NMNAT1 is the nuclear isoform of nicotinamide/nicotinic acid mononucleotide adenylyltransferase, one of three human NMNAT isoenzymes (NMNAT1 nuclear, NMNAT2 Golgi, NMNAT3 mitochondrial). It catalyses the central, committed adenylyl-transfer step shared by all routes of NAD+ biosynthesis: transfer of an adenylyl group from ATP to nicotinamide mononucleotide (NMN) to form NAD+ with release of pyrophosphate (EC 2.7.7.1), and, with comparable efficiency, to the deamidated substrate nicotinate mononucleotide (NaMN) to form nicotinate adenine dinucleotide (deamido-NAD+/NaAD; EC 2.7.7.18). NMNAT1 therefore sits at the convergence of the de novo (kynurenine), salvage and Preiss-Handler pathways. The enzyme requires a divalent metal cofactor (Zn2+ gives higher activity than Mg2+), assembles into a homohexamer, and is imported into the nucleus via a nuclear localization signal. In the nucleus it supplies NAD+ locally to NAD+-consuming enzymes such as PARP1 and the sirtuin SIRT1, and participates in nuclear ATP generation from poly-ADP-ribose that supports chromatin remodeling. In humans, loss-of-function variants cause Leber congenital amaurosis 9 and the multisystem SHILCA syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004515 nicotinate-nucleotide adenylyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) call of the NaMN adenylyltransferase (EC 2.7.7.18) activity. This is a core, experimentally verified catalytic function of NMNAT1 and is consistent with UniProt EC 2.7.7.18 and the Reactome NaMN->NaAD reaction. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Reaction=nicotinate beta-D-ribonucleotide + ATP + H(+) = deamido-NAD(+) |
| GO:0000309 nicotinamide-nucleotide adenylyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) call of the NMN adenylyltransferase (EC 2.7.7.1) activity, the defining core molecular function of NMNAT1. Consistent with direct experimental evidence. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Catalyzes the formation of NAD(+) from nicotinamide |
| GO:0034355 NAD+ biosynthetic process via the salvage pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: NMNAT1 catalyses the final adenylyl-transfer step of the NAD+ salvage route (NMN -> NAD+). The salvage-pathway framing is correct but narrower than NMNAT1's actual role, since the same enzyme also acts in the de novo and Preiss-Handler routes (NaMN -> NaAD). Retained as a valid, if pathway-specific, biological process annotation. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Catalyzes the formation of NAD(+) from nicotinamide |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: NMNAT1 is the nuclear NMNAT isoform, imported via an NLS and confirmed nuclear by immunofluorescence and biochemistry. Core localization. Supporting Evidence: PMID:16118205 localization confirmed NMNAT1 to be a nuclear protein, whereas NMNAT2 and -3 |
| GO:0000309 nicotinamide-nucleotide adenylyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assertion of the core NMN adenylyltransferase (EC 2.7.7.1) activity, redundant with and confirmed by the direct experimental annotations. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Catalyzes the formation of NAD(+) from nicotinamide |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Root-level catalytic activity term from InterPro. Correct but entirely subsumed by the specific adenylyltransferase activities (GO:0000309, GO:0004515); uninformative as a standalone annotation. |
| GO:0004515 nicotinate-nucleotide adenylyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assertion of the core NaMN adenylyltransferase (EC 2.7.7.18) activity, redundant with and confirmed by the direct experimental annotations. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Reaction=nicotinate beta-D-ribonucleotide + ATP + H(+) = deamido-NAD(+) |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic nucleus annotation, consistent with the well-established nuclear localization of NMNAT1. Supporting Evidence: PMID:16118205 localization confirmed NMNAT1 to be a nuclear protein, whereas NMNAT2 and -3 |
| GO:0006163 purine nucleotide metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA electronic annotation. NMNAT1 consumes ATP as an adenylyl donor, but its biological role is NAD+ (pyridine nucleotide) biosynthesis, not purine nucleotide metabolism. This term is over-broad and tangential; the pyridine nucleotide / NAD biosynthesis terms capture the true process. |
| GO:0009165 nucleotide biosynthetic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Generic parent of NAD+ biosynthetic process. True but non-specific; retained as a non-core annotation, with GO:0009435 the informative child. |
| GO:0009435 NAD+ biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Core biological process. NMNAT1 catalyses the committed adenylyl-transfer step of NAD+ biosynthesis shared by de novo, salvage and Preiss-Handler routes. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Catalyzes the formation of NAD(+) from nicotinamide |
| GO:0016779 nucleotidyltransferase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-derived parent term. Correct (NMNAT1 is an adenylyltransferase, a nucleotidyltransferase) but subsumed by the specific EC 2.7.7.1/2.7.7.18 MF terms. |
| GO:0005515 protein binding | IPI PMID:19478080 Enzymes in the NAD+ salvage pathway regulate SIRT1 activity ... | KEEP AS NON CORE | Summary: Bare protein binding. This IPI records the functionally meaningful NMNAT1-SIRT1 interaction, in which NMNAT1 is recruited to SIRT1 target promoters to supply nuclear NAD+ for deacetylation. The interaction is informative, but the GO term "protein binding" is uninformative and does not capture the adaptor/NAD+-supply function. Supporting Evidence: PMID:19478080 NMNAT-1 interacts with, and is recruited to |
| GO:0005515 protein binding | IPI PMID:24722188 Protein interaction network of alternatively spliced isoform... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding datapoint from a high-throughput brain spliceform interactome screen. Uninformative bare term; retained per policy but marked as over-annotated. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Generic protein-binding datapoint from a proteome-scale interactome map. Uninformative bare term. |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding datapoint from a high-throughput alternative-splicing interactome screen. Uninformative bare term. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding datapoint from a proteome-scale interactome (BioPlex). Uninformative bare term. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding datapoint from a high-throughput interactome/variant screen. Uninformative bare term. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein-binding datapoints from the HuRI reference binary interactome (the largest single source of NMNAT1 protein-binding IPI annotations). Uninformative bare term. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding datapoint from a proteome-scale AP-MS interactome (BioPlex 3.0). Uninformative bare term. |
| GO:0042802 identical protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | KEEP AS NON CORE | Summary: Self-interaction. NMNAT1 is a homohexamer in solution, so identical protein binding is biologically real. Kept as a non-core structural annotation. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Homohexamer (PubMed:11751893). |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Self-interaction consistent with the NMNAT1 homohexamer. Non-core structural annotation. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Homohexamer (PubMed:11751893). |
| GO:0042802 identical protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | KEEP AS NON CORE | Summary: Self-interaction consistent with the NMNAT1 homohexamer. Non-core structural annotation. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Homohexamer (PubMed:11751893). |
| GO:0042802 identical protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Self-interaction consistent with the NMNAT1 homohexamer. Non-core structural annotation. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Homohexamer (PubMed:11751893). |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Self-interaction consistent with the NMNAT1 homohexamer. Non-core structural annotation. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Homohexamer (PubMed:11751893). |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence (HPA) localization to the nucleoplasm, consistent with the nuclear localization of NMNAT1. Core localization at finer granularity than nucleus. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence detection in nuclear bodies. Plausible sub-nuclear compartment but not a core, functionally established localization; kept as non-core. |
| GO:0000309 nicotinamide-nucleotide adenylyltransferase activity | EXP PMID:17402747 Initial-rate kinetics of human NMN-adenylyltransferases: sub... | ACCEPT | Summary: Direct experimental (initial-rate kinetics) evidence for the core NMN adenylyltransferase (EC 2.7.7.1) activity. Defining molecular function. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Catalyzes the formation of NAD(+) from nicotinamide |
| GO:0004515 nicotinate-nucleotide adenylyltransferase activity | EXP PMID:17402747 Initial-rate kinetics of human NMN-adenylyltransferases: sub... | ACCEPT | Summary: Direct experimental (initial-rate kinetics) evidence for the core NaMN adenylyltransferase (EC 2.7.7.18) activity; NMNAT1 uses NaMN with the same efficiency as NMN. Defining molecular function. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Reaction=nicotinate beta-D-ribonucleotide + ATP + H(+) = deamido-NAD(+) |
| GO:0000309 nicotinamide-nucleotide adenylyltransferase activity | IDA PMID:16118205 Subcellular compartmentation and differential catalytic prop... | ACCEPT | Summary: Direct assay of NMN adenylyltransferase activity for the NMNAT1 isoform. Core molecular function. Supporting Evidence: PMID:16118205 as opposed to preferred NAD+ synthesis by |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity (By similarity, from mouse Nmnat1) transfer. NMNAT1 contributes to transcriptional repression through its role in supplying nuclear NAD+ to SIRT1 and directing PARP1 activity at chromatin. A real but indirect, non-core regulatory role that depends on the catalytic/adaptor functions. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt ADP-ribosylation by directing PARP1 catalytic activity to glutamate and |
| GO:0140768 protein ADP-ribosyltransferase-substrate adaptor activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: By-similarity (from mouse Nmnat1) activity: NMNAT1 acts as a cofactor that directs PARP1 catalytic activity toward glutamate/aspartate residues on histones, i.e. an ADP-ribosyltransferase-substrate adaptor. A genuine moonlighting function distinct from the core NAD+-synthetic activity; kept as non-core. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt ADP-ribosylation by directing PARP1 catalytic activity to glutamate and |
| GO:0009165 nucleotide biosynthetic process | IC PMID:16118205 Subcellular compartmentation and differential catalytic prop... | KEEP AS NON CORE | Summary: Curator inference (from the NaMN adenylyltransferase activity) of the generic parent process. True but non-specific relative to NAD+ biosynthetic process; kept as non-core. |
| GO:1990966 ATP generation from poly-ADP-D-ribose | IDA PMID:27257257 ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is requir... | KEEP AS NON CORE | Summary: Direct evidence that NMNAT1 participates (with PARP1, PARG and NUDT5/NUDIX5) in nuclear ATP generation from poly-ADP-ribose that supports chromatin remodeling. A real but specialized, non-core niche role. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt ATP in the nucleus, together with PARP1, PARG and NUDT5 |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: High-throughput proteomic detection of NMNAT1 in the human sperm nucleus. Consistent with the established nuclear localization. Supporting Evidence: PMID:16118205 localization confirmed NMNAT1 to be a nuclear protein, whereas NMNAT2 and -3 |
| GO:0004515 nicotinate-nucleotide adenylyltransferase activity | IDA PMID:16118205 Subcellular compartmentation and differential catalytic prop... | ACCEPT | Summary: Direct assay of NaMN adenylyltransferase (EC 2.7.7.18) activity for the NMNAT1 isoform. Core molecular function. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Reaction=nicotinate beta-D-ribonucleotide + ATP + H(+) = deamido-NAD(+) |
| GO:0005634 nucleus | IDA PMID:16118205 Subcellular compartmentation and differential catalytic prop... | ACCEPT | Summary: Direct immunofluorescence localization of the NMNAT1 isoform to the nucleus. Core localization. Supporting Evidence: PMID:16118205 localization confirmed NMNAT1 to be a nuclear protein, whereas NMNAT2 and -3 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-200512 | ACCEPT | Summary: Reactome-curated nucleoplasm location for the NMNAT1 NaMN->NaAD reaction. Consistent with nuclear localization. |
| GO:0000309 nicotinamide-nucleotide adenylyltransferase activity | IDA PMID:11027696 Molecular cloning, chromosomal localization, tissue mRNA lev... | ACCEPT | Summary: Direct assay of NMN adenylyltransferase (EC 2.7.7.1) activity for the recombinant human enzyme (primary characterization). Core molecular function. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Catalyzes the formation of NAD(+) from nicotinamide |
| GO:0005515 protein binding | IPI PMID:11248244 Characterization of recombinant human nicotinamide mononucle... | KEEP AS NON CORE | Summary: Bare protein binding, but this IPI captures the functionally meaningful physical interaction with PARP1 (UniProtKB:P09874) demonstrated in the primary NMNAT1 characterization, where NMNAT1 strongly inhibits PARP1. The interaction is informative; the GO term itself is uninformative, so kept as non-core. Supporting Evidence: file:human/NMNAT1/NMNAT1-uniprot.txt Interacts with ADPRT/PARP1 |
| GO:0005634 nucleus | IDA PMID:11248244 Characterization of recombinant human nicotinamide mononucle... | ACCEPT | Summary: Direct evidence (immunofluorescence confirming the predicted NLS) for nuclear localization from the primary characterization. Core localization. Supporting Evidence: PMID:11248244 putative nuclear localization signal was confirmed by immunofluorescence |
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