N-alpha-acetyltransferase 10

Definition:

Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity. Acetylates amino termini that are devoid of initiator methionine. The alpha (N-terminal) acetyltransferase activity may be important for vascular, hematopoietic and neuronal growth and development. Without NAA15, displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation. Represses MYLK kinase activity by acetylation, and thus represses tumor cell migration. Acetylates, and stabilizes TSC2, thereby repressing mTOR activity and suppressing cancer development. Acetylates HSPA1A and HSPA1B at 'Lys-77' which enhances its chaperone activity and leads to preferential binding to co-chaperone HOPX. Acetylates HIST1H4A. Acts as a negative regulator of sister chromatid cohesion during mitosis.

References:

[1]. Joo Won Jeong, et al. Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell. 2002 Nov 27;111(5):709-20. [Content Brief]

[2]. Sunbin Deng, et al. Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK. Nat Commun. 2020 Feb 10;11(1):818. [Content Brief]

[3]. Ji Hae Seo, et al. ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation. Nat Commun. 2016 Oct 6;7:12882. [Content Brief]

[4]. Hsu-Ping Kuo, et al. ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway. Sci Signal. 2010 Feb 9;3(108):ra9. [Content Brief]

[5]. Dong Hoon Shin, et al. Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase. PLoS One. 2009 Oct 14;4(10):e7451. [Content Brief]

[6]. Leah Gottlieb, et al. Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK. Structure. 2018 Jul 3;26(7):925-935.e8. [Content Brief]

[7]. Thomas Arnesen, et al. Identification and characterization of the human ARD1-NATH protein acetyltransferase complex. Biochem J. 2005 Mar 15;386(Pt 3):433-43. [Content Brief]

[8]. Line M Myklebust, et al. Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects. Hum Mol Genet. 2015 Apr 1;24(7):1956-76. [Content Brief]

[9]. Ziye Rong, et al. Opposing Functions of the N-terminal Acetyltransferases Naa50 and NatA in Sister-chromatid Cohesion. J Biol Chem. 2016 Sep 2;291(36):19079-91. [Content Brief]

[10]. Thomas Arnesen, et al. The chaperone-like protein HYPK acts together with NatA in cotranslational N-terminal acetylation and prevention of Huntingtin aggregation. Mol Cell Biol. 2010 Apr;30(8):1898-909. [Content Brief]

[11]. Thomas Arnesen, et al. Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8157-62. [Content Brief]

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