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NAA15

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NAA15
Identifiers
AliasesNAA15, Ga19, NARG1, NAT1P, NATH, TBDN, TBDN100, N(alpha)-acetyltransferase 15, NatA auxiliary subunit, MRD50, N-alpha-acetyltransferase 15, NatA auxiliary subunit
External IDsOMIM: 608000; MGI: 1922088; HomoloGene: 14211; GeneCards: NAA15; OMA:NAA15 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

80155

74838

Ensembl

ENSG00000164134

ENSMUSG00000063273

UniProt

Q9BXJ9

Q80UM3

RefSeq (mRNA)

NM_057175

NM_053089

RefSeq (protein)

NP_476516

n/a

Location (UCSC)Chr 4: 139.3 – 139.42 MbChr 3: 51.32 – 51.38 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

N-alpha-acetyltransferase 15, NatA auxiliary subunit also known as gastric cancer antigen Ga19 (GA19), NMDA receptor-regulated protein 1 (NARG1), and Tbdn100 is a protein that in humans is encoded by the NAA15 gene.[5] NARG1 is the auxiliary subunit of the NatA (Nα-acetyltransferase A) complex. This NatA complex can associate with the ribosome and catalyzes the transfer of an acetyl group to the Nα-terminal amino group of proteins as they emerge from the exit tunnel.

Gene and transcripts

Human NAA15 is located on chromosome 4q31.1 and contains 23 exons. Initially, 2 mRNA species were identified, of size 4.6 and 5.8 kb, both harboring the same open reading frame encoding a putative protein of 866 amino acids (~105 kDa) protein that can be detected in most human adult tissues.[5] According to RefSeq/NCBI, only one human transcript variant exists, although 2 more isoforms are predicted.[6] In addition to full length Naa15, an N-terminally truncated variant of Naa15 (named tubedown-1), Naa15273-865 has been described; however, in mouse only full length Naa15 is widely expressed, whereas smaller transcripts seem to visualized only in heart and testis.[7][8]

In addition to this, a NAA15 gene duplication, NAA16, has been identified, and the encoded protein shares 70% sequence identity to hNaa15 and is expressed in a variety of human cell lines, but is generally less abundant as compared to hNaa15.[9] Three isoforms of Naa16 are validated so far (NCBI RefSeq). Mouse NAA15 is located on chromosome 2 D and contains 20 exons, whereas mouse NAA16 is located on chromosome 14 D3 and consists of 21 exons.

In principle, NatA can assemble from all the Naa10 and Naa15 isoforms in human and mouse, creating a more complex and flexible system for Nα-terminal acetylation as compared to lower eukaryotes.[9][10][11]

Structure

The X-ray crystal structure of the holo-NatA complex (Naa10/Naa15) from S. pombe revealed that Naa15 is composed of 13 conserved helical bundle tetratricopeptide repeat (TPR) motifs and adopts a ring-like topology that wraps around the catalytic subunit of NatA, Naa10.[12] This interaction induces conformational changes in the catalytic center of Naa10 that allows the acetylation of conventional NatA substrates.[12] The crystal structure of human NatA bound to the protein HYPK has also been solved.[13]

Because TPR motifs mediate protein–protein interactions, it has been postulated that this domain may facilitate the interaction with other NatA-binding partners such as the ribosome and Naa50/NatE.[12] Naa15 harbors a putative NLS between residues 612-628 (KKNAEKEKQQRNQKKKK); however, analysis of the nuclear localization of Naa15 revealed discrepant results.[8][14]

Function

Naa15, together with its catalytic subunit Naa10, constitutes the evolutionarily conserved NatA (Nα-acetyltransferase A) complex, which acetylates the α-amino group of the first amino acid residue of proteins starting with small side chains like serine, glycine, alanine, threonine and cysteine, after the initiator methionine has been cleaved by methionine aminopeptidases.[14][15][16][17][18][19][20]

Both, Naa15 and Naa16 interact with the ribosome in yeast (via the ribosomal proteins, uL23 and uL29), humans and rat, thereby linking the NatA/Naa10 to the ribosome and facilitating co-translational acetylation of nascent polypeptide chains as they emerges from the exit tunnel.[9][21][22][23][24][25] Furthermore, Naa15 might act as a scaffold for other factors, including the chaperone like protein HYPK (Huntingtin Interacting Protein K) and Naa50, the catalytic acetyltransferase subunit of NatE[22][23][26][27] In S. cerevisiae, NAA15Δ and NAA10Δ knockout cells exhibit the same phenotype, and biochemical data indicate that uncomplexed Naa15 is unstable and gets degraded.[12][28][29][30] Therefore, Naa15 function has been closely linked to the acetyltransferase activity of Naa10 as part of the NatA complex.

NatA may also regulate co-translational protein folding and protein targeting to the endoplasmic reticulum, possibly through competition with SRP and NAC for the same ribosomal binding sites or through yet unknown interference with other ribosome-associated protein biogenesis factors, such as the MetAPs, the chaperones Hsp70/Hsp40, SRP and NAC, which act on newly synthesized proteins as soon as they emerge from the ribosome exit tunnel.[21][24][31][32][33][34][35] However, the exact mechanism of such action is obscure. Apart from this, Naa15 has been linked to many cellular processes, including the maintenance of a healthy retina,[36][37][38] endothelial cell permeability,[38] tumor progression,[5][39] generation and differentiation of neurons[15][40][41] apoptosis[9][42] and transcriptional regulation;[8] however, it is not well understood whether these are NatA-independent or -dependent functions of Naa15.

Disease

Two damaging de novo NAA15 mutations were reported by exome sequencing in parent-offspring trios with congenital heart disease.[43] Patient 1 harbors a frameshift mutation (p. Lys335fs) and displays heterotaxy (dextrocardia, total anomalous pulmonary venous return, left superior vena cava, hypoplastic TV, double outlet right ventricle, hypoplastic RV, D-transposition of the great arteries, pulmonic stenosis) and hydronephrosis, asplenia, malrotation and abnormal neuro-development, the second patient harbors a nonsense mutation (p.S761X) and displays conotruncal defects (tetralogy of Fallot, single left coronary artery).

Notes

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164134 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063273 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c Fluge Ø, Bruland O, Akslen LA, Varhaug JE, Lillehaug JR (2002). "NATH, a novel gene overexpressed in papillary thyroid carcinomas". Oncogene. 21 (33): 5056–68. doi:10.1038/sj.onc.1205687. PMID 12140756.
  6. ^ 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.
  7. ^ Gendron RL, Adams LC, Paradis H (June 2000). "Tubedown-1, a novel acetyltransferase associated with blood vessel development". Developmental Dynamics. 218 (2): 300–15. doi:10.1002/(sici)1097-0177(200006)218:2<300::aid-dvdy5>3.0.co;2-k. PMID 10842358.
  8. ^ a b c Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA (4 October 2002). "Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex". The Journal of Biological Chemistry. 277 (40): 37280–91. doi:10.1074/jbc.m206482200. PMID 12145306.
  9. ^ a b c d Arnesen T, Gromyko D, Kagabo D, Betts MJ, Starheim KK, Varhaug JE, Anderson D, Lillehaug JR (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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ 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.
  12. ^ a b c d 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.
  13. ^ 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.
  14. ^ a b 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.
  15. ^ a b Sugiura N, Adams SM, Corriveau RA (10 October 2003). "An evolutionarily conserved N-terminal acetyltransferase complex associated with neuronal development". The Journal of Biological Chemistry. 278 (41): 40113–20. doi:10.1074/jbc.m301218200. PMID 12888564.
  16. ^ Park EC, Szostak JW (June 1992). "ARD1 and NAT1 proteins form a complex that has N-terminal acetyltransferase activity". The EMBO Journal. 11 (6): 2087–93. doi:10.1002/j.1460-2075.1992.tb05267.x. PMC 556675. PMID 1600941.
  17. ^ Mullen JR, Kayne PS, Moerschell RP, Tsunasawa S, Gribskov M, Colavito-Shepanski M, Grunstein M, Sherman F, Sternglanz R (July 1989). "Identification and characterization of genes and mutants for an N-terminal acetyltransferase from yeast". The EMBO Journal. 8 (7): 2067–75. doi:10.1002/j.1460-2075.1989.tb03615.x. PMC 401092. PMID 2551674.
  18. ^ Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N, Varhaug JE, Vandekerckhove J, Lillehaug JR, Sherman F, Gevaert K (19 May 2009). "Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans". Proceedings of the National Academy of Sciences of the United States of America. 106 (20): 8157–62. Bibcode:2009PNAS..106.8157A. doi:10.1073/pnas.0901931106. PMC 2688859. PMID 19420222.
  19. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  20. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  21. ^ a b Polevoda B, Brown S, Cardillo TS, Rigby S, Sherman F (1 February 2008). "Yeast N(alpha)-terminal acetyltransferases are associated with ribosomes". Journal of Cellular Biochemistry. 103 (2): 492–508. doi:10.1002/jcb.21418. PMID 17541948.
  22. ^ a b Gautschi M, Just S, Mun A, Ross S, Rücknagel P, Dubaquié Y, Ehrenhofer-Murray A, Rospert S (October 2003). "The yeast N(alpha)-acetyltransferase NatA is quantitatively anchored to the ribosome and interacts with nascent polypeptides". Molecular and Cellular Biology. 23 (20): 7403–14. doi:10.1128/mcb.23.20.7403-7414.2003. PMC 230319. PMID 14517307.
  23. ^ a b Arnesen T, Starheim KK, Van Damme P, Evjenth R, Dinh H, Betts MJ, Ryningen A, Vandekerckhove J, Gevaert K, Anderson D (April 2010). "The chaperone-like protein HYPK acts together with NatA in cotranslational N-terminal acetylation and prevention of Huntingtin aggregation". Molecular and Cellular Biology. 30 (8): 1898–909. doi:10.1128/mcb.01199-09. PMC 2849469. PMID 20154145.
  24. ^ a b Raue U, Oellerer S, Rospert S (16 March 2007). "Association of protein biogenesis factors at the yeast ribosomal tunnel exit is affected by the translational status and nascent polypeptide sequence". The Journal of Biological Chemistry. 282 (11): 7809–16. doi:10.1074/jbc.m611436200. PMID 17229726.
  25. ^ Yamada R, Bradshaw RA (29 January 1991). "Rat liver polysome N alpha-acetyltransferase: isolation and characterization". Biochemistry. 30 (4): 1010–6. doi:10.1021/bi00218a018. PMID 1989673.
  26. ^ Williams BC, Garrett-Engele CM, Li Z, Williams EV, Rosenman ED, Goldberg ML (2 December 2003). "Two putative acetyltransferases, san and deco, are required for establishing sister chromatid cohesion in Drosophila". Current Biology. 13 (23): 2025–36. doi:10.1016/j.cub.2003.11.018. PMID 14653991.
  27. ^ Arnesen T, Anderson D, Torsvik J, Halseth HB, Varhaug JE, Lillehaug JR (26 April 2006). "Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex". Gene. 371 (2): 291–5. doi:10.1016/j.gene.2005.12.008. PMID 16507339.
  28. ^ Vinarová E, Vinar O, Zvolský P (July 1977). "Predictors of prophylactic lithium response". Activitas Nervosa Superior. 19 Suppl 2: 384–5. PMID 551674.
  29. ^ Lee FJ, Lin LW, Smith JA (November 1989). "N alpha acetylation is required for normal growth and mating of Saccharomyces cerevisiae". Journal of Bacteriology. 171 (11): 5795–802. doi:10.1128/jb.171.11.5795-5802.1989. PMC 210438. PMID 2681143.
  30. ^ 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.
  31. ^ Forte GM, Pool MR, Stirling CJ (May 2011). "N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum". PLOS Biology. 9 (5): e1001073. doi:10.1371/journal.pbio.1001073. PMC 3104963. PMID 21655302.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  32. ^ Pool MR, Stumm J, Fulga TA, Sinning I, Dobberstein B (23 August 2002). "Distinct modes of signal recognition particle interaction with the ribosome". Science. 297 (5585): 1345–8. Bibcode:2002Sci...297.1345P. doi:10.1126/science.1072366. PMID 12193787.
  33. ^ Wegrzyn RD, Hofmann D, Merz F, Nikolay R, Rauch T, Graf C, Deuerling E (3 February 2006). "A conserved motif is prerequisite for the interaction of NAC with ribosomal protein L23 and nascent chains". The Journal of Biological Chemistry. 281 (5): 2847–57. doi:10.1074/jbc.m511420200. PMID 16316984.
  34. ^ Pech M, Spreter T, Beckmann R, Beatrix B (18 June 2010). "Dual binding mode of the nascent polypeptide-associated complex reveals a novel universal adapter site on the ribosome". The Journal of Biological Chemistry. 285 (25): 19679–87. doi:10.1074/jbc.m109.092536. PMC 2885246. PMID 20410297.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  35. ^ Zhang Y, Berndt U, Gölz H, Tais A, Oellerer S, Wölfle T, Fitzke E, Rospert S (August 2012). "NAC functions as a modulator of SRP during the early steps of protein targeting to the endoplasmic reticulum". Molecular Biology of the Cell. 23 (16): 3027–40. doi:10.1091/mbc.e12-02-0112. PMC 3418300. PMID 22740632.
  36. ^ Gendron RL, Good WV, Miskiewicz E, Tucker S, Phelps DL, Paradis H (22 February 2006). "Tubedown-1 (Tbdn-1) suppression in oxygen-induced retinopathy and in retinopathy of prematurity". Molecular Vision. 12: 108–16. PMID 16518308.
  37. ^ Gendron RL, Laver NV, Good WV, Grossniklaus HE, Miskiewicz E, Whelan MA, Walker J, Paradis H (October 2010). "Loss of tubedown expression as a contributing factor in the development of age-related retinopathy". Investigative Ophthalmology & Visual Science. 51 (10): 5267–77. doi:10.1167/iovs.09-4527. PMID 20463314.
  38. ^ a b Paradis H, Islam T, Tucker S, Tao L, Koubi S, Gendron RL (15 June 2008). "Tubedown associates with cortactin and controls permeability of retinal endothelial cells to albumin". Journal of Cell Science. 121 (Pt 12): 1965–72. doi:10.1242/jcs.028597. PMID 18495841.
  39. ^ Martin DT, Gendron RL, Jarzembowski JA, Perry A, Collins MH, Pushpanathan C, Miskiewicz E, Castle VP, Paradis H (1 March 2007). "Tubedown expression correlates with the differentiation status and aggressiveness of neuroblastic tumors". Clinical Cancer Research. 13 (5): 1480–7. doi:10.1158/1078-0432.ccr-06-1716. PMID 17332292.
  40. ^ Sugiura N, Patel RG, Corriveau RA (27 April 2001). "N-methyl-D-aspartate receptors regulate a group of transiently expressed genes in the developing brain". The Journal of Biological Chemistry. 276 (17): 14257–63. doi:10.1074/jbc.M100011200. PMID 11297529.
  41. ^ Wang N, Gray GR (5 March 1997). "Reductive cleavage of permethylated polysaccharides with borane-methyl sulfide complex and butyltin trichloride". Carbohydrate Research. 298 (3): 131–7. doi:10.1016/s0008-6215(96)00312-6. PMID 9090811.
  42. ^ Arnesen T, Gromyko D, Pendino F, Ryningen A, Varhaug JE, Lillehaug JR (20 July 2006). "Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-alpha-acetyltransferase complex". Oncogene. 25 (31): 4350–60. doi:10.1038/sj.onc.1209469. PMID 16518407.
  43. ^ Zaidi S, Choi M, Wakimoto H, Ma L, Jiang J, Overton JD, Romano-Adesman A, Bjornson RD, Breitbart RE, Brown KK, Carriero NJ, Cheung YH, Deanfield J, DePalma S, Fakhro KA, Glessner J, Hakonarson H, Italia MJ, Kaltman JR, Kaski J, Kim R, Kline JK, Lee T, Leipzig J, Lopez A, Mane SM, Mitchell LE, Newburger JW, Parfenov M, Pe'er I, Porter G, Roberts AE, Sachidanandam R, Sanders SJ, Seiden HS, State MW, Subramanian S, Tikhonova IR, Wang W, Warburton D, White PS, Williams IA, Zhao H, Seidman JG, Brueckner M, Chung WK, Gelb BD, Goldmuntz E, Seidman CE, Lifton RP (13 June 2013). "De novo mutations in histone-modifying genes in congenital heart disease". Nature. 498 (7453): 220–3. Bibcode:2013Natur.498..220Z. doi:10.1038/nature12141. PMC 3706629. PMID 23665959.

Further reading

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