N-alpha-acetyltransferase 10: Difference between revisions

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{{Infobox gene}}
{{Infobox gene}}
'''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]].<ref name="pmid7981673">{{cite journal | vauthors = Tribioli C, Mancini M, Plassart E, Bione S, Rivella S, Sala C, Torri G, Toniolo D | title = Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae | journal = Hum Mol Genet | volume = 3 | issue = 7 | pages = 1061–7 | date = Jan 1995 | pmid = 7981673 | pmc =  | doi = 10.1093/hmg/3.7.1061 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ARD1A ARD1 homolog A, N-acetyltransferase (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8260| accessdate = }}</ref>
'''N-alpha-acetyltransferase 10''' (NAA10) also known as '''NatA catalytic subunit Naa10''' and '''arrest-defective protein 1 homolog A''' (ARD1A) is an [[enzyme]] [[Protein subunit|subunit]] that in humans is encoded ''NAA10'' [[gene]].<ref name="pmid7981673">{{cite journal | vauthors = Tribioli C, Mancini M, Plassart E, Bione S, Rivella S, Sala C, Torri G, Toniolo D | title = Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae | journal = Hum Mol Genet | volume = 3 | issue = 7 | pages = 1061–7 | date = Jan 1995 | pmid = 7981673 | pmc =  | doi = 10.1093/hmg/3.7.1061 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ARD1A ARD1 homolog A, N-acetyltransferase (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8260| accessdate = }}</ref>
Together with its auxiliary subunit [[NAA15|Naa15]], Naa10 constitutes the NatA (N<sup>α</sup>-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.<ref name="Starheim_2012">{{cite journal | vauthors = Starheim KK, Gevaert K, Arnesen T | title = Protein N-terminal acetyltransferases: when the start matters. | journal = Trends in Biochemical Sciences | volume = 37 | issue = 4 | pages = 152–61 | date = April 2012 | pmid = 22405572 | doi=10.1016/j.tibs.2012.02.003}}</ref>
Together with its auxiliary subunit [[NAA15|Naa15]], Naa10 constitutes the [[NatA acetyltransferase|NatA]] (N<sup>α</sup>-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.<ref name="Starheim_2012">{{cite journal | vauthors = Starheim KK, Gevaert K, Arnesen T | title = Protein N-terminal acetyltransferases: when the start matters | journal = Trends in Biochemical Sciences | volume = 37 | issue = 4 | pages = 152–61 | date = April 2012 | pmid = 22405572 | doi=10.1016/j.tibs.2012.02.003}}</ref>


== Gene and transcripts ==
== Gene and transcripts ==
The human ''NAA10'' is located on chromosome Xq28 and is encoded by 8 [[exon]]s 2 encoding three different [[protein isoform|isoforms]] derived from [[alternate splicing]].<ref>{{cite journal | vauthors = Pruitt KD, Tatusova T, Maglott DR | title = NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. | journal = Nucleic Acids Research | volume = 35 | issue = Database issue | pages = D61-5 | date = January 2007 | pmid = 17130148 | doi=10.1093/nar/gkl842 | pmc=1716718}}</ref> Additionally, a processed ''NAA10'' gene duplication ''NAA11'' (''ARD2'') has been identified that is expressed in several human cell lines;<ref>{{cite journal | vauthors = Arnesen T, Betts MJ, Pendino F, Liberles DA, Anderson D, Caro J, Kong X, Varhaug JE, Lillehaug JR | title = Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-alpha-acetyltransferase. | journal = BMC Biochemistry | volume = 7 | pages = 13 | date = 25 April 2006 | pmid = 16638120 | doi=10.1186/1471-2091-7-13 | pmc=1475586}}</ref> however, later studies indicate that Naa11 is not expressed in the human cell lines [[HeLa]] and [[HEK 293 cells|HEK293]] or in cancerous tissues, and ''NAA11'' transcripts were only detected in [[testicular]] and [[placental]] tissues.<ref>{{cite journal | vauthors = Pang AL, Clark J, Chan WY, Rennert OM | title = Expression of human NAA11 (ARD1B) gene is tissue-specific and is regulated by DNA methylation. | journal = Epigenetics | volume = 6 | issue = 11 | pages = 1391–9 | date = November 2011 | pmid = 22048246 | doi=10.4161/epi.6.11.18125 | pmc=3242813}}</ref> Naa11 has also been found in mouse, where it is mainly expressed in the testis.<ref>{{cite journal | vauthors = Pang AL, Peacock S, Johnson W, Bear DH, Rennert OM, Chan WY | title = Cloning, characterization, and expression analysis of the novel acetyltransferase retrogene Ard1b in the mouse. | journal = Biology of Reproduction | volume = 81 | issue = 2 | pages = 302–9 | date = August 2009 | pmid = 19246321 | doi=10.1095/biolreprod.108.073221 | pmc=2849813}}</ref> ''NAA11'' is located on chromosome 4q21.21 in human and 5 E3 in mouse, and only contains two exons.
The human ''NAA10'' is located on chromosome Xq28 and contains 8 [[exon]]s, 2 encoding three different [[protein isoform|isoforms]] derived from [[alternate splicing]].<ref>{{cite journal | vauthors = Pruitt KD, Tatusova T, Maglott DR | title = NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins | journal = Nucleic Acids Research | volume = 35 | issue = Database issue | pages = D61–5 | date = January 2007 | pmid = 17130148 | doi=10.1093/nar/gkl842 | pmc=1716718}}</ref> Additionally, a processed ''NAA10'' gene duplication ''NAA11'' (''ARD2'') has been identified that is expressed in several human cell lines;<ref>{{cite journal | vauthors = Arnesen T, Betts MJ, Pendino F, Liberles DA, Anderson D, Caro J, Kong X, Varhaug JE, Lillehaug JR | title = Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-alpha-acetyltransferase | journal = BMC Biochemistry | volume = 7 | pages = 13 | date = 25 April 2006 | pmid = 16638120 | doi=10.1186/1471-2091-7-13 | pmc=1475586}}</ref> however, later studies indicate that Naa11 is not expressed in the human cell lines [[HeLa]] and [[HEK 293 cells|HEK293]] or in cancerous tissues, and ''NAA11'' transcripts were only detected in [[testicular]] and [[placental]] tissues.<ref>{{cite journal | vauthors = Pang AL, Clark J, Chan WY, Rennert OM | title = Expression of human NAA11 (ARD1B) gene is tissue-specific and is regulated by DNA methylation | journal = Epigenetics | volume = 6 | issue = 11 | pages = 1391–9 | date = November 2011 | pmid = 22048246 | doi=10.4161/epi.6.11.18125 | pmc=3242813}}</ref> Naa11 has also been found in mouse, where it is mainly expressed in the testis.<ref>{{cite journal | vauthors = Pang AL, Peacock S, Johnson W, Bear DH, Rennert OM, Chan WY | title = Cloning, characterization, and expression analysis of the novel acetyltransferase retrogene Ard1b in the mouse | journal = Biology of Reproduction | volume = 81 | issue = 2 | pages = 302–9 | date = August 2009 | pmid = 19246321 | doi=10.1095/biolreprod.108.073221 | pmc=2849813}}</ref> ''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, mNaa10<sub>235</sub> and mNaa10<sub>225</sub>, were reported in NIH-3T3 and JB6 cells that may have different activities and function in different subcellular compartments.<ref name="Chun_2007">{{cite journal | vauthors = Chun KH, Cho SJ, Choi JS, Kim SH, Kim KW, Lee SK | title = Differential regulation of splicing, localization and stability of mammalian ARD1235 and ARD1225 isoforms. | journal = Biochemical and Biophysical Research Communications | volume = 353 | issue = 1 | pages = 18–25 | date = 2 February 2007 | pmid = 17161380 | doi=10.1016/j.bbrc.2006.11.131}}</ref>
In mouse, ''NAA10'' is located on chromosome X A7.3 and contains 9 exons. Two alternative splicing products of mouse Naa10, mNaa10<sub>235</sub> and mNaa10<sub>225</sub>, were reported in NIH-3T3 and JB6 cells that may have different activities and function in different subcellular compartments.<ref name="Chun_2007">{{cite journal | vauthors = Chun KH, Cho SJ, Choi JS, Kim SH, Kim KW, Lee SK | title = Differential regulation of splicing, localization and stability of mammalian ARD1235 and ARD1225 isoforms | journal = Biochemical and Biophysical Research Communications | volume = 353 | issue = 1 | pages = 18–25 | date = 2 February 2007 | pmid = 17161380 | doi=10.1016/j.bbrc.2006.11.131}}</ref>


Homologues for Naa10 have been identified in almost all kingdoms of life analyzed, including plants,<ref name="Polevoda_2003">{{cite journal | vauthors = Polevoda B, Sherman F | title = N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins. | journal = Journal of Molecular Biology | volume = 325 | issue = 4 | pages = 595–622 | date = 24 January 2003 | pmid = 12507466 | doi=10.1016/s0022-2836(02)01269-x}}</ref><ref>{{cite journal | vauthors = Liu CC, Zhu HY, Dong XM, Ning DL, Wang HX, Li WH, Yang CP, Wang BC | title = Identification and analysis of the acetylated status of poplar proteins reveals analogous N-terminal protein processing mechanisms with other eukaryotes. | journal = PLOS ONE | volume = 8 | issue = 3 | pages = e58681 | date = 2013 | pmid = 23536812 | doi=10.1371/journal.pone.0058681 | pmc=3594182}}</ref><ref>{{cite journal | vauthors = Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C | title = Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-α-acetylation features. | journal = Molecular & Cellular Proteomics | volume = 11 | issue = 6 | pages = M111.015131 | date = June 2012 | pmid = 22223895 | doi=10.1074/mcp.m111.015131 | pmc=3433923}}</ref> fungi,<ref name="Polevoda_2003"/><ref name = "Whiteway_1985">{{cite journal | vauthors = Whiteway M, Szostak JW | title = The ARD1 gene of yeast functions in the switch between the mitotic cell cycle and alternative developmental pathways. | journal = Cell | volume = 43 | issue = 2 Pt 1 | pages = 483–92 | date = December 1985 | pmid = 3907857 | doi=10.1016/0092-8674(85)90178-3}}</ref> [[amoebozoa]],<ref name="Polevoda_2003"/> [[archaeabacteria]]<ref name="Polevoda_2003"/><ref>{{cite journal | vauthors = Mackay DT, Botting CH, Taylor GL, White MF | title = An acetylase with relaxed specificity catalyses protein N-terminal acetylation in Sulfolobus solfataricus. | journal = Molecular Microbiology | volume = 64 | issue = 6 | pages = 1540–8 | date = June 2007 | pmid = 17511810 | doi=10.1111/j.1365-2958.2007.05752.x}}</ref><ref>{{cite journal | vauthors = Han SH, Ha JY, Kim KH, Oh SJ, Kim do J, Kang JY, Yoon HJ, Kim SH, Seo JH, Kim KW, Suh SW | title = Expression, crystallization and preliminary X-ray crystallographic analyses of two N-terminal acetyltransferase-related proteins from Thermoplasma acidophilum. | journal = Acta Crystallographica Section F | volume = 62 | issue = Pt 11 | pages = 1127–30 | date = 1 November 2006 | pmid = 17077495 | doi=10.1107/s1744309106040267 | pmc=2225214}}</ref><ref name = "Ma_2014">{{cite journal | vauthors = Ma C, Pathak C, Jang S, Lee SJ, Nam M, Kim SJ, Im H, Lee BJ | title = Structure of Thermoplasma volcanium Ard1 belongs to N-acetyltransferase family member suggesting multiple ligand binding modes with acetyl coenzyme A and coenzyme A. | journal = Biochimica et Biophysica Acta | volume = 1844 | issue = 10 | pages = 1790–7 | date = October 2014 | pmid = 25062911 | doi=10.1016/j.bbapap.2014.07.011}}</ref> and [[protozoa]].<ref name = "Ingram_2000">{{cite journal | vauthors = Ingram AK, Cross GA, Horn D | title = Genetic manipulation indicates that ARD1 is an essential N(alpha)-acetyltransferase in Trypanosoma brucei. | journal = Molecular and biochemical parasitology | volume = 111 | issue = 2 | pages = 309–17 | date = December 2000 | pmid = 11163439 | doi=10.1016/s0166-6851(00)00322-4}}</ref><ref>{{cite journal | vauthors = Chang HH, Falick AM, Carlton PM, Sedat JW, DeRisi JL, Marletta MA | title = N-terminal processing of proteins exported by malaria parasites. | journal = Molecular and biochemical parasitology | volume = 160 | issue = 2 | pages = 107–15 | date = August 2008 | pmid = 18534695 | doi=10.1016/j.molbiopara.2008.04.011 | pmc=2922945}}</ref> In [[eubacteria]], 3 N<sup>α</sup>-acetyltransferases, RimI, RimJ and RimL, have been identified<ref>{{cite journal | vauthors = Isono K, Isono S | title = Ribosomal protein modification in Escherichia coli. II. Studies of a mutant lacking the N-terminal acetylation of protein S18. | journal = Molecular & general genetics : MGG | volume = 177 | issue = 4 | pages = 645–51 | date = 1980 | pmid = 6991870 | doi=10.1007/bf00272675}}</ref><ref>{{cite journal | vauthors = Cumberlidge AG, Isono K | title = Ribosomal protein modification in Escherichia coli. I. A mutant lacking the N-terminal acetylation of protein S5 exhibits thermosensitivity. | journal = Journal of Molecular Biology | volume = 131 | issue = 2 | pages = 169–89 | date = 25 June 1979 | pmid = 385889 | doi = 10.1016/0022-2836(79)90072-X}}</ref><ref>{{cite journal | vauthors = Isono S, Isono K | title = Ribosomal protein modification in Escherichia coli. III. Studies of mutants lacking an acetylase activity specific for protein L12. | journal = Molecular & general genetics : MGG | volume = 183 | issue = 3 | pages = 473–7 | date = 1981 | pmid = 7038378 | doi=10.1007/bf00268767}}</ref> 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.<ref>{{cite journal | vauthors = Vetting MW, Bareich DC, Yu M, Blanchard JS | title = Crystal structure of RimI from Salmonella typhimurium LT2, the GNAT responsible for N(alpha)-acetylation of ribosomal protein S18. | journal = Protein Science | volume = 17 | issue = 10 | pages = 1781–90 | date = October 2008 | pmid = 18596200 | doi=10.1110/ps.035899.108 | pmc=2548364}}</ref><ref>{{cite journal | vauthors = Polevoda B, Sherman F | title = Composition and function of the eukaryotic N-terminal acetyltransferase subunits. | journal = Biochemical and Biophysical Research Communications | volume = 308 | issue = 1 | pages = 1–11 | date = 15 August 2003 | pmid = 12890471 | doi=10.1016/s0006-291x(03)01316-0}}</ref>
Homologues for Naa10 have been identified in almost all kingdoms of life analyzed, including plants,<ref name="Polevoda_2003">{{cite journal | vauthors = Polevoda B, Sherman F | title = N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins | journal = Journal of Molecular Biology | volume = 325 | issue = 4 | pages = 595–622 | date = 24 January 2003 | pmid = 12507466 | doi=10.1016/s0022-2836(02)01269-x}}</ref><ref>{{cite journal | vauthors = Liu CC, Zhu HY, Dong XM, Ning DL, Wang HX, Li WH, Yang CP, Wang BC | title = Identification and analysis of the acetylated status of poplar proteins reveals analogous N-terminal protein processing mechanisms with other eukaryotes | journal = PLOS ONE | volume = 8 | issue = 3 | pages = e58681 | date = 2013 | pmid = 23536812 | doi=10.1371/journal.pone.0058681 | pmc=3594182}}</ref><ref>{{cite journal | vauthors = Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C | title = Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-α-acetylation features | journal = Molecular & Cellular Proteomics | volume = 11 | issue = 6 | pages = M111.015131 | date = June 2012 | pmid = 22223895 | doi=10.1074/mcp.m111.015131 | pmc=3433923}}</ref> fungi,<ref name="Polevoda_2003"/><ref name = "Whiteway_1985">{{cite journal | vauthors = Whiteway M, Szostak JW | title = The ARD1 gene of yeast functions in the switch between the mitotic cell cycle and alternative developmental pathways | journal = Cell | volume = 43 | issue = 2 Pt 1 | pages = 483–92 | date = December 1985 | pmid = 3907857 | doi=10.1016/0092-8674(85)90178-3}}</ref> [[amoebozoa]],<ref name="Polevoda_2003"/> [[archaeabacteria]]<ref name="Polevoda_2003"/><ref>{{cite journal | vauthors = Mackay DT, Botting CH, Taylor GL, White MF | title = An acetylase with relaxed specificity catalyses protein N-terminal acetylation in Sulfolobus solfataricus | journal = Molecular Microbiology | volume = 64 | issue = 6 | pages = 1540–8 | date = June 2007 | pmid = 17511810 | doi=10.1111/j.1365-2958.2007.05752.x}}</ref><ref>{{cite journal | vauthors = Han SH, Ha JY, Kim KH, Oh SJ, Kim do J, Kang JY, Yoon HJ, Kim SH, Seo JH, Kim KW, Suh SW | title = Expression, crystallization and preliminary X-ray crystallographic analyses of two N-terminal acetyltransferase-related proteins from Thermoplasma acidophilum | journal = Acta Crystallographica Section F | volume = 62 | issue = Pt 11 | pages = 1127–30 | date = 1 November 2006 | pmid = 17077495 | doi=10.1107/s1744309106040267 | pmc=2225214}}</ref><ref name = "Ma_2014">{{cite journal | vauthors = Ma C, Pathak C, Jang S, Lee SJ, Nam M, Kim SJ, Im H, Lee BJ | title = Structure of Thermoplasma volcanium Ard1 belongs to N-acetyltransferase family member suggesting multiple ligand binding modes with acetyl coenzyme A and coenzyme A | journal = Biochimica et Biophysica Acta | volume = 1844 | issue = 10 | pages = 1790–7 | date = October 2014 | pmid = 25062911 | doi=10.1016/j.bbapap.2014.07.011}}</ref> and [[protozoa]].<ref name = "Ingram_2000">{{cite journal | vauthors = Ingram AK, Cross GA, Horn D | title = Genetic manipulation indicates that ARD1 is an essential N(alpha)-acetyltransferase in Trypanosoma brucei | journal = Molecular and Biochemical Parasitology | volume = 111 | issue = 2 | pages = 309–17 | date = December 2000 | pmid = 11163439 | doi=10.1016/s0166-6851(00)00322-4}}</ref><ref>{{cite journal | vauthors = Chang HH, Falick AM, Carlton PM, Sedat JW, DeRisi JL, Marletta MA | title = N-terminal processing of proteins exported by malaria parasites | journal = Molecular and Biochemical Parasitology | volume = 160 | issue = 2 | pages = 107–15 | date = August 2008 | pmid = 18534695 | doi=10.1016/j.molbiopara.2008.04.011 | pmc=2922945}}</ref> In [[eubacteria]], 3 N<sup>α</sup>-acetyltransferases, RimI, RimJ and RimL, have been identified<ref>{{cite journal | vauthors = Isono K, Isono S | title = Ribosomal protein modification in Escherichia coli. II. Studies of a mutant lacking the N-terminal acetylation of protein S18 | journal = Molecular & General Genetics : MGG | volume = 177 | issue = 4 | pages = 645–51 | date = 1980 | pmid = 6991870 | doi=10.1007/bf00272675}}</ref><ref>{{cite journal | vauthors = Cumberlidge AG, Isono K | title = Ribosomal protein modification in Escherichia coli. I. A mutant lacking the N-terminal acetylation of protein S5 exhibits thermosensitivity | journal = Journal of Molecular Biology | volume = 131 | issue = 2 | pages = 169–89 | date = 25 June 1979 | pmid = 385889 | doi = 10.1016/0022-2836(79)90072-X}}</ref><ref>{{cite journal | vauthors = Isono S, Isono K | title = Ribosomal protein modification in Escherichia coli. III. Studies of mutants lacking an acetylase activity specific for protein L12 | journal = Molecular & General Genetics : MGG | volume = 183 | issue = 3 | pages = 473–7 | date = 1981 | pmid = 7038378 | doi=10.1007/bf00268767}}</ref> 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.<ref>{{cite journal | vauthors = Vetting MW, Bareich DC, Yu M, Blanchard JS | title = Crystal structure of RimI from Salmonella typhimurium LT2, the GNAT responsible for N(alpha)-acetylation of ribosomal protein S18 | journal = Protein Science | volume = 17 | issue = 10 | pages = 1781–90 | date = October 2008 | pmid = 18596200 | doi=10.1110/ps.035899.108 | pmc=2548364}}</ref><ref>{{cite journal | vauthors = Polevoda B, Sherman F | title = Composition and function of the eukaryotic N-terminal acetyltransferase subunits | journal = Biochemical and Biophysical Research Communications | volume = 308 | issue = 1 | pages = 1–11 | date = 15 August 2003 | pmid = 12890471 | doi=10.1016/s0006-291x(03)01316-0}}</ref>


== Structure ==
== Structure ==
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]].<ref>{{cite journal | vauthors = Sánchez-Puig N, Fersht AR | title = Characterization of the native and fibrillar conformation of the human Nalpha-acetyltransferase ARD1. | journal = Protein Science | volume = 15 | issue = 8 | pages = 1968–76 | date = August 2006 | pmid = 16823041 | doi=10.1110/ps.062264006 | pmc=2242591}}</ref> 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 N<sup>α</sup>-acetyltransferase.<ref name = "Liszczak_2013">{{cite journal | vauthors = Liszczak G, Goldberg JM, Foyn H, Petersson EJ, Arnesen T, Marmorstein R | title = Molecular basis for N-terminal acetylation by the heterodimeric NatA complex. | journal = Nature Structural & Molecular Biology | volume = 20 | issue = 9 | pages = 1098–105 | date = September 2013 | pmid = 23912279 | doi=10.1038/nsmb.2636 | pmc=3766382}}</ref> 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.<ref name = "Ma_2014"/> 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.<ref name = "Liszczak_2013"/>
[[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]].<ref>{{cite journal | vauthors = Sánchez-Puig N, Fersht AR | title = Characterization of the native and fibrillar conformation of the human Nalpha-acetyltransferase ARD1 | journal = Protein Science | volume = 15 | issue = 8 | pages = 1968–76 | date = August 2006 | pmid = 16823041 | doi=10.1110/ps.062264006 | pmc=2242591}}</ref> 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 N<sup>α</sup>-acetyltransferase.<ref name = "Liszczak_2013">{{cite journal | vauthors = Liszczak G, Goldberg JM, Foyn H, Petersson EJ, Arnesen T, Marmorstein R | title = Molecular basis for N-terminal acetylation by the heterodimeric NatA complex | journal = Nature Structural & Molecular Biology | volume = 20 | issue = 9 | pages = 1098–105 | date = September 2013 | pmid = 23912279 | doi=10.1038/nsmb.2636 | pmc=3766382}}</ref> 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.<ref name = "Ma_2014"/> 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.<ref name = "Liszczak_2013"/> An [[X-ray crystal structure]] of human Naa10 in complex with Naa15 and HYPK has been reported.<ref>{{cite journal |last1=Gottlieb |first1=Leah |last2=Marmorstein |first2=Ronen |title=Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK. |journal=Structure |volume=26 |issue=7 |pages=925–935.e8 |date=10 May 2018 |pmid=29754825 |pmc=6031454 |doi=10.1016/j.str.2018.04.003 }}</ref>


A functional [[nuclear localization signal]] in the [[C-terminus]] of hNaa10 between residues 78 and 83 (KRSHRR) has been described.<ref>{{cite journal | vauthors = Arnesen T, Anderson D, Baldersheim C, Lanotte M, Varhaug JE, Lillehaug JR | title = Identification and characterization of the human ARD1-NATH protein acetyltransferase complex. | journal = The Biochemical Journal | volume = 386 | issue = Pt 3 | pages = 433–43 | date = 15 March 2005 | pmid = 15496142 | doi=10.1042/bj20041071 | pmc=1134861}}</ref><ref>{{cite journal | vauthors = Park JH, Seo JH, Wee HJ, Vo TT, Lee EJ, Choi H, Cha JH, Ahn BJ, Shin MW, Bae SJ, Kim KW | title = Nuclear translocation of hARD1 contributes to proper cell cycle progression. | journal = PLOS ONE | volume = 9 | issue = 8 | pages = e105185 | date = 2014 | pmid = 25133627 | doi=10.1371/journal.pone.0105185 | pmc=4136855}}</ref>
A functional [[nuclear localization signal]] in the [[C-terminus]] of hNaa10 between residues 78 and 83 (KRSHRR) has been described.<ref>{{cite journal | vauthors = Arnesen T, Anderson D, Baldersheim C, Lanotte M, Varhaug JE, Lillehaug JR | title = Identification and characterization of the human ARD1-NATH protein acetyltransferase complex | journal = The Biochemical Journal | volume = 386 | issue = Pt 3 | pages = 433–43 | date = 15 March 2005 | pmid = 15496142 | doi=10.1042/bj20041071 | pmc=1134861}}</ref><ref>{{cite journal | vauthors = Park JH, Seo JH, Wee HJ, Vo TT, Lee EJ, Choi H, Cha JH, Ahn BJ, Shin MW, Bae SJ, Kim KW | title = Nuclear translocation of hARD1 contributes to proper cell cycle progression | journal = PLOS ONE | volume = 9 | issue = 8 | pages = e105185 | date = 2014 | pmid = 25133627 | doi=10.1371/journal.pone.0105185 | pmc=4136855}}</ref>


== Function ==
== Function ==
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 aminopeptidase]]s (MetAP).<ref>{{cite journal | vauthors = Arnesen T, Gromyko D, Kagabo D, Betts MJ, Starheim KK, Varhaug JE, Anderson D, Lillehaug JR | title = A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1). | journal = BMC Biochemistry | volume = 10 | pages = 15 | date = 29 May 2009 | pmid = 19480662 | doi=10.1186/1471-2091-10-15 | pmc=2695478}}</ref> Furthermore, post-translational acetylation by non-ribosome-associated Naa10 might occur. About 40-50 % of all proteins are potential NatA substrates.<ref name="Starheim_2012"/><ref>{{cite journal | vauthors = Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T | title = NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation. | journal = PLOS Genetics | volume = 7 | issue = 7 | pages = e1002169 | date = July 2011 | pmid = 21750686 | doi=10.1371/journal.pgen.1002169 | pmc=3131286}}</ref> Additionally, in a monomeric state, structural rearrangements of the substrate binding pocket Naa10 allow acetylation of N-termini with acidic side chains.<ref name = "Liszczak_2013"/><ref>{{cite journal | vauthors = Van Damme P, Evjenth R, Foyn H, Demeyer K, De Bock PJ, Lillehaug JR, Vandekerckhove J, Arnesen T, Gevaert K | title = 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. | journal = Molecular & Cellular Proteomics | volume = 10 | issue = 5 | pages = M110.004580 | date = May 2011 | pmid = 21383206 | doi=10.1074/mcp.m110.004580 | pmc=3098586}}</ref> Furthermore, N<sup>ε</sup>-acetyltransferase activity<ref>{{cite journal | vauthors = Lin S, Tsai SC, Lee CC, Wang BW, Liou JY, Shyu KG | title = Berberine inhibits HIF-1alpha expression via enhanced proteolysis. | journal = Molecular Pharmacology | volume = 66 | issue = 3 | pages = 612–9 | date = September 2004 | pmid = 15322253 | doi=10.1124/mol.66.3}}</ref><ref>{{cite journal | vauthors = Shin SH, Yoon H, Chun YS, Shin HW, Lee MN, Oh GT, Park JW | title = Arrest defective 1 regulates the oxidative stress response in human cells and mice by acetylating methionine sulfoxide reductase A. | journal = Cell death & disease | volume = 5 | pages = e1490 | date = 23 October 2014 | pmid = 25341044 | doi=10.1038/cddis.2014.456 | issue=10 | pmc=4649535}}</ref><ref name = "Lim_2006">{{cite journal | vauthors = Lim JH, Park JW, Chun YS | title = Human arrest defective 1 acetylates and activates beta-catenin, promoting lung cancer cell proliferation. | journal = Cancer Research | volume = 66 | issue = 22 | pages = 10677–82 | date = 15 November 2006 | pmid = 17108104 | doi=10.1158/0008-5472.can-06-3171}}</ref><ref name = "Lim_2008">{{cite journal | vauthors = Lim JH, Chun YS, Park JW | title = Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin. | journal = Cancer Research | volume = 68 | issue = 13 | pages = 5177–84 | date = 1 July 2008 | pmid = 18593917 | doi=10.1158/0008-5472.can-07-6234}}</ref><ref name = "Jeong_2002">{{cite journal | vauthors = Jeong JW, Bae MK, Ahn MY, Kim SH, Sohn TK, Bae MH, Yoo MA, Song EJ, Lee KJ, Kim KW | title = Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. | journal = Cell | volume = 111 | issue = 5 | pages = 709–20 | date = 27 November 2002 | pmid = 12464182 | doi=10.1016/S0092-8674(02)01085-1}}</ref><ref>{{cite journal | vauthors = Lee MN, Lee SN, Kim SH, Kim B, Jung BK, Seo JH, Park JH, Choi JH, Yim SH, Lee MR, Park JG, Yoo JY, Kim JH, Lee ST, Kim HM, Ryeom S, Kim KW, Oh GT | title = Roles of arrest-defective protein 1(225) and hypoxia-inducible factor 1alpha in tumor growth and metastasis. | journal = Journal of the National Cancer Institute | volume = 102 | issue = 6 | pages = 426–42 | date = 17 March 2010 | pmid = 20194889 | doi=10.1093/jnci/djq026 | pmc=2841038}}</ref><ref name = "Yoo_2006">{{cite journal | vauthors = Yoo YG, Kong G, Lee MO | title = Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. | journal = The EMBO Journal | volume = 25 | issue = 6 | pages = 1231–41 | date = 22 March 2006 | pmid = 16511565 | doi=10.1038/sj.emboj.7601025 | pmc=1422150}}</ref> and N-terminal propionyltransferase activity <ref>{{cite journal | vauthors = Foyn H, Van Damme P, Støve SI, Glomnes N, Evjenth R, Gevaert K, Arnesen T | title = Protein N-terminal acetyltransferases act as N-terminal propionyltransferases in vitro and in vivo. | journal = Molecular & Cellular Proteomics | volume = 12 | issue = 1 | pages = 42–54 | date = January 2013 | pmid = 23043182 | doi=10.1074/mcp.m112.019299 | pmc=3536908}}</ref> have been reported.
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 aminopeptidase]]s (MetAP).<ref>{{cite journal | vauthors = Arnesen T, Gromyko D, Kagabo D, Betts MJ, Starheim KK, Varhaug JE, Anderson D, Lillehaug JR | title = A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1) | journal = BMC Biochemistry | volume = 10 | pages = 15 | date = 29 May 2009 | pmid = 19480662 | doi=10.1186/1471-2091-10-15 | pmc=2695478}}</ref> Furthermore, post-translational acetylation by non-ribosome-associated Naa10 might occur. About 40-50 % of all proteins are potential NatA substrates.<ref name="Starheim_2012"/><ref>{{cite journal | vauthors = Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T | title = NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation | journal = PLOS Genetics | volume = 7 | issue = 7 | pages = e1002169 | date = July 2011 | pmid = 21750686 | doi=10.1371/journal.pgen.1002169 | pmc=3131286}}</ref> Additionally, in a monomeric state, structural rearrangements of the substrate binding pocket Naa10 allow acetylation of N-termini with acidic side chains.<ref name = "Liszczak_2013"/><ref>{{cite journal | vauthors = Van Damme P, Evjenth R, Foyn H, Demeyer K, De Bock PJ, Lillehaug JR, Vandekerckhove J, Arnesen T, Gevaert K | title = 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 | journal = Molecular & Cellular Proteomics | volume = 10 | issue = 5 | pages = M110.004580 | date = May 2011 | pmid = 21383206 | doi=10.1074/mcp.m110.004580 | pmc=3098586}}</ref> Furthermore, N<sup>ε</sup>-acetyltransferase activity<ref>{{cite journal | vauthors = Lin S, Tsai SC, Lee CC, Wang BW, Liou JY, Shyu KG | title = Berberine inhibits HIF-1alpha expression via enhanced proteolysis | journal = Molecular Pharmacology | volume = 66 | issue = 3 | pages = 612–9 | date = September 2004 | pmid = 15322253 | doi=10.1124/mol.66.3| doi-broken-date = 2018-10-01 }}</ref><ref>{{cite journal | vauthors = Shin SH, Yoon H, Chun YS, Shin HW, Lee MN, Oh GT, Park JW | title = Arrest defective 1 regulates the oxidative stress response in human cells and mice by acetylating methionine sulfoxide reductase A | journal = Cell Death & Disease | volume = 5 | pages = e1490 | date = 23 October 2014 | pmid = 25341044 | doi=10.1038/cddis.2014.456 | issue=10 | pmc=4649535}}</ref><ref name = "Lim_2006">{{cite journal | vauthors = Lim JH, Park JW, Chun YS | title = Human arrest defective 1 acetylates and activates beta-catenin, promoting lung cancer cell proliferation | journal = Cancer Research | volume = 66 | issue = 22 | pages = 10677–82 | date = 15 November 2006 | pmid = 17108104 | doi=10.1158/0008-5472.can-06-3171}}</ref><ref name = "Lim_2008">{{cite journal | vauthors = Lim JH, Chun YS, Park JW | title = Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin | journal = Cancer Research | volume = 68 | issue = 13 | pages = 5177–84 | date = 1 July 2008 | pmid = 18593917 | doi=10.1158/0008-5472.can-07-6234}}</ref><ref name = "Jeong_2002">{{cite journal | vauthors = Jeong JW, Bae MK, Ahn MY, Kim SH, Sohn TK, Bae MH, Yoo MA, Song EJ, Lee KJ, Kim KW | title = Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation | journal = Cell | volume = 111 | issue = 5 | pages = 709–20 | date = 27 November 2002 | pmid = 12464182 | doi=10.1016/S0092-8674(02)01085-1}}</ref><ref>{{cite journal | vauthors = Lee MN, Lee SN, Kim SH, Kim B, Jung BK, Seo JH, Park JH, Choi JH, Yim SH, Lee MR, Park JG, Yoo JY, Kim JH, Lee ST, Kim HM, Ryeom S, Kim KW, Oh GT | title = Roles of arrest-defective protein 1(225) and hypoxia-inducible factor 1alpha in tumor growth and metastasis | journal = Journal of the National Cancer Institute | volume = 102 | issue = 6 | pages = 426–42 | date = 17 March 2010 | pmid = 20194889 | doi=10.1093/jnci/djq026 | pmc=2841038}}</ref><ref name = "Yoo_2006">{{cite journal | vauthors = Yoo YG, Kong G, Lee MO | title = Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1 | journal = The EMBO Journal | volume = 25 | issue = 6 | pages = 1231–41 | date = 22 March 2006 | pmid = 16511565 | doi=10.1038/sj.emboj.7601025 | pmc=1422150}}</ref> and N-terminal propionyltransferase activity <ref>{{cite journal | vauthors = Foyn H, Van Damme P, Støve SI, Glomnes N, Evjenth R, Gevaert K, Arnesen T | title = Protein N-terminal acetyltransferases act as N-terminal propionyltransferases in vitro and in vivo | journal = Molecular & Cellular Proteomics | volume = 12 | issue = 1 | pages = 42–54 | date = January 2013 | pmid = 23043182 | doi=10.1074/mcp.m112.019299 | pmc=3536908}}</ref> have been reported.


Despite the fact that N<sup>α</sup>-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 signaling pathway|Wnt/β-catenin]],<ref name = "Lim_2006"/><ref name = "Lim_2008"/><ref name = "Seo_2010">{{cite journal | vauthors = Seo JH, Cha JH, Park JH, Jeong CH, Park ZY, Lee HS, Oh SH, Kang JH, Suh SW, Kim KH, Ha JY, Han SH, Kim SH, Lee JW, Park JA, Jeong JW, Lee KJ, Oh GT, Lee MN, Kwon SW, Lee SK, Chun KH, Lee SJ, Kim KW | title = Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation. | journal = Cancer Research | volume = 70 | issue = 11 | pages = 4422–32 | date = 1 June 2010 | pmid = 20501853 | doi=10.1158/0008-5472.can-09-3258}}</ref><ref>{{cite journal | vauthors = Lee CF, Ou DS, Lee SB, Chang LH, Lin RK, Li YS, Upadhyay AK, Cheng X, Wang YC, Hsu HS, Hsiao M, Wu CW, Juan LJ | title = hNaa10p contributes to tumorigenesis by facilitating DNMT1-mediated tumor suppressor gene silencing. | journal = The Journal of Clinical Investigation | volume = 120 | issue = 8 | pages = 2920–30 | date = August 2010 | pmid = 20592467 | doi=10.1172/jci42275 | pmc=2912195}}</ref> [[Mitogen-activated protein kinase|MAPK]],<ref name = "Seo_2010"/> [[JAK-STAT signaling pathway|JAK/STAT]],<ref>{{cite journal | vauthors = Zeng Y, Min L, Han Y, Meng L, Liu C, Xie Y, Dong B, Wang L, Jiang B, Xu H, Zhuang Q, Zhao C, Qu L, Shou C | title = Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis. | journal = Carcinogenesis | volume = 35 | issue = 10 | pages = 2244–53 | date = October 2014 | pmid = 24925029 | doi=10.1093/carcin/bgu132}}</ref> and [[NF-κB]],<ref>{{cite journal | vauthors = Kuo HP, Lee DF, Xia W, Lai CC, Li LY, Hung MC | title = Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and degradation. | journal = Biochemical and Biophysical Research Communications | volume = 389 | issue = 1 | pages = 156–61 | date = 6 November 2009 | pmid = 19716809 | doi=10.1016/j.bbrc.2009.08.127 | pmc=2753275}}</ref><ref>{{cite journal | vauthors = Park J, Kanayama A, Yamamoto K, Miyamoto Y | title = ARD1 binding to RIP1 mediates doxorubicin-induced NF-κB activation. | journal = Biochemical and Biophysical Research Communications | volume = 422 | issue = 2 | pages = 291–7 | date = 1 June 2012 | pmid = 22580278 | doi=10.1016/j.bbrc.2012.04.150}}</ref><ref name = "Xu_2012">{{cite journal | vauthors = Xu H, Jiang B, Meng L, Ren T, Zeng Y, Wu J, Qu L, Shou C | title = N-α-acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression. | journal = Carcinogenesis | volume = 33 | issue = 6 | pages = 1193–202 | date = June 2012 | pmid = 22496479 | doi=10.1093/carcin/bgs144}}</ref><ref name = "Yoon_2014">{{cite journal | vauthors = Yoon H, Kim HL, Chun YS, Shin DH, Lee KH, Shin CS, Lee DY, Kim HH, Lee ZH, Ryoo HM, Lee MN, Oh GT, Park JW | title = NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2. | journal = Nature Communications | volume = 5 | pages = 5176 | date = 7 November 2014 | pmid = 25376646 | doi=10.1038/ncomms6176}}</ref> thereby regulating various cellular processes, including cell migration,<ref>{{cite journal | vauthors = Hua KT, Tan CT, Johansson G, Lee JM, Yang PW, Lu HY, Chen CK, Su JL, Chen PB, Wu YL, Chi CC, Kao HJ, Shih HJ, Chen MW, Chien MH, Chen PS, Lee WJ, Cheng TY, Rosenberger G, Chai CY, Yang CJ, Huang MS, Lai TC, Chou TY, Hsiao M, Kuo ML | title = N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity. | journal = Cancer Cell | volume = 19 | issue = 2 | pages = 218–31 | date = 15 February 2011 | pmid = 21295525 | doi=10.1016/j.ccr.2010.11.010}}</ref><ref>{{cite journal | vauthors = Shin DH, Chun YS, Lee KH, Shin HW, Park JW | title = Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase. | journal = PLOS ONE | volume = 4 | issue = 10 | pages = e7451 | date = 14 October 2009 | pmid = 19826488 | doi=10.1371/journal.pone.0007451 | pmc=2758594}}</ref> cell cycle control,<ref>{{cite journal | vauthors = Kaidi A, Williams AC, Paraskeva C | title = Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia. | journal = Nature Cell Biology | volume = 9 | issue = 2 | pages = 210–7 | date = February 2007 | pmid = 17220880 | doi=10.1038/ncb1534}}</ref><ref name = "Gromyko_2010">{{cite journal | vauthors = Gromyko D, Arnesen T, Ryningen A, Varhaug JE, Lillehaug JR | title = Depletion of the human Nα-terminal acetyltransferase A induces p53-dependent apoptosis and p53-independent growth inhibition. | journal = International Journal of Cancer | volume = 127 | issue = 12 | pages = 2777–89 | date = 15 December 2010 | pmid = 21351257 | doi=10.1002/ijc.25275}}</ref><ref>{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network. | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = 20 October 2005 | pmid = 16189514 | doi=10.1038/nature04209}}</ref> DNA damage control,<ref name = "Xu_2012"/><ref name = "Yi_2007">{{cite journal | vauthors = Yi CH, Sogah DK, Boyce M, Degterev A, Christofferson DE, Yuan J | title = A genome-wide RNAi screen reveals multiple regulators of caspase activation. | journal = The Journal of Cell Biology | volume = 179 | issue = 4 | pages = 619–26 | date = 19 November 2007 | pmid = 17998402 | doi=10.1083/jcb.200708090 | pmc=2080898}}</ref> caspase-dependent cell death,<ref name = "Yi_2007"/><ref>{{cite journal | vauthors = Yi CH, Pan H, Seebacher J, Jang IH, Hyberts SG, Heffron GJ, Vander Heiden MG, Yang R, Li F, Locasale JW, Sharfi H, Zhai B, Rodriguez-Mias R, Luithardt H, Cantley LC, Daley GQ, Asara JM, Gygi SP, Wagner G, Liu CF, Yuan J | title = Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival. | journal = Cell | volume = 146 | issue = 4 | pages = 607–20 | date = 19 August 2011 | pmid = 21854985 | doi=10.1016/j.cell.2011.06.050 | pmc=3182480}}</ref> p53 dependent apoptosis,<ref name = "Gromyko_2010"/> cell proliferation and autophagy <ref>{{cite journal | vauthors = Kuo HP, Lee DF, Chen CT, Liu M, Chou CK, Lee HJ, Du Y, Xie X, Wei Y, Xia W, Weihua Z, Yang JY, Yen CJ, Huang TH, Tan M, Xing G, Zhao Y, Lin CH, Tsai SF, Fidler IJ, Hung MC | title = ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway. | journal = Science signaling | volume = 3 | issue = 108 | pages = ra9 | date = 9 February 2010 | pmid = 20145209 | doi=10.1126/scisignal.2000590 | pmc=2874891}}</ref> as well as hypoxia,<ref name = "Lim_2008"/><ref name = "Jeong_2002"/><ref name = "Yoo_2006"/><ref>{{cite journal | vauthors = Ke Q, Kluz T, Costa M | title = 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. | journal = International journal of environmental research and public health | volume = 2 | issue = 1 | pages = 10–3 | date = April 2005 | pmid = 16705796 | doi=10.3390/ijerph2005010010 | pmc=3814691}}</ref><ref>{{cite journal | vauthors = Chang CC, Lin MT, Lin BR, Jeng YM, Chen ST, Chu CY, Chen RJ, Chang KJ, Yang PC, Kuo ML | title = Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis. | journal = Journal of the National Cancer Institute | volume = 98 | issue = 14 | pages = 984–95 | date = 19 July 2006 | pmid = 16849681 | doi=10.1093/jnci/djj242}}</ref> although there are some major discrepancies regarding hypoxia<ref>{{cite journal | vauthors = Arnesen T, Kong X, Evjenth R, Gromyko D, Varhaug JE, Lin Z, Sang N, Caro J, Lillehaug JR | title = Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha. | journal = FEBS Letters | volume = 579 | issue = 28 | pages = 6428–32 | date = 21 November 2005 | pmid = 16288748 | doi=10.1016/j.febslet.2005.10.036}}</ref><ref>{{cite journal | vauthors = Fisher TS, Etages SD, Hayes L, Crimin K, Li B | title = Analysis of ARD1 function in hypoxia response using retroviral RNA interference. | journal = The Journal of Biological Chemistry | volume = 280 | issue = 18 | pages = 17749–57 | date = 6 May 2005 | pmid = 15755738 | doi=10.1074/jbc.m412055200}}</ref><ref>{{cite journal | vauthors = Bilton R, Mazure N, Trottier E, Hattab M, Déry MA, Richard DE, Pouysségur J, Brahimi-Horn MC | title = Arrest-defective-1 protein, an acetyltransferase, does not alter stability of hypoxia-inducible factor (HIF)-1alpha and is not induced by hypoxia or HIF. | journal = The Journal of Biological Chemistry | volume = 280 | issue = 35 | pages = 31132–40 | date = 2 September 2005 | pmid = 15994306 | doi=10.1074/jbc.m504482200}}</ref><ref>{{cite journal | vauthors = Fath DM, Kong X, Liang D, Lin Z, Chou A, Jiang Y, Fang J, Caro J, Sang N | title = Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha. | journal = The Journal of Biological Chemistry | volume = 281 | issue = 19 | pages = 13612–9 | date = 12 May 2006 | pmid = 16543236 | doi=10.1074/jbc.m600456200 | pmc=1564196}}</ref><ref>{{cite journal | vauthors = Murray-Rust TA, Oldham NJ, Hewitson KS, Schofield CJ | title = Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF-1alpha fragments in vitro. | journal = FEBS Letters | volume = 580 | issue = 8 | pages = 1911–8 | date = 3 April 2006 | pmid = 16500650 | doi=10.1016/j.febslet.2006.02.012}}</ref> and even isoform specific effects of Naa10 functions have been reported in mouse.<ref name="Chun_2007"/><ref>{{cite journal | vauthors = Kim SH, Park JA, Kim JH, Lee JW, Seo JH, Jung BK, Chun KH, Jeong JW, Bae MK, Kim KW | title = Characterization of ARD1 variants in mammalian cells. | journal = Biochemical and Biophysical Research Communications | volume = 340 | issue = 2 | pages = 422–7 | date = 10 February 2006 | pmid = 16376303 | doi=10.1016/j.bbrc.2005.12.018}}</ref>
Despite the fact that N<sup>α</sup>-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 signaling pathway|Wnt/β-catenin]],<ref name = "Lim_2006"/><ref name = "Lim_2008"/><ref name = "Seo_2010">{{cite journal | vauthors = Seo JH, Cha JH, Park JH, Jeong CH, Park ZY, Lee HS, Oh SH, Kang JH, Suh SW, Kim KH, Ha JY, Han SH, Kim SH, Lee JW, Park JA, Jeong JW, Lee KJ, Oh GT, Lee MN, Kwon SW, Lee SK, Chun KH, Lee SJ, Kim KW | title = Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation | journal = Cancer Research | volume = 70 | issue = 11 | pages = 4422–32 | date = 1 June 2010 | pmid = 20501853 | doi=10.1158/0008-5472.can-09-3258}}</ref><ref>{{cite journal | vauthors = Lee CF, Ou DS, Lee SB, Chang LH, Lin RK, Li YS, Upadhyay AK, Cheng X, Wang YC, Hsu HS, Hsiao M, Wu CW, Juan LJ | title = hNaa10p contributes to tumorigenesis by facilitating DNMT1-mediated tumor suppressor gene silencing | journal = The Journal of Clinical Investigation | volume = 120 | issue = 8 | pages = 2920–30 | date = August 2010 | pmid = 20592467 | doi=10.1172/jci42275 | pmc=2912195}}</ref> [[Mitogen-activated protein kinase|MAPK]],<ref name = "Seo_2010"/> [[JAK-STAT signaling pathway|JAK/STAT]],<ref>{{cite journal | vauthors = Zeng Y, Min L, Han Y, Meng L, Liu C, Xie Y, Dong B, Wang L, Jiang B, Xu H, Zhuang Q, Zhao C, Qu L, Shou C | title = Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis | journal = Carcinogenesis | volume = 35 | issue = 10 | pages = 2244–53 | date = October 2014 | pmid = 24925029 | doi=10.1093/carcin/bgu132}}</ref> and [[NF-κB]],<ref>{{cite journal | vauthors = Kuo HP, Lee DF, Xia W, Lai CC, Li LY, Hung MC | title = Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and degradation | journal = Biochemical and Biophysical Research Communications | volume = 389 | issue = 1 | pages = 156–61 | date = 6 November 2009 | pmid = 19716809 | doi=10.1016/j.bbrc.2009.08.127 | pmc=2753275}}</ref><ref>{{cite journal | vauthors = Park J, Kanayama A, Yamamoto K, Miyamoto Y | title = ARD1 binding to RIP1 mediates doxorubicin-induced NF-κB activation | journal = Biochemical and Biophysical Research Communications | volume = 422 | issue = 2 | pages = 291–7 | date = 1 June 2012 | pmid = 22580278 | doi=10.1016/j.bbrc.2012.04.150}}</ref><ref name = "Xu_2012">{{cite journal | vauthors = Xu H, Jiang B, Meng L, Ren T, Zeng Y, Wu J, Qu L, Shou C | title = N-α-acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression | journal = Carcinogenesis | volume = 33 | issue = 6 | pages = 1193–202 | date = June 2012 | pmid = 22496479 | doi=10.1093/carcin/bgs144}}</ref><ref name = "Yoon_2014">{{cite journal | vauthors = Yoon H, Kim HL, Chun YS, Shin DH, Lee KH, Shin CS, Lee DY, Kim HH, Lee ZH, Ryoo HM, Lee MN, Oh GT, Park JW | title = NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2 | journal = Nature Communications | volume = 5 | pages = 5176 | date = 7 November 2014 | pmid = 25376646 | doi=10.1038/ncomms6176}}</ref> thereby regulating various cellular processes, including cell migration,<ref>{{cite journal | vauthors = Hua KT, Tan CT, Johansson G, Lee JM, Yang PW, Lu HY, Chen CK, Su JL, Chen PB, Wu YL, Chi CC, Kao HJ, Shih HJ, Chen MW, Chien MH, Chen PS, Lee WJ, Cheng TY, Rosenberger G, Chai CY, Yang CJ, Huang MS, Lai TC, Chou TY, Hsiao M, Kuo ML | title = N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity | journal = Cancer Cell | volume = 19 | issue = 2 | pages = 218–31 | date = 15 February 2011 | pmid = 21295525 | doi=10.1016/j.ccr.2010.11.010}}</ref><ref>{{cite journal | vauthors = Shin DH, Chun YS, Lee KH, Shin HW, Park JW | title = Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase | journal = PLOS ONE | volume = 4 | issue = 10 | pages = e7451 | date = 14 October 2009 | pmid = 19826488 | doi=10.1371/journal.pone.0007451 | pmc=2758594}}</ref> cell cycle control,<ref>{{cite journal | vauthors = Kaidi A, Williams AC, Paraskeva C | title = Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia | journal = Nature Cell Biology | volume = 9 | issue = 2 | pages = 210–7 | date = February 2007 | pmid = 17220880 | doi=10.1038/ncb1534}}</ref><ref name = "Gromyko_2010">{{cite journal | vauthors = Gromyko D, Arnesen T, Ryningen A, Varhaug JE, Lillehaug JR | title = Depletion of the human Nα-terminal acetyltransferase A induces p53-dependent apoptosis and p53-independent growth inhibition | journal = International Journal of Cancer | volume = 127 | issue = 12 | pages = 2777–89 | date = 15 December 2010 | pmid = 21351257 | doi=10.1002/ijc.25275}}</ref><ref>{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = 20 October 2005 | pmid = 16189514 | doi=10.1038/nature04209}}</ref> DNA damage control,<ref name = "Xu_2012"/><ref name = "Yi_2007">{{cite journal | vauthors = Yi CH, Sogah DK, Boyce M, Degterev A, Christofferson DE, Yuan J | title = A genome-wide RNAi screen reveals multiple regulators of caspase activation | journal = The Journal of Cell Biology | volume = 179 | issue = 4 | pages = 619–26 | date = 19 November 2007 | pmid = 17998402 | doi=10.1083/jcb.200708090 | pmc=2080898}}</ref> caspase-dependent cell death,<ref name = "Yi_2007"/><ref>{{cite journal | vauthors = Yi CH, Pan H, Seebacher J, Jang IH, Hyberts SG, Heffron GJ, Vander Heiden MG, Yang R, Li F, Locasale JW, Sharfi H, Zhai B, Rodriguez-Mias R, Luithardt H, Cantley LC, Daley GQ, Asara JM, Gygi SP, Wagner G, Liu CF, Yuan J | title = Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival | journal = Cell | volume = 146 | issue = 4 | pages = 607–20 | date = 19 August 2011 | pmid = 21854985 | doi=10.1016/j.cell.2011.06.050 | pmc=3182480}}</ref> p53 dependent apoptosis,<ref name = "Gromyko_2010"/> cell proliferation and autophagy <ref>{{cite journal | vauthors = Kuo HP, Lee DF, Chen CT, Liu M, Chou CK, Lee HJ, Du Y, Xie X, Wei Y, Xia W, Weihua Z, Yang JY, Yen CJ, Huang TH, Tan M, Xing G, Zhao Y, Lin CH, Tsai SF, Fidler IJ, Hung MC | title = ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway | journal = Science Signaling | volume = 3 | issue = 108 | pages = ra9 | date = 9 February 2010 | pmid = 20145209 | doi=10.1126/scisignal.2000590 | pmc=2874891}}</ref> as well as hypoxia,<ref name = "Lim_2008"/><ref name = "Jeong_2002"/><ref name = "Yoo_2006"/><ref>{{cite journal | vauthors = Ke Q, Kluz T, Costa M | title = 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 | journal = International Journal of Environmental Research and Public Health | volume = 2 | issue = 1 | pages = 10–3 | date = April 2005 | pmid = 16705796 | doi=10.3390/ijerph2005010010 | pmc=3814691}}</ref><ref>{{cite journal | vauthors = Chang CC, Lin MT, Lin BR, Jeng YM, Chen ST, Chu CY, Chen RJ, Chang KJ, Yang PC, Kuo ML | title = Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis | journal = Journal of the National Cancer Institute | volume = 98 | issue = 14 | pages = 984–95 | date = 19 July 2006 | pmid = 16849681 | doi=10.1093/jnci/djj242}}</ref> although there are some major discrepancies regarding hypoxia<ref>{{cite journal | vauthors = Arnesen T, Kong X, Evjenth R, Gromyko D, Varhaug JE, Lin Z, Sang N, Caro J, Lillehaug JR | title = Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha | journal = FEBS Letters | volume = 579 | issue = 28 | pages = 6428–32 | date = 21 November 2005 | pmid = 16288748 | doi=10.1016/j.febslet.2005.10.036| pmc = 4505811 }}</ref><ref>{{cite journal | vauthors = Fisher TS, Etages SD, Hayes L, Crimin K, Li B | title = Analysis of ARD1 function in hypoxia response using retroviral RNA interference | journal = The Journal of Biological Chemistry | volume = 280 | issue = 18 | pages = 17749–57 | date = 6 May 2005 | pmid = 15755738 | doi=10.1074/jbc.m412055200}}</ref><ref>{{cite journal | vauthors = Bilton R, Mazure N, Trottier E, Hattab M, Déry MA, Richard DE, Pouysségur J, Brahimi-Horn MC | title = Arrest-defective-1 protein, an acetyltransferase, does not alter stability of hypoxia-inducible factor (HIF)-1alpha and is not induced by hypoxia or HIF | journal = The Journal of Biological Chemistry | volume = 280 | issue = 35 | pages = 31132–40 | date = 2 September 2005 | pmid = 15994306 | doi=10.1074/jbc.m504482200}}</ref><ref>{{cite journal | vauthors = Fath DM, Kong X, Liang D, Lin Z, Chou A, Jiang Y, Fang J, Caro J, Sang N | title = Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha | journal = The Journal of Biological Chemistry | volume = 281 | issue = 19 | pages = 13612–9 | date = 12 May 2006 | pmid = 16543236 | doi=10.1074/jbc.m600456200 | pmc=1564196}}</ref><ref>{{cite journal | vauthors = Murray-Rust TA, Oldham NJ, Hewitson KS, Schofield CJ | title = Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF-1alpha fragments in vitro | journal = FEBS Letters | volume = 580 | issue = 8 | pages = 1911–8 | date = 3 April 2006 | pmid = 16500650 | doi=10.1016/j.febslet.2006.02.012}}</ref> and even isoform specific effects of Naa10 functions have been reported in mouse.<ref name="Chun_2007"/><ref>{{cite journal | vauthors = Kim SH, Park JA, Kim JH, Lee JW, Seo JH, Jung BK, Chun KH, Jeong JW, Bae MK, Kim KW | title = Characterization of ARD1 variants in mammalian cells | journal = Biochemical and Biophysical Research Communications | volume = 340 | issue = 2 | pages = 422–7 | date = 10 February 2006 | pmid = 16376303 | doi=10.1016/j.bbrc.2005.12.018}}</ref>


Naa10 is essential in ''[[D. melanogaster]]'',<ref>{{cite journal | vauthors = Wang Y, Mijares M, Gall MD, Turan T, Javier A, Bornemann DJ, Manage K, Warrior R | title = Drosophila variable nurse cells encodes arrest defective 1 (ARD1), the catalytic subunit of the major N-terminal acetyltransferase complex. | journal = Developmental Dynamics | volume = 239 | issue = 11 | pages = 2813–27 | date = November 2010 | pmid = 20882681 | doi=10.1002/dvdy.22418 | pmc=3013298}}</ref> ''[[Caenorhabditis elegans|C. elegans]]''<ref>{{cite journal | vauthors = Chen D, Zhang J, Minnerly J, Kaul T, Riddle DL, Jia K | title = daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan. | journal = PLOS Genetics | volume = 10 | issue = 10 | pages = e1004699 | date = October 2014 | pmid = 25330189 | doi=10.1371/journal.pgen.1004699 | pmc=4199510}}</ref> and T. brucei.<ref name = "Ingram_2000"/> In ''[[S. cerevisiae]]'', Naa10 function is not essential but y''NAA10''Δ cells display severe defects including de-repression of the silent mating type locus (''HML''), failure to enter G<sub>o</sub> phase, temperature sensitivity, and impaired growth.<ref name = "Whiteway_1985"/><ref>{{cite journal | vauthors = Whiteway M, Freedman R, Van Arsdell S, Szostak JW, Thorner J | title = The yeast ARD1 gene product is required for repression of cryptic mating-type information at the HML locus. | journal = Molecular and Cellular Biology | volume = 7 | issue = 10 | pages = 3713–22 | date = October 1987 | pmid = 3316986 | pmc=368027}}</ref> Naa10-knockout mice have very recently been reported to be viable, displaying a defect in bone development.<ref name = "Yoon_2014"/>
Naa10 is essential in ''[[D. melanogaster]]'',<ref>{{cite journal | vauthors = Wang Y, Mijares M, Gall MD, Turan T, Javier A, Bornemann DJ, Manage K, Warrior R | title = Drosophila variable nurse cells encodes arrest defective 1 (ARD1), the catalytic subunit of the major N-terminal acetyltransferase complex | journal = Developmental Dynamics | volume = 239 | issue = 11 | pages = 2813–27 | date = November 2010 | pmid = 20882681 | doi=10.1002/dvdy.22418 | pmc=3013298}}</ref> ''[[Caenorhabditis elegans|C. elegans]]''<ref>{{cite journal | vauthors = Chen D, Zhang J, Minnerly J, Kaul T, Riddle DL, Jia K | title = daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan | journal = PLOS Genetics | volume = 10 | issue = 10 | pages = e1004699 | date = October 2014 | pmid = 25330189 | doi=10.1371/journal.pgen.1004699 | pmc=4199510}}</ref> and ''[[T. brucei]]''.<ref name = "Ingram_2000"/> In ''[[S. cerevisiae]]'', Naa10 function is not essential but y''NAA10''Δ cells display severe defects including de-repression of the silent mating type locus (''HML''), failure to enter G<sub>o</sub> phase, temperature sensitivity, and impaired growth.<ref name = "Whiteway_1985"/><ref>{{cite journal | vauthors = Whiteway M, Freedman R, Van Arsdell S, Szostak JW, Thorner J | title = The yeast ARD1 gene product is required for repression of cryptic mating-type information at the HML locus | journal = Molecular and Cellular Biology | volume = 7 | issue = 10 | pages = 3713–22 | date = October 1987 | pmid = 3316986 | pmc=368027}}</ref> Naa10-knockout mice have very recently been reported to be viable, displaying a defect in bone development.<ref name = "Yoon_2014"/>


== Disease ==
== Disease ==
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 arrhythmia]]s.<ref name = "Rope_2011">{{cite journal | vauthors = Rope AF, Wang K, Evjenth R, Xing J, Johnston JJ, Swensen JJ, Johnson WE, Moore B, Huff CD, Bird LM, Carey JC, Opitz JM, Stevens CA, Jiang T, Schank C, Fain HD, Robison R, Dalley B, Chin S, South ST, Pysher TJ, Jorde LB, Hakonarson H, Lillehaug JR, Biesecker LG, Yandell M, Arnesen T, Lyon GJ | title = Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency. | journal = American Journal of Human Genetics | volume = 89 | issue = 1 | pages = 28–43 | date = 15 July 2011 | pmid = 21700266 | doi=10.1016/j.ajhg.2011.05.017 | pmc=3135802}}</ref> Patient [[fibroblast]]s displayed altered [[cell morphology|morphology]], growth and [[cell migration|migration]] characteristics and molecular studies indicate that this S37P mutation disrupts the NatA complex and decreases Naa10 enzymatic activity ''in vitro'' and ''in vivo''.<ref name = "Rope_2011"/><ref>{{cite journal | vauthors = Myklebust LM, Van Damme P, Støve SI, Dörfel MJ, Abboud A, Kalvik TV, Grauffel C, Jonckheere V, Wu Y, Swensen J, Kaasa H, Liszczak G, Marmorstein R, Reuter N, Lyon GJ, Gevaert K, Arnesen T | title = Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects. | journal = Human Molecular Genetics | date = 8 December 2014 | pmid = 25489052 | doi=10.1093/hmg/ddu611 | volume=24 | pages=1956–76 | pmc=4355026}}</ref><ref>{{cite journal | vauthors = Van Damme P, Støve SI, Glomnes N, Gevaert K, Arnesen T | title = A Saccharomyces cerevisiae model reveals in vivo functional impairment of the Ogden syndrome N-terminal acetyltransferase NAA10 Ser37Pro mutant. | journal = Molecular & Cellular Proteomics | volume = 13 | issue = 8 | pages = 2031–41 | date = August 2014 | pmid = 24408909 | doi=10.1074/mcp.m113.035402 | pmc=4125735}}</ref>
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 arrhythmia]]s.<ref name = "Rope_2011">{{cite journal | vauthors = Rope AF, Wang K, Evjenth R, Xing J, Johnston JJ, Swensen JJ, Johnson WE, Moore B, Huff CD, Bird LM, Carey JC, Opitz JM, Stevens CA, Jiang T, Schank C, Fain HD, Robison R, Dalley B, Chin S, South ST, Pysher TJ, Jorde LB, Hakonarson H, Lillehaug JR, Biesecker LG, Yandell M, Arnesen T, Lyon GJ | title = Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency | journal = American Journal of Human Genetics | volume = 89 | issue = 1 | pages = 28–43 | date = 15 July 2011 | pmid = 21700266 | doi=10.1016/j.ajhg.2011.05.017 | pmc=3135802}}</ref> Patient [[fibroblast]]s displayed altered [[cell morphology|morphology]], growth and [[cell migration|migration]] characteristics and molecular studies indicate that this S37P mutation disrupts the NatA complex and decreases Naa10 enzymatic activity ''in vitro'' and ''in vivo''.<ref name = "Rope_2011"/><ref>{{cite journal | vauthors = Myklebust LM, Van Damme P, Støve SI, Dörfel MJ, Abboud A, Kalvik TV, Grauffel C, Jonckheere V, Wu Y, Swensen J, Kaasa H, Liszczak G, Marmorstein R, Reuter N, Lyon GJ, Gevaert K, Arnesen T | title = Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects | journal = Human Molecular Genetics | date = 8 December 2014 | pmid = 25489052 | doi=10.1093/hmg/ddu611 | volume=24 | issue = 7 | pages=1956–76 | pmc=4355026}}</ref><ref>{{cite journal | vauthors = Van Damme P, Støve SI, Glomnes N, Gevaert K, Arnesen T | title = A Saccharomyces cerevisiae model reveals in vivo functional impairment of the Ogden syndrome N-terminal acetyltransferase NAA10 Ser37Pro mutant | journal = Molecular & Cellular Proteomics | volume = 13 | issue = 8 | pages = 2031–41 | date = August 2014 | pmid = 24408909 | doi=10.1074/mcp.m113.035402 | pmc=4125735}}</ref>


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.<ref>{{cite journal | vauthors = Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Röpke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schröck E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM | title = Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. | journal = Lancet | volume = 380 | issue = 9854 | pages = 1674–82 | date = 10 November 2012 | pmid = 23020937 | doi=10.1016/s0140-6736(12)61480-9}}</ref><ref>{{cite journal | vauthors = Popp B, Støve SI, Endele S, Myklebust LM, Hoyer J, Sticht H, Azzarello-Burri S, Rauch A, Arnesen T, Reis A | title = De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females. | journal = European Journal of Human Genetics | date = 6 August 2014 | pmid = 25099252 | doi=10.1038/ejhg.2014.150 | volume=23 | pages=602–609 | pmc=4402627}}</ref> 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.
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.<ref>{{cite journal | vauthors = Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Röpke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schröck E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM | title = Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study | journal = Lancet | volume = 380 | issue = 9854 | pages = 1674–82 | date = 10 November 2012 | pmid = 23020937 | doi=10.1016/s0140-6736(12)61480-9}}</ref><ref>{{cite journal | vauthors = Popp B, Støve SI, Endele S, Myklebust LM, Hoyer J, Sticht H, Azzarello-Burri S, Rauch A, Arnesen T, Reis A | title = De novo missense mutations in the NAA10 gene cause severe non-syndromic developmental delay in males and females | journal = European Journal of Human Genetics | date = 6 August 2014 | pmid = 25099252 | doi=10.1038/ejhg.2014.150 | volume=23 | issue = 5 | pages=602–609 | pmc=4402627}}</ref> 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.<ref name = "Esmailpour_2014">{{cite journal | vauthors = Esmailpour T, Riazifar H, Liu L, Donkervoort S, Huang VH, Madaan S, Shoucri BM, Busch A, Wu J, Towbin A, Chadwick RB, Sequeira A, Vawter MP, Sun G, Johnston JJ, Biesecker LG, Kawaguchi R, Sun H, Kimonis V, Huang T | title = A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome. | journal = Journal of Medical Genetics | volume = 51 | issue = 3 | pages = 185–96 | date = March 2014 | pmid = 24431331 | doi=10.1136/jmedgenet-2013-101660 | pmc=4278941}}</ref> Patient fibroblasts displayed cell proliferation defects, dysregulation of genes involved in [[retinoic acid]] signaling pathway, such as [[STRA6]], and deficiencies in [[retinol]] uptake.<ref name = "Esmailpour_2014"/>
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.<ref name = "Esmailpour_2014">{{cite journal | vauthors = Esmailpour T, Riazifar H, Liu L, Donkervoort S, Huang VH, Madaan S, Shoucri BM, Busch A, Wu J, Towbin A, Chadwick RB, Sequeira A, Vawter MP, Sun G, Johnston JJ, Biesecker LG, Kawaguchi R, Sun H, Kimonis V, Huang T | title = A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome | journal = Journal of Medical Genetics | volume = 51 | issue = 3 | pages = 185–96 | date = March 2014 | pmid = 24431331 | doi=10.1136/jmedgenet-2013-101660 | pmc=4278941}}</ref> Patient fibroblasts displayed cell proliferation defects, dysregulation of genes involved in [[retinoic acid]] signaling pathway, such as [[STRA6]], and deficiencies in [[retinol]] uptake.<ref name = "Esmailpour_2014"/>


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.<ref>{{cite journal | vauthors = Asaumi M, Iijima K, Sumioka A, Iijima-Ando K, Kirino Y, Nakaya T, Suzuki T | title = Interaction of N-terminal acetyltransferase with the cytoplasmic domain of beta-amyloid precursor protein and its effect on A beta secretion. | journal = Journal of Biochemistry | volume = 137 | issue = 2 | pages = 147–55 | date = February 2005 | pmid = 15749829 | doi=10.1093/jb/mvi014}}</ref><ref>{{cite journal | vauthors = Pezza JA, Langseth SX, Raupp Yamamoto R, Doris SM, Ulin SP, Salomon AR, Serio TR | title = The NatA acetyltransferase couples Sup35 prion complexes to the [PSI+] phenotype. | journal = Molecular Biology of the Cell | volume = 20 | issue = 3 | pages = 1068–80 | date = February 2009 | pmid = 19073888 | doi=10.1091/mbc.e08-04-0436 | pmc=2633373}}</ref><ref>{{cite journal | vauthors = Pezza JA, Villali J, Sindi SS, Serio TR | title = Amyloid-associated activity contributes to the severity and toxicity of a prion phenotype. | journal = Nature Communications | volume = 5 | pages = 4384 | date = 15 July 2014 | pmid = 25023996 | doi=10.1038/ncomms5384 | pmc=4156856}}</ref><ref>{{cite journal | vauthors = Holmes WM, Mannakee BK, Gutenkunst RN, Serio TR | title = Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding. | journal = Nature Communications | volume = 5 | pages = 4383 | date = 15 July 2014 | pmid = 25023910 | doi=10.1038/ncomms5383 | pmc=4140192}}</ref>
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.<ref>{{cite journal | vauthors = Asaumi M, Iijima K, Sumioka A, Iijima-Ando K, Kirino Y, Nakaya T, Suzuki T | title = Interaction of N-terminal acetyltransferase with the cytoplasmic domain of beta-amyloid precursor protein and its effect on A beta secretion | journal = Journal of Biochemistry | volume = 137 | issue = 2 | pages = 147–55 | date = February 2005 | pmid = 15749829 | doi=10.1093/jb/mvi014}}</ref><ref>{{cite journal | vauthors = Pezza JA, Langseth SX, Raupp Yamamoto R, Doris SM, Ulin SP, Salomon AR, Serio TR | title = The NatA acetyltransferase couples Sup35 prion complexes to the [PSI+] phenotype | journal = Molecular Biology of the Cell | volume = 20 | issue = 3 | pages = 1068–80 | date = February 2009 | pmid = 19073888 | doi=10.1091/mbc.e08-04-0436 | pmc=2633373}}</ref><ref>{{cite journal | vauthors = Pezza JA, Villali J, Sindi SS, Serio TR | title = Amyloid-associated activity contributes to the severity and toxicity of a prion phenotype | journal = Nature Communications | volume = 5 | pages = 4384 | date = 15 July 2014 | pmid = 25023996 | doi=10.1038/ncomms5384 | pmc=4156856}}</ref><ref>{{cite journal | vauthors = Holmes WM, Mannakee BK, Gutenkunst RN, Serio TR | title = Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding | journal = Nature Communications | volume = 5 | pages = 4383 | date = 15 July 2014 | pmid = 25023910 | doi=10.1038/ncomms5383 | pmc=4140192}}</ref>


==Notes==
==Notes==
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== Further reading ==
== Further reading ==
{{refbegin|35em}}
{{refbegin|35em}}
* {{cite journal | vauthors = Brenner V, Nyakatura G, Rosenthal A, Platzer M | title = Genomic organization of two novel genes on human Xq28: compact head to head arrangement of IDH gamma and TRAP delta is conserved in rat and mouse. | journal = Genomics | volume = 44 | issue = 1 | pages = 8–14 | year = 1997 | pmid = 9286695 | doi = 10.1006/geno.1997.4822 }}
* {{cite journal | vauthors = Brenner V, Nyakatura G, Rosenthal A, Platzer M | title = Genomic organization of two novel genes on human Xq28: compact head to head arrangement of IDH gamma and TRAP delta is conserved in rat and mouse | journal = Genomics | volume = 44 | issue = 1 | pages = 8–14 | year = 1997 | pmid = 9286695 | doi = 10.1006/geno.1997.4822 }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination. | journal = Genome Res. | volume = 10 | issue = 11 | pages = 1788–95 | year = 2001 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Res. | volume = 10 | issue = 11 | pages = 1788–95 | year = 2001 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. | journal = EMBO Rep. | volume = 1 | issue = 3 | pages = 287–92 | year = 2001 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
* {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Rep. | volume = 1 | issue = 3 | pages = 287–92 | year = 2001 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
* {{cite journal | vauthors = Sugiura N, Adams SM, Corriveau RA | title = An evolutionarily conserved N-terminal acetyltransferase complex associated with neuronal development. | journal = J. Biol. Chem. | volume = 278 | issue = 41 | pages = 40113–20 | year = 2003 | pmid = 12888564 | doi = 10.1074/jbc.M301218200 }}
* {{cite journal | vauthors = Sugiura N, Adams SM, Corriveau RA | title = An evolutionarily conserved N-terminal acetyltransferase complex associated with neuronal development | journal = J. Biol. Chem. | volume = 278 | issue = 41 | pages = 40113–20 | year = 2003 | pmid = 12888564 | doi = 10.1074/jbc.M301218200 }}
* {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | title = From ORFeome to biology: a functional genomics pipeline. | journal = Genome Res. | volume = 14 | issue = 10B | pages = 2136–44 | year = 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}
* {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Res. | volume = 14 | issue = 10B | pages = 2136–44 | year = 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}
* {{cite journal | vauthors = Arnesen T, Gromyko D, Horvli O, Fluge Ø, Lillehaug J, Varhaug JE | title = Expression of N-acetyl transferase human and human Arrest defective 1 proteins in thyroid neoplasms. | journal = Thyroid | volume = 15 | issue = 10 | pages = 1131–6 | year = 2006 | pmid = 16279846 | doi = 10.1089/thy.2005.15.1131 }}
* {{cite journal | vauthors = Arnesen T, Gromyko D, Horvli O, Fluge Ø, Lillehaug J, Varhaug JE | title = Expression of N-acetyl transferase human and human Arrest defective 1 proteins in thyroid neoplasms | journal = Thyroid | volume = 15 | issue = 10 | pages = 1131–6 | year = 2006 | pmid = 16279846 | doi = 10.1089/thy.2005.15.1131 }}
* {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | title = The LIFEdb database in 2006. | journal = Nucleic Acids Res. | volume = 34 | issue = Database issue | pages = D415–8 | year = 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}
* {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | title = The LIFEdb database in 2006 | journal = Nucleic Acids Res. | volume = 34 | issue = Database issue | pages = D415–8 | year = 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}
* {{cite journal | vauthors = Arnesen T, Gromyko D, Pendino F, Ryningen A, Varhaug JE, Lillehaug JR | title = Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-alpha-acetyltransferase complex. | journal = Oncogene | volume = 25 | issue = 31 | pages = 4350–60 | year = 2006 | pmid = 16518407 | doi = 10.1038/sj.onc.1209469 }}
* {{cite journal | vauthors = Arnesen T, Gromyko D, Pendino F, Ryningen A, Varhaug JE, Lillehaug JR | title = Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-alpha-acetyltransferase complex | journal = Oncogene | volume = 25 | issue = 31 | pages = 4350–60 | year = 2006 | pmid = 16518407 | doi = 10.1038/sj.onc.1209469 }}
* {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization. | journal = Nat. Biotechnol. | volume = 24 | issue = 10 | pages = 1285–92 | year = 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 }}
* {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nat. Biotechnol. | volume = 24 | issue = 10 | pages = 1285–92 | year = 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 }}
{{refend}}
{{refend}}
{{Use dmy dates|date=April 2017}}
{{Use dmy dates|date=April 2017}}


[[Category:Enzymes]]
[[Category:Enzymes]]

Latest revision as of 08:50, 1 October 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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N-alpha-acetyltransferase 10 (NAA10) also known as NatA catalytic subunit Naa10 and arrest-defective protein 1 homolog A (ARD1A) is an enzyme subunit that in humans is encoded NAA10 gene.[1][2] 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.[3]

Gene and transcripts

The human NAA10 is located on chromosome Xq28 and contains 8 exons, 2 encoding three different isoforms derived from alternate splicing.[4] Additionally, a processed NAA10 gene duplication NAA11 (ARD2) has been identified that is expressed in several human cell lines;[5] 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.[6] Naa11 has also been found in mouse, where it is mainly expressed in the testis.[7] 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.[8]

Homologues for Naa10 have been identified in almost all kingdoms of life analyzed, including plants,[9][10][11] fungi,[9][12] amoebozoa,[9] archaeabacteria[9][13][14][15] and protozoa.[16][17] In eubacteria, 3 Nα-acetyltransferases, RimI, RimJ and RimL, have been identified[18][19][20] 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.[21][22]

Structure

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.[23] 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.[24] 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.[15] 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.[24] An X-ray crystal structure of human Naa10 in complex with Naa15 and HYPK has been reported.[25]

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

Function

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.[3][29] Additionally, in a monomeric state, structural rearrangements of the substrate binding pocket Naa10 allow acetylation of N-termini with acidic side chains.[24][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.[8][61]

Naa10 is essential in D. melanogaster,[62] C. elegans[63] and T. brucei.[16] 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.[12][64] Naa10-knockout mice have very recently been reported to be viable, displaying a defect in bone development.[45]

Disease

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]

Notes


References

  1. ↑ Tribioli C, Mancini M, Plassart E, Bione S, Rivella S, Sala C, Torri G, Toniolo D (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.
  2. ↑ "Entrez Gene: ARD1A ARD1 homolog A, N-acetyltransferase (S. cerevisiae)".
  3. ↑ 3.0 3.1 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.
  4. ↑ 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.
  5. ↑ Arnesen T, Betts MJ, Pendino F, Liberles DA, Anderson D, Caro J, Kong X, Varhaug JE, Lillehaug JR (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. PMC 1475586. PMID 16638120.
  6. ↑ 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. 6 (11): 1391–9. doi:10.4161/epi.6.11.18125. PMC 3242813. PMID 22048246.
  7. ↑ 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. PMC 2849813. PMID 19246321.
  8. ↑ 8.0 8.1 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.
  9. ↑ 9.0 9.1 9.2 9.3 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.
  10. ↑ Liu CC, Zhu HY, Dong XM, Ning DL, Wang HX, Li WH, Yang CP, Wang BC (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. PMC 3594182. PMID 23536812.
  11. ↑ Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C (June 2012). "Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-α-acetylation features". Molecular & Cellular Proteomics. 11 (6): M111.015131. doi:10.1074/mcp.m111.015131. PMC 3433923. PMID 22223895.
  12. ↑ 12.0 12.1 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.
  13. ↑ 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.
  14. ↑ Han SH, Ha JY, Kim KH, Oh SJ, Kim do J, Kang JY, Yoon HJ, Kim SH, Seo JH, Kim KW, Suh SW (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. 62 (Pt 11): 1127–30. doi:10.1107/s1744309106040267. PMC 2225214. PMID 17077495.
  15. ↑ 15.0 15.1 Ma C, Pathak C, Jang S, Lee SJ, Nam M, Kim SJ, Im H, Lee BJ (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.
  16. ↑ 16.0 16.1 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.
  17. ↑ 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. PMC 2922945. PMID 18534695.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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. 17 (10): 1781–90. doi:10.1110/ps.035899.108. PMC 2548364. PMID 18596200.
  22. ↑ 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.
  23. ↑ Sánchez-Puig N, Fersht AR (August 2006). "Characterization of the native and fibrillar conformation of the human Nalpha-acetyltransferase ARD1". Protein Science. 15 (8): 1968–76. doi:10.1110/ps.062264006. PMC 2242591. PMID 16823041.
  24. ↑ 24.0 24.1 24.2 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. PMC 3766382. PMID 23912279.
  25. ↑ Gottlieb, Leah; Marmorstein, Ronen (10 May 2018). "Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK". Structure. 26 (7): 925–935.e8. doi:10.1016/j.str.2018.04.003. PMC 6031454. PMID 29754825.
  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. PMC 1134861. PMID 15496142.
  27. ↑ Park JH, Seo JH, Wee HJ, Vo TT, Lee EJ, Choi H, Cha JH, Ahn BJ, Shin MW, Bae SJ, Kim KW (2014). "Nuclear translocation of hARD1 contributes to proper cell cycle progression". PLOS ONE. 9 (8): e105185. doi:10.1371/journal.pone.0105185. PMC 4136855. PMID 25133627.
  28. ↑ Arnesen T, Gromyko D, Kagabo D, Betts MJ, Starheim KK, Varhaug JE, Anderson D, Lillehaug JR (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. PMC 2695478. PMID 19480662.
  29. ↑ Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T (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. PMC 3131286. PMID 21750686.
  30. ↑ Van Damme P, Evjenth R, Foyn H, Demeyer K, De Bock PJ, Lillehaug JR, Vandekerckhove J, Arnesen T, Gevaert K (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. 10 (5): M110.004580. doi:10.1074/mcp.m110.004580. PMC 3098586. 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 (inactive 2018-10-01). PMID 15322253.
  32. ↑ Shin SH, Yoon H, Chun YS, Shin HW, Lee MN, Oh GT, Park JW (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. PMC 4649535. PMID 25341044.
  33. ↑ 33.0 33.1 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. ↑ 34.0 34.1 34.2 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. ↑ 35.0 35.1 Jeong JW, Bae MK, Ahn MY, Kim SH, Sohn TK, Bae MH, Yoo MA, Song EJ, Lee KJ, Kim KW (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, Park JH, Choi JH, Yim SH, Lee MR, Park JG, Yoo JY, Kim JH, Lee ST, Kim HM, Ryeom S, Kim KW, Oh GT (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. PMC 2841038. PMID 20194889.
  37. ↑ 37.0 37.1 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. PMC 1422150. PMID 16511565.
  38. ↑ Foyn H, Van Damme P, Støve SI, Glomnes N, Evjenth R, Gevaert K, Arnesen T (January 2013). "Protein N-terminal acetyltransferases act as N-terminal propionyltransferases in vitro and in vivo". Molecular & Cellular Proteomics. 12 (1): 42–54. doi:10.1074/mcp.m112.019299. PMC 3536908. PMID 23043182.
  39. ↑ 39.0 39.1 Seo JH, Cha JH, Park JH, Jeong CH, Park ZY, Lee HS, Oh SH, Kang JH, Suh SW, Kim KH, Ha JY, Han SH, Kim SH, Lee JW, Park JA, Jeong JW, Lee KJ, Oh GT, Lee MN, Kwon SW, Lee SK, Chun KH, Lee SJ, Kim KW (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, Upadhyay AK, Cheng X, Wang YC, Hsu HS, Hsiao M, Wu CW, Juan LJ (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. PMC 2912195. PMID 20592467.
  41. ↑ Zeng Y, Min L, Han Y, Meng L, Liu C, Xie Y, Dong B, Wang L, Jiang B, Xu H, Zhuang Q, Zhao C, Qu L, Shou C (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. PMC 2753275. 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. ↑ 44.0 44.1 Xu H, Jiang B, Meng L, Ren T, Zeng Y, Wu J, Qu L, Shou C (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. ↑ 45.0 45.1 Yoon H, Kim HL, Chun YS, Shin DH, Lee KH, Shin CS, Lee DY, Kim HH, Lee ZH, Ryoo HM, Lee MN, Oh GT, Park JW (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, Chen CK, Su JL, Chen PB, Wu YL, Chi CC, Kao HJ, Shih HJ, Chen MW, Chien MH, Chen PS, Lee WJ, Cheng TY, Rosenberger G, Chai CY, Yang CJ, Huang MS, Lai TC, Chou TY, Hsiao M, Kuo ML (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. PMC 2758594. 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. ↑ 49.0 49.1 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. 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, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (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. ↑ 51.0 51.1 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. PMC 2080898. PMID 17998402.
  52. ↑ Yi CH, Pan H, Seebacher J, Jang IH, Hyberts SG, Heffron GJ, Vander Heiden MG, Yang R, Li F, Locasale JW, Sharfi H, Zhai B, Rodriguez-Mias R, Luithardt H, Cantley LC, Daley GQ, Asara JM, Gygi SP, Wagner G, Liu CF, Yuan J (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. PMC 3182480. PMID 21854985.
  53. ↑ Kuo HP, Lee DF, Chen CT, Liu M, Chou CK, Lee HJ, Du Y, Xie X, Wei Y, Xia W, Weihua Z, Yang JY, Yen CJ, Huang TH, Tan M, Xing G, Zhao Y, Lin CH, Tsai SF, Fidler IJ, Hung MC (9 February 2010). "ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway". Science Signaling. 3 (108): ra9. doi:10.1126/scisignal.2000590. PMC 2874891. 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. PMC 3814691. PMID 16705796.
  55. ↑ Chang CC, Lin MT, Lin BR, Jeng YM, Chen ST, Chu CY, Chen RJ, Chang KJ, Yang PC, Kuo ML (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, Sang N, Caro J, Lillehaug JR (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. PMC 4505811. 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, Pouysségur J, Brahimi-Horn MC (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, Fang J, Caro J, Sang N (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. PMC 1564196. 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, Chun KH, Jeong JW, Bae MK, Kim KW (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, Manage K, Warrior R (November 2010). "Drosophila variable nurse cells encodes arrest defective 1 (ARD1), the catalytic subunit of the major N-terminal acetyltransferase complex". Developmental Dynamics. 239 (11): 2813–27. doi:10.1002/dvdy.22418. PMC 3013298. 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. PMC 4199510. 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. PMC 368027. PMID 3316986.
  65. ↑ 65.0 65.1 Rope AF, Wang K, Evjenth R, Xing J, Johnston JJ, Swensen JJ, Johnson WE, Moore B, Huff CD, Bird LM, Carey JC, Opitz JM, Stevens CA, Jiang T, Schank C, Fain HD, Robison R, Dalley B, Chin S, South ST, Pysher TJ, Jorde LB, Hakonarson H, Lillehaug JR, Biesecker LG, Yandell M, Arnesen T, Lyon GJ (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. PMC 3135802. PMID 21700266.
  66. ↑ Myklebust LM, Van Damme P, Støve SI, Dörfel MJ, Abboud A, Kalvik TV, Grauffel C, Jonckheere V, Wu Y, Swensen J, Kaasa H, Liszczak G, Marmorstein R, Reuter N, Lyon GJ, Gevaert K, Arnesen T (8 December 2014). "Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects". Human Molecular Genetics. 24 (7): 1956–76. doi:10.1093/hmg/ddu611. PMC 4355026. 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. 13 (8): 2031–41. doi:10.1074/mcp.m113.035402. PMC 4125735. PMID 24408909.
  68. ↑ Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Röpke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schröck E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM (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, Azzarello-Burri S, Rauch A, Arnesen T, Reis A (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. 23 (5): 602–609. doi:10.1038/ejhg.2014.150. PMC 4402627. PMID 25099252.
  70. ↑ 70.0 70.1 Esmailpour T, Riazifar H, Liu L, Donkervoort S, Huang VH, Madaan S, Shoucri BM, Busch A, Wu J, Towbin A, Chadwick RB, Sequeira A, Vawter MP, Sun G, Johnston JJ, Biesecker LG, Kawaguchi R, Sun H, Kimonis V, Huang T (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. PMC 4278941. PMID 24431331.
  71. ↑ Asaumi M, Iijima K, Sumioka A, Iijima-Ando K, Kirino Y, Nakaya T, Suzuki T (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, Serio TR (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. PMC 2633373. 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. PMC 4156856. 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. PMC 4140192. PMID 25023910.

Further reading

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