| Category | Summary | Key specifics/examples | Evidence |
|---|---|---|---|
| Gene/protein identity | Human **NAA30** (also called **MAK3**, **NAT12**) is the **catalytic subunit** of the **NatC N-terminal acetyltransferase complex**. It belongs to the GNAT-family acetyltransferases and functions in co-translational protein N-terminal acetylation. | NatC is conserved from yeast to human; human NAA30 can functionally replace yeast Mak3/Naa30 in complementation assays. | (pqac-00000002, pqac-00000004, pqac-00000014) |
| Enzymatic reaction | NAA30 catalyzes transfer of an **acetyl group from acetyl-CoA** to the **free α-amino group at the protein N-terminus** of nascent substrates. | Reaction: **protein N-terminus + acetyl-CoA → N-acetyl-protein + CoA**; modification is generally considered irreversible. | (pqac-00000000, pqac-00000004, pqac-00000014) |
| NatC complex composition | NatC is a **heterotrimeric complex** composed of **NAA30** (catalytic), **NAA35** (large auxiliary/ribosome-anchoring subunit), and **NAA38** (small auxiliary subunit). | Structural work shows NAA30 adopts the GNAT fold; NAA35 and NAA38 stabilize the complex; NAA38 broadens substrate specificity and increases thermostability. | (pqac-00000000, pqac-00000003, pqac-00000005, pqac-00000010) |
| Substrate specificity: general rule | NatC acetylates proteins that **retain the initiator methionine** and usually have a **hydrophobic or amphipathic residue at position 2**. Residues at positions 3-4 also contribute to recognition. | Human NatC/NAA30 is described as modifying Met-starting proteins not targeted by NatB. Structural studies indicate the first four substrate residues contribute to recognition. | (pqac-00000000, pqac-00000003, pqac-00000005, pqac-00000006) |
| Substrate specificity: canonical human sequences | Canonical human NatC-type N-termini include **ML, MI, MF, MW** and expanded in vivo classes include **MV, MH, MK, MM**. | The 2016 human N-terminomics study identified 46 direct/likely human NatC substrates and expanded specificity beyond the classic ML/MI/MF/MW set. | (pqac-00000004, pqac-00000018) |
| Substrate specificity: broader recent view | Recent reviews also summarize human NatC substrates as including **ML, MI, MF, MV, MY, MW, MH, MK**; yeast work shows overlap and some redundancy with NatE/Naa50 for certain methionine-starting N-termini. | This indicates NatC specificity is broader than originally appreciated, though not every compatible N-terminus is fully acetylated in vivo. | (pqac-00000005, pqac-00000017) |
| Acetylation coverage and scale | NatC is one of the major human NATs and, together with NatE/F, covers a substantial subset of methionine-retaining proteins; human cells showed **46** NAA30-dependent substrates and yeast **57** NatC substrates in proteome-scale analyses. | NatC-type proteins are often only **partially acetylated** across the cellular protein pool, unlike many NatB substrates. | (pqac-00000005, pqac-00000017, pqac-00000018) |
| Known substrate examples: trafficking proteins | NAA30/NatC acetylates proteins involved in membrane trafficking and organelle targeting. | **ARL8B/hArl8b** is a validated human NatC substrate important for lysosomal localization; **ARFRP1/Arl3** localization to Golgi depends on NatC-mediated N-terminal acetylation and interaction with **SYS1**. | (pqac-00000004, pqac-00000006, pqac-00000007, pqac-00000011) |
| Known substrate examples: neddylation pathway | NatC-mediated acetylation is important for the cullin neddylation machinery. | **UBE2M/UBC12** and **UBE2F** are particularly important NatC-relevant targets; their N-terminal acetylation promotes stability and productive interaction with cognate E3 ligases such as **DCN1**. | (pqac-00000006, pqac-00000015) |
| Known substrate examples: mitochondrial/organellar proteins | Proteomics and phenotype analyses indicate that multiple mitochondrial or organellar proteins are directly or indirectly affected by NAA30 loss. | Human NAA30 depletion reduced levels of several mitochondrial proteins; some were identified among NatC substrates in organellar fractions. | (pqac-00000004, pqac-00000018) |
| Subcellular localization of function | NAA30 primarily functions as a **ribosome-associated, co-translational enzyme** in the cytosol as part of NatC. | Human NatC subunits co-sediment with ribosomes; structural work identified a ribosome-binding patch in NatC. A truncated/splice-associated nuclear NAA30 isoform has also been reported in some cancer contexts. | (pqac-00000000, pqac-00000004, pqac-00000010) |
| Pathway/process: protein quality control | A major current model is that NatC-mediated N-terminal acetylation **shields hydrophobic Met-starting proteins from degradation** by the Arg/N-degron pathway. | Unacetylated NatC-type N-termini are recognized by **UBR4-KCMF1**, **UBR1**, and **UBR2**; NatC knockout phenotypes can be reversed by disrupting these ubiquitin ligases. | (pqac-00000006, pqac-00000015, pqac-00000016) |
| Pathway/process: Golgi and vesicle trafficking | NatC is linked to **Golgi vesicle transport**, endosomal transport, and secretory pathway organization. | CRISPR genetic interaction screens in human cells found negative interactions with **ARL1, ARFRP1, SYS1, RAB1A/B, RAB2A, RAB14, COG5, COG7** and enrichment for Golgi vesicle transport pathways. | (pqac-00000011, pqac-00000016) |
| Pathway/process: mitochondrial integrity | NatC/NAA30 supports **mitochondrial membrane potential, morphology, and likely import/biogenesis of selected proteins**. | NAA30 knockdown caused **mitochondrial fragmentation** and **loss of membrane potential**; yeast and comparative analyses suggest mitochondrial targeting sequences are enriched for NatC-compatible residue patterns. | (pqac-00000004, pqac-00000012, pqac-00000015, pqac-00000017) |
| Pathway/process: cell survival and proliferation | NAA30 contributes to **cell growth and survival**. | Knockdown of NAA30 stabilizes **p53** and induces apoptosis; in glioblastoma-initiating cells, NAA30 knockdown reduces viability, sphere formation, and hypoxia tolerance. | (pqac-00000000, pqac-00000005, pqac-00000015) |
| Disease/cancer relevance | NAA30 is increasingly implicated in cancer biology, especially glioblastoma, and NAT dysregulation more broadly is disease-relevant. | NAA30 protein upregulation has been reported in glioblastoma; orthotopic xenograft studies found longer survival in mice receiving NAA30-knockdown glioblastoma cells. | (pqac-00000000, pqac-00000005) |
| Key phenotypes of NAA30 loss in human cells | Loss of NAA30 causes distinct cell biological defects rather than a generic collapse of all organelles. | Reported phenotypes include **mitochondrial fragmentation**, **loss of mitochondrial membrane potential**, **reduced expression of mitochondrial matrix proteins**, **Golgi fragmentation**, **reduced cell growth**, and **apoptosis**. | (pqac-00000004, pqac-00000010, pqac-00000015) |
| Key phenotypes in model organisms | NatC deficiency causes conserved organismal and stress phenotypes across species. | Yeast NatC mutants show **poor growth on non-fermentable carbon sources** and salt/stress sensitivity; Drosophila NatC loss causes **reduced longevity**, **age-dependent motility defects**, and **male sterility**; zebrafish knockout data indicate developmental defects. | (pqac-00000002, pqac-00000006, pqac-00000010, pqac-00000017) |
| Practical interpretation | The best-supported primary function of human NAA30 is **co-translational N-terminal acetylation of a methionine-retaining, largely hydrophobic-starting subset of proteins**, thereby regulating their stability, targeting, and organelle-related functions. | Particularly strong mechanistic support exists for roles in **N-degron shielding**, **Golgi/vesicle trafficking**, **cullin neddylation via UBE2M/UBE2F**, and **mitochondrial integrity**. | (pqac-00000004, pqac-00000006, pqac-00000011, pqac-00000015) |


*Table: This table summarizes the main experimentally supported properties of human NAA30 and the NatC complex, including composition, substrate rules, representative substrates, localization, pathways, and loss-of-function phenotypes. It is useful as a compact evidence map for functional annotation.*