Existing Annotations Review

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: file:human/NAA15/NAA15-goa.tsv GO:0043022 ribosome binding molecular_function IDA PMID:19480662
GO:0005515 protein binding	IPI PMID:15496142 Identification and characterization of the human ARD1-NATH p...	KEEP AS NON CORE	Summary: IntAct interaction with NAA10 (P41227), the catalytic NatA subunit. Generic protein binding term recording the central NatA dimer. Reason: Records the functionally central NAA15-NAA10 interaction; informative MF captured by complex/activator annotations. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:15496142 UniProtKB:P41227
GO:0005515 protein binding	IPI PMID:16507339 Cloning and characterization of hNAT5/hSAN: an evolutionaril...	KEEP AS NON CORE	Summary: IntAct interaction with NAA50 (Q9GZZ1), the NatE catalytic subunit that docks onto NatA via NAA15. Generic protein binding term. Reason: Real NAA50 interaction underlying NatE assembly; informative function captured elsewhere. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:16507339 UniProtKB:Q9GZZ1
GO:0005515 protein binding	IPI PMID:16638120 Characterization of hARD2, a processed hARD1 gene duplicate,...	KEEP AS NON CORE	Summary: IntAct interaction with NAA11 (Q9BSU3), the NAA10 paralog that can also partner NAA15. Generic protein binding term. Reason: Real interaction with the alternative catalytic subunit NAA11; generic MF kept non-core. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:16638120 UniProtKB:Q9BSU3
GO:0005515 protein binding	IPI PMID:19480662 A novel human NatA Nalpha-terminal acetyltransferase complex...	KEEP AS NON CORE	Summary: IntAct interaction with NAA10 (P41227). Generic protein binding term. Reason: Records the central NatA dimer interaction; generic MF kept non-core. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:19480662 UniProtKB:P41227
GO:0005515 protein binding	IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme...	KEEP AS NON CORE	Summary: IntAct interaction with HYPK (Q9NX55), the NatA-associated chaperone/ regulator. Generic protein binding term. Reason: Real HYPK interaction underlying NatA/HYPK complex formation; generic MF kept non-core. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:24981860 UniProtKB:Q9NX55
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: IntAct interactions with NatA-related partners (NAA10 P41227, NAA50 Q9GZZ1, HYPK Q9NX55). Generic protein binding term. Reason: Records real NatA-partner interactions; informative function captured elsewhere. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:28514442 UniProtKB:P41227
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: IntAct interaction with HYPK (Q9NX55). Generic protein binding term. Reason: Real HYPK interaction; generic MF kept non-core. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:32296183 UniProtKB:Q9NX55
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex interactome capturing NatA-related partners (NAA10, NAA11, NAA50, HYPK). Generic protein binding term. Reason: Records real NatA-partner interactions; informative function captured elsewhere. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:33961781 UniProtKB:P41227
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: Multimodal cell-maps interactome capturing NatA-related partners (NAA10, NAA50, HYPK). Generic protein binding term. Reason: Records real NatA-partner interactions; informative function captured elsewhere. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:40205054 UniProtKB:P41227
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. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005829 cytosol cellular_component IDA GO_REF:0000052 HPA
GO:0016604 nuclear body	IDA GO_REF:0000052	KEEP AS NON CORE	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. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0016604 nuclear body cellular_component IDA GO_REF:0000052
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: file:human/NAA15/NAA15-goa.tsv GO:0005737 cytoplasm cellular_component IDA PMID:15496142 Homo sapiens ComplexPortal
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. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005737 cytoplasm cellular_component NAS PMID:16638120
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 ...	KEEP AS NON CORE	Summary: IntAct interaction with NAA10 (P41227), the catalytic NatA subunit. Generic protein binding term. Reason: Records the central NatA dimer interaction; generic MF kept non-core. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:25489052 UniProtKB:P41227
GO:0005515 protein binding	IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-...	KEEP AS NON CORE	Summary: IntAct interaction (Q9ULZ3) from a high-throughput study. Generic protein binding term. Reason: High-throughput interaction; uninformative as core MF. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:24407287 UniProtKB:Q9ULZ3
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: file:human/NAA15/NAA15-goa.tsv GO:0016020 membrane cellular_component HDA PMID:19946888
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: file:human/NAA15/NAA15-goa.tsv GO:0003723 RNA binding molecular_function HDA PMID:22658674
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: file:human/NAA15/NAA15-goa.tsv GO:0043022 ribosome binding molecular_function IDA PMID:19480662
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: file:human/NAA15/NAA15-goa.tsv GO:0005737 cytoplasm cellular_component IDA PMID:12140756
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: file:human/NAA15/NAA15-goa.tsv GO:0043022 ribosome binding molecular_function IDA PMID:15496142
GO:0005515 protein binding	IPI PMID:12145306 Regulation of osteocalcin gene expression by a novel Ku anti...	KEEP AS NON CORE	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: Records the Ku70/Ku80 interaction underlying the osteocalcin-promoter transcription role; specialized and non-core. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005515 protein binding molecular_function IPI PMID:12145306 UniProtKB:P12956
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. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005634 nucleus cellular_component IDA PMID:12140756
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. Supporting Evidence: file:human/NAA15/NAA15-goa.tsv GO:0005634 nucleus cellular_component IDA PMID:12145306
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

Core Functions

Non-catalytic auxiliary subunit of the NatA N-terminal acetyltransferase complex that binds and activates the catalytic subunit NAA10, conferring N-terminal substrate specificity and serving as the scaffold for the NatA-associated factors HYPK and NAA50.

Molecular Function:

acetyltransferase activator activity

In Complex:

NatA complex

Supporting Evidence:

file:human/NAA15/NAA15-uniprot.txt
Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity

Anchors the NatA complex to the ribosome near the polypeptide exit tunnel, enabling co-translational N-terminal acetylation of nascent chains.

Molecular Function:

ribosome binding

Cellular Locations:

cytoplasm

Supporting Evidence:

file:human/NAA15/NAA15-goa.tsv
GO:0043022 ribosome binding molecular_function IDA PMID:19480662

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Gene Ontology annotation based on rules generated from ARBA automatic annotation

PMID:12140756

NATH, a novel gene overexpressed in papillary thyroid carcinomas.

NAA15 (Tubedown-1) is an acetyltransferase-associated protein with cytoplasmic and nuclear localization in endothelial cells.

PMID:12145306

Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex.

NAA15 forms a nuclear complex with XRCC6 (Ku70) and XRCC5 (Ku80) that up-regulates transcription from the osteocalcin promoter.

PMID:15496142

Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.

NAA15 (NATH) is the auxiliary subunit of the human NatA complex, partnering the catalytic subunit NAA10 (ARD1) and conferring ribosome association.

PMID:16507339

Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex.

NAA50 associates with NAA15 in the NatA complex.

PMID:16638120

Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-alpha-acetyltransferase.

NAA15 interacts with NAA11, an NAA10 paralog, forming an alternative NatA-type complex.

PMID:19480662

A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1).

NAA15 anchors the NatA complex to the ribosome enabling co-translational N-terminal acetylation.

PMID:19946888

Defining the membrane proteome of NK cells.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:24407287

Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation.

PMID:24981860

Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.

HYPK interacts with NAA15 within the NatA/HYPK complex.

PMID:25489052

Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects.

Crystal structure of NatA shows NAA15 wrapping around NAA10 and activating/orienting it for N-terminal acetylation.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

Suggested Experiments

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.

📚 Additional Documentation

Notes

(NAA15-notes.md)

NAA15 (Q9BXJ9) research notes

Summary

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.

Core functions (from review)

GO:0010698 acetyltransferase activator activity — Non-catalytic auxiliary subunit of the NatA N-terminal acetyltransferase complex that binds and activates the catalytic subunit NAA10, conferring N-terminal substrate specificity and serving as the scaffold for the NatA-associated factors HYPK and NAA50.
GO:0043022 ribosome binding — Anchors the NatA complex to the ribosome near the polypeptide exit tunnel, enabling co-translational N-terminal acetylation of nascent chains.

Provenance

Research and verbatim supporting quotes are recorded inline in NAA15-ai-review.yaml (per-annotation supported_by and references findings). This notes file summarizes the completed review; see the YAML for evidence citations.

Pn Notes

(NAA15-pn-notes.md)

NAA15 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9BXJ9
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-07c
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/NAA15/NAA15-ai-review.yaml
AIGR review HTML: present - genes/human/NAA15/NAA15-ai-review.html
Gene notes: present - genes/human/NAA15/NAA15-notes.md
GOA TSV: present - genes/human/NAA15/NAA15-goa.tsv
UniProt record: present - genes/human/NAA15/NAA15-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/NAA15.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/NAA15.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 14; KEEP_AS_NON_CORE: 19; MARK_AS_OVER_ANNOTATED: 3

PN Consistency Summary

Consistency: Agreement on identity and complex: review (notes, deep-research) and PN agree NAA15 is the auxiliary, non-catalytic NatA subunit — NatA complex (GO:0031415, IBA/IPI/IDA accepted) and ribosome anchoring (GO:0043022 IDA accepted) and activator activity (GO:0010698 IBA accepted). The review is careful that NAA15 is NOT catalytic (it MARK_AS_OVER_ANNOTATED'd the bare GO:0016407 acetyltransferase activity contributes_to). One tension: the PN projects the BP GO:0006474 (the acetylation process) onto NAA15; the review captures the auxiliary contribution via the activator MF (GO:0010698) and ribosome binding, not via a process term — but NAA15 "involved_in N-terminal acetylation" is defensible as process participation, so this is a soft, not hard, divergence.
PN story / NEW pressure: No NEW pressure. NatA membership and the activator/ribosome-anchoring functions are fully captured. The PN GO:0006474 process projection is broader/less specific than the review's precise non-catalytic MF framing and risks implying catalytic involvement.
Evidence alignment: PN row carries no reference titles. Review anchors on PMID:15496142, 19480662, 25489052 (VERIFIED, NatA structure/complex) plus the moonlighting Ku70/Ku80 osteocalcin role (PMID:12145306, kept non-core). No conflict.
Verdict: Consistent on complex/auxiliary identity; non-catalytic role correctly emphasized. No edits required. Caveat: prefer the activator MF (GO:0010698) over the catalytic-flavored BP GO:0006474 when describing NAA15's contribution.

Full Consistency Review

UniProt: Q9BXJ9 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
PN placement: Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatA/NatE complex component (TR only). PN-node mapping: subtype→GO:0031415 NatA complex (mapped, CC); type→GO:0006474 N-terminal protein amino acid acetylation (mapped, BP); group no_mapping; class/branch context_only.
Consistency: Agreement on identity and complex: review (notes, deep-research) and PN agree NAA15 is the auxiliary, non-catalytic NatA subunit — NatA complex (GO:0031415, IBA/IPI/IDA accepted) and ribosome anchoring (GO:0043022 IDA accepted) and activator activity (GO:0010698 IBA accepted). The review is careful that NAA15 is NOT catalytic (it MARK_AS_OVER_ANNOTATED'd the bare GO:0016407 acetyltransferase activity contributes_to). One tension: the PN projects the BP GO:0006474 (the acetylation process) onto NAA15; the review captures the auxiliary contribution via the activator MF (GO:0010698) and ribosome binding, not via a process term — but NAA15 "involved_in N-terminal acetylation" is defensible as process participation, so this is a soft, not hard, divergence.
PN story / NEW pressure: No NEW pressure. NatA membership and the activator/ribosome-anchoring functions are fully captured. The PN GO:0006474 process projection is broader/less specific than the review's precise non-catalytic MF framing and risks implying catalytic involvement.
Mapping strategy: GO:0031415 NatA complex (CC) projection is exact and appropriate for NAA15 — this is the right shared term for both NAA10 and NAA15 at the complex-component subtype. The BP GO:0006474 node mapping is fine at the type node generically, but at gene level for an auxiliary subunit it over-reaches toward catalysis; the activator MF is the more honest gene-level term.
Evidence alignment: PN row carries no reference titles. Review anchors on PMID:15496142, 19480662, 25489052 (VERIFIED, NatA structure/complex) plus the moonlighting Ku70/Ku80 osteocalcin role (PMID:12145306, kept non-core). No conflict.
Verdict: Consistent on complex/auxiliary identity; non-catalytic role correctly emphasized. No edits required. Caveat: prefer the activator MF (GO:0010698) over the catalytic-flavored BP GO:0006474 when describing NAA15's contribution.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-07c
review_yaml: genes/human/NAA15/NAA15-ai-review.yaml
PN workbook rows: 1

PN row 1: Translation | Cytosolic translation | Nascent peptide husbandry | N-terminal acetylation of nascent peptide | NatA/NatE complex component

UniProt: Q9BXJ9
In branches: TR
PN-node mapping records (path + ancestors):
- [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatA/NatE complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0031415 NatA complex]
  rationale: This subtype is an exact cellular-component match: members are subunits of the NatA N-terminal acetyltransferase complex. The parent maps the BP (GO:0006474 N-terminal protein amino acid acetylation); this node adds the complementary, non-redundant complex-membership CC term.
- [type] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006474 N-terminal protein amino acid acetylation]
  rationale: This PN type denotes N-terminal acetyltransferase machinery acting on nascent peptides. The GO N-terminal acetylation process is the direct target.
- [group] Translation|Cytosolic translation|Nascent peptide husbandry
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [class] Translation|Cytosolic translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
  rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
  status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
  rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (1)

GO:0006474 N-terminal protein amino acid acetylation | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q9BXJ9
gene_symbol: NAA15
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
alternative_products:
- name: 1 (Long)
  id: Q9BXJ9-1
- name: 2 (Short)
  id: Q9BXJ9-4
  sequence_note: VSP_012560, VSP_012561
existing_annotations:
- term:
    id: GO:0010698
    label: acetyltransferase activator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: NAA15 is a defining component of the NatA complex (NAA10-NAA15).
    action: ACCEPT
    reason: Core complex membership; NAA15 is one of the two NatA subunits.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation of nuclear localization, consistent with the documented nuclear pool of NAA15.
    action: KEEP_AS_NON_CORE
    reason: Nuclear pool is documented but the core NatA function is cytoplasmic/ ribosome-associated; nuclear localization kept non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm. Nucleus.'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation of cytoplasmic localization, the principal site of NatA action.
    action: ACCEPT
    reason: Cytoplasm is where ribosome-associated NatA acts; well supported.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm. Nucleus.'
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: Electronic (ARBA) annotation of NatA complex membership, consistent with experimental evidence.
    action: ACCEPT
    reason: Core complex membership; redundant with IBA/IDA NatA annotations.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: NAA15 anchors the NatA complex to the ribosome, a core auxiliary function enabling co-translational acetylation.
    action: ACCEPT
    reason: Ribosome binding/anchoring is a documented core function of NAA15.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0043022 ribosome binding molecular_function IDA PMID:19480662
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15496142
  qualifier: enables
  review:
    summary: IntAct interaction with NAA10 (P41227), the catalytic NatA subunit. Generic protein binding term recording the central NatA dimer.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally central NAA15-NAA10 interaction; informative MF captured by complex/activator annotations.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:15496142 UniProtKB:P41227
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16507339
  qualifier: enables
  review:
    summary: IntAct interaction with NAA50 (Q9GZZ1), the NatE catalytic subunit that docks onto NatA via NAA15. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Real NAA50 interaction underlying NatE assembly; informative function captured elsewhere.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:16507339 UniProtKB:Q9GZZ1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16638120
  qualifier: enables
  review:
    summary: IntAct interaction with NAA11 (Q9BSU3), the NAA10 paralog that can also partner NAA15. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with the alternative catalytic subunit NAA11; generic MF kept non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:16638120 UniProtKB:Q9BSU3
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19480662
  qualifier: enables
  review:
    summary: IntAct interaction with NAA10 (P41227). Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records the central NatA dimer interaction; generic MF kept non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:19480662 UniProtKB:P41227
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24981860
  qualifier: enables
  review:
    summary: IntAct interaction with HYPK (Q9NX55), the NatA-associated chaperone/ regulator. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Real HYPK interaction underlying NatA/HYPK complex formation; generic MF kept non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:24981860 UniProtKB:Q9NX55
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: IntAct interactions with NatA-related partners (NAA10 P41227, NAA50 Q9GZZ1, HYPK Q9NX55). Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records real NatA-partner interactions; informative function captured elsewhere.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:28514442 UniProtKB:P41227
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: IntAct interaction with HYPK (Q9NX55). Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Real HYPK interaction; generic MF kept non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:32296183 UniProtKB:Q9NX55
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex interactome capturing NatA-related partners (NAA10, NAA11, NAA50, HYPK). Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records real NatA-partner interactions; informative function captured elsewhere.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:33961781 UniProtKB:P41227
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome capturing NatA-related partners (NAA10, NAA50, HYPK). Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records real NatA-partner interactions; informative function captured elsewhere.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:40205054 UniProtKB:P41227
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) cytosolic localization, consistent with ribosome-associated NatA function.
    action: ACCEPT
    reason: Cytosol is the principal site of NatA action.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component IDA GO_REF:0000052 HPA
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence placing a NAA15 pool in nuclear bodies; a specialized localization not central to NatA function.
    action: KEEP_AS_NON_CORE
    reason: Documented but specialized localization; non-core relative to cytoplasmic NatA activity.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0016604 nuclear body cellular_component IDA GO_REF:0000052
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: involved_in
  review:
    summary: As part of NatA, NAA15 participates in co-translational protein maturation (N-terminal acetylation); a broad downstream BP.
    action: KEEP_AS_NON_CORE
    reason: Maturation is a downstream process of NatA activity; non-core relative to the activator/ribosome-binding MF.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization (ComplexPortal NatA).
    action: ACCEPT
    reason: Core localization for NatA function.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component IDA PMID:15496142 Homo sapiens ComplexPortal
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:16638120
  qualifier: located_in
  review:
    summary: Non-traceable author statement of cytoplasmic localization, consistent with the core localization.
    action: ACCEPT
    reason: Consistent with well-supported cytoplasmic localization of NatA.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component NAS PMID:16638120
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IPI
  original_reference_id: PMID:15496142
  qualifier: part_of
  review:
    summary: Direct evidence for NatA complex membership (NAA10-NAA15).
    action: ACCEPT
    reason: Core complex membership.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IPI
  original_reference_id: PMID:16638120
  qualifier: part_of
  review:
    summary: Direct evidence for NatA complex membership.
    action: ACCEPT
    reason: Core complex membership.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25489052
  qualifier: enables
  review:
    summary: IntAct interaction with NAA10 (P41227), the catalytic NatA subunit. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records the central NatA dimer interaction; generic MF kept non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:25489052 UniProtKB:P41227
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24407287
  qualifier: enables
  review:
    summary: IntAct interaction (Q9ULZ3) from a high-throughput study. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; uninformative as core MF.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:24407287 UniProtKB:Q9ULZ3
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: Membrane localization from a high-throughput membrane proteome dataset; inconsistent with NAA15's soluble cytoplasmic/ribosome-associated function.
    action: MARK_AS_OVER_ANNOTATED
    reason: HDA membrane-proteome hit; likely reflects co-purification rather than a genuine integral-membrane localization.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0016020 membrane cellular_component HDA PMID:19946888
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: RNA binding from a high-throughput mRNA-interactome capture; plausibly reflects ribosome/rRNA proximity rather than a sequence-specific RNA-binding function.
    action: MARK_AS_OVER_ANNOTATED
    reason: HDA RNA-interactome hit without a defined RNA-binding role; likely an artifact of ribosome association, not a core function.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0003723 RNA binding molecular_function HDA PMID:22658674
- term:
    id: GO:0031415
    label: NatA complex
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: part_of
  review:
    summary: Direct evidence for NatA complex membership.
    action: ACCEPT
    reason: Core complex membership.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:19480662
  qualifier: enables
  review:
    summary: Direct evidence that NAA15 binds the ribosome, anchoring NatA for co-translational acetylation. This is the core auxiliary MF.
    action: ACCEPT
    reason: Ribosome binding/anchoring is the defining non-catalytic function of NAA15.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0043022 ribosome binding molecular_function IDA PMID:19480662
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12140756
  qualifier: located_in
  review:
    summary: Direct cytoplasmic localization of NAA15.
    action: ACCEPT
    reason: Core localization for NatA function.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005737 cytoplasm cellular_component IDA PMID:12140756
- term:
    id: GO:0016407
    label: acetyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: contributes_to
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:15496142
  qualifier: contributes_to
  review:
    summary: Direct evidence that NAA15 contributes ribosome binding to the NatA complex; core auxiliary MF.
    action: ACCEPT
    reason: Ribosome anchoring is a defining function of NAA15.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0043022 ribosome binding molecular_function IDA PMID:15496142
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12145306
  qualifier: enables
  review:
    summary: IntAct interactions with XRCC6/Ku70 (P12956) and XRCC5/Ku80 (P13010), the basis of the reported nuclear transcription-regulatory complex. Generic protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Records the Ku70/Ku80 interaction underlying the osteocalcin-promoter transcription role; specialized and non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function IPI PMID:12145306 UniProtKB:P12956
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12140756
  qualifier: located_in
  review:
    summary: Direct nuclear localization of NAA15.
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool; non-core relative to cytoplasmic NatA function.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component IDA PMID:12140756
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:12145306
  qualifier: located_in
  review:
    summary: Direct nuclear localization in the context of the Ku70/Ku80 transcription complex.
    action: KEEP_AS_NON_CORE
    reason: Documented nuclear pool; specialized and non-core.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-goa.tsv
      supporting_text: GO:0005634 nucleus cellular_component IDA PMID:12145306
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IDA
  original_reference_id: PMID:12145306
  qualifier: part_of
  review:
    summary: NAA15 reported in a nuclear complex with XRCC6/XRCC5 that up-regulates the osteocalcin promoter; a specialized moonlighting context.
    action: KEEP_AS_NON_CORE
    reason: A documented but specialized nuclear role distinct from the core cytoplasmic NatA auxiliary function.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:12145306
  qualifier: involved_in
  review:
    summary: NAA15 (with Ku70/Ku80) positively regulates osteocalcin-promoter transcription; a specialized moonlighting role.
    action: KEEP_AS_NON_CORE
    reason: Documented but specialized; not the core NatA auxiliary function.
    supported_by:
    - reference_id: file:human/NAA15/NAA15-uniprot.txt
      supporting_text: In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Gene Ontology annotation based on rules generated from ARBA automatic annotation
  findings: []
- id: PMID:12140756
  title: 'NATH, a novel gene overexpressed in papillary thyroid carcinomas.'
  findings:
  - statement: NAA15 (Tubedown-1) is an acetyltransferase-associated protein with cytoplasmic and nuclear localization in endothelial cells.
    reference_section_type: RESULTS
- id: PMID:12145306
  title: 'Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex.'
  findings:
  - statement: NAA15 forms a nuclear complex with XRCC6 (Ku70) and XRCC5 (Ku80) that up-regulates transcription from the osteocalcin promoter.
    reference_section_type: RESULTS
- id: PMID:15496142
  title: 'Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.'
  findings:
  - statement: NAA15 (NATH) is the auxiliary subunit of the human NatA complex, partnering the catalytic subunit NAA10 (ARD1) and conferring ribosome association.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: 'Not cached, but anchored to GOA: this PMID supports IDA to GO:0031415 (NatA complex) and GO:0043022 (ribosome binding) for NAA15. Complex-characterization paper establishing NAA15 as the NatA auxiliary subunit, the gene''s core role.'
- id: PMID:16507339
  title: 'Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex.'
  findings:
  - statement: NAA50 associates with NAA15 in the NatA complex.
    reference_section_type: RESULTS
- id: PMID:16638120
  title: 'Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-alpha-acetyltransferase.'
  findings:
  - statement: NAA15 interacts with NAA11, an NAA10 paralog, forming an alternative NatA-type complex.
    reference_section_type: RESULTS
- id: PMID:19480662
  title: 'A novel human NatA Nalpha-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1).'
  findings:
  - statement: NAA15 anchors the NatA complex to the ribosome enabling co-translational N-terminal acetylation.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: 'Not cached, but anchored to GOA: this PMID supports IDA to GO:0043022 (ribosome binding) for NAA15, directly supporting its core ribosome-anchoring role for the NatA complex.'
- id: PMID:19946888
  title: 'Defining the membrane proteome of NK cells.'
  findings: []
- id: PMID:22658674
  title: 'Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.'
  findings: []
- id: PMID:24407287
  title: 'Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation.'
  findings: []
- id: PMID:24981860
  title: 'Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.'
  findings:
  - statement: HYPK interacts with NAA15 within the NatA/HYPK complex.
    reference_section_type: RESULTS
- id: PMID:25489052
  title: 'Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects.'
  findings:
  - statement: Crystal structure of NatA shows NAA15 wrapping around NAA10 and activating/orienting it for N-terminal acetylation.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: 'Definitive NatA crystal structure (GOA anchors this PMID to IPI protein binding for NAA15); shows NAA15 wrapping around and activating NAA10, establishing the structural basis of the auxiliary-subunit function.'
- id: PMID:28514442
  title: 'Architecture of the human interactome defines protein communities and disease networks.'
  findings: []
- id: PMID:32296183
  title: 'A reference map of the human binary protein interactome.'
  findings: []
- id: PMID:33961781
  title: 'Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.'
  findings: []
- id: PMID:40205054
  title: 'Multimodal cell maps as a foundation for structural and functional genomics.'
  findings: []
core_functions:
- description: Non-catalytic auxiliary subunit of the NatA N-terminal acetyltransferase complex that binds and activates the catalytic subunit NAA10, conferring N-terminal substrate specificity and serving as the scaffold for the NatA-associated factors HYPK and NAA50.
  molecular_function:
    id: GO:0010698
    label: acetyltransferase activator activity
  in_complex:
    id: GO:0031415
    label: NatA complex
  supported_by:
  - reference_id: file:human/NAA15/NAA15-uniprot.txt
    supporting_text: Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity
- description: Anchors the NatA complex to the ribosome near the polypeptide exit tunnel, enabling co-translational N-terminal acetylation of nascent chains.
  molecular_function:
    id: GO:0043022
    label: ribosome binding
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/NAA15/NAA15-goa.tsv
    supporting_text: GO:0043022 ribosome binding molecular_function IDA PMID:19480662
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: How do NAA15 neurodevelopmental/congenital-heart-disease variants impair NatA assembly, NAA10 activation, and ribosome anchoring?
suggested_experiments:
- description: 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.
- description: 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.
- description: Test whether the Tubedown-1/endothelial vascular phenotypes depend on NatA catalytic activity by rescue with acetyltransferase-dead NAA10.

NAA15

Gene Description