NAA25

UniProt ID: Q14CX7
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

NAA25 (N-alpha-acetyltransferase 25; also MDM20, NAP1, p120) is the large non-catalytic auxiliary subunit of the human NatB N-terminal acetyltransferase complex. NatB is composed of the catalytic subunit NAA20 and the auxiliary subunit NAA25, and it co-translationally acetylates the alpha-amino group of N-terminal methionine residues that are retained in front of acidic or amide side chains (Met-Asp, Met-Glu, Met-Asn and Met-Gln N-termini). NAA25 is a TPR-repeat/alpha-solenoid protein that cradles and stabilizes the catalytic NAA20 subunit and anchors the complex to ribosomes, positioning it to act on nascent polypeptides. It is a cytoplasmic protein and is required for normal cell-cycle progression. Loss of NatB activity (e.g. NAA20 variants) is associated with neurodevelopmental disease, underscoring the physiological importance of NatB-mediated N-terminal acetylation.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0007010 cytoskeleton organization
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Phylogenetically inferred from NatB orthologs (yeast/fly), where NatB-mediated N-terminal acetylation of actin and tropomyosin affects actin cytoskeleton and tropomyosin function. For human NAA25 this is a downstream biological-process consequence of NatB substrate acetylation, not a direct molecular activity of the auxiliary subunit.
Reason: Plausible process annotation inherited by phylogenetic transfer from NatB orthologs whose substrates (tropomyosin/actin) link N-terminal acetylation to the cytoskeleton; it is indirect and peripheral to NAA25's core complex/scaffold role.
Supporting Evidence:
file:human/NAA25/NAA25-goa.tsv
GO:0007010 cytoskeleton organization biological_process ECO:0000318 IBA
GO:0010698 acetyltransferase activator activity
IBA
GO_REF:0000033 		ACCEPT
Summary: NAA25 is the non-catalytic auxiliary subunit of NatB that binds and activates/scaffolds the catalytic subunit NAA20. Acetyltransferase activator activity is the appropriate molecular function for this auxiliary role, since NAA25 itself does not catalyze acetyl transfer but is required for full NatB activity.
Reason: This term correctly captures NAA25's core non-catalytic function as the activating/scaffolding subunit of the NatB acetyltransferase, consistent with the requirement of NAA25 for the NatB complex to display N-terminal acetyltransferase activity.
Supporting Evidence:
PMID:18570629
They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-.
file:human/NAA25/NAA25-uniprot.txt
Non-catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln.
GO:0031416 NatB complex
IBA
GO_REF:0000033 		ACCEPT
Summary: NAA25 is a constitutive component of the NatB N-terminal acetyltransferase complex (NAA20 + NAA25). This is the core cellular component for the gene.
Reason: Membership in the NatB complex is established experimentally (co-purification, cryo-EM) and by phylogenetic inference; it is the defining cellular component of NAA25.
Supporting Evidence:
file:human/NAA25/NAA25-uniprot.txt
Component of the N-terminal acetyltransferase B (NatB) complex which is composed of NAA20 and NAA25.
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation of cytoplasmic localization, consistent with the experimentally documented cytoplasmic location of NatB.
Reason: Correct compartment for this cytoplasmic, ribosome-associated complex subunit; agrees with experimental IDA evidence.
Supporting Evidence:
file:human/NAA25/NAA25-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005515 protein binding
IPI
PMID:18570629
Identification of the human N(alpha)-acetyltransferase compl... 		KEEP AS NON CORE
Summary: IntAct-derived interaction with NAA20 (P61599), the catalytic NatB subunit. The bare protein binding term is uninformative; the biologically meaningful interaction is assembly of the NatB complex, already captured by the NatB complex annotation.
Reason: Records a real, functionally relevant interaction (with the catalytic subunit NAA20) but the uninformative GO:0005515 term is not core; the informative content is the NatB complex membership.
Supporting Evidence:
file:human/NAA25/NAA25-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18570629 UniProtKB:P61599
GO:0005829 cytosol
IDA
GO_REF:0000052 		ACCEPT
Summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent with NAA25's role in the cytoplasmic NatB complex.
Reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic site of action of NatB.
Supporting Evidence:
file:human/NAA25/NAA25-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005737 cytoplasm
IDA
PMID:18570629
Identification of the human N(alpha)-acetyltransferase compl... 		ACCEPT
Summary: Direct experimental evidence (ComplexPortal, from the hNatB identification study) for cytoplasmic localization of the NatB complex.
Reason: Experimentally supported cytoplasmic localization consistent with co-translational action on ribosomes.
Supporting Evidence:
file:human/NAA25/NAA25-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0031416 NatB complex
IPI
PMID:18570629
Identification of the human N(alpha)-acetyltransferase compl... 		ACCEPT
Summary: ComplexPortal/IPI evidence that NAA25 is part of the NatB complex, from the study that identified the human NatB complex.
Reason: Direct experimental support for NatB complex membership; the defining cellular component of NAA25.
Supporting Evidence:
PMID:18570629
They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-.
GO:0005515 protein binding
IPI
PMID:34230638
Missense NAA20 variants impairing the NatB protein N-termina... 		KEEP AS NON CORE
Summary: Interaction with NAA20 (P61599) documented in the study of disease-causing NAA20 variants. The bare protein binding term is uninformative; the interaction reflects NatB complex assembly.
Reason: Real interaction with the catalytic NatB subunit but uninformative as a GO:0005515 annotation; the NatB complex membership term captures the meaningful content.
Supporting Evidence:
file:human/NAA25/NAA25-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:34230638 UniProtKB:P61599

Core Functions

Non-catalytic auxiliary subunit of the NatB N-terminal acetyltransferase complex that binds, activates and scaffolds the catalytic subunit NAA20, enabling co-translational N-terminal acetylation of Met-Asp/Met-Glu/Met-Asn/Met-Gln protein N-termini.

Molecular Function:
acetyltransferase activator activity
Cellular Locations:
cytoplasm
In Complex:
NatB complex
Supporting Evidence:
  • file:human/NAA25/NAA25-uniprot.txt
    Non-catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln.
  • PMID:18570629
    They form a stable complex and in vitro display sequence-specific N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-.

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:18570629
Identification of the human N(alpha)-acetyltransferase complex B (hNatB): a complex important for cell-cycle progression.
  • The human NatB complex consists of the catalytic subunit hNAT3 (NAA20) and the auxiliary subunit hMDM20 (NAA25); they form a stable complex with sequence-specific N-terminal acetyltransferase activity on Met-Asp- N-termini.
  • hNAT3 and hMDM20 co-sediment with ribosomal pellets, supporting co-translational action of NatB on nascent polypeptides.
  • Knockdown of hMDM20 (NAA25) disrupts normal cell-cycle progression and inhibits growth of HeLa cells.
PMID:34230638
Missense NAA20 variants impairing the NatB protein N-terminal acetyltransferase cause autosomal recessive developmental delay, intellectual disability, and microcephaly.
  • NatB is composed of NAA20 and NAA25; impairment of NatB N-terminal acetyltransferase activity by NAA20 variants causes a recessive neurodevelopmental disorder, underscoring the physiological importance of NatB.

Suggested Questions for Experts

Q: Does the NAA25 alpha-solenoid scaffold contribute to ribosome anchoring of NatB independently of NAA20, and which surface mediates ribosome binding?

Q: Are there human NAA25 (as opposed to NAA20) loss-of-function variants, and do they phenocopy the NAA20-associated neurodevelopmental disorder?

Suggested Experiments

Experiment: Cryo-EM of the NatB-ribosome-nascent chain complex to define how NAA25 positions the catalytic NAA20 subunit at the ribosomal exit tunnel.

Experiment: Separation-of-function mutagenesis of the NAA25 TPR/solenoid surfaces to dissect NAA20-binding (activation) from ribosome-anchoring, assayed by in vitro N-terminal acetylation and ribosome co-sedimentation.

Experiment: N-terminomics (e.g. SILAC-based COFRADIC) of NAA25-depleted human cells to map the NatB substrate repertoire whose N-terminal acetylation depends on the auxiliary subunit.

๐Ÿ“š Additional Documentation

Notes

(NAA25-notes.md)

NAA25 (N-alpha-acetyltransferase 25, NatB auxiliary subunit / MDM20) research notes

Identity

  • UniProt Q14CX7; HGNC:25783; aka MDM20, NAP1, C12orf30, p120. 972 aa, TPR-repeat / ฮฑ-solenoid protein.
  • AUXILIARY (non-catalytic) subunit of the human NatB N-terminal acetyltransferase complex. NatB = NAA20 (catalytic) + NAA25 (auxiliary). The catalytic subunit (acetyltransferase activity) is NAA20, NOT NAA25.

Core function

  • Non-catalytic scaffold of NatB; NatB acetylates N-terminal Met of substrates retaining iMet before acidic/amide residues (Met-Asp, Met-Glu, Met-Asn, Met-Gln).
    PMID:18570629
  • NatB acts co-translationally; subunits co-sediment with ribosomes.
    PMID:18570629
  • hMDM20/NAA25 is required for normal cell-cycle progression; knockdown disrupts cell cycle.
    PMID:18570629
  • NatB N-terminal acetylation of actin/tropomyosin in yeast is linked to actin cytoskeleton/tropomyosin function (origin of the IBA "cytoskeleton organization" annotation from yeast/fly NatB phenotypes). In humans this is an inferred downstream BP, not a direct molecular activity of NAA25.

Structure / complex

  • NatB complex composed of NAA20 + NAA25. [UniProt SUBUNIT "composed of NAA20 and NAA25"; PMID:34230638]
  • Cryo-EM structures of human NatB (PDB 6VP9, 7STX, 8G0L) confirm NAA25 as the large ฮฑ-solenoid auxiliary subunit cradling catalytic NAA20.
  • NAA20 missense variants impairing NatB cause autosomal-recessive developmental delay/ID/microcephaly. PMID:34230638

Annotation notes

  • GO:0010698 acetyltransferase activator activity (IBA) โ€” appropriate MF for an auxiliary subunit that activates/scaffolds the catalytic subunit; this is the best available non-catalytic MF. ACCEPT as core (auxiliary role).
  • GO:0031416 NatB complex (part_of) โ€” well supported (IBA/IPI/ComplexPortal). Core CC.
  • GO:0007010 cytoskeleton organization (IBA) โ€” downstream BP from yeast NatB substrate (tropomyosin/actin); keep non-core.
  • protein binding IPI (PMID:18570629, PMID:34230638) both WITH NAA20 (P61599) โ€” the real catalytic partner; better captured by NatB complex membership. Non-core / modify-adjacent; KEEP_AS_NON_CORE.
  • cytoplasm/cytosol localizations consistent (IDA HPA, IDA ComplexPortal, IEA). Golgi IDA (HPA) is in UniProt DR but not in the GOA stub โ€” not reviewed.

Pn Notes

(NAA25-pn-notes.md)

NAA25 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q14CX7
  • 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: NAA25 (N-alpha-acetyltransferase 25; also MDM20, NAP1, p120) is the large non-catalytic auxiliary subunit of the human NatB N-terminal acetyltransferase complex. NatB is composed of the catalytic subunit NAA20 and the auxiliary subunit NAA25, and it co-translationally acetylates the alpha-amino group of N-terminal methionine residues that are retained in front of acidic or amide side chains (Met-Asp, Met-Glu, Met-Asn and Met-Gln N-termini). NAA25 is a TPR-repeat/alpha-solenoid protein that cradles and stabilizes the catalytic NAA20 subunit and anchors the complex to ribosomes, positioning it to act on nascent polypeptides. It is a cytoplasmic protein and is required for normal cell-cycle progression. Loss of NatB activity (e.g. NAA20 variants) is associated with neurodevelopmental disease, underscoring the physiological importance of NatB-mediated N-terminal acetylation.
  • Existing/core annotation action counts: ACCEPT: 6; KEEP_AS_NON_CORE: 3

PN Consistency Summary

  • Consistency: Strong agreement. Review, notes, and PN concur NAA25 is the auxiliary, non-catalytic subunit of NatB (catalytic subunit is NAA20, not NAA25): NatB complex (GO:0031416, IBA/IPI/ComplexPortal accepted), activator activity (GO:0010698 IBA accepted), cytoplasm. Critically the PN subtype is correctly NatB (GO:0031416), not NatA โ€” distinct from NAA10/NAA15. No contradictions.
  • PN story / NEW pressure: Modest. The PN BP GO:0006474 is flagged new_to_goa for NAA25 (NAA25's GOA has GO:0031416, GO:0010698, GO:0007010, localizations, GO:0005515 โ€” but no GO:0006474). So "N-terminal protein amino acid acetylation" as a process annotation would be genuinely new to NAA25's GOA. It is defensible as process participation (NAA25 is required for NatB activity), but for a non-catalytic scaffold the review prefers the activator MF + complex CC. Verdict: borderline ADD vs already-captured-by-proxy; lean already captured via GO:0010698 + GO:0031416, since GO:0006474 risks implying catalytic involvement by the auxiliary subunit.
  • Evidence alignment: PN row carries no reference titles. Review anchors on PMID:18570629 (hNatB identification, VERIFIED) and PMID:34230638 (NAA20 disease variants, VERIFIED, contextual). Good overlap with the primary NatB literature; no divergence.
  • Verdict: Consistent; auxiliary NatB-subunit identity correct and properly distinguished from NatA. No edits. The PN GO:0006474 BP projection is new-to-GOA but optional โ€” the activator MF + NatB CC already convey the function without over-attributing catalysis.

Full Consistency Review

  • UniProt: Q14CX7 ยท batch: proteostasis-batch-2026-06-07c ยท review status: COMPLETE
  • PN placement: Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatB complex component (TR only). PN-node mapping: subtypeโ†’GO:0031416 NatB complex (mapped, CC); typeโ†’GO:0006474 N-terminal protein amino acid acetylation (mapped, BP); group no_mapping; class/branch context_only.
  • Consistency: Strong agreement. Review, notes, and PN concur NAA25 is the auxiliary, non-catalytic subunit of NatB (catalytic subunit is NAA20, not NAA25): NatB complex (GO:0031416, IBA/IPI/ComplexPortal accepted), activator activity (GO:0010698 IBA accepted), cytoplasm. Critically the PN subtype is correctly NatB (GO:0031416), not NatA โ€” distinct from NAA10/NAA15. No contradictions.
  • PN story / NEW pressure: Modest. The PN BP GO:0006474 is flagged new_to_goa for NAA25 (NAA25's GOA has GO:0031416, GO:0010698, GO:0007010, localizations, GO:0005515 โ€” but no GO:0006474). So "N-terminal protein amino acid acetylation" as a process annotation would be genuinely new to NAA25's GOA. It is defensible as process participation (NAA25 is required for NatB activity), but for a non-catalytic scaffold the review prefers the activator MF + complex CC. Verdict: borderline ADD vs already-captured-by-proxy; lean already captured via GO:0010698 + GO:0031416, since GO:0006474 risks implying catalytic involvement by the auxiliary subunit.
  • Mapping strategy: GO:0031416 NatB complex (CC) is exact and the correct shared term โ€” properly distinguishes NAA25 (NatB) from the NAA10/NAA15 NatA node. The cytoskeleton-organization IBA (GO:0007010, from yeast/fly NatB substrate acetylation) is correctly KEEP_AS_NON_CORE; the PN does not project it. No node change needed.
  • Evidence alignment: PN row carries no reference titles. Review anchors on PMID:18570629 (hNatB identification, VERIFIED) and PMID:34230638 (NAA20 disease variants, VERIFIED, contextual). Good overlap with the primary NatB literature; no divergence.
  • Verdict: Consistent; auxiliary NatB-subunit identity correct and properly distinguished from NatA. No edits. The PN GO:0006474 BP projection is new-to-GOA but optional โ€” the activator MF + NatB CC already convey the function without over-attributing catalysis.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/NAA25/NAA25-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q14CX7
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [subtype] Translation|Cytosolic translation|Nascent peptide husbandry|N-terminal acetylation of nascent peptide|NatB complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0031416 NatB complex]
      rationale: Exact cellular-component match: members are subunits of the NatB 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.

๐Ÿ“„ View Raw YAML

 
id: Q14CX7
gene_symbol: NAA25
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: NAA25 (N-alpha-acetyltransferase 25; also MDM20, NAP1, p120) is the large
  non-catalytic auxiliary subunit of the human NatB N-terminal acetyltransferase complex.
  NatB is composed of the catalytic subunit NAA20 and the auxiliary subunit NAA25,
  and it co-translationally acetylates the alpha-amino group of N-terminal methionine
  residues that are retained in front of acidic or amide side chains (Met-Asp, Met-Glu,
  Met-Asn and Met-Gln N-termini). NAA25 is a TPR-repeat/alpha-solenoid protein that
  cradles and stabilizes the catalytic NAA20 subunit and anchors the complex to ribosomes,
  positioning it to act on nascent polypeptides. It is a cytoplasmic protein and is
  required for normal cell-cycle progression. Loss of NatB activity (e.g. NAA20 variants)
  is associated with neurodevelopmental disease, underscoring the physiological importance
  of NatB-mediated N-terminal acetylation.
alternative_products:
- name: '1'
  id: Q14CX7-1
- name: '2'
  id: Q14CX7-2
  sequence_note: VSP_026629, VSP_026630
existing_annotations:
- term:
    id: GO:0007010
    label: cytoskeleton organization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically inferred from NatB orthologs (yeast/fly), where NatB-mediated
      N-terminal acetylation of actin and tropomyosin affects actin cytoskeleton and
      tropomyosin function. For human NAA25 this is a downstream biological-process
      consequence of NatB substrate acetylation, not a direct molecular activity of
      the auxiliary subunit.
    action: KEEP_AS_NON_CORE
    reason: Plausible process annotation inherited by phylogenetic transfer from NatB
      orthologs whose substrates (tropomyosin/actin) link N-terminal acetylation to
      the cytoskeleton; it is indirect and peripheral to NAA25's core complex/scaffold
      role.
    supported_by:
    - reference_id: file:human/NAA25/NAA25-goa.tsv
      supporting_text: GO:0007010 cytoskeleton organization biological_process ECO:0000318
        IBA
- term:
    id: GO:0010698
    label: acetyltransferase activator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: NAA25 is the non-catalytic auxiliary subunit of NatB that binds and activates/scaffolds
      the catalytic subunit NAA20. Acetyltransferase activator activity is the appropriate
      molecular function for this auxiliary role, since NAA25 itself does not catalyze
      acetyl transfer but is required for full NatB activity.
    action: ACCEPT
    reason: This term correctly captures NAA25's core non-catalytic function as the
      activating/scaffolding subunit of the NatB acetyltransferase, consistent with
      the requirement of NAA25 for the NatB complex to display N-terminal acetyltransferase
      activity.
    supported_by:
    - reference_id: PMID:18570629
      supporting_text: They form a stable complex and in vitro display sequence-specific
        N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-.
    - reference_id: file:human/NAA25/NAA25-uniprot.txt
      supporting_text: Non-catalytic subunit of the NatB complex which catalyzes acetylation
        of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu,
        Met-Asn and Met-Gln.
- term:
    id: GO:0031416
    label: NatB complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: NAA25 is a constitutive component of the NatB N-terminal acetyltransferase
      complex (NAA20 + NAA25). This is the core cellular component for the gene.
    action: ACCEPT
    reason: Membership in the NatB complex is established experimentally (co-purification,
      cryo-EM) and by phylogenetic inference; it is the defining cellular component
      of NAA25.
    supported_by:
    - reference_id: file:human/NAA25/NAA25-uniprot.txt
      supporting_text: Component of the N-terminal acetyltransferase B (NatB) complex
        which is composed of NAA20 and NAA25.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic annotation of cytoplasmic localization, consistent with the
      experimentally documented cytoplasmic location of NatB.
    action: ACCEPT
    reason: Correct compartment for this cytoplasmic, ribosome-associated complex subunit;
      agrees with experimental IDA evidence.
    supported_by:
    - reference_id: file:human/NAA25/NAA25-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18570629
  qualifier: enables
  review:
    summary: IntAct-derived interaction with NAA20 (P61599), the catalytic NatB subunit.
      The bare protein binding term is uninformative; the biologically meaningful interaction
      is assembly of the NatB complex, already captured by the NatB complex annotation.
    action: KEEP_AS_NON_CORE
    reason: Records a real, functionally relevant interaction (with the catalytic subunit
      NAA20) but the uninformative GO:0005515 term is not core; the informative content
      is the NatB complex membership.
    supported_by:
    - reference_id: file:human/NAA25/NAA25-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:18570629 UniProtKB:P61599
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) evidence for cytosolic localization, consistent
      with NAA25's role in the cytoplasmic NatB complex.
    action: ACCEPT
    reason: IDA-supported cytosolic localization agrees with the documented cytoplasmic
      site of action of NatB.
    supported_by:
    - reference_id: file:human/NAA25/NAA25-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000314 IDA GO_REF:0000052
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18570629
  qualifier: located_in
  review:
    summary: Direct experimental evidence (ComplexPortal, from the hNatB identification
      study) for cytoplasmic localization of the NatB complex.
    action: ACCEPT
    reason: Experimentally supported cytoplasmic localization consistent with co-translational
      action on ribosomes.
    supported_by:
    - reference_id: file:human/NAA25/NAA25-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0031416
    label: NatB complex
  evidence_type: IPI
  original_reference_id: PMID:18570629
  qualifier: part_of
  review:
    summary: ComplexPortal/IPI evidence that NAA25 is part of the NatB complex, from
      the study that identified the human NatB complex.
    action: ACCEPT
    reason: Direct experimental support for NatB complex membership; the defining cellular
      component of NAA25.
    supported_by:
    - reference_id: PMID:18570629
      supporting_text: They form a stable complex and in vitro display sequence-specific
        N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34230638
  qualifier: enables
  review:
    summary: Interaction with NAA20 (P61599) documented in the study of disease-causing
      NAA20 variants. The bare protein binding term is uninformative; the interaction
      reflects NatB complex assembly.
    action: KEEP_AS_NON_CORE
    reason: Real interaction with the catalytic NatB subunit but uninformative as a
      GO:0005515 annotation; the NatB complex membership term captures the meaningful
      content.
    supported_by:
    - reference_id: file:human/NAA25/NAA25-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:34230638 UniProtKB:P61599
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  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:18570629
  title: 'Identification of the human N(alpha)-acetyltransferase complex B (hNatB):
    a complex important for cell-cycle progression.'
  findings:
  - statement: The human NatB complex consists of the catalytic subunit hNAT3 (NAA20)
      and the auxiliary subunit hMDM20 (NAA25); they form a stable complex with sequence-specific
      N-terminal acetyltransferase activity on Met-Asp- N-termini.
    reference_section_type: ABSTRACT
  - statement: hNAT3 and hMDM20 co-sediment with ribosomal pellets, supporting co-translational
      action of NatB on nascent polypeptides.
    reference_section_type: ABSTRACT
  - statement: Knockdown of hMDM20 (NAA25) disrupts normal cell-cycle progression and
      inhibits growth of HeLa cells.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches the YAML title; GOA also anchors this PMID to IPI for GO:0031416 (NatB complex). This is the NatB complex-characterization paper establishing NAA25 (hMDM20) as the auxiliary subunit partnering NAA20, the gene's core function.
- id: PMID:34230638
  title: Missense NAA20 variants impairing the NatB protein N-terminal acetyltransferase
    cause autosomal recessive developmental delay, intellectual disability, and microcephaly.
  findings:
  - statement: NatB is composed of NAA20 and NAA25; impairment of NatB N-terminal acetyltransferase
      activity by NAA20 variants causes a recessive neurodevelopmental disorder, underscoring
      the physiological importance of NatB.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached publication title matches the YAML title; concerns disease variants in the catalytic subunit NAA20 (not NAA25 itself) but establishes the physiological importance of the NatB complex of which NAA25 is the auxiliary subunit. Supporting/contextual for NAA25.
core_functions:
- description: Non-catalytic auxiliary subunit of the NatB N-terminal acetyltransferase
    complex that binds, activates and scaffolds the catalytic subunit NAA20, enabling
    co-translational N-terminal acetylation of Met-Asp/Met-Glu/Met-Asn/Met-Gln protein
    N-termini.
  molecular_function:
    id: GO:0010698
    label: acetyltransferase activator activity
  in_complex:
    id: GO:0031416
    label: NatB complex
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/NAA25/NAA25-uniprot.txt
    supporting_text: Non-catalytic subunit of the NatB complex which catalyzes acetylation
      of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu,
      Met-Asn and Met-Gln.
  - reference_id: PMID:18570629
    supporting_text: They form a stable complex and in vitro display sequence-specific
      N(alpha)-acetyltransferase activity on a peptide with the N-terminus Met-Asp-.
proposed_new_terms: []
suggested_questions:
- question: Does the NAA25 alpha-solenoid scaffold contribute to ribosome anchoring
    of NatB independently of NAA20, and which surface mediates ribosome binding?
- question: Are there human NAA25 (as opposed to NAA20) loss-of-function variants,
    and do they phenocopy the NAA20-associated neurodevelopmental disorder?
suggested_experiments:
- description: Cryo-EM of the NatB-ribosome-nascent chain complex to define how NAA25
    positions the catalytic NAA20 subunit at the ribosomal exit tunnel.
- description: Separation-of-function mutagenesis of the NAA25 TPR/solenoid surfaces
    to dissect NAA20-binding (activation) from ribosome-anchoring, assayed by in vitro
    N-terminal acetylation and ribosome co-sedimentation.
- description: N-terminomics (e.g. SILAC-based COFRADIC) of NAA25-depleted human cells
    to map the NatB substrate repertoire whose N-terminal acetylation depends on the
    auxiliary subunit.