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

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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)

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Pn Notes

(NAA38-pn-notes.md)

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