaa10p as the post-translational actin N(alpha)-acetyltransferase.". Molecular & cellular proteomics : MCP 10 (5): M110.004580. doi:10.1074/mcp.m110.004580. PMID 21383206. 
  31. ^ Lin S, Tsai SC, Lee CC, Wang BW, Liou JY, Shyu KG (September 2004). "Berberine inhibits HIF-1alpha expression via enhanced proteolysis.". Molecular Pharmacology 66 (3): 612–9. doi:10.1124/mol.66.3. PMID 15322253. 
  32. ^ Shin SH, Yoon H, Chun YS, Shin HW, Lee MN, Oh GT et al. (23 October 2014). "Arrest defective 1 regulates the oxidative stress response in human cells and mice by acetylating methionine sulfoxide reductase A.". Cell death & disease 5 (10): e1490. doi:10.1038/cddis.2014.456. PMID 25341044. 
  33. ^ a b Lim JH, Park JW, Chun YS (15 November 2006). "Human arrest defective 1 acetylates and activates beta-catenin, promoting lung cancer cell proliferation.". Cancer Research 66 (22): 10677–82. doi:10.1158/0008-5472.can-06-3171. PMID 17108104. 
  34. ^ a b c Lim JH, Chun YS, Park JW (1 July 2008). "Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin.". Cancer Research 68 (13): 5177–84. doi:10.1158/0008-5472.can-07-6234. PMID 18593917. 
  35. ^ a b Jeong JW, Bae MK, Ahn MY, Kim SH, Sohn TK, Bae MH et al. (27 November 2002). "Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation.". Cell 111 (5): 709–20. doi:10.1016/S0092-8674(02)01085-1. PMID 12464182. 
  36. ^ Lee MN, Lee SN, Kim SH, Kim B, Jung BK, Seo JH et al. (17 March 2010). "Roles of arrest-defective protein 1(225) and hypoxia-inducible factor 1alpha in tumor growth and metastasis.". Journal of the National Cancer Institute 102 (6): 426–42. doi:10.1093/jnci/djq026. PMID 20194889. 
  37. ^ a b Yoo YG, Kong G, Lee MO (22 March 2006). "Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1.". The EMBO Journal 25 (6): 1231–41. doi:10.1038/sj.emboj.7601025. PMID 16511565. 
  38. ^ Foyn H, Van Damme P, Støve SI, Glomnes N, Evjenth R, Gevaert K et al. (January 2013). "Protein N-terminal acetyltransferases act as N-terminal propionyltransferases in vitro and in vivo.". Molecular & cellular proteomics : MCP 12 (1): 42–54. doi:10.1074/mcp.m112.019299. PMID 23043182. 
  39. ^ a b Seo JH, Cha JH, Park JH, Jeong CH, Park ZY, Lee HS et al. (1 June 2010). "Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation.". Cancer Research 70 (11): 4422–32. doi:10.1158/0008-5472.can-09-3258. PMID 20501853. 
  40. ^ Lee CF, Ou DS, Lee SB, Chang LH, Lin RK, Li YS et al. (August 2010). "hNaa10p contributes to tumorigenesis by facilitating DNMT1-mediated tumor suppressor gene silencing.". The Journal of Clinical Investigation 120 (8): 2920–30. doi:10.1172/jci42275. PMID 20592467. 
  41. ^ Zeng Y, Min L, Han Y, Meng L, Liu C, Xie Y et al. (October 2014). "Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis.". Carcinogenesis 35 (10): 2244–53. doi:10.1093/carcin/bgu132. PMID 24925029. 
  42. ^ Kuo HP, Lee DF, Xia W, Lai CC, Li LY, Hung MC (6 November 2009). "Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and degradation.". Biochemical and Biophysical Research Communications 389 (1): 156–61. doi:10.1016/j.bbrc.2009.08.127. PMID 19716809. 
  43. ^ Park J, Kanayama A, Yamamoto K, Miyamoto Y (1 June 2012). "ARD1 binding to RIP1 mediates doxorubicin-induced NF-κB activation.". Biochemical and Biophysical Research Communications 422 (2): 291–7. doi:10.1016/j.bbrc.2012.04.150. PMID 22580278. 
  44. ^ a b Xu H, Jiang B, Meng L, Ren T, Zeng Y, Wu J et al. (June 2012). "N-α-acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression.". Carcinogenesis 33 (6): 1193–202. doi:10.1093/carcin/bgs144. PMID 22496479. 
  45. ^ a b Yoon H, Kim HL, Chun YS, Shin DH, Lee KH, Shin CS et al. (7 November 2014). "NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2.". Nature communications 5: 5176. doi:10.1038/ncomms6176. PMID 25376646. 
  46. ^ Hua KT, Tan CT, Johansson G, Lee JM, Yang PW, Lu HY et al. (15 February 2011). "N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity.". Cancer Cell 19 (2): 218–31. doi:10.1016/j.ccr.2010.11.010. PMID 21295525. 
  47. ^ Shin DH, Chun YS, Lee KH, Shin HW, Park JW (14 October 2009). "Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase.". PLOS ONE 4 (10): e7451. doi:10.1371/journal.pone.0007451. PMID 19826488. 
  48. ^ Kaidi A, Williams AC, Paraskeva C (February 2007). "Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia.". Nature Cell Biology 9 (2): 210–7. doi:10.1038/ncb1534. PMID 17220880. 
  49. ^ a b Gromyko D, Arnesen T, Ryningen A, Varhaug JE, Lillehaug JR (15 December 2010). "Depletion of the human Nα-terminal acetyltransferase A induces p53-dependent apoptosis and p53-independent growth inhibition.". International Journal of Cancer. Journal International Du Cancer 127 (12): 2777–89. doi:10.1002/ijc.25275. PMID 21351257. 
  50. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N et al. (20 October 2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  51. ^ a b Yi CH, Sogah DK, Boyce M, Degterev A, Christofferson DE, Yuan J (19 November 2007). "A genome-wide RNAi screen reveals multiple regulators of caspase activation.". The Journal of Cell Biology 179 (4): 619–26. doi:10.1083/jcb.200708090. PMID 17998402. 
  52. ^ Yi CH, Pan H, Seebacher J, Jang IH, Hyberts SG, Heffron GJ et al. (19 August 2011). "Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival.". Cell 146 (4): 607–20. doi:10.1016/j.cell.2011.06.050. PMID 21854985. 
  53. ^ Kuo HP, Lee DF, Chen CT, Liu M, Chou CK, Lee HJ et al. (9 February 2010). "ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway.". Science signaling 3 (108): ra9. doi:10.1126/scisignal.2000590. PMID 20145209. 
  54. ^ Ke Q, Kluz T, Costa M (April 2005). "Down-regulation of the expression of the FIH-1 and ARD-1 genes at the transcriptional level by nickel and cobalt in the human lung adenocarcinoma A549 cell line.". International journal of environmental research and public health 2 (1): 10–3. doi:10.3390/ijerph2005010010. PMID 16705796. 
  55. ^ Chang CC, Lin MT, Lin BR, Jeng YM, Chen ST, Chu CY et al. (19 July 2006). "Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis.". Journal of the National Cancer Institute 98 (14): 984–95. doi:10.1093/jnci/djj242. PMID 16849681. 
  56. ^ Arnesen T, Kong X, Evjenth R, Gromyko D, Varhaug JE, Lin Z et al. (21 November 2005). "Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha.". FEBS Letters 579 (28): 6428–32. doi:10.1016/j.febslet.2005.10.036. PMID 16288748. 
  57. ^ Fisher TS, Etages SD, Hayes L, Crimin K, Li B (6 May 2005). "Analysis of ARD1 function in hypoxia response using retroviral RNA interference.". The Journal of Biological Chemistry 280 (18): 17749–57. doi:10.1074/jbc.m412055200. PMID 15755738. 
  58. ^ Bilton R, Mazure N, Trottier E, Hattab M, Déry MA, Richard DE et al. (2 September 2005). "Arrest-defective-1 protein, an acetyltransferase, does not alter stability of hypoxia-inducible factor (HIF)-1alpha and is not induced by hypoxia or HIF.". The Journal of Biological Chemistry 280 (35): 31132–40. doi:10.1074/jbc.m504482200. PMID 15994306. 
  59. ^ Fath DM, Kong X, Liang D, Lin Z, Chou A, Jiang Y et al. (12 May 2006). "Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha.". The Journal of Biological Chemistry 281 (19): 13612–9. doi:10.1074/jbc.m600456200. PMID 16543236. 
  60. ^ Murray-Rust TA, Oldham NJ, Hewitson KS, Schofield CJ (3 April 2006). "Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF-1alpha fragments in vitro.". FEBS Letters 580 (8): 1911–8. doi:10.1016/j.febslet.2006.02.012. PMID 16500650. 
  61. ^ Kim SH, Park JA, Kim JH, Lee JW, Seo JH, Jung BK et al. (10 February 2006). "Characterization of ARD1 variants in mammalian cells.". Biochemical and Biophysical Research Communications 340 (2): 422–7. doi:10.1016/j.bbrc.2005.12.018. PMID 16376303. 
  62. ^ Wang Y, Mijares M, Gall MD, Turan T, Javier A, Bornemann DJ et al. (November 2010). "Drosophila variable nurse cells encodes arrest defective 1 (ARD1), the catalytic subunit of the major N-terminal acetyltransferase complex.". Developmental dynamics : an official publication of the American Association of Anatomists 239 (11): 2813–27. doi:10.1002/dvdy.22418. PMID 20882681. 
  63. ^ Chen D, Zhang J, Minnerly J, Kaul T, Riddle DL, Jia K (October 2014). "daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.". PLoS genetics 10 (10): e1004699. doi:10.1371/journal.pgen.1004699. PMID 25330189. 
  64. ^ Whiteway M, Freedman R, Van Arsdell S, Szostak JW, Thorner J (October 1987). "The yeast ARD1 gene product is required for repression of cryptic mating-type information at the HML locus.". Molecular and Cellular Biology 7 (10): 3713–22. PMID 3316986. 
  65. ^ a b Rope AF, Wang K, Evjenth R, Xing J, Johnston JJ, Swensen JJ et al. (15 July 2011). "Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency.". American Journal of Human Genetics 89 (1): 28–43. doi:10.1016/j.ajhg.2011.05.017. PMID 21700266. 
  66. ^ Myklebust LM, Van Damme P, Støve SI, Dörfel MJ, Abboud A, Kalvik TV et al. (8 December 2014). "Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects.". Human Molecular Genetics. doi:10.1093/hmg/ddu611. PMID 25489052. 
  67. ^ Van Damme P, Støve SI, Glomnes N, Gevaert K, Arnesen T (August 2014). "A Saccharomyces cerevisiae model reveals in vivo functional impairment of the Ogden syndrome N-terminal acetyltransferase NAA10 Ser37Pro mutant.". Molecular & cellular proteomics : MCP 13 (8): 2031–41. doi:10.1074/mcp.m113.035402. PMID 24408909. 
  68. ^ Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T et al. (10 November 2012). "Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.". Lancet 380 (9854): 1674–82. doi:10.1016/s0140-6736(12)61480-9. PMID 23020937. 
  69. ^ Popp B, Støve SI, Endele S, Myklebust LM, Hoyer J, Sticht H et al. (6 August 2014). "De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females.". European journal of human genetics : EJHG. doi:10.1038/ejhg.2014.150. PMID 25099252. 
  70. ^ a b Esmailpour T, Riazifar H, Liu L, Donkervoort S, Huang VH, Madaan S et al. (March 2014). "A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome.". Journal of medical genetics 51 (3): 185–96. doi:10.1136/jmedgenet-2013-101660. PMID 24431331. 
  71. ^ Asaumi M, Iijima K, Sumioka A, Iijima-Ando K, Kirino Y, Nakaya T et al. (February 2005). "Interaction of N-terminal acetyltransferase with the cytoplasmic domain of beta-amyloid precursor protein and its effect on A beta secretion.". Journal of biochemistry 137 (2): 147–55. doi:10.1093/jb/mvi014. PMID 15749829. 
  72. ^ Pezza JA, Langseth SX, Raupp Yamamoto R, Doris SM, Ulin SP, Salomon AR et al. (February 2009). "The NatA acetyltransferase couples Sup35 prion complexes to the [PSI+] phenotype.". Molecular Biology of the Cell 20 (3): 1068–80. doi:10.1091/mbc.e08-04-0436. PMID 19073888. 
  73. ^ Pezza JA, Villali J, Sindi SS, Serio TR (15 July 2014). "Amyloid-associated activity contributes to the severity and toxicity of a prion phenotype.". Nature communications 5: 4384. doi:10.1038/ncomms5384. PMID 25023996. 
  74. ^ Holmes WM, Mannakee BK, Gutenkunst RN, Serio TR (15 July 2014). "Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding.". Nature communications 5: 4383. doi:10.1038/ncomms5383. PMID 25023910. 

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