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.