NAA15 (N-alpha-acetyltransferase 15, NatA auxiliary subunit; also NARG1, NATH, Tubedown-1) is the large, non-catalytic auxiliary subunit of the NatA N-terminal acetyltransferase complex. It dimerizes with the catalytic subunit NAA10, where its TPR-repeat-rich solenoid wraps around NAA10, anchoring the complex to the ribosome near the exit tunnel and orienting nascent polypeptide N-termini for co-translational acetylation. NAA15 itself has no acetyltransferase catalytic activity; rather it activates and confers ribosomal targeting and substrate specificity on NAA10, and is required for NatA-type N-terminal acetylation in vivo. It also serves as the scaffold for the NatA-associated factors HYPK and NAA50 (forming NatE). NAA15 is predominantly cytoplasmic with a nuclear pool, and a nuclear NAA15-containing complex with the Ku70/Ku80 (XRCC6/ XRCC5) heterodimer has been reported to up-regulate transcription from the osteocalcin promoter. NAA15 (as Tubedown-1) has additional reported roles in endothelial/retinal vascular biology, and NAA15 variants are associated with neurodevelopmental and congenital heart phenotypes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0010698 acetyltransferase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: NAA15 is the auxiliary subunit that activates the NAA10 catalytic subunit and confers N-terminal substrate specificity; this activator MF captures its non-catalytic role precisely. Reason: NAA15 has no catalytic activity itself but is required to activate and direct NAA10 NatA-type acetylation; activator activity is the correct, informative MF. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity |
| GO:0031415 NatA complex | IBA GO_REF:0000033 | ACCEPT | Summary: NAA15 is a defining component of the NatA complex (NAA10-NAA15). Reason: Core complex membership; NAA15 is one of the two NatA subunits. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation of nuclear localization, consistent with the documented nuclear pool of NAA15. Reason: Nuclear pool is documented but the core NatA function is cytoplasmic/ ribosome-associated; nuclear localization kept non-core. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. Nucleus. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation of cytoplasmic localization, the principal site of NatA action. Reason: Cytoplasm is where ribosome-associated NatA acts; well supported. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. Nucleus. |
| GO:0031415 NatA complex | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic (ARBA) annotation of NatA complex membership, consistent with experimental evidence. Reason: Core complex membership; redundant with IBA/IDA NatA annotations. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15 |
| GO:0043022 ribosome binding | IEA GO_REF:0000117 | ACCEPT | Summary: NAA15 anchors the NatA complex to the ribosome, a core auxiliary function enabling co-translational acetylation. Reason: Ribosome binding/anchoring is a documented core function of NAA15. Supporting Evidence: PMID:15496142 NATH and hARD1 interact with ribosomal subunits, indicating a co-translational acetyltransferase function PMID:19480662 hNaa15p (hNat1) and hNaa10p (hArd1) were demonstrated to form a stable ribosome associated NAT complex |
| GO:0005515 protein binding | IPI PMID:15496142 Identification and characterization of the human ARD1-NATH p... | REMOVE | Summary: IntAct interaction with NAA10 (P41227), the catalytic NatA subunit. Generic protein binding term recording the central NatA dimer. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:16507339 Cloning and characterization of hNAT5/hSAN: an evolutionaril... | REMOVE | Summary: IntAct interaction with NAA50 (Q9GZZ1), the NatE catalytic subunit that docks onto NatA via NAA15. Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:16638120 Characterization of hARD2, a processed hARD1 gene duplicate,... | REMOVE | Summary: IntAct interaction with NAA11 (Q9BSU3), the NAA10 paralog that can also partner NAA15. Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:19480662 A novel human NatA Nalpha-terminal acetyltransferase complex... | REMOVE | Summary: IntAct interaction with NAA10 (P41227). Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: IntAct interaction with HYPK (Q9NX55), the NatA-associated chaperone/ regulator. Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IntAct interactions with NatA-related partners (NAA10 P41227, NAA50 Q9GZZ1, HYPK Q9NX55). Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IntAct interaction with HYPK (Q9NX55). Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex interactome capturing NatA-related partners (NAA10, NAA11, NAA50, HYPK). Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Multimodal cell-maps interactome capturing NatA-related partners (NAA10, NAA50, HYPK). Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence (HPA) cytosolic localization, consistent with ribosome-associated NatA function. Reason: Cytosol is the principal site of NatA action. Experimental data place NAA15 in the cytoplasm on free cytosolic polysomes. Supporting Evidence: PMID:15496142 NATH is localized in the cytoplasm file:human/NAA15/NAA15-uniprot.txt Present in the free cytosolic and cytoskeleton-bound polysomes, but not in the membrane-bound polysomes. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | UNDECIDED | Summary: HPA immunofluorescence placing a NAA15 pool in nuclear bodies; a specialized localization not central to NatA function. Reason: Documented but specialized localization; non-core relative to cytoplasmic NatA activity. Previously KEEP_AS_NON_CORE; set to UNDECIDED because the only cited support was the GOA row for this annotation, which records the annotation rather than evidence for it. |
| GO:0051604 protein maturation | IDA PMID:15496142 Identification and characterization of the human ARD1-NATH p... | KEEP AS NON CORE | Summary: As part of NatA, NAA15 participates in co-translational protein maturation (N-terminal acetylation); a broad downstream BP. Reason: Maturation is a downstream process of NatA activity; non-core relative to the activator/ribosome-binding MF. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity |
| GO:0005737 cytoplasm | IDA PMID:15496142 Identification and characterization of the human ARD1-NATH p... | ACCEPT | Summary: Direct cytoplasmic localization (ComplexPortal NatA). Reason: Core localization for NatA function. Supporting Evidence: PMID:15496142 NATH is localized in the cytoplasm |
| GO:0005737 cytoplasm | NAS PMID:16638120 Characterization of hARD2, a processed hARD1 gene duplicate,... | ACCEPT | Summary: Non-traceable author statement of cytoplasmic localization, consistent with the core localization. Reason: Consistent with well-supported cytoplasmic localization of NatA. The cited paper's own sentence on the cytoplasm concerns NATH's partner hARD2, so the support quoted is the direct localization of NATH from PMID:12140756. Supporting Evidence: PMID:12140756 Recombinant in vitro expression showed that NATH protein was located mainly in the cytoplasm |
| GO:0031415 NatA complex | IPI PMID:15496142 Identification and characterization of the human ARD1-NATH p... | ACCEPT | Summary: Direct evidence for NatA complex membership (NAA10-NAA15). Reason: Core complex membership. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15 |
| GO:0031415 NatA complex | IPI PMID:16638120 Characterization of hARD2, a processed hARD1 gene duplicate,... | ACCEPT | Summary: Direct evidence for NatA complex membership. Reason: Core complex membership. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15 |
| GO:0005515 protein binding | IPI PMID:25489052 Biochemical and cellular analysis of Ogden syndrome reveals ... | REMOVE | Summary: IntAct interaction with NAA10 (P41227), the catalytic NatA subunit. Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | REMOVE | Summary: IntAct interaction (Q9ULZ3) from a high-throughput study. Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Membrane localization from a high-throughput membrane proteome dataset; inconsistent with NAA15's soluble cytoplasmic/ribosome-associated function. Reason: HDA membrane-proteome hit; likely reflects co-purification rather than a genuine integral-membrane localization. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. file:human/NAA15/NAA15-uniprot.txt Present in the free cytosolic and cytoskeleton-bound polysomes, but not in the membrane-bound polysomes. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: RNA binding from a high-throughput mRNA-interactome capture; plausibly reflects ribosome/rRNA proximity rather than a sequence-specific RNA-binding function. Reason: HDA RNA-interactome hit without a defined RNA-binding role; likely an artifact of ribosome association, not a core function. Supporting Evidence: PMID:22658674 We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria |
| GO:0031415 NatA complex | IDA PMID:15496142 Identification and characterization of the human ARD1-NATH p... | ACCEPT | Summary: Direct evidence for NatA complex membership. Reason: Core complex membership. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15 |
| GO:0043022 ribosome binding | IDA PMID:19480662 A novel human NatA Nalpha-terminal acetyltransferase complex... | ACCEPT | Summary: Direct evidence that NAA15 binds the ribosome, anchoring NatA for co-translational acetylation. This is the core auxiliary MF. Reason: Ribosome binding/anchoring is the defining non-catalytic function of NAA15. Supporting Evidence: PMID:19480662 hNaa15p (hNat1) and hNaa10p (hArd1) were demonstrated to form a stable ribosome associated NAT complex PMID:19480662 Analyses of isolated polysomes demonstrated that hNaa16p-FLAG, as well as hNaa15p and hNaa10p, were both present in the polysomal and the soluble fractions |
| GO:0005737 cytoplasm | IDA PMID:12140756 NATH, a novel gene overexpressed in papillary thyroid carcin... | ACCEPT | Summary: Direct cytoplasmic localization of NAA15. Reason: Core localization for NatA function. Supporting Evidence: PMID:12140756 Recombinant in vitro expression showed that NATH protein was located mainly in the cytoplasm |
| GO:0016407 acetyltransferase activity | IDA PMID:15496142 Identification and characterization of the human ARD1-NATH p... | MARK AS OVER ANNOTATED | Summary: NAA15 contributes (as auxiliary subunit) to the acetyltransferase activity of the NatA complex, but is not itself catalytic. The generic acetyltransferase MF risks implying catalysis by NAA15. Reason: NAA15 is non-catalytic; catalysis is performed by NAA10. The contributes_to qualifier is technically defensible but the bare acetyltransferase MF over-attributes catalytic activity to the auxiliary subunit. Its activator role is better captured by GO:0010698. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity |
| GO:0043022 ribosome binding | IDA PMID:15496142 Identification and characterization of the human ARD1-NATH p... | ACCEPT | Summary: Direct evidence that NAA15 contributes ribosome binding to the NatA complex; core auxiliary MF. Reason: Ribosome anchoring is a defining function of NAA15. Supporting Evidence: PMID:15496142 NATH and hARD1 interact with ribosomal subunits, indicating a co-translational acetyltransferase function |
| GO:0005515 protein binding | IPI PMID:12145306 Regulation of osteocalcin gene expression by a novel Ku anti... | REMOVE | Summary: IntAct interactions with XRCC6/Ku70 (P12956) and XRCC5/Ku80 (P13010), the basis of the reported nuclear transcription-regulatory complex. Generic protein binding term. Reason: Bare GO:0005515 protein binding carries no functional information, so under the generic protein-binding policy this row is REMOVE. Removal does not mean the reported interaction is false; the summary and any supporting text keep it on record. |
| GO:0005634 nucleus | IDA PMID:12140756 NATH, a novel gene overexpressed in papillary thyroid carcin... | KEEP AS NON CORE | Summary: Direct nuclear localization of NAA15. Reason: Documented nuclear pool; non-core relative to cytoplasmic NatA function. The abstract reports a mainly (not exclusively) cytoplasmic localization; the nuclear call defers to the curator who read the full text, and UniProt notes a nuclear pool. Supporting Evidence: PMID:12140756 Recombinant in vitro expression showed that NATH protein was located mainly in the cytoplasm file:human/NAA15/NAA15-uniprot.txt Note=Mainly cytoplasmic, nuclear in some cases. |
| GO:0005634 nucleus | IDA PMID:12145306 Regulation of osteocalcin gene expression by a novel Ku anti... | KEEP AS NON CORE | Summary: Direct nuclear localization in the context of the Ku70/Ku80 transcription complex. Reason: Documented nuclear pool; specialized and non-core. Promoter association of the Tbdn100 (NAA15 variant) complex implies a nuclear pool; the IDA defers to the curator who read the full text. Supporting Evidence: PMID:12145306 chromatin immunoprecipitation assays confirm association of Ku and Tbdn100 with the endogenous OC promoter |
| GO:0005667 transcription regulator complex | IDA PMID:12145306 Regulation of osteocalcin gene expression by a novel Ku anti... | KEEP AS NON CORE | Summary: NAA15 reported in a nuclear complex with XRCC6/XRCC5 that up-regulates the osteocalcin promoter; a specialized moonlighting context. Reason: A documented but specialized nuclear role distinct from the core cytoplasmic NatA auxiliary function. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:12145306 Regulation of osteocalcin gene expression by a novel Ku anti... | KEEP AS NON CORE | Summary: NAA15 (with Ku70/Ku80) positively regulates osteocalcin-promoter transcription; a specialized moonlighting role. Reason: Documented but specialized; not the core NatA auxiliary function. Supporting Evidence: file:human/NAA15/NAA15-uniprot.txt In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter |
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Download this section (compressed HTML)Q: Is the nuclear NAA15-Ku70/Ku80 transcription-regulatory role a genuine NatA-independent moonlighting function, or a consequence of NatA-dependent acetylation of nuclear substrates?
Q: How do NAA15 neurodevelopmental/congenital-heart-disease variants impair NatA assembly, NAA10 activation, and ribosome anchoring?
Experiment: Reconstitute NatA from purified NAA10 and NAA15 variants and measure N-terminal acetyltransferase activity and ribosome binding to map the NAA15 surfaces required for NAA10 activation versus ribosome anchoring.
Experiment: N-terminal acetylome profiling after NAA15 depletion to confirm that loss of the auxiliary subunit abolishes NatA-type (Ser/Ala/Thr/Gly/Cys) acetylation in cells.
Experiment: Test whether the Tubedown-1/endothelial vascular phenotypes depend on NatA catalytic activity by rescue with acetyltransferase-dead NAA10.
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