NME2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004550 nucleoside diphosphate kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Correct and core. NME2/NDPK-B catalyzes phosphotransfer between nucleoside diphosphates and triphosphates through His118 phosphohistidine chemistry. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0042981 regulation of apoptotic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0001726 ruffle	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Kept as non-core. Peripheral membrane/actin-edge localizations fit NME2 roles in local GTP supply and membrane remodeling but are not its primary localization. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md cytosolic NME1 and NME2 provide local GTP to dynamins at the plasma membrane
GO:0003677 DNA binding	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Use the specific G-quadruplex DNA binding annotation where possible rather than generic DNA binding.
GO:0004550 nucleoside diphosphate kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Correct and core. NME2/NDPK-B catalyzes phosphotransfer between nucleoside diphosphates and triphosphates through His118 phosphohistidine chemistry. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0004673 protein histidine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: Correct. NME2 has histidine kinase/phosphohistidine-generating capacity in mammalian phosphohistidine signaling contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md In mammalian cells, the NME family (including NME2) is considered among the limited set of enzymes with histidine kinase / phosphohistidine-generating capacity, despite technical challenges associated with phosphohistidine lability.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0005737 cytoplasm	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Prefer specific cytosol and nucleus annotations over generic cytoplasm.
GO:0006183 GTP biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0006228 UTP biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0006241 CTP biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0009117 nucleotide metabolic process	IEA GO_REF:0000043	ACCEPT	Summary: Accepted broadly as nucleotide metabolic process, but NME2 is more specifically an NDP kinase maintaining NTP/dNTP pools. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0009142 nucleoside triphosphate biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0016301 kinase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Use nucleoside diphosphate kinase activity rather than generic kinase/transferase activity.
GO:0016740 transferase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Use nucleoside diphosphate kinase activity rather than generic kinase/transferase activity.
GO:0030027 lamellipodium	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Kept as non-core. Peripheral membrane/actin-edge localizations fit NME2 roles in local GTP supply and membrane remodeling but are not its primary localization. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md cytosolic NME1 and NME2 provide local GTP to dynamins at the plasma membrane
GO:0046872 metal ion binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This cofactor/nucleotide-binding annotation should not drive the core function summary.
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Kept as non-core. Peripheral membrane/actin-edge localizations fit NME2 roles in local GTP supply and membrane remodeling but are not its primary localization. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md cytosolic NME1 and NME2 provide local GTP to dynamins at the plasma membrane
GO:0005515 protein binding	IPI PMID:11919189 Integrin cytoplasmic domain-associated protein 1alpha (ICAP-...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005515 protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005515 protein binding	IPI PMID:17314099 NM23-H1 tumor suppressor physically interacts with serine-th...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005515 protein binding	IPI PMID:24970086 Membrane trafficking. Nucleoside diphosphate kinases fuel dy...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005515 protein binding	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0042802 identical protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0042802 identical protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0042304 regulation of fatty acid biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0120225 coenzyme A binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Supported as a non-core recent NME1/2 metabolic regulatory finding involving CoA/acyl-CoA binding. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME1/2 are described as housekeeping NDP kinases that bind CoA and CoA-derivatives (AcCoA, SucCoA, long-chain fatty acyl–CoA).
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0001216 DNA-binding transcription activator activity	IDA PMID:8392752 Human c-myc transcription factor PuF identified as nm23-H2 n...	KEEP AS NON CORE	Summary: Supported as a non-core DNA/G-quadruplex transcriptional regulator role; the primary molecular function remains NDP kinase activity. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:0051880 G-quadruplex DNA binding	IDA PMID:19033359 Metastases suppressor NM23-H2 interaction with G-quadruplex ...	ACCEPT	Summary: Correct and informative. NME2/NM23-H2 binds promoter G-quadruplex DNA structures, classically in c-MYC-related transcriptional regulation. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:0051880 G-quadruplex DNA binding	IDA PMID:19435876 NM23-H2 may play an indirect role in transcriptional activat...	ACCEPT	Summary: Correct and informative. NME2/NM23-H2 binds promoter G-quadruplex DNA structures, classically in c-MYC-related transcriptional regulation. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:2000144 positive regulation of DNA-templated transcription initiation	IDA PMID:19033359 Metastases suppressor NM23-H2 interaction with G-quadruplex ...	KEEP AS NON CORE	Summary: Supported as a non-core transcriptional output of NME2 promoter/G-quadruplex binding rather than the primary catalytic function. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:2000144 positive regulation of DNA-templated transcription initiation	IDA PMID:19435876 NM23-H2 may play an indirect role in transcriptional activat...	KEEP AS NON CORE	Summary: Supported as a non-core transcriptional output of NME2 promoter/G-quadruplex binding rather than the primary catalytic function. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:0004518 nuclease activity	IDA NOT PMID:19435876 NM23-H2 may play an indirect role in transcriptional activat...	KEEP AS NON CORE	Summary: Correct negated annotation. NME2 was tested for nuclease activity in this c-MYC/NHE context and found not to cleave the substrate. Reason: The NOT annotation is biologically correct and should be retained as documented non-core negative evidence; NME2 is a phosphotransferase and DNA/G4-binding regulator, not a nuclease.
GO:0006183 GTP biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0003677 DNA binding	IDA PMID:11121025 Catalysis of DNA cleavage and nucleoside triphosphate synthe...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Use the specific G-quadruplex DNA binding annotation where possible rather than generic DNA binding.
GO:0004550 nucleoside diphosphate kinase activity	IDA PMID:16313181 Characterization of the 3' --> 5' exonuclease activity found...	ACCEPT	Summary: Correct and core. NME2/NDPK-B catalyzes phosphotransfer between nucleoside diphosphates and triphosphates through His118 phosphohistidine chemistry. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0004673 protein histidine kinase activity	IDA PMID:17157250 Histidine phosphorylation of the potassium channel KCa3.1 by...	ACCEPT	Summary: Correct. NME2 has histidine kinase/phosphohistidine-generating capacity in mammalian phosphohistidine signaling contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md In mammalian cells, the NME family (including NME2) is considered among the limited set of enzymes with histidine kinase / phosphohistidine-generating capacity, despite technical challenges associated with phosphohistidine lability.
GO:0046042 ITP biosynthetic process	IDA PMID:1851158 Nucleoside diphosphate kinase from human erythrocytes. Struc...	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0016301 kinase activity	IDA PMID:8529641 A novel serine/threonine-specific protein phosphotransferase...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Use nucleoside diphosphate kinase activity rather than generic kinase/transferase activity.
GO:0005829 cytosol	TAS Reactome:R-HSA-482619	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0005829 cytosol	TAS Reactome:R-HSA-482621	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0005829 cytosol	TAS Reactome:R-HSA-9748969	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0005829 cytosol	TAS Reactome:R-HSA-9748999	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0005829 cytosol	TAS Reactome:R-HSA-9755013	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0004550 nucleoside diphosphate kinase activity	IDA PMID:9488696 Substrate specificity of human nucleoside-diphosphate kinase...	ACCEPT	Summary: Correct and core. NME2/NDPK-B catalyzes phosphotransfer between nucleoside diphosphates and triphosphates through His118 phosphohistidine chemistry. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0005515 protein binding	IPI PMID:17532299 NM23-H2 involves in negative regulation of Diva and Bcl2L10 ...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Generic protein/identical protein binding is less informative than hexameric NDPK activity, G4 binding, and specific signaling complex contexts.
GO:0005737 cytoplasm	IDA PMID:17532299 NM23-H2 involves in negative regulation of Diva and Bcl2L10 ...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Prefer specific cytosol and nucleus annotations over generic cytoplasm.
GO:0045893 positive regulation of DNA-templated transcription	IDA PMID:8392752 Human c-myc transcription factor PuF identified as nm23-H2 n...	KEEP AS NON CORE	Summary: Supported as a non-core transcriptional output of NME2 promoter/G-quadruplex binding rather than the primary catalytic function. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:0003677 DNA binding	IDA PMID:19435876 NM23-H2 may play an indirect role in transcriptional activat...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Use the specific G-quadruplex DNA binding annotation where possible rather than generic DNA binding.
GO:0019003 GDP binding	IMP PMID:19435876 NM23-H2 may play an indirect role in transcriptional activat...	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This cofactor/nucleotide-binding annotation should not drive the core function summary.
GO:0045893 positive regulation of DNA-templated transcription	IMP PMID:19435876 NM23-H2 may play an indirect role in transcriptional activat...	KEEP AS NON CORE	Summary: Supported as a non-core transcriptional output of NME2 promoter/G-quadruplex binding rather than the primary catalytic function. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:0051880 G-quadruplex DNA binding	IDA PMID:25679041 The maize (Zea mays L.) nucleoside diphosphate kinase1 (ZmND...	ACCEPT	Summary: Correct and informative. NME2/NM23-H2 binds promoter G-quadruplex DNA structures, classically in c-MYC-related transcriptional regulation. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:0004550 nucleoside diphosphate kinase activity	IDA PMID:25679041 The maize (Zea mays L.) nucleoside diphosphate kinase1 (ZmND...	ACCEPT	Summary: Correct and core. NME2/NDPK-B catalyzes phosphotransfer between nucleoside diphosphates and triphosphates through His118 phosphohistidine chemistry. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0009142 nucleoside triphosphate biosynthetic process	IDA PMID:25679041 The maize (Zea mays L.) nucleoside diphosphate kinase1 (ZmND...	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Kept as non-core. Extracellular or granule/exosome detection is observed in some contexts but is secondary to nucleo-cytosolic NME2 functions.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Kept as non-core. Extracellular or granule/exosome detection is observed in some contexts but is secondary to nucleo-cytosolic NME2 functions.
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	KEEP AS NON CORE	Summary: Kept as non-core. Extracellular or granule/exosome detection is observed in some contexts but is secondary to nucleo-cytosolic NME2 functions.
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	KEEP AS NON CORE	Summary: Kept as non-core. Extracellular or granule/exosome detection is observed in some contexts but is secondary to nucleo-cytosolic NME2 functions.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: Kept as non-core. Extracellular or granule/exosome detection is observed in some contexts but is secondary to nucleo-cytosolic NME2 functions.
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	ACCEPT	Summary: Correct. NME2 localizes to both cytosolic and nuclear compartments consistent with nucleotide homeostasis/signaling and gene regulation roles. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md NME2/NM23-H2 is described as localized in both cytoplasm and nucleus, aligning with dual roles in nucleotide homeostasis/signaling (cytosol) and gene regulation (nucleus).
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	KEEP AS NON CORE	Summary: Kept as non-core. Extracellular or granule/exosome detection is observed in some contexts but is secondary to nucleo-cytosolic NME2 functions.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: Kept as non-core. Extracellular or granule/exosome detection is observed in some contexts but is secondary to nucleo-cytosolic NME2 functions.
GO:0005737 cytoplasm	IDA PMID:15703214 Nuclear translocation of integrin cytoplasmic domain-associa...	MARK AS OVER ANNOTATED	Summary: Correct or plausible but too broad for useful NME2 annotation. Reason: Prefer specific cytosol and nucleus annotations over generic cytoplasm.
GO:0005925 focal adhesion	IDA NOT PMID:11919189 Integrin cytoplasmic domain-associated protein 1alpha (ICAP-...	KEEP AS NON CORE	Summary: Kept as non-core. Peripheral membrane/actin-edge localizations fit NME2 roles in local GTP supply and membrane remodeling but are not its primary localization. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md cytosolic NME1 and NME2 provide local GTP to dynamins at the plasma membrane
GO:0007229 integrin-mediated signaling pathway	IDA PMID:11919189 Integrin cytoplasmic domain-associated protein 1alpha (ICAP-...	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:15703214 Nuclear translocation of integrin cytoplasmic domain-associa...	KEEP AS NON CORE	Summary: Supported as a non-core transcriptional output of NME2 promoter/G-quadruplex binding rather than the primary catalytic function. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md A distinct concept in the NME2 literature is its role as the c-MYC purine-binding factor (PuF): NME2/NM23-H2 binds particular DNA elements and also binds non-B DNA structures such as promoter G-quadruplexes (G4), linking DNA secondary structure to transcriptional output.
GO:0071944 cell periphery	IDA PMID:11919189 Integrin cytoplasmic domain-associated protein 1alpha (ICAP-...	KEEP AS NON CORE	Summary: Kept as non-core. Peripheral membrane/actin-edge localizations fit NME2 roles in local GTP supply and membrane remodeling but are not its primary localization. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md cytosolic NME1 and NME2 provide local GTP to dynamins at the plasma membrane
GO:0004550 nucleoside diphosphate kinase activity	IDA PMID:1851158 Nucleoside diphosphate kinase from human erythrocytes. Struc...	ACCEPT	Summary: Correct and core. NME2/NDPK-B catalyzes phosphotransfer between nucleoside diphosphates and triphosphates through His118 phosphohistidine chemistry. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0009142 nucleoside triphosphate biosynthetic process	IDA PMID:1851158 Nucleoside diphosphate kinase from human erythrocytes. Struc...	ACCEPT	Summary: Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md Definition: NDPKs catalyze the transfer of a terminal phosphate from a nucleoside triphosphate donor (often ATP) to a nucleoside diphosphate acceptor (often GDP), thereby supporting balanced intracellular pools of NTPs/dNTPs.
GO:0043066 negative regulation of apoptotic process	IMP PMID:16862176 Novel roles of NM23 proteins in skin homeostasis, repair and...	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0045618 positive regulation of keratinocyte differentiation	IMP PMID:16862176 Novel roles of NM23 proteins in skin homeostasis, repair and...	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0045682 regulation of epidermis development	IMP PMID:16862176 Novel roles of NM23 proteins in skin homeostasis, repair and...	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0050679 positive regulation of epithelial cell proliferation	IMP PMID:16862176 Novel roles of NM23 proteins in skin homeostasis, repair and...	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0001726 ruffle	IDA PMID:11919189 Integrin cytoplasmic domain-associated protein 1alpha (ICAP-...	KEEP AS NON CORE	Summary: Kept as non-core. Peripheral membrane/actin-edge localizations fit NME2 roles in local GTP supply and membrane remodeling but are not its primary localization. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md cytosolic NME1 and NME2 provide local GTP to dynamins at the plasma membrane
GO:0007155 cell adhesion	TAS PMID:11919189 Integrin cytoplasmic domain-associated protein 1alpha (ICAP-...	KEEP AS NON CORE	Summary: Supported or plausible for NME2 but non-core relative to its primary NDP kinase/phosphohistidine chemistry and nuclear G-quadruplex transcriptional role. This downstream cell-process annotation should not drive the core function summary.
GO:0030027 lamellipodium	IDA PMID:11919189 Integrin cytoplasmic domain-associated protein 1alpha (ICAP-...	KEEP AS NON CORE	Summary: Kept as non-core. Peripheral membrane/actin-edge localizations fit NME2 roles in local GTP supply and membrane remodeling but are not its primary localization. Supporting Evidence: file:human/NME2/NME2-deep-research-falcon.md cytosolic NME1 and NME2 provide local GTP to dynamins at the plasma membrane

Gene Description

Existing Annotations Review

Core Functions

NME2 is an NDP kinase whose core function is phosphohistidine-mediated nucleotide phosphotransfer, maintaining cellular NTP/dNTP pools and supplying local GTP in signaling and membrane-remodeling contexts. It also has a supported nuclear G-quadruplex DNA-binding role in transcriptional regulation.

References

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Deep Research

Falcon

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