InterPro domain: IPR044034

In eukaryotes, the Nascent polypeptide-Associated Complex (NAC) is a heterodimeric cytosolic protein complex composed of alpha and beta subunits. NAC binds reversibly to the ribosome where it is in contact with nascent chains as they emerge from the ribosome and protects them against inappropriate interaction with cytosolic factors. However, the cellular function of NAC seems to be much more diverse as it is also involved in transcription regulation and mitochondrial translocation [ 1 ]. Alpha and beta NACs share homology with each other, both contain a NAC A/B domain, responsible for the complex dimerisation. In archaea no beta NAC proteins are found; the complex is an homodimer of NAC alpha [ 2 , 3 ]. These proteins have an additional ubiquitin-associated (UBA) domain which suggests the involvement of NAC in the cellular protein quality control system via the ubiquitination pathway [ 4 ].

This entry represents the UBA domain found at the C-terminal of the Nascent polypeptide-Associated Complex (NAC) subunit alpha. This domain is also found in HYPK (Huntingtin-interacting protein K) in which mediates a constitutively protein interaction with Naa15 auxiliary subunit from N-terminal acetyltransferase NatA. NatA associates with the ribosome and nascent polypeptides, suggesting that HYPK also interacts with these polypeptides possibly to facilitate Nt-acetylation fidelity [ 4 ].

1. Nascent-polypeptide-associated complex. Cell. Mol. Life Sci. 59, 1632-9
2. Comparative genomics of the Archaea (Euryarchaeota): evolution of conserved protein families, the stable core, and the variable shell. Genome Res. 9, 608-28
3. The crystal structure of archaeal nascent polypeptide-associated complex (NAC) reveals a unique fold and the presence of a ubiquitin-associated domain. J. Biol. Chem. 280, 15849-54
4. Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK. Structure 26, 925-935.e8