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Composition and biological significance of the human Nalpha-terminal acetyltransferases.

Starheim KK, Gromyko D, Velde R, Varhaug JE, Arnesen T - BMC Proc (2009)

Bottom Line: Still, little is known about the functional role of Nalpha-terminal acetylation.Recently, the three major human N-acetyltransferase complexes, hNatA, hNatB and hNatC, were identified and characterized.We here summarize the identified N-terminal acetyltransferase complexes in humans, and we review the biological studies on Nalpha-terminal acetylation in humans and other higher eukaryotes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway. Kristian.Starheim@mbi.uib.no

ABSTRACT
Protein Nalpha-terminal acetylation is one of the most common protein modifications in eukaryotic cells, occurring on approximately 80% of soluble human proteins. An increasing number of studies links Nalpha-terminal acetylation to cell differentiation, cell cycle, cell survival, and cancer. Thus, Nalpha-terminal acetylation is an essential modification for normal cell function in humans. Still, little is known about the functional role of Nalpha-terminal acetylation. Recently, the three major human N-acetyltransferase complexes, hNatA, hNatB and hNatC, were identified and characterized. We here summarize the identified N-terminal acetyltransferase complexes in humans, and we review the biological studies on Nalpha-terminal acetylation in humans and other higher eukaryotes.

No MeSH data available.


Related in: MedlinePlus

Composition of the four different hNatA complexes. The hNatA subunits hNaa10p, hNaa11p, hNaa15p and hNaa16p can combine to form four variants of the hNatA complex. All subunits tested bind to ribosomes (hNaa11p not tested yet), suggesting that all four variants can acetylate nascent polypeptides (e.g polypeptide with an N-terminal Serine) co-translationally. The gradient illustrates the expected abundance of the various complexes. Based on EST data and immunoprecipitation experiments [21], hNaa10p-hNaa15p forms the most abundant version of the complex, displaying a stochiometric relationship of 6:1 compared to the hNaa10p-hNaa16p complex in HEK293 cells. The hNaa11p-hNaa15p and hNaa11p-hNaa16p complexes are probably present to an even lesser extent in most tissues, except for tissues like testis, where hNaa11p is upregulated. In the lower part of the figure it is indicated which experimental data that forms the evidence of the complex formations. IP, immunoprecipitation; MS, Mass Spectrometry; WB, Western Blotting.
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Figure 1: Composition of the four different hNatA complexes. The hNatA subunits hNaa10p, hNaa11p, hNaa15p and hNaa16p can combine to form four variants of the hNatA complex. All subunits tested bind to ribosomes (hNaa11p not tested yet), suggesting that all four variants can acetylate nascent polypeptides (e.g polypeptide with an N-terminal Serine) co-translationally. The gradient illustrates the expected abundance of the various complexes. Based on EST data and immunoprecipitation experiments [21], hNaa10p-hNaa15p forms the most abundant version of the complex, displaying a stochiometric relationship of 6:1 compared to the hNaa10p-hNaa16p complex in HEK293 cells. The hNaa11p-hNaa15p and hNaa11p-hNaa16p complexes are probably present to an even lesser extent in most tissues, except for tissues like testis, where hNaa11p is upregulated. In the lower part of the figure it is indicated which experimental data that forms the evidence of the complex formations. IP, immunoprecipitation; MS, Mass Spectrometry; WB, Western Blotting.

Mentions: The hNatA complex is conserved from yeast with respect to subunit homology [1] and substrate specificity [9]. The most characterized human hNatA complex consists of the catalytic subunit hNaa10p (hArd1), and the auxiliary subunit hNaa15p (NATH/hNat1) [1,2,10]. They are orthologues of the yeast NatA components yNaa10p and yNaa15p. Both hNaa10p and hNaa15p are associated with ribosomes, suggesting a model where hNatA performs co-translational acetylation of nascent polypeptides [1]. Interestingly, a significant portion of hNaa10p and hNaa15p is also found to be non-ribosomal. Paralogues of hNaa10p, hNaa11p (hArd2), and of hNaa15p, hNaa16p (hNat2), have been suggested to participate in functional hNatA complexes [11,12]. This allows for four possible hNatA complexes, resulting in a more complex subunit composition in humans as compared to yeast (Figure 1). Based on expression sequence tag data (EST) from UniGene Cluster, and experimental evidence [12], we here describe hNaa10p and hNaa15p as components of the abundant form of the hNatA complex, and hNat11p and hNat16p as alternative and less abundant subunits in the hNatA complex (Figure 1).


Composition and biological significance of the human Nalpha-terminal acetyltransferases.

Starheim KK, Gromyko D, Velde R, Varhaug JE, Arnesen T - BMC Proc (2009)

Composition of the four different hNatA complexes. The hNatA subunits hNaa10p, hNaa11p, hNaa15p and hNaa16p can combine to form four variants of the hNatA complex. All subunits tested bind to ribosomes (hNaa11p not tested yet), suggesting that all four variants can acetylate nascent polypeptides (e.g polypeptide with an N-terminal Serine) co-translationally. The gradient illustrates the expected abundance of the various complexes. Based on EST data and immunoprecipitation experiments [21], hNaa10p-hNaa15p forms the most abundant version of the complex, displaying a stochiometric relationship of 6:1 compared to the hNaa10p-hNaa16p complex in HEK293 cells. The hNaa11p-hNaa15p and hNaa11p-hNaa16p complexes are probably present to an even lesser extent in most tissues, except for tissues like testis, where hNaa11p is upregulated. In the lower part of the figure it is indicated which experimental data that forms the evidence of the complex formations. IP, immunoprecipitation; MS, Mass Spectrometry; WB, Western Blotting.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2722096&req=5

Figure 1: Composition of the four different hNatA complexes. The hNatA subunits hNaa10p, hNaa11p, hNaa15p and hNaa16p can combine to form four variants of the hNatA complex. All subunits tested bind to ribosomes (hNaa11p not tested yet), suggesting that all four variants can acetylate nascent polypeptides (e.g polypeptide with an N-terminal Serine) co-translationally. The gradient illustrates the expected abundance of the various complexes. Based on EST data and immunoprecipitation experiments [21], hNaa10p-hNaa15p forms the most abundant version of the complex, displaying a stochiometric relationship of 6:1 compared to the hNaa10p-hNaa16p complex in HEK293 cells. The hNaa11p-hNaa15p and hNaa11p-hNaa16p complexes are probably present to an even lesser extent in most tissues, except for tissues like testis, where hNaa11p is upregulated. In the lower part of the figure it is indicated which experimental data that forms the evidence of the complex formations. IP, immunoprecipitation; MS, Mass Spectrometry; WB, Western Blotting.
Mentions: The hNatA complex is conserved from yeast with respect to subunit homology [1] and substrate specificity [9]. The most characterized human hNatA complex consists of the catalytic subunit hNaa10p (hArd1), and the auxiliary subunit hNaa15p (NATH/hNat1) [1,2,10]. They are orthologues of the yeast NatA components yNaa10p and yNaa15p. Both hNaa10p and hNaa15p are associated with ribosomes, suggesting a model where hNatA performs co-translational acetylation of nascent polypeptides [1]. Interestingly, a significant portion of hNaa10p and hNaa15p is also found to be non-ribosomal. Paralogues of hNaa10p, hNaa11p (hArd2), and of hNaa15p, hNaa16p (hNat2), have been suggested to participate in functional hNatA complexes [11,12]. This allows for four possible hNatA complexes, resulting in a more complex subunit composition in humans as compared to yeast (Figure 1). Based on expression sequence tag data (EST) from UniGene Cluster, and experimental evidence [12], we here describe hNaa10p and hNaa15p as components of the abundant form of the hNatA complex, and hNat11p and hNat16p as alternative and less abundant subunits in the hNatA complex (Figure 1).

Bottom Line: Still, little is known about the functional role of Nalpha-terminal acetylation.Recently, the three major human N-acetyltransferase complexes, hNatA, hNatB and hNatC, were identified and characterized.We here summarize the identified N-terminal acetyltransferase complexes in humans, and we review the biological studies on Nalpha-terminal acetylation in humans and other higher eukaryotes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway. Kristian.Starheim@mbi.uib.no

ABSTRACT
Protein Nalpha-terminal acetylation is one of the most common protein modifications in eukaryotic cells, occurring on approximately 80% of soluble human proteins. An increasing number of studies links Nalpha-terminal acetylation to cell differentiation, cell cycle, cell survival, and cancer. Thus, Nalpha-terminal acetylation is an essential modification for normal cell function in humans. Still, little is known about the functional role of Nalpha-terminal acetylation. Recently, the three major human N-acetyltransferase complexes, hNatA, hNatB and hNatC, were identified and characterized. We here summarize the identified N-terminal acetyltransferase complexes in humans, and we review the biological studies on Nalpha-terminal acetylation in humans and other higher eukaryotes.

No MeSH data available.


Related in: MedlinePlus