Nat8l

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0031966 mitochondrial membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: The mitochondrial membrane annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Mitochondrion membrane {ECO:0000269\|PubMed:18621030}; Single-pass membrane protein
GO:0017188 L-aspartate N-acetyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Nat8l is a N-acetylaspartate synthetase; the L-aspartate N-acetyltransferase activity annotation is supported by the fetched UniProt/GOA evidence (IBA, GO_REF:0000033) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Nat8l core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:D3ZVU9 Reaction=L-aspartate + acetyl-CoA = N-acetyl-L-aspartate + CoA + H(+) file:rat/Nat8l/Nat8l-deep-research-falcon.md Rattus norvegicus Nat8l encodes N-acetylaspartate synthetase / aspartate N-acetyltransferase (NAT8L; Asp-NAT; EC 2.3.1.17), the enzyme that synthesizes N-acetylaspartate (NAA) from acetyl‑CoA and L‑aspartate.
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: The cytoplasm annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250\|UniProtKB:Q8N9F0}.
GO:0005739 mitochondrion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: The mitochondrion annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Mitochondrion membrane {ECO:0000269\|PubMed:18621030}; Single-pass membrane protein
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: The endoplasmic reticulum membrane annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Falcon deep research notes a microsomal/ER-associated pool consistent with this localization. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q3UGX3}; Single-pass membrane protein file:rat/Nat8l/Nat8l-deep-research-falcon.md Localization remains somewhat mixed across experimental approaches, but NAT8L is consistently described as a membrane-associated enzyme with microsomal/ER-associated and mitochondrial-associated pools.
GO:0008080 N-acetyltransferase activity	IEA GO_REF:0000002	MODIFY	Summary: The N-acetyltransferase activity annotation is related to Nat8l function, but it is too generic compared with the supported specific term(s): L-aspartate N-acetyltransferase activity. Reason: The annotation is directionally related to Nat8l but is too broad; the specific catalytic activity is more informative. Proposed replacements: L-aspartate N-acetyltransferase activity Supporting Evidence: UniProtKB:D3ZVU9 FUNCTION: Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA (PubMed:18621030). file:rat/Nat8l/Nat8l-deep-research-falcon.md Substrate specificity: NAT8L/Asp-NAT is reported to be highly selective for aspartate. Enzymology summarized by Moffett et al. indicates <3% activity with glutamate/asparagine/glutamine compared with aspartate (stringent specificity), and also notes an approximately ~10-fold preference for aspartate over glutamate in other reports.
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	IEA GO_REF:0000002	MODIFY	Summary: The acyltransferase activity, transferring groups other than amino-acyl groups annotation is related to Nat8l function, but it is too generic compared with the supported specific term(s): L-aspartate N-acetyltransferase activity. Reason: The annotation is directionally related to Nat8l but is too broad; the specific catalytic activity is more informative. Proposed replacements: L-aspartate N-acetyltransferase activity Supporting Evidence: UniProtKB:D3ZVU9 FUNCTION: Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA (PubMed:18621030).
GO:0017188 L-aspartate N-acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Nat8l is a N-acetylaspartate synthetase; the L-aspartate N-acetyltransferase activity annotation is supported by the fetched UniProt/GOA evidence (IEA, GO_REF:0000120) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Nat8l core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:D3ZVU9 Reaction=L-aspartate + acetyl-CoA = N-acetyl-L-aspartate + CoA + H(+)
GO:0031966 mitochondrial membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: The mitochondrial membrane annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Mitochondrion membrane {ECO:0000269\|PubMed:18621030}; Single-pass membrane protein
GO:0005737 cytoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: The cytoplasm annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250\|UniProtKB:Q8N9F0}.
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: The endoplasmic reticulum membrane annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q3UGX3}; Single-pass membrane protein
GO:0031966 mitochondrial membrane	EXP PMID:18621030 N-acetylaspartate synthesis in the brain: mitochondria vs. m...	KEEP AS NON CORE	Summary: The mitochondrial membrane annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Falcon deep research notes localization is genuinely unresolved (microsomal/ER and mitochondrial pools), so a single-compartment claim should be avoided. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Mitochondrion membrane {ECO:0000269\|PubMed:18621030}; Single-pass membrane protein file:rat/Nat8l/Nat8l-deep-research-falcon.md NAT8L’s precise subcellular localization (ER/microsome vs mitochondria, or dual) and native complex organization remain debated, with evidence supporting multiple fractions and large complexes
GO:0005759 mitochondrial matrix	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: The mitochondrial matrix annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: Asp-NAT activity in rat brain fractionates predominantly with mitochondria, so a mitochondrial site of action is supported; the sub-mitochondrial compartment is less certain, since UniProt describes a single-pass mitochondrial membrane protein rather than a soluble matrix enzyme. Kept as non-core localization context. Supporting Evidence: PMID:18621030 about 70% of the total Asp-NAT activity in the crude supernatant was present in the mitochondrial fraction
GO:0006083 acetate metabolic process	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: Nat8l does not directly participate in acetate metabolism. Its product is N-acetylaspartate (NAA); acetate is generated two enzymatic steps and one cell-type boundary downstream, when oligodendroglial ASPA hydrolyzes NAA into acetate and aspartate. This term therefore over-annotates Nat8l with a downstream pathway product it does not produce. Reason: Acetate is produced by ASPA in oligodendrocytes, not by Nat8l. Nat8l synthesizes NAA in neurons; the acetate it ultimately gives rise to is a downstream catabolite generated by a different enzyme in a different cell type, so this is an over-annotation rather than a direct or core function. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:2447776 · mouse Nat8l SUPPORTS SOURCE BUT NOT TARGET The mouse Nat8l donor annotation covers NAA synthesis; the acetate moiety is only released downstream by ASPA in a different cell type, so the acetate-metabolism term conflates substrate chemistry with the enzyme's role. Supporting Evidence: UniProtKB:D3ZVU9 Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA file:rat/Nat8l/Nat8l-deep-research-falcon.md NAT8L initiates the NAA pathway in neurons. NAA is transferred to oligodendrocytes, where ASPA hydrolyzes NAA → acetate + aspartate; acetate supports acetyl-CoA, lipid/myelin synthesis, and acetylation reactions.
GO:0006531 aspartate metabolic process	ISO GO_REF:0000121	ACCEPT	Summary: Nat8l is a N-acetylaspartate synthetase; the aspartate metabolic process annotation is supported by the fetched UniProt/GOA evidence (ISO, GO_REF:0000121) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Nat8l core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:D3ZVU9 Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA file:rat/Nat8l/Nat8l-deep-research-falcon.md Rattus norvegicus Nat8l encodes N-acetylaspartate synthetase / aspartate N-acetyltransferase (NAT8L; Asp-NAT; EC 2.3.1.17), the enzyme that synthesizes N-acetylaspartate (NAA) from acetyl‑CoA and L‑aspartate.
GO:0005739 mitochondrion	IDA PMID:18621030 N-acetylaspartate synthesis in the brain: mitochondria vs. m...	KEEP AS NON CORE	Summary: The mitochondrion annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Mitochondrion membrane {ECO:0000269\|PubMed:18621030}; Single-pass membrane protein
GO:0017188 L-aspartate N-acetyltransferase activity	ISO GO_REF:0000121	ACCEPT	Summary: Nat8l is a N-acetylaspartate synthetase; the L-aspartate N-acetyltransferase activity annotation is supported by the fetched UniProt/GOA evidence (ISO, GO_REF:0000121) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Nat8l core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:D3ZVU9 Reaction=L-aspartate + acetyl-CoA = N-acetyl-L-aspartate + CoA + H(+)
GO:0017188 L-aspartate N-acetyltransferase activity	IDA PMID:18621030 N-acetylaspartate synthesis in the brain: mitochondria vs. m...	ACCEPT	Summary: Nat8l is a N-acetylaspartate synthetase; the L-aspartate N-acetyltransferase activity annotation is supported by the fetched UniProt/GOA evidence (IDA, PMID:18621030) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Nat8l core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:D3ZVU9 Reaction=L-aspartate + acetyl-CoA = N-acetyl-L-aspartate + CoA + H(+)
GO:0043231 intracellular membrane-bounded organelle	IDA PMID:18621030 N-acetylaspartate synthesis in the brain: mitochondria vs. m...	KEEP AS NON CORE	Summary: The intracellular membrane-bounded organelle annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Microsome membrane {ECO:0000269\|PubMed:18621030}; Single-pass type I membrane protein
GO:0051586 positive regulation of dopamine uptake involved in synaptic transmission	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: The positive regulation of dopamine uptake involved in synaptic transmission annotation reflects an indirect link (mouse Shati/Nat8l promotes dopamine uptake via TNF expression), not a direct molecular activity. Nat8l has no transporter or signaling activity at the synapse; its established biochemical role is NAA synthesis. Reason: Nat8l does not act in the dopamine uptake machinery. UniProt (by similarity to mouse Shati/Nat8l) records that it promotes dopamine uptake by regulating TNF expression, i.e. an indirect effect mediated by a cytokine; the term, which specifies a role in synaptic transmission, overstates this upstream influence relative to the enzyme's established NAA-synthesis activity. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:2447776 · mouse Nat8l SUPPORTS SOURCE BUT NOT TARGET The mouse Nat8l (Shati) donor annotation reflects increased dopamine uptake mediated through TNF expression, an indirect effect; the mouse experiment itself is not adjudicated here, but the term overstates the mechanism when transferred to rat Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Promotes dopamine uptake by regulating TNF expression (By similarity).
GO:0005737 cytoplasm	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: The cytoplasm annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250\|UniProtKB:Q8N9F0}.
GO:0005789 endoplasmic reticulum membrane	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: The endoplasmic reticulum membrane annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q3UGX3}; Single-pass membrane protein
GO:0031966 mitochondrial membrane	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: The mitochondrial membrane annotation is plausible for Nat8l but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Nat8l. Supporting Evidence: UniProtKB:D3ZVU9 Mitochondrion membrane {ECO:0000269\|PubMed:18621030}; Single-pass membrane protein
GO:0008080 N-acetyltransferase activity	IBA GO_REF:0000033	MODIFY	Summary: N-acetyltransferase activity inferred by PAINT from the NAT8-family ancestral node PTN000358947 (experimental donors include human NAT8 and NAT8B). The function is correctly inherited, but for Nat8l the specific acceptor is known. Reason: There is no evidence that Nat8l lies outside the clade that inherited N-acetyltransferase activity, and the annotation is correct. However, Nat8l's acceptor substrate is established (L-aspartate), so the specific child term GO:0017188 is more informative; this matches the action on the InterPro-based IEA row for the same term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000358947 SUPPORTS TRANSFER NAT8-family ancestral node; N-acetyltransferase activity is sound for Nat8l but less specific than its known L-aspartate N-acetyltransferase activity. Proposed replacements: L-aspartate N-acetyltransferase activity Supporting Evidence: UniProtKB:D3ZVU9 Reaction=L-aspartate + acetyl-CoA = N-acetyl-L-aspartate + CoA + H(+)
GO:0017188 L-aspartate N-acetyltransferase activity	ISO GO_REF:0000121	ACCEPT	Summary: L-aspartate N-acetyltransferase activity transferred by orthology from human NAT8L (UniProtKB:Q8N9F0); donor-split duplicate of the ISO row from mouse Nat8l (MGI:2447776). Reason: Human NAT8L is the direct ortholog and catalyses NAA synthesis from L-aspartate and acetyl-CoA, the conserved core activity; the activity is also recorded for rat Asp-NAT directly (IDA, PMID:18621030). The transfer from the human donor is sound. Supporting Evidence: UniProtKB:D3ZVU9 Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA

Gene Description

Proposed New Ontology Terms

N-acetyl-L-aspartate biosynthetic process

Existing Annotations Review

Core Functions

Nat8l encodes rat N-acetylaspartate synthetase. FUNCTION: Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA (PubMed:18621030).

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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