NAA38

UniProt ID: Q9BRA0
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

NAA38 (N-alpha-acetyltransferase 38; also LSMD1, MAK31) is a small Sm-like (LSm-fold) non-catalytic auxiliary subunit of the human NatC N-terminal acetyltransferase complex (NatC = NAA30 catalytic + NAA35 + NAA38). It does not catalyze acetyl transfer but is a structural component of NatC, which co-translationally acetylates the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues; this modification shields substrates from N-degron-mediated ubiquitination and degradation. NAA38 is predominantly cytoplasmic (ribosome-associated) with some nuclear localization. Loss of NatC subunits triggers p53-dependent apoptosis.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003723 RNA binding
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: InterPro-based electronic annotation transferred from the Sm/LSm-domain family signature. NAA38 has an Sm-like fold, but there is no experimental evidence that it binds RNA in its role as a NatC subunit; this is a family-level transfer.
Reason: RNA binding is inferred purely from the Sm-like domain signature and does not reflect a demonstrated function of NAA38 within NatC; the experimentally supported role is as a non-catalytic NatC subunit.
Supporting Evidence:
file:human/NAA38/NAA38-goa.tsv
GO:0003723 RNA binding molecular_function ECO:0000256 IEA GO_REF:0000002 InterPro:IPR047575
GO:0005634 nucleus
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Electronic (UniProt SubCell) annotation of nuclear localization, mirroring the IDA nuclear localization reported by PMID:19398576. NatC predominantly acts cotranslationally in the cytoplasm; the nuclear pool is secondary.
Reason: Nuclear localization is reported experimentally but secondary to the cytoplasmic ribosome-associated site where NatC functions.
Supporting Evidence:
file:human/NAA38/NAA38-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: Electronic (UniProt SubCell) annotation of cytoplasmic localization, the primary compartment for NatC activity.
Reason: Cytoplasm is the principal, experimentally supported compartment of NatC.
Supporting Evidence:
file:human/NAA38/NAA38-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0031417 NatC complex
IEA
GO_REF:0000120 		ACCEPT
Summary: Rule/InterPro-based electronic annotation of NatC complex membership, redundant with and consistent with stronger experimental evidence.
Reason: Correct and well-corroborated NatC complex membership.
Supporting Evidence:
file:human/NAA38/NAA38-uniprot.txt
Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
GO:0005515 protein binding
IPI
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		KEEP AS NON CORE
Summary: IntAct interaction with NAA35 (Q5VZE5), the NatC scaffold subunit. The bare protein binding term is uninformative; the relevant interaction is NatC complex assembly.
Reason: Records a genuine intra-complex interaction with the NAA35 auxiliary subunit, but the uninformative GO:0005515 term is non-core; NatC complex membership captures the meaningful content.
Supporting Evidence:
file:human/NAA38/NAA38-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19398576 UniProtKB:Q5VZE5
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		KEEP AS NON CORE
Summary: Yeast two-hybrid interactome interactions with PDE9A (O76083), PRR20C (P86479) and N4BP2L2 (Q92802), none of which are NatC components or functionally connected to N-terminal acetylation. Isolated high-throughput interactions.
Reason: Bare protein binding from a single high-throughput screen with partners outside the NatC complex; uninformative and not part of the core function.
Supporting Evidence:
file:human/NAA38/NAA38-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25416956 UniProtKB:O76083
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ... 		KEEP AS NON CORE
Summary: Neurodegeneration interactome screen interactions with ATN1 (Q86V38) and KLK6 (Q92876), unrelated to NatC function. Isolated high-throughput interactions.
Reason: Bare protein binding from a single high-throughput screen with partners outside the NatC complex; uninformative and not part of the core function.
Supporting Evidence:
file:human/NAA38/NAA38-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32814053 UniProtKB:Q86V38
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		KEEP AS NON CORE
Summary: BioPlex interactome interaction with NAA35 (Q5VZE5), the NatC scaffold subunit. Uninformative bare protein binding term reflecting NatC complex assembly.
Reason: Real interaction with the NAA35 auxiliary subunit; non-core as a bare protein binding annotation, subsumed by the NatC complex term.
Supporting Evidence:
file:human/NAA38/NAA38-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q5VZE5
GO:0005654 nucleoplasm
IDA
GO_REF:0000052 		KEEP AS NON CORE
Summary: Direct immunofluorescence (HPA) evidence for nucleoplasmic localization. A nuclear pool of NAA38 exists, but NatC's core activity is cytoplasmic and ribosome-associated.
Reason: Experimentally supported nuclear localization, but secondary to the cytoplasmic ribosome-associated site of NatC function.
Supporting Evidence:
file:human/NAA38/NAA38-goa.tsv
GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005737 cytoplasm
NAS
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		ACCEPT
Summary: Non-traceable author statement (ComplexPortal) of cytoplasmic localization, consistent with the documented cytoplasmic site of NatC.
Reason: Consistent with the primary cytoplasmic localization of NatC.
Supporting Evidence:
file:human/NAA38/NAA38-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0031417 NatC complex
IPI
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		ACCEPT
Summary: ComplexPortal/IPI evidence that NAA38 is part of the NatC complex, from the study that identified the human NatC complex.
Reason: Direct experimental support for NatC complex membership.
Supporting Evidence:
PMID:19398576
the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
GO:0031417 NatC complex
IDA
PMID:37891180
N-terminal acetylation shields proteins from degradation and... 		ACCEPT
Summary: Direct experimental confirmation of NatC complex membership in the protein-shielding/longevity study.
Reason: Well-supported NatC complex membership.
Supporting Evidence:
file:human/NAA38/NAA38-uniprot.txt
Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
GO:0005634 nucleus
IDA
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		KEEP AS NON CORE
Summary: Direct experimental evidence for a nuclear pool of NAA38. NatC predominantly acts cotranslationally in the cytoplasm; the nuclear localization is secondary.
Reason: Experimentally observed nuclear localization, but secondary to the cytoplasmic ribosome-associated site of NatC function.
Supporting Evidence:
file:human/NAA38/NAA38-uniprot.txt
Nucleus {ECO:0000269|PubMed:19398576}
GO:0005737 cytoplasm
IDA
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		ACCEPT
Summary: Direct experimental cytoplasmic localization of NAA38, consistent with ribosome-associated NatC activity.
Reason: Cytoplasm is the principal experimentally supported compartment of NatC.
Supporting Evidence:
PMID:19398576
This complex associates with ribosomes
GO:0031417 NatC complex
IDA
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		ACCEPT
Summary: Direct experimental identification of NAA38 (hMak31) as an auxiliary subunit of the human NatC complex.
Reason: Defining cellular component, directly demonstrated.
Supporting Evidence:
PMID:19398576
the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
GO:0043066 negative regulation of apoptotic process
IMP
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		KEEP AS NON CORE
Summary: Mutant-phenotype evidence that NatC subunit knockdown (including NAA38/hMak31) induces p53-dependent apoptosis, indicating NatC normally suppresses apoptosis. Downstream consequence of complex function.
Reason: Real phenotype-based process annotation, but indirect and downstream of NatC's core acetyltransferase activity.
Supporting Evidence:
PMID:19398576
results in p53-dependent cell death
GO:0006474 N-terminal protein amino acid acetylation
IC
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase comple... 		NEW
Summary: NAA38/hMak31 is a non-catalytic auxiliary subunit of human NatC, the complex responsible for cotranslational N-terminal acetylation.
Reason: PN correctly flagged that the review captures NatC complex membership but not the BP carried out by that complex. This recommends process involvement for the auxiliary subunit while explicitly not assigning catalytic acetyltransferase MF to NAA38.
Supporting Evidence:
PMID:19398576
the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
PMID:19398576
the human NatC complex functions in cotranslational N-terminal acetylation

Core Functions

Small Sm-like non-catalytic auxiliary subunit of the NatC N-terminal acetyltransferase complex, a structural component required for the NatC complex that co-translationally acetylates N-terminal methionine residues of substrates with bulky/hydrophobic second residues.

Directly Involved In:
N-terminal protein amino acid acetylation
Cellular Locations:
cytoplasm
In Complex:
NatC complex
Supporting Evidence:
  • file:human/NAA38/NAA38-uniprot.txt
    Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
  • PMID:19398576
    the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:19398576
Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization.
  • NatC contains the catalytic subunit hMak3 (NAA30) and auxiliary subunits hMak10 (NAA35) and hMak31 (NAA38); the complex associates with ribosomes.
  • Knockdown of NatC subunits results in p53-dependent cell death, indicating NatC normally suppresses apoptosis.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:37891180
N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.
  • NatC-mediated N-terminal acetylation shields substrate proteins from degradation, promoting protein stabilization, motility and longevity.

Suggested Questions for Experts

Q: Does the Sm-like fold of NAA38 mediate protein-protein contacts within NatC, or does it retain any nucleic-acid-binding capacity relevant to a moonlighting function?

Q: Is NAA38 strictly required for NatC catalytic activity, or does it modulate substrate range/stability of the complex?

Suggested Experiments

Experiment: Reconstitute NatC in vitro with and without NAA38 to test its contribution to complex stability, catalytic activity and substrate selectivity.

Experiment: RNA-binding assays (e.g. CLIP or EMSA) on purified NAA38 and NatC to test whether the Sm-like fold binds RNA in a physiologically relevant manner.

Experiment: Cryo-EM of the human NatC complex to define how the small NAA38 subunit is positioned relative to NAA30 and NAA35.

📚 Additional Documentation

Notes

(NAA38-notes.md)

NAA38 (N-alpha-acetyltransferase 38, NatC auxiliary subunit / LSMD1 / MAK31) notes

Identity

  • UniProt Q9BRA0; aka LSMD1 (LSM-domain-containing 1), MAK31, PFAAP2. 125 aa, small Sm-like (LSm) fold protein.
  • Small AUXILIARY (non-catalytic) subunit of the human NatC complex (NatC = NAA30 catalytic + NAA35 + NAA38). Belongs to the snRNP Sm proteins family.

Function

  • Auxiliary component of NatC; NatC acetylates N-terminal Met before bulky/hydrophobic residues.
    [UniProt FUNCTION "Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues"]
  • NatC N-terminal acetylation protects substrates from N-end-rule ubiquitination/degradation. PMID:37891180
  • NatC KD -> p53-dependent apoptosis. PMID:19398576

Annotation notes

  • Sm-like fold -> IEA RNA binding (GO:0003723, InterPro IPR047575). NAA38 is the Sm-like subunit of NatC; there is no evidence it binds RNA in its NatC role. This is a domain-family IEA transfer; likely an over-annotation in the NatC context. MARK_AS_OVER_ANNOTATED.
  • NatC complex (IEA/IPI/IDA) — core CC.
  • protein binding IPI: PMID:19398576 WITH NAA35 (Q5VZE5) = real NatC partner -> KEEP_AS_NON_CORE. PMID:25416956 (Y2H) WITH PDE9A/PRR20C/N4BP2L2; PMID:32814053 (neurodegeneration interactome) WITH ATN1/KLK6 — isolated HT interactions, unrelated -> MARK_AS_OVER_ANNOTATED.
  • negative regulation of apoptotic process (IMP PMID:19398576): NatC KD -> apoptosis; downstream BP -> KEEP_AS_NON_CORE.
  • Localizations: cytoplasm (IDA/NAS/IEA) primary; nucleus (IDA PMID:19398576, IEA) and nucleoplasm (IDA HPA) reported -> keep nucleus non-core, cytoplasm accept.

Pn Notes

(NAA38-pn-notes.md)

NAA38 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9BRA0
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07c
  • Batch change status: added

Source Files Checked

Deep Research Files

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

AIGR Review Snapshot

  • Description: NAA38 (N-alpha-acetyltransferase 38; also LSMD1, MAK31) is a small Sm-like (LSm-fold) non-catalytic auxiliary subunit of the human NatC N-terminal acetyltransferase complex (NatC = NAA30 catalytic + NAA35 + NAA38). It does not catalyze acetyl transfer but is a structural component of NatC, which co-translationally acetylates the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues; this modification shields substrates from N-degron-mediated ubiquitination and degradation. NAA38 is predominantly cytoplasmic (ribosome-associated) with some nuclear localization. Loss of NatC subunits triggers p53-dependent apoptosis.
  • Existing/core annotation action counts: ACCEPT: 7; KEEP_AS_NON_CORE: 8; MARK_AS_OVER_ANNOTATED: 1; NEW: 1

PN Consistency Summary

  • Consistency: Strong. All sources agree NAA38 (LSMD1/MAK31) is the small Sm-like (LSm-fold) non-catalytic auxiliary subunit of NatC; correctly no catalytic MF. PN-node mapping matches.
  • PN story / NEW pressure: PN projects BP GO:0006474 (verified real; confirmed absent from NAA38 GOA). As with NAA35, an involved_in BP for the auxiliary subunit of the acetylating complex is defensible and complements the CC-only core. Conclusion: ADD GO:0006474 (involved_in) reasonable; catalytic MF must NOT be added. Separately, the review correctly flags the family-level GO:0003723 (RNA binding, from the Sm-like signature) as MARK_AS_OVER_ANNOTATED — consistent with the PN treatment as a NatC subunit, not an RNA-binding protein. Not an over-reach.
  • Evidence alignment: Concordant. Review/notes anchor to PMID:19398576 (NatC; hMak31; IDA GO:0031417, IMP GO:0043066) and PMID:37891180. PN row carries no titles. No divergence.
  • Verdict: Consistent, high-quality. Same minor notes-vs-YAML mismatch as NAA35: notes say HT protein-binding PMID:25416956/PMID:32814053 should be MARK_AS_OVER_ANNOTATED, YAML uses KEEP_AS_NON_CORE. Recommended edits: Add BP GO:0006474 (involved_in, auxiliary subunit) to NAA38 review [YAML]; optionally reconcile PMID:25416956 / PMID:32814053 protein-binding actions with notes [YAML].

Full Consistency Review

  • UniProt: Q9BRA0 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE
  • PN placement: Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatC complex component ; PN-node mapping: subtype mapped→GO:0031417 NatC complex (ok_for_propagation); type mapped→GO:0006474 N-terminal protein amino acid acetylation (ok_for_propagation, new_to_goa)
  • Consistency: Strong. All sources agree NAA38 (LSMD1/MAK31) is the small Sm-like (LSm-fold) non-catalytic auxiliary subunit of NatC; correctly no catalytic MF. PN-node mapping matches.
  • PN story / NEW pressure: PN projects BP GO:0006474 (verified real; confirmed absent from NAA38 GOA). As with NAA35, an involved_in BP for the auxiliary subunit of the acetylating complex is defensible and complements the CC-only core. Conclusion: ADD GO:0006474 (involved_in) reasonable; catalytic MF must NOT be added. Separately, the review correctly flags the family-level GO:0003723 (RNA binding, from the Sm-like signature) as MARK_AS_OVER_ANNOTATED — consistent with the PN treatment as a NatC subunit, not an RNA-binding protein. Not an over-reach.
  • Mapping strategy: Correct. Subtype→NatC complex exact CC; BP at type level. No node-mapping change warranted.
  • Evidence alignment: Concordant. Review/notes anchor to PMID:19398576 (NatC; hMak31; IDA GO:0031417, IMP GO:0043066) and PMID:37891180. PN row carries no titles. No divergence.
  • Verdict: Consistent, high-quality. Same minor notes-vs-YAML mismatch as NAA35: notes say HT protein-binding PMID:25416956/PMID:32814053 should be MARK_AS_OVER_ANNOTATED, YAML uses KEEP_AS_NON_CORE. Recommended edits: Add BP GO:0006474 (involved_in, auxiliary subunit) to NAA38 review [YAML]; optionally reconcile PMID:25416956 / PMID:32814053 protein-binding actions with notes [YAML].
  • 2026-06-18 follow-up: Implemented the high-confidence YAML edit: added GO:0006474 N-terminal protein amino acid acetylation as a NEW BP recommendation and core process for the NatC auxiliary subunit, using IC to reflect inference from NatC complex membership rather than direct catalytic activity. The optional protein-binding action-style reconciliation remains separate.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/NAA38/NAA38-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q9BRA0
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatC complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0031417 NatC complex]
      rationale: Exact cellular-component match: members are subunits of the NatC N-terminal acetyltransferase complex. Complements the parent BP mapping with the 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=new_to_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: Q9BRA0
gene_symbol: NAA38
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: NAA38 (N-alpha-acetyltransferase 38; also LSMD1, MAK31) is a small Sm-like (LSm-fold) non-catalytic auxiliary subunit of the human NatC N-terminal acetyltransferase complex (NatC = NAA30 catalytic + NAA35 + NAA38). It does not catalyze acetyl transfer but is a structural component of NatC, which co-translationally acetylates the alpha-amino group of N-terminal methionine residues retained in front of bulky/hydrophobic residues; this modification shields substrates from N-degron-mediated ubiquitination and degradation. NAA38 is predominantly cytoplasmic (ribosome-associated) with some nuclear localization. Loss of NatC subunits triggers p53-dependent apoptosis.
alternative_products:
- name: '1'
  id: Q9BRA0-1
- name: '2'
  id: Q9BRA0-2
  sequence_note: VSP_027566
existing_annotations:
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based electronic annotation transferred from the Sm/LSm-domain family signature. NAA38 has an Sm-like fold, but there is no experimental evidence that it binds RNA in its role as a NatC subunit; this is a family-level transfer.
    action: MARK_AS_OVER_ANNOTATED
    reason: RNA binding is inferred purely from the Sm-like domain signature and does not reflect a demonstrated function of NAA38 within NatC; the experimentally supported role is as a non-catalytic NatC subunit.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-goa.tsv
      supporting_text: GO:0003723 RNA binding molecular_function ECO:0000256 IEA GO_REF:0000002 InterPro:IPR047575
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic (UniProt SubCell) annotation of nuclear localization, mirroring the IDA nuclear localization reported by PMID:19398576. NatC predominantly acts cotranslationally in the cytoplasm; the nuclear pool is secondary.
    action: KEEP_AS_NON_CORE
    reason: Nuclear localization is reported experimentally but secondary to the cytoplasmic ribosome-associated site where NatC functions.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic (UniProt SubCell) annotation of cytoplasmic localization, the primary compartment for NatC activity.
    action: ACCEPT
    reason: Cytoplasm is the principal, experimentally supported compartment of NatC.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: Rule/InterPro-based electronic annotation of NatC complex membership, redundant with and consistent with stronger experimental evidence.
    action: ACCEPT
    reason: Correct and well-corroborated NatC complex membership.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19398576
  qualifier: enables
  review:
    summary: IntAct interaction with NAA35 (Q5VZE5), the NatC scaffold subunit. The bare protein binding term is uninformative; the relevant interaction is NatC complex assembly.
    action: KEEP_AS_NON_CORE
    reason: Records a genuine intra-complex interaction with the NAA35 auxiliary subunit, but the uninformative GO:0005515 term is non-core; NatC complex membership captures the meaningful content.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:19398576 UniProtKB:Q5VZE5
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Yeast two-hybrid interactome interactions with PDE9A (O76083), PRR20C (P86479) and N4BP2L2 (Q92802), none of which are NatC components or functionally connected to N-terminal acetylation. Isolated high-throughput interactions.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from a single high-throughput screen with partners outside the NatC complex; uninformative and not part of the core function.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25416956 UniProtKB:O76083
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Neurodegeneration interactome screen interactions with ATN1 (Q86V38) and KLK6 (Q92876), unrelated to NatC function. Isolated high-throughput interactions.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from a single high-throughput screen with partners outside the NatC complex; uninformative and not part of the core function.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32814053 UniProtKB:Q86V38
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex interactome interaction with NAA35 (Q5VZE5), the NatC scaffold subunit. Uninformative bare protein binding term reflecting NatC complex assembly.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with the NAA35 auxiliary subunit; non-core as a bare protein binding annotation, subsumed by the NatC complex term.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q5VZE5
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) evidence for nucleoplasmic localization. A nuclear pool of NAA38 exists, but NatC's core activity is cytoplasmic and ribosome-associated.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported nuclear localization, but secondary to the cytoplasmic ribosome-associated site of NatC function.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-goa.tsv
      supporting_text: GO:0005654 nucleoplasm cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:19398576
  qualifier: located_in
  review:
    summary: Non-traceable author statement (ComplexPortal) of cytoplasmic localization, consistent with the documented cytoplasmic site of NatC.
    action: ACCEPT
    reason: Consistent with the primary cytoplasmic localization of NatC.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IPI
  original_reference_id: PMID:19398576
  qualifier: part_of
  review:
    summary: ComplexPortal/IPI evidence that NAA38 is part of the NatC complex, from the study that identified the human NatC complex.
    action: ACCEPT
    reason: Direct experimental support for NatC complex membership.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IDA
  original_reference_id: PMID:37891180
  qualifier: part_of
  review:
    summary: Direct experimental confirmation of NatC complex membership in the protein-shielding/longevity study.
    action: ACCEPT
    reason: Well-supported NatC complex membership.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19398576
  qualifier: located_in
  review:
    summary: Direct experimental evidence for a nuclear pool of NAA38. NatC predominantly acts cotranslationally in the cytoplasm; the nuclear localization is secondary.
    action: KEEP_AS_NON_CORE
    reason: Experimentally observed nuclear localization, but secondary to the cytoplasmic ribosome-associated site of NatC function.
    supported_by:
    - reference_id: file:human/NAA38/NAA38-uniprot.txt
      supporting_text: Nucleus {ECO:0000269|PubMed:19398576}
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19398576
  qualifier: located_in
  review:
    summary: Direct experimental cytoplasmic localization of NAA38, consistent with ribosome-associated NatC activity.
    action: ACCEPT
    reason: Cytoplasm is the principal experimentally supported compartment of NatC.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: This complex associates with ribosomes
- term:
    id: GO:0031417
    label: NatC complex
  evidence_type: IDA
  original_reference_id: PMID:19398576
  qualifier: part_of
  review:
    summary: Direct experimental identification of NAA38 (hMak31) as an auxiliary subunit of the human NatC complex.
    action: ACCEPT
    reason: Defining cellular component, directly demonstrated.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:19398576
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that NatC subunit knockdown (including NAA38/hMak31) induces p53-dependent apoptosis, indicating NatC normally suppresses apoptosis. Downstream consequence of complex function.
    action: KEEP_AS_NON_CORE
    reason: Real phenotype-based process annotation, but indirect and downstream of NatC's core acetyltransferase activity.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: results in p53-dependent cell death
- term:
    id: GO:0006474
    label: N-terminal protein amino acid acetylation
  evidence_type: IC
  original_reference_id: PMID:19398576
  qualifier: involved_in
  review:
    summary: NAA38/hMak31 is a non-catalytic auxiliary subunit of human NatC, the complex responsible for cotranslational N-terminal acetylation.
    action: NEW
    reason: PN correctly flagged that the review captures NatC complex membership but not the BP carried out by that complex. This recommends process involvement for the auxiliary subunit while explicitly not assigning catalytic acetyltransferase MF to NAA38.
    supported_by:
    - reference_id: PMID:19398576
      supporting_text: the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
      reference_section_type: ABSTRACT
    - reference_id: PMID:19398576
      supporting_text: the human NatC complex functions in cotranslational N-terminal acetylation
      reference_section_type: ABSTRACT
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:19398576
  title: Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization.
  findings:
  - statement: NatC contains the catalytic subunit hMak3 (NAA30) and auxiliary subunits hMak10 (NAA35) and hMak31 (NAA38); the complex associates with ribosomes.
    reference_section_type: ABSTRACT
  - statement: Knockdown of NatC subunits results in p53-dependent cell death, indicating NatC normally suppresses apoptosis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches the YAML title; GOA anchors this PMID to IDA for GO:0031417 (NatC complex) and IMP for GO:0043066 for NAA38. This is the NatC complex-characterization paper establishing NAA38 (hMak31) as the small Sm-like auxiliary subunit, the gene's core function.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:37891180
  title: N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.
  findings:
  - statement: NatC-mediated N-terminal acetylation shields substrate proteins from degradation, promoting protein stabilization, motility and longevity.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached publication title matches the YAML title; GOA anchors this PMID to IDA for GO:0031417 (NatC complex). Supports the biological significance of the NatC complex of which NAA38 is the Sm-like auxiliary subunit.
core_functions:
- description: Small Sm-like non-catalytic auxiliary subunit of the NatC N-terminal acetyltransferase complex, a structural component required for the NatC complex that co-translationally acetylates N-terminal methionine residues of substrates with bulky/hydrophobic second residues.
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/NAA38/NAA38-uniprot.txt
    supporting_text: Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
  - reference_id: PMID:19398576
    supporting_text: the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31
  in_complex:
    id: GO:0031417
    label: NatC complex
  directly_involved_in:
  - id: GO:0006474
    label: N-terminal protein amino acid acetylation
proposed_new_terms: []
suggested_questions:
- question: Does the Sm-like fold of NAA38 mediate protein-protein contacts within NatC, or does it retain any nucleic-acid-binding capacity relevant to a moonlighting function?
- question: Is NAA38 strictly required for NatC catalytic activity, or does it modulate substrate range/stability of the complex?
suggested_experiments:
- description: Reconstitute NatC in vitro with and without NAA38 to test its contribution to complex stability, catalytic activity and substrate selectivity.
- description: RNA-binding assays (e.g. CLIP or EMSA) on purified NAA38 and NatC to test whether the Sm-like fold binds RNA in a physiologically relevant manner.
- description: Cryo-EM of the human NatC complex to define how the small NAA38 subunit is positioned relative to NAA30 and NAA35.