Nucleophosmin (NPM1/B23) is an abundant, multifunctional nucleolar phosphoprotein involved in ribosome biogenesis, centrosome duplication, histone chaperoning, protein chaperoning, cell proliferation, genomic stability, and regulation of tumor suppressors p53/TP53 and ARF. It functions as a pentamer/decamer and shuttles between the nucleolus, nucleoplasm, and cytoplasm via CRM1/XPO1-dependent nuclear export. NPM1 is modular, comprising an N-terminal oligomerization domain (OD) that assembles pentamers and higher-order oligomers, a central acidic intrinsically disordered region (IDR) that mediates histone binding and regulates interactions, and a C-terminal globular nucleic-acid-binding domain containing the nucleolar localization signal (NoLS) and key aromatic residues (W288/W290) essential for nucleolar targeting (DOI:10.3390/cells13151266, DOI:10.3390/ijms24043161). NPM1 is a major driver of nucleolar liquid-liquid phase separation (LLPS), forming homotypic and heterotypic condensate droplets with arginine-rich proteins and rRNA that help establish nucleolar granular component (GC) structure and ribosome-production capacity. A 2023 mechanistic study demonstrated that oligomer stability, tunable by phosphorylation (e.g. Ser125 phosphomimetics) and acidic IDR charge patterning, controls droplet fluidity, providing a concrete route by which post-translational modifications regulate nucleolar dynamics across the cell cycle (DOI:10.1101/2023.01.23.525122). NPM1 acts as a histone chaperone for core histones H3, H2B, and H4, and also exhibits broader molecular chaperone activity preventing protein aggregation and promoting refolding of denatured proteins. It serves as a rate-limiting nuclear export chaperone for ribosomal subunits. Stress-responsive relocalization occurs via oxidation and S-glutathionylation at Cys275, which triggers NPM1 release from the nucleolus to the nucleoplasm during nucleolar stress responses (DOI:10.3390/cells13151266). NPM1 increasingly is recognized as participating in DNA damage responses and repair pathway execution, interacting with p53/HDM2 regulatory circuits in the context of stress and genome stability (DOI:10.3390/cells13151266). Mutations in NPM1 exon 12 causing aberrant cytoplasmic localization (NPM1c+) are among the most common genetic alterations in acute myeloid leukemia (AML), accounting for approximately 30-35% of adult AML cases and enriched in normal-karyotype AML (approximately 50-60%); these mutations disrupt the C-terminal fold/NoLS and introduce a nuclear export signal, shifting NPM1 to the cytoplasm (DOI:10.1158/2643-3230.bcd-23-0144). NPM1 is also involved in the NPM1-ALK fusion oncogene in anaplastic large cell lymphoma.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 is a well-established histone chaperone that binds core histones H3, H2B, and H4 (PMID:11602260, PMID:16107701), mediates nucleosome assembly/disassembly, and enhances acetylation-dependent chromatin transcription. Chromatin binding is consistent with its histone chaperone function. The IBA annotation is phylogenetically supported and appropriate. Reason: NPM1 directly binds histones and chromatin as part of its histone chaperone activity. PMID:16107701 showed NPM1 enhances acetylation-dependent chromatin transcription, and PMID:11602260 demonstrated histone binding and nucleosome assembly. Chromatin binding is a core function. Supporting Evidence: PMID:16107701 Human histone chaperone nucleophosmin interacts with the core histones H3, H2B, and H4 but that this histone interaction is not sufficient to confer the chaperone activity. PMID:11602260 Nucleophosmin/B23 was shown to bind to histones, preferentially to histone H3, to mediate formation of nucleosome, and to decondense sperm chromatin. |
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 is primarily nucleolar but translocates to the nucleoplasm under various conditions including serum starvation, anticancer drug treatment, and DNA damage. UniProt confirms nucleoplasm localization (ECO:0000269|PubMed:25818168). The IBA annotation is appropriate. Reason: NPM1 is well-documented to localize to the nucleoplasm, particularly under stress conditions. Multiple IDA evidence supports this localization. |
| GO:0005730 nucleolus | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is mediated by RNA binding activity of the C-terminal domain (PMID:24106084). Multiple IDA annotations confirm nucleolar localization. This is a core localization for NPM1. Reason: Nucleolus is the primary localization of NPM1 and is essential for its core functions in ribosome biogenesis and histone chaperoning. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 is a nucleocytoplasmic shuttling protein. It is found in the cytoplasm both during normal shuttling (PMID:9121481) and aberrantly in AML with NPM1c mutations. IDA evidence from PMID:9121481 confirms cytoplasmic localization. Reason: NPM1 shuttles between nucleus and cytoplasm as part of its function in ribosome export and other transport roles. Cytoplasmic localization is well-established. |
| GO:0003723 RNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 binds RNA, particularly rRNA, through its C-terminal domain and intrinsically disordered basic region (PMID:24106084, PMID:12058066). RNA binding is modulated by phosphorylation and is essential for nucleolar localization and ribosome biogenesis. This is a core molecular function of NPM1. Reason: RNA binding is a core function of NPM1 essential for ribosome biogenesis. Well-supported by multiple direct assay experiments. Supporting Evidence: PMID:24106084 Nucleophosmin (NPM1/B23) is a nucleolar protein implicated in growth-associated functions, in which the RNA binding activity of B23 plays essential roles in ribosome biogenesis. PMID:12058066 It has been shown that B23 binds to nucleic acids, digests RNA, and is localized in nucleolar granular components from which preribosomal particles are transported to cytoplasm. |
| GO:0042393 histone binding | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 binds core histones H3, H2B, and H4 as part of its histone chaperone activity (PMID:11602260, PMID:16107701). Histone binding is a core molecular function of NPM1 and is prerequisite for its nucleosome assembly activity. Reason: Histone binding is a core function of NPM1, directly demonstrated by IDA in PMID:11602260. Supporting Evidence: PMID:11602260 Nucleophosmin/B23 was shown to bind to histones, preferentially to histone H3, to mediate formation of nucleosome, and to decondense sperm chromatin. |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 functions as a histone chaperone that mediates nucleosome assembly/disassembly and enhances acetylation-dependent chromatin transcription (PMID:16107701). It also decondenses sperm chromatin (PMID:11602260). These activities constitute chromatin remodeling. The IBA annotation is phylogenetically supported and appropriate. Reason: NPM1 is a histone chaperone involved in nucleosome dynamics and chromatin structure changes. Multiple studies support a role in chromatin remodeling. Supporting Evidence: PMID:16107701 Presumably, nucleophosmin disrupts the nucleosomal structure in an acetylation-dependent manner, resulting in the transcriptional activation. |
| GO:0000055 ribosomal large subunit export from nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 serves as a rate-limiting nuclear export chaperone for ribosomal subunits (PMID:18809582). It directly binds ribosomal large subunits and mediates their export via CRM1-dependent pathway. PMID:16648475 showed NPM1 is essential for ribosomal protein L5 nuclear export and associates with maturing nuclear 60S ribosomal subunits. This is a core function of NPM1. Reason: Ribosomal large subunit export is a core function of NPM1, directly demonstrated by multiple experimental studies. Supporting Evidence: PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. PMID:16648475 Direct interaction of NPM with rpL5 mediated the colocalization of NPM with maturing nuclear 60S ribosomal subunits, as well as newly exported and assembled 80S ribosomes and polysomes. |
| GO:0000056 ribosomal small subunit export from nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 binds ribosomal small subunits (PMID:18809582) and serves as a nuclear export chaperone for ribosomal subunits. The IBA annotation is phylogenetically supported. Reason: PMID:18809582 demonstrated NPM1 binds both ribosomal large and small subunits and serves as a rate-limiting export chaperone. Supporting Evidence: PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. |
| GO:0005813 centrosome | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 associates with unduplicated centrosomes and dissociates upon CDK2/cyclin E-mediated phosphorylation to initiate centrosome duplication (PMID:11051553). UniProt confirms centrosome localization. Multiple IDA annotations support this. Reason: Centrosome localization is well-established for NPM1 and is functionally important for regulating centrosome duplication. Supporting Evidence: PMID:11051553 NPM/B23 associates specifically with unduplicated centrosomes, and NPM/B23 dissociates from centrosomes by CDK2/cyclin E-mediated phosphorylation. |
| GO:0010824 regulation of centrosome duplication | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 negatively regulates centrosome duplication by associating with unduplicated centrosomes; its dissociation after phosphorylation by CDK2/cyclin E initiates duplication (PMID:11051553). PLK2 phosphorylation of NPM1 at Ser4 triggers centriole duplication (PMID:20352051). Ran-Crm1 controls NPM1 association with centrosomes (PMID:16041368). This is a core function of NPM1. Reason: Regulation of centrosome duplication is a well-established core function of NPM1, supported by multiple experimental studies in high-impact journals. Supporting Evidence: PMID:11051553 We identified nucleophosmin (NPM/B23) as a substrate of CDK2/cyclin E in centrosome duplication. NPM/B23 associates specifically with unduplicated centrosomes, and NPM/B23 dissociates from centrosomes by CDK2/cyclin E-mediated phosphorylation. PMID:20352051 Plk2 phosphorylates NPM/B23 on serine 4 |
| GO:0042273 ribosomal large subunit biogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 is essential for ribosomal large subunit biogenesis. It binds the large ribosomal subunit (PMID:18809582), is essential for ribosomal protein L5 nuclear export (PMID:16648475), and stores/protects ribosomal protein S9 in nucleoli (PMID:18420587). This is a core function. Reason: Ribosome biogenesis is one of the most well-established core functions of NPM1. Supporting Evidence: PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. PMID:16648475 Nucleophosmin is essential for ribosomal protein L5 nuclear export. |
| GO:0042274 ribosomal small subunit biogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 binds the small ribosomal subunit (PMID:18809582) and interacts with ribosomal protein S9 to facilitate its nucleolar storage and ribosome biogenesis (PMID:18420587). The IBA annotation is phylogenetically supported. Reason: NPM1 is involved in both large and small ribosomal subunit biogenesis through its chaperone and export functions. Supporting Evidence: PMID:18420587 Our results suggest that B23 selectively stores, and protects ribosomal protein S9 in nucleoli and therefore could facilitate ribosome biogenesis. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: NPM1 acts as a transcription coactivator. It enhances acetylation-dependent chromatin transcription (PMID:16107701), acts as an NF-kappaB coactivator for SOD2 induction (PMID:15087454), and in complex with MYC enhances MYC target gene transcription (PMID:25956029). However, NPM1 can also act as a transcriptional corepressor with AP2alpha (PMID:17318229). The positive regulation annotation is appropriate but represents a non-core pleiotropic function rather than a core molecular activity. Reason: Transcriptional coactivation is a documented activity of NPM1 but is secondary to its core histone chaperone and ribosome biogenesis functions. |
| GO:1990904 ribonucleoprotein complex | IBA GO_REF:0000033 | ACCEPT | Summary: NPM1 is associated with ribonucleoprotein complexes, consistent with its role in ribosome biogenesis and its binding to ribosomal subunits (PMID:18809582). IDA evidence from PMID:18809582 supports this localization. Reason: NPM1 is a component of ribonucleoprotein complexes as part of its core role in ribosome biogenesis. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000120 | ACCEPT | Summary: NPM1 binds both RNA (rRNA, mRNA) and DNA. This IEA annotation to nucleic acid binding is a parent of the more specific RNA binding (GO:0003723) already accepted via IBA. While correct, it is redundant with more specific annotations. Reason: NPM1 binds nucleic acids broadly. The IEA is consistent with accepted IBA for RNA binding. Acceptable as a broader IEA even though more specific terms exist. |
| GO:0003723 RNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation duplicating the IBA for RNA binding already accepted. NPM1 RNA binding is well-established experimentally (PMID:24106084, PMID:12058066). Reason: Consistent with IBA and IDA evidence for RNA binding. Redundant but not incorrect. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for nucleoplasm. NPM1 translocates to the nucleoplasm under stress or serum starvation. Consistent with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is well-established for NPM1. Redundant with IBA but correct. |
| GO:0005730 nucleolus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for nucleolus. NPM1 is one of the most abundant nucleolar proteins. Redundant with IBA and many IDA annotations. Reason: Nucleolus is the primary localization of NPM1. Correct and consistent. |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for centrosome. NPM1 associates with unduplicated centrosomes (PMID:11051553). Consistent with IBA and IDA annotations. Reason: Centrosome localization is well-established. Redundant but correct. |
| GO:0010604 positive regulation of macromolecule metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very broad IEA annotation. NPM1 does positively regulate macromolecule metabolism through its roles in ribosome biogenesis and transcription coactivation. However, this term is too general to be informative. Reason: While technically correct, this is an extremely broad term that adds no informative value beyond what is captured by more specific annotations for ribosome biogenesis and transcription regulation. |
| GO:0042127 regulation of cell population proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: NPM1 regulates cell proliferation through multiple mechanisms including ribosome biogenesis, centrosome duplication, p53 regulation, and ATF5 degradation (PMID:22528486, PMID:12080348). This is a pleiotropic downstream consequence. Reason: Cell proliferation regulation is an indirect consequence of NPM1 core functions (ribosome biogenesis, centrosome duplication, p53/ARF regulation). Not a core molecular function but is well-supported. |
| GO:0042254 ribosome biogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation for ribosome biogenesis. NPM1 is central to ribosome biogenesis through rRNA processing, ribosomal protein chaperoning, and ribosomal subunit export (PMID:18809582, PMID:16648475, PMID:18420587). Consistent with IBA annotations for large and small subunit biogenesis. Reason: Ribosome biogenesis is a core function of NPM1. This is a parent term of the more specific subunit biogenesis terms already accepted. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation for negative regulation of apoptosis. NPM1 inhibits apoptosis through PKR inhibition (PMID:12882984) and p53 regulation. This is a pleiotropic downstream effect. Reason: Anti-apoptotic activity is a secondary consequence of NPM1 core functions, particularly PKR inhibition. Well-supported but not a core molecular activity. |
| GO:0005515 protein binding | IPI PMID:15144954 Nucleolar protein NPM interacts with HDM2 and protects tumor... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:15144954 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:15161933 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:15989956 ARF-BP1/Mule is a critical mediator of the ARF tumor suppres... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:15989956 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:16376884 Characterisation of the interface between nucleophosmin (NPM... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:16376884 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:16540653 Delocalization and destabilization of the Arf tumor suppress... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:16540653 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:16957780 Antiviral action of the tumor suppressor ARF. | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:16957780 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:17318229 Nucleophosmin acts as a novel AP2alpha-binding transcription... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:17318229 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:17353931 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:17602943 Physical and functional interaction between a nucleolar prot... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:17602943 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:18243139 The nucleocapsid protein of SARS-associated coronavirus inhi... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:18243139 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:18259216 The nucleolar SUMO-specific protease SENP3 reverses SUMO mod... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:18259216 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:20618440 Proteomic and biochemical analysis of 14-3-3-binding protein... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:20618440 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:20701745 Karyopherin alpha7 (KPNA7), a divergent member of the import... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:20701745 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:21326211 The SUMO system controls nucleolar partitioning of a novel m... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:21326211 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:21822216 Nucleophosmin deposition during mRNA 3' end processing influ... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:21822216 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:21988832 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:22510990 AKT-dependent phosphorylation of Niban regulates nucleophosm... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:22510990 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:22712502 Erythroid differentiation-associated gene interacts with NPM... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:22712502 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:23816991 Exploration of binary virus-host interactions using an infec... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:23816991 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:23892143 Human respiratory syncytial virus N, P and M protein interac... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:23892143 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:24462683 Interaction between nucleophosmin and HBV core protein incre... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:24462683 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:24857377 Phosphorylation of multifunctional nucleolar protein nucleop... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:24857377 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:25416956 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:26496610 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:28255170 Nucleophosmin Interacts with PIN2/TERF1-interacting Telomera... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:28255170 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:28611246 Inhibition of Avian Influenza A Virus Replication in Human C... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:28611246 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:29568061 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:30021884 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:31515488 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:32296183 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:32814053 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:33961781 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:35271311 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:35709258 Spatial centrosome proteome of human neural cells uncovers d... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:35709258 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:38029384 Proteomics analysis identifies the ribosome associated coile... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:38029384 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:39251607 Systematic identification of post-transcriptional regulatory... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:39251607 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0001652 granular component | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for granular component of the nucleolus. NPM1 co-localizes with methylated RPS10 in the GC region (UniProt). The GC is where pre-ribosomal particles mature, consistent with NPM1 ribosome biogenesis role. Reason: NPM1 is well-documented to localize in the granular component of the nucleolus where pre-ribosomal particles are assembled. Consistent with core function. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for nucleus. NPM1 is primarily a nuclear protein (nucleolar). This is a very broad term but consistent with multiple IDA annotations. Reason: NPM1 is a nuclear protein. Correct and consistent, though very broad. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for cytoplasm. NPM1 shuttles to the cytoplasm as part of ribosome export function (PMID:9121481). Consistent with IBA annotation. Reason: Cytoplasmic localization is consistent with NPM1 nucleocytoplasmic shuttling. Redundant with IBA but correct. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for cytosol. NPM1 can be found in the cytosol as part of its shuttling function and in the NPM1-ALK fusion context. Reason: Cytosol localization is consistent with NPM1 nucleocytoplasmic shuttling. More specific than cytoplasm. |
| GO:0015934 large ribosomal subunit | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for large ribosomal subunit localization. NPM1 directly binds the large ribosomal subunit as part of its nuclear export chaperone function (PMID:18809582, PMID:16648475). Reason: NPM1 associates with maturing 60S ribosomal subunits. Consistent with its ribosome export chaperone function. |
| GO:0015935 small ribosomal subunit | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for small ribosomal subunit localization. NPM1 binds both large and small ribosomal subunits (PMID:18809582). Reason: NPM1 binds small ribosomal subunits. Consistent with its rate-limiting ribosome export chaperone role. |
| GO:0016607 nuclear speck | IEA GO_REF:0000107 | UNDECIDED | Summary: IEA annotation for nuclear speck localization. While NPM1 is primarily nucleolar, some evidence suggests it may transiently associate with nuclear speckles. However, this is not well-established as a core localization. Reason: Nuclear speck localization for NPM1 is not well-characterized in the primary literature. The IEA transfer may be based on weak or indirect evidence. Unable to confirm without access to the original ortholog data. |
| GO:0019843 rRNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for rRNA binding. NPM1 binds rRNA through its C-terminal domain and intrinsically disordered basic region (PMID:24106084). This is more specific than the accepted RNA binding and directly supports ribosome biogenesis. Reason: rRNA binding is a well-established core function of NPM1. More specific than the accepted RNA binding term. |
| GO:0042802 identical protein binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for identical protein binding. NPM1 forms pentamers and decamers through homooligomerization (PMID:24106084, PMID:9121481). This is confirmed by IDA for protein homodimerization activity. Reason: NPM1 oligomerization is a fundamental property. Consistent with IDA for homodimerization. Oligomerization is essential for NPM1 function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation for positive regulation of transcription by Pol II. Redundant with the IBA and IDA annotations for this term already reviewed. Reason: Transcriptional coactivation is a non-core pleiotropic function of NPM1. Redundant with IBA annotation already reviewed. |
| GO:1904751 positive regulation of protein localization to nucleolus | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation for positive regulation of protein localization to nucleolus. NPM1 mediates nucleolar localization of several proteins including HIV Tat (PMID:9094689), ribosomal proteins (PMID:18420587), and WRN helicase. This is consistent with its chaperoning/shuttling function. Reason: NPM1 acts as a chaperone/shuttle for nucleolar localization of multiple proteins. Well-supported by multiple studies. |
| GO:0004860 protein kinase inhibitor activity | IDA PMID:12882984 Nucleophosmin interacts with and inhibits the catalytic func... | ACCEPT | Summary: NPM1 inhibits PKR (EIF2AK2) autophosphorylation and catalytic function in a dose-dependent manner (PMID:12882984). Overexpression of NPM suppressed PKR activity, enhanced protein synthesis, and inhibited apoptosis. This is a specific molecular function. Reason: PMID:12882984 directly demonstrated that recombinant NPM inhibited PKR activation in kinase assays. This is a genuine enzymatic inhibitor activity. Supporting Evidence: PMID:12882984 Kinase assays demonstrated that recombinant NPM inhibited PKR activation in a dose-dependent manner. |
| GO:0007249 canonical NF-kappaB signal transduction | IMP PMID:15087454 Identification of nucleophosmin as an NF-kappaB co-activator... | KEEP AS NON CORE | Summary: PMID:15087454 showed NPM1 acts as an NF-kappaB coactivator for SOD2 gene induction. NPM physically interacts with NF-kappaB and increasing NPM expression leads to increased SOD2 transcription. This represents involvement in NF-kappaB signaling. Reason: NF-kappaB signaling involvement is a pleiotropic downstream effect of NPM1 transcription coactivator function. Not a core molecular function. Supporting Evidence: PMID:15087454 Co-immunoprecipitation studies suggest a physical interaction between NPM and NF-kappaB proteins. |
| GO:2000767 positive regulation of cytoplasmic translation | IDA PMID:12882984 Nucleophosmin interacts with and inhibits the catalytic func... | KEEP AS NON CORE | Summary: PMID:12882984 showed that overexpression of NPM enhanced protein synthesis by inhibiting PKR, which normally phosphorylates eIF2alpha to suppress translation. This is an indirect effect mediated through PKR inhibition. Reason: Enhanced translation is a downstream consequence of PKR inhibition by NPM1, not a direct translational regulation activity. Supporting Evidence: PMID:12882984 Overexpression of NPM suppressed PKR activity, enhanced protein synthesis, and inhibited apoptosis. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation based on immunofluorescence data curation (GO_REF:0000052). NPM1 is found in the nucleoplasm under stress or specific conditions. Consistent with IBA and other IDA annotations. Reason: Nucleoplasm localization is well-established for NPM1 across multiple evidence types. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: IDA annotation based on immunofluorescence data curation. NPM1 is one of the most abundant nucleolar proteins. Consistent with IBA and many other IDA annotations. Reason: Nucleolus is the primary localization of NPM1. Well-established across many studies. |
| GO:0005634 nucleus | IDA PMID:38231884 ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differe... | ACCEPT | Summary: IDA annotation for nucleus from PMID:38231884 which studied ARID3C-NPM1 interaction. NPM1 was shown to shuttle between cytoplasm and nucleus, mediating ARID3C nuclear import. Reason: Nuclear localization of NPM1 is well-established. PMID:38231884 confirmed NPM1 is nuclear. |
| GO:0006606 protein import into nucleus | IDA PMID:38231884 ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differe... | KEEP AS NON CORE | Summary: PMID:38231884 demonstrated that NPM1 mediates ARID3C nuclear shuttling. ARID3C forms a complex with NPM1 to translocate to the nucleus. When the ARID3C-NPM1 binding site was mutated, ARID3C was retained in the cytoplasm. Reason: NPM1 acts as a nuclear import adaptor for ARID3C. This is consistent with NPM1 general protein chaperoning function but is a specific case, not a core function. Supporting Evidence: PMID:38231884 ARID3C forms a complex with NPM1 to translocate to the nucleus, acting as a transcription factor that promotes the expression of the genes involved in monocyte-to-macrophage differentiation. |
| GO:0030225 macrophage differentiation | IDA PMID:38231884 ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differe... | MARK AS OVER ANNOTATED | Summary: PMID:38231884 showed ARID3C-NPM1 complex promotes monocyte-to-macrophage differentiation. NPM1 role is as an adaptor for ARID3C nuclear import, not a direct driver of macrophage differentiation. Reason: NPM1 is an adaptor for ARID3C nuclear import. The macrophage differentiation activity is primarily driven by ARID3C as transcription factor, not by NPM1 directly. This annotation over-attributes the differentiation process to NPM1. Supporting Evidence: PMID:38231884 ARID3C was found to predominantly localize with the nucleus, where it functioned as a transcription factor for genes STAT3, STAT1, and JUNB, thereby facilitating monocyte-to-macrophage differentiation. |
| GO:0060090 molecular adaptor activity | IDA PMID:38231884 ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differe... | ACCEPT | Summary: PMID:38231884 demonstrated NPM1 acts as an adaptor for ARID3C nuclear shuttling. NPM1 brings ARID3C to the nucleus through selective binding. This represents a genuine adaptor function. Reason: NPM1 acts as a molecular adaptor for ARID3C nuclear import. This is consistent with NPM1 broader role as a nucleocytoplasmic shuttling chaperone for multiple cargo proteins. Supporting Evidence: PMID:38231884 Mutating this binding site prevented ARID3C from interacting with NPM1, resulting in its retention in the cytoplasm instead of translocation to the nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9725009 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-9725009). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9725023 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-9725023). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9725030 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-9725030). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851090 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-9851090). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700181 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9700181). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700190 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9700190). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700193 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9700193). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9710914 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9710914). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9710917 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9710917). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712078 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712078). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712079 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712079). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712081 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712081). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712082 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712082). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712083 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712083). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712084 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712084). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712085 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712085). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712086 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712086). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712087 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712087). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712088 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9712088). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9724099 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9724099). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9725009 | ACCEPT | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9725009). NPM1 shuttles to the cytoplasm/cytosol as part of its normal function in ribosome export and protein transport. Reason: Cytosol localization is consistent with NPM1 nucleocytoplasmic shuttling function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9850958 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9850958). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0019843 rRNA binding | IPI PMID:24106084 Intrinsically disordered regions of nucleophosmin/B23 regula... | ACCEPT | Summary: PMID:24106084 demonstrated that NPM1/B23 RNA binding activity is essential for ribosome biogenesis, with the C-terminal domain and intrinsically disordered basic region mediating RNA binding. The basic IDR alone strongly binds to RNA. Reason: rRNA binding is a core molecular function of NPM1. Directly demonstrated in PMID:24106084. Supporting Evidence: PMID:24106084 Nucleophosmin (NPM1/B23) is a nucleolar protein implicated in growth-associated functions, in which the RNA binding activity of B23 plays essential roles in ribosome biogenesis. |
| GO:0042803 protein homodimerization activity | IPI PMID:24106084 Intrinsically disordered regions of nucleophosmin/B23 regula... | ACCEPT | Summary: PMID:24106084 showed NPM1 forms homo-oligomers (pentamers/decamers) through inter-molecular interactions of its IDRs. The N-terminal domain mediates oligomerization. Reason: NPM1 forms pentamers and decamers through homooligomerization. This is a fundamental property confirmed by crystal structure (PDB:2P1B) and multiple biochemical studies. Supporting Evidence: PMID:24106084 Chemical cross-linking experiments and fluorescent labeling of bipartite tetracysteine-tagged proteins suggested that the inter- and intra-molecular interactions between the two IDRs contribute to the regulation of the RNA binding activity of CTD to control the cellular localization and functions of B23. |
| GO:0005515 protein binding | IPI PMID:23972994 ABH2 couples regulation of ribosomal DNA transcription with ... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:23972994 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0090398 cellular senescence | IMP PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | KEEP AS NON CORE | Summary: PMID:12080348 showed NPM1 regulates p53 stability and transcriptional activity. NPM1 overexpression suppressed cell growth. The connection to senescence is through p53 regulation. Reason: Cellular senescence is a downstream phenotypic consequence of NPM1 effects on p53 stabilization. Not a core molecular function but a pleiotropic effect. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4086088 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-4086088). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4086059 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-4086059). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005515 protein binding | IPI PMID:25956029 The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regula... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:25956029 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700131 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9700131). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700179 | KEEP AS NON CORE | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9700179). This annotation relates to the NPM1-ALK fusion oncoprotein signaling pathway in anaplastic large cell lymphoma. The cytosol localization reflects the ALK fusion context, not normal NPM1 function. Reason: Cytosol localization in this context is specific to the NPM1-ALK fusion oncoprotein. Not relevant to normal NPM1 function but reflects a real disease-associated biology. |
| GO:1990904 ribonucleoprotein complex | IDA PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape... | ACCEPT | Summary: IDA annotation from PMID:18809582 which demonstrated NPM1 serves as a rate-limiting nuclear export chaperone for the mammalian ribosome. NPM1 was found associated with ribonucleoprotein complexes. Reason: NPM1 associates with ribonucleoprotein complexes as part of its core ribosome biogenesis and export function. Directly demonstrated. Supporting Evidence: PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. |
| GO:0005730 nucleolus | IDA PMID:19208757 Nucleolar structure and function are regulated by the deubiq... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:19208757. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:1902629 regulation of mRNA stability involved in cellular response to UV | IMP PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | UNDECIDED | Summary: PMID:12080348 primarily demonstrated NPM1 regulation of p53 stability and transcriptional activity. The connection to mRNA stability in UV response seems tenuous for this reference. Reason: The specific mechanism by which NPM1 regulates mRNA stability in UV response is not clearly demonstrated in PMID:12080348. Need to verify this annotation against the primary data. |
| GO:0001652 granular component | TAS Reactome:R-HSA-9727886 | ACCEPT | Summary: TAS annotation for granular component from Reactome (SARS-CoV-1 N protein binds NPM1). NPM1 localizes to the GC of the nucleolus. This Reactome entry is about viral interaction but the localization is correct. Reason: NPM1 localizes to the granular component of the nucleolus. Correct localization, consistent with IEA annotation and UniProt. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-180728 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-180728). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-180736 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-180736). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-606287 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-606287). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-606289 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-606289). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-606326 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-606326). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8869542 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-8869542). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8869543 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-8869543). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8869549 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-8869549). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8869568 | ACCEPT | Summary: TAS annotation for nucleoplasm from Reactome (Reactome:R-HSA-8869568). NPM1 nucleoplasm localization is well-established. Redundant with IBA and multiple IDA annotations. Reason: Nucleoplasm localization is correct for NPM1. Redundant but consistent with existing evidence. |
| GO:0005730 nucleolus | IDA PMID:25956029 The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regula... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:25956029. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:25956029 The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regula... | KEEP AS NON CORE | Summary: PMID:25956029 showed NPM1 in complex with MYC enhances transcription of MYC target genes. NOP53 acts as upstream negative regulator by competing with MYC for NPM1 binding. Reason: Transcription coactivation is a non-core pleiotropic function. Redundant with IBA annotation. Supporting Evidence: PMID:25956029 The nucleolar protein GLTSCR2 is an upstream negative regulator of the oncogenic Nucleophosmin-MYC axis. |
| GO:0001046 core promoter sequence-specific DNA binding | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | UNDECIDED | Summary: PMID:19160485 studied the L23-NPM1-Miz1 circuit. NPM1 was shown to be present at core promoters in complex with Miz1. However, NPM1 DNA binding may be indirect through the complex. Reason: NPM1 is primarily known as a histone/RNA chaperone, not a DNA-binding protein per se. Its presence at promoters may be through protein complexes rather than direct DNA sequence-specific binding. Need more evidence to confirm direct DNA binding. |
| GO:0003713 transcription coactivator activity | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | KEEP AS NON CORE | Summary: PMID:19160485 showed NPM1 coordinates Miz1 function with cell growth through the L23-NPM1-Miz1 circuit. NPM1 acts as a coactivator in this context. Reason: Transcription coactivator activity is a non-core function of NPM1. It is documented but secondary to histone chaperoning and ribosome biogenesis. |
| GO:0005515 protein binding | IPI PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:19160485 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005654 nucleoplasm | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | ACCEPT | Summary: IDA annotation for nucleoplasm from PMID:19160485, which studied the ribosomal protein L23-NPM1 circuit coordinating Miz1 function with cell growth. NPM1 was shown in the nucleoplasm in this context. Reason: Nucleoplasm localization is well-established for NPM1. Consistent with multiple other evidence. |
| GO:0005730 nucleolus | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:19160485. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0032991 protein-containing complex | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | ACCEPT | Summary: IDA annotation for protein-containing complex from PMID:19160485. NPM1 forms complexes with many proteins including the L23-Miz1 complex. Reason: NPM1 exists in multiple protein complexes (pentamer/decamer, ribosomal complexes, transcription complexes). This is a general but correct localization term. |
| GO:0032993 protein-DNA complex | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | KEEP AS NON CORE | Summary: IDA annotation for protein-DNA complex. PMID:19160485 showed NPM1 is found in protein-DNA complexes at promoters in the L23-Miz1 circuit. Reason: NPM1 association with protein-DNA complexes is context-dependent and related to its transcription coactivator function, not a core activity. |
| GO:0034644 cellular response to UV | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | KEEP AS NON CORE | Summary: PMID:19160485 showed NPM1 role in cellular response to UV through the L23-NPM1-Miz1 pathway. Under UV stress, ribosomal stress releases L23 which disrupts NPM1-Miz1 complex. Reason: UV response involvement is a stress-related function secondary to NPM1 core roles. NPM1 translocates from nucleolus under stress conditions. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | KEEP AS NON CORE | Summary: IDA annotation for positive regulation of transcription from PMID:19160485 studying L23-NPM1-Miz1 circuit. Redundant with other transcription coactivation annotations. Reason: Transcription coactivation is a non-core function. Redundant with IBA annotation already reviewed. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:19160485 A ribosomal protein L23-nucleophosmin circuit coordinates Mi... | ACCEPT | Summary: PMID:19160485 showed NPM1 interacts with Miz1 transcription factor. NPM1 also interacts with AP2alpha (PMID:17318229), NF-kappaB (PMID:15087454), and MYC (PMID:25956029). Reason: NPM1 binds multiple transcription factors as part of its coactivator/corepressor function. This is more specific than protein binding and captures a real molecular function. Supporting Evidence: PMID:17318229 Nucleophosmin (NPM) is an important nucleolar phosphoprotein with pleiotropic functions in various cellular processes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6801675 | ACCEPT | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-6801675). NPM1 shuttles to the cytoplasm/cytosol as part of its normal function in ribosome export and protein transport. Reason: Cytosol localization is consistent with NPM1 nucleocytoplasmic shuttling function. |
| GO:0005515 protein binding | IPI PMID:23019224 DDX31 regulates the p53-HDM2 pathway and rRNA gene transcrip... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:23019224 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:22528486 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005730 nucleolus | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:22528486. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | KEEP AS NON CORE | Summary: PMID:22528486 showed NPM1 antagonizes ATF5 inhibitory effect on cell proliferation and promotes ATF5 degradation in hepatocellular carcinoma cells. Reason: Cell proliferation promotion through ATF5 degradation is a context-specific pleiotropic effect, not a core molecular function. Supporting Evidence: PMID:22528486 NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | KEEP AS NON CORE | Summary: PMID:22528486 showed NPM1 promotes ATF5 degradation, relieving ATF5-mediated transcriptional repression. This is an indirect transcription regulation effect. Reason: Positive transcription regulation through ATF5 degradation is indirect. Not a core function. |
| GO:1902751 positive regulation of cell cycle G2/M phase transition | IDA PMID:22528486 Nucleophosmin (NPM1/B23) interacts with activating transcrip... | KEEP AS NON CORE | Summary: PMID:22528486 showed NPM1 relieves ATF5-induced G2/M blockade through ATF5 degradation. Reason: G2/M transition regulation is an indirect consequence of ATF5 degradation by NPM1. Not a core function. Supporting Evidence: PMID:22528486 NPM1 interaction with ATF5 displaces HSP70, a known ATF5-interacting protein, from ATF5 protein complexes and antagonizes its role in stabilization of ATF5 protein. |
| GO:0005515 protein binding | IPI PMID:20075868 Nucleolar retention of a translational C/EBPalpha isoform st... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:20075868 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | REMOVE | Summary: HDA annotation for focal adhesion from a high-throughput proteomics study of myosin-II-responsive focal adhesion proteome. NPM1 is primarily nucleolar, not known to have focal adhesion functions. Reason: Focal adhesion localization is likely an artifact of the high-throughput proteomics approach. NPM1 is a nucleolar protein with no established role in focal adhesions. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | REMOVE | Summary: HDA annotation for membrane from a high-throughput study defining the membrane proteome of NK cells. NPM1 is not a membrane protein. Reason: Membrane localization is likely a contaminant in the high-throughput proteomics screen. NPM1 is a nucleolar/nuclear protein with no transmembrane domain or membrane association. |
| GO:0005515 protein binding | IPI PMID:22720776 PHF6 interacts with the nucleosome remodeling and deacetylat... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:22720776 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005634 nucleus | IDA PMID:22720776 PHF6 interacts with the nucleosome remodeling and deacetylat... | ACCEPT | Summary: IDA annotation for nucleus from PMID:22720776 (PHF6 interacts with NuRD complex). NPM1 is well-established as a nuclear protein. Reason: Nuclear localization is fundamental to NPM1. Consistent with all other evidence. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: HDA annotation for nucleus from PMID:21630459 (proteomic characterization of human sperm nucleus). NPM1 is a nuclear protein. Reason: Nuclear localization is correct for NPM1. Consistent with all other evidence. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: HDA annotation for RNA binding from PMID:22658674 (atlas of mammalian mRNA-binding proteins). NPM1 binds RNA including mRNA and rRNA. Reason: RNA binding is a core function of NPM1. Consistent with IBA and IDA evidence. Supporting Evidence: PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: HDA annotation for RNA binding from PMID:22681889 (mRNA-bound proteome study). NPM1 was identified as an mRNA-binding protein. Reason: RNA binding is a core function of NPM1. Consistent with extensive evidence. |
| GO:0005515 protein binding | IPI PMID:12882984 Nucleophosmin interacts with and inhibits the catalytic func... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:12882984 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:12882984 Nucleophosmin interacts with and inhibits the catalytic func... | KEEP AS NON CORE | Summary: PMID:12882984 showed NPM1 overexpression inhibited apoptosis through PKR inhibition. Enforced NPM expression in FA lymphoblasts reduced aberrant apoptotic responses. Reason: Anti-apoptotic function through PKR inhibition is well-demonstrated but is a secondary pleiotropic effect, not a core molecular function. Supporting Evidence: PMID:12882984 Overexpression of NPM suppressed PKR activity, enhanced protein synthesis, and inhibited apoptosis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-180725 | ACCEPT | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-180725). NPM1 shuttles to the cytoplasm/cytosol as part of its normal function in ribosome export and protein transport. Reason: Cytosol localization is consistent with NPM1 nucleocytoplasmic shuttling function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835328 | ACCEPT | Summary: TAS annotation for cytosol from Reactome (Reactome:R-HSA-9835328). NPM1 shuttles to the cytoplasm/cytosol as part of its normal function in ribosome export and protein transport. Reason: Cytosol localization is consistent with NPM1 nucleocytoplasmic shuttling function. |
| GO:0019901 protein kinase binding | IPI PMID:20352051 Polo-like kinase 2-dependent phosphorylation of NPM/B23 on s... | ACCEPT | Summary: PMID:20352051 showed NPM1 directly interacts with PLK2 in a Polo-box dependent manner. PLK2 phosphorylates NPM1 at Ser4 to trigger centriole duplication. Reason: NPM1 binds protein kinases PLK2, CDK2/cyclin E, ROCK2, and Aurora kinases as part of its regulatory roles. More specific than protein binding. Supporting Evidence: PMID:20352051 We find that Plk2 and NPM/B23 interact in vitro in a Polo-box dependent manner. An association between both proteins was also observed in vivo. |
| GO:0046599 regulation of centriole replication | IMP PMID:20352051 Polo-like kinase 2-dependent phosphorylation of NPM/B23 on s... | ACCEPT | Summary: PMID:20352051 demonstrated PLK2 phosphorylation of NPM1 at Ser4 triggers centriole duplication. Non-phosphorylatable S4A mutant interfered with centriole reduplication. Reason: Regulation of centriole replication is a core function of NPM1, demonstrated through phospho-mutant analysis. Supporting Evidence: PMID:20352051 Notably, expression of a non-phosphorylatable NPM/B23 S4A mutant interferes with centriole reduplication in S-phase arrested cells and leads to a dilution of centriole numbers in unperturbed U2OS cells. |
| GO:0005515 protein binding | IPI PMID:17015463 Interaction between ROCK II and nucleophosmin/B23 in the reg... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:17015463 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005730 nucleolus | IDA PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:18809582. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0006281 DNA repair | IDA PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a r... | KEEP AS NON CORE | Summary: PMID:19188445 showed NPM1 interacts with APEX1/Ref-1 in nucleoli and plays a role in rRNA quality control. NPM1 stimulates APEX1 endonuclease activity on AP double-stranded DNA. This represents a role in DNA repair within the rDNA context. Reason: DNA repair involvement is secondary to NPM1 core nucleolar function. The role is specifically in rRNA quality control through APEX1 regulation. Supporting Evidence: PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. |
| GO:0005515 protein binding | IPI PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a r... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:19188445 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005730 nucleolus | IDA PMID:19188445 APE1/Ref-1 interacts with NPM1 within nucleoli and plays a r... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:19188445. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0005515 protein binding | IPI PMID:20159986 Methylation of ribosomal protein S10 by protein-arginine met... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:20159986 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005515 protein binding | IPI PMID:19410545 HJURP is a cell-cycle-dependent maintenance and deposition f... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:19410545 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0043023 ribosomal large subunit binding | IDA PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape... | ACCEPT | Summary: PMID:18809582 directly demonstrated NPM1 binds the large ribosomal subunit as part of its rate-limiting nuclear export chaperone function. Reason: Large ribosomal subunit binding is a core molecular function of NPM1. Directly demonstrated. Supporting Evidence: PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. |
| GO:0043024 ribosomal small subunit binding | IDA PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape... | ACCEPT | Summary: PMID:18809582 demonstrated NPM1 binds both large and small ribosomal subunits. Reason: Small ribosomal subunit binding is a core molecular function of NPM1. Directly demonstrated. Supporting Evidence: PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. |
| GO:0010826 negative regulation of centrosome duplication | IMP PMID:16041368 Temporal and spatial control of nucleophosmin by the Ran-Crm... | ACCEPT | Summary: PMID:16041368 showed Ran-Crm1 controls NPM1 association with centrosomes. NPM1 acts as a negative regulator - its presence on unduplicated centrosomes prevents duplication until it is phosphorylated and released. Reason: Negative regulation of centrosome duplication is a core function of NPM1. NPM1 licensing of centrosome duplication through its phosphorylation-dependent dissociation. |
| GO:0003723 RNA binding | IDA PMID:12058066 The RNA binding activity of a ribosome biogenesis factor, nu... | ACCEPT | Summary: IDA annotation for RNA binding from PMID:12058066 which showed RNA binding activity of B23 is modulated by phosphorylation with cell cycle-dependent kinase. Reason: RNA binding is a core function of NPM1. Directly demonstrated by IDA. Supporting Evidence: PMID:12058066 It has been shown that B23 binds to nucleic acids, digests RNA, and is localized in nucleolar granular components from which preribosomal particles are transported to cytoplasm. |
| GO:0005654 nucleoplasm | IDA PMID:12058066 The RNA binding activity of a ribosome biogenesis factor, nu... | ACCEPT | Summary: IDA annotation for nucleoplasm from PMID:12058066. NPM1 is found in the nucleoplasm particularly when phosphorylated. Consistent with other evidence. Reason: Nucleoplasm localization is well-established. Consistent with other evidence. |
| GO:0005730 nucleolus | IDA PMID:16041368 Temporal and spatial control of nucleophosmin by the Ran-Crm... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:16041368. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0006913 nucleocytoplasmic transport | IDA PMID:16041368 Temporal and spatial control of nucleophosmin by the Ran-Crm... | ACCEPT | Summary: IDA annotation for nucleocytoplasmic transport from PMID:16041368 showing Ran-Crm1 controls NPM1 shuttling for centrosome duplication regulation. Reason: Nucleocytoplasmic transport is a core function of NPM1, regulated by Ran-Crm1 pathway. |
| GO:0007165 signal transduction | NAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | MARK AS OVER ANNOTATED | Summary: NAS annotation for signal transduction from PMID:16130169 (proteomics of etoposide-induced apoptosis in endothelial cells). Very broad term. NPM1 has indirect roles in signaling through p53, ARF, and PKR pathways. Reason: Signal transduction is far too broad for NPM1. Its signaling roles are indirect, through specific pathways (p53, PKR inhibition). The NAS evidence from a proteomics study is weak. |
| GO:0031616 spindle pole centrosome | IDA PMID:16041368 Temporal and spatial control of nucleophosmin by the Ran-Crm... | ACCEPT | Summary: IDA annotation for spindle pole centrosome from PMID:16041368 which showed NPM1 associates with centrosomes during mitosis, controlled by Ran-Crm1. Reason: NPM1 localizes to spindle pole centrosomes during mitosis. Consistent with its centrosome cycle regulation function. |
| GO:0043066 negative regulation of apoptotic process | NAS PMID:16130169 Proteomics of human umbilical vein endothelial cells applied... | KEEP AS NON CORE | Summary: NAS annotation for negative regulation of apoptosis from PMID:16130169 (proteomics study). NPM1 anti-apoptotic activity is better supported by PMID:12882984 (PKR inhibition). Reason: Anti-apoptotic function is a secondary pleiotropic effect. Better supported by other evidence. NAS from proteomics is weak but the function is real. |
| GO:0005515 protein binding | IPI PMID:16648475 Nucleophosmin is essential for ribosomal protein L5 nuclear ... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:16648475 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0006334 nucleosome assembly | IDA PMID:11602260 Function of nucleophosmin/B23, a nucleolar acidic protein, a... | ACCEPT | Summary: PMID:11602260 directly demonstrated NPM1 mediates nucleosome assembly and decondenses sperm chromatin. This is a histone chaperone function. Reason: Nucleosome assembly is a core function of NPM1 as a histone chaperone. Directly demonstrated. Supporting Evidence: PMID:11602260 Nucleophosmin/B23 was shown to bind to histones, preferentially to histone H3, to mediate formation of nucleosome, and to decondense sperm chromatin. |
| GO:0042393 histone binding | IDA PMID:11602260 Function of nucleophosmin/B23, a nucleolar acidic protein, a... | ACCEPT | Summary: IDA annotation for histone binding from PMID:11602260. NPM1 binds core histones H3, H2B, and H4. Consistent with IBA annotation already accepted. Reason: Histone binding is a core molecular function of NPM1. Directly demonstrated. Supporting Evidence: PMID:11602260 Nucleophosmin/B23 was shown to bind to histones, preferentially to histone H3, to mediate formation of nucleosome, and to decondense sperm chromatin. |
| GO:0005515 protein binding | IPI PMID:18420587 Ribosomal protein S9 is a novel B23/NPM-binding protein requ... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:18420587 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0008104 intracellular protein localization | IDA PMID:18420587 Ribosomal protein S9 is a novel B23/NPM-binding protein requ... | ACCEPT | Summary: PMID:18420587 showed NPM1 selectively stores and protects ribosomal protein S9 in nucleoli, facilitating ribosome biogenesis. Reason: NPM1 controls intracellular localization of ribosomal proteins and other cargo. This is part of its core chaperoning function. Supporting Evidence: PMID:18420587 Our results suggest that B23 selectively stores, and protects ribosomal protein S9 in nucleoli and therefore could facilitate ribosome biogenesis. |
| GO:0005515 protein binding | IPI PMID:17475909 The human Shwachman-Diamond syndrome protein, SBDS, associat... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:17475909 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005730 nucleolus | IDA PMID:17475909 The human Shwachman-Diamond syndrome protein, SBDS, associat... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:17475909. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0005515 protein binding | IPI PMID:17438371 Detection and identification of transcription factors as int... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:17438371 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005730 nucleolus | IDA PMID:11420665 Diverged nuclear localization of Werner helicase in human an... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:11420665. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0005515 protein binding | IPI PMID:15184379 Nucleophosmin/B23 is a candidate substrate for the BRCA1-BAR... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:15184379 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0030957 Tat protein binding | IDA PMID:9094689 Protein B23 is an important human factor for the nucleolar l... | KEEP AS NON CORE | Summary: PMID:9094689 showed NPM1/B23 binds HIV Tat protein and is necessary for its nucleolar localization. This is a host-virus interaction. Reason: HIV Tat binding is a specific host-virus interaction, not a core function of NPM1. However, it reflects NPM1 general role as a nucleolar shuttle protein. Supporting Evidence: PMID:9094689 Nucleolar shuttle protein B23 was found to bind to human immunodeficiency virus protein Tat, and this binding required the nucleolar localization motif of Tat. |
| GO:0051082 unfolded protein binding | IDA PMID:10211837 Nucleolar protein B23 has molecular chaperone activities. | MODIFY | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). The annotation is based on PMID:10211837 (Szebeni & Olson, 1999), which demonstrated that NPM1/B23 has genuine molecular chaperone activities including both holdase (anti-aggregation) and foldase (refolding) functions using multiple protein substrates. B23 inhibited aggregation of HIV-1 Rev protein, protected LADH, carboxypeptidase A, citrate synthase, and rhodanese from thermal aggregation, preserved LADH enzyme activity during heat stress, and promoted restoration of LADH activity after guanidine-HCl denaturation. It preferentially bound denatured substrates and exposed hydrophobic regions when complexed with denatured proteins. The demonstrated refolding activity (foldase function) best maps to GO:0044183 (protein folding chaperone). UniProt also classifies NPM1 with the keyword "Chaperone" and describes it as acting "as a chaperonin for the core histones H3, H2B and H4" (citing PMID:16107701). The histone chaperone activity is separately supported by PMID:11602260, which showed NPM1 binds histones (preferentially H3), mediates nucleosome formation, and decondenses sperm chromatin, and is better captured by GO:0140713 (histone chaperone activity). Since the evidence in PMID:10211837 specifically demonstrates protein folding chaperone activity (not just binding to unfolded proteins), MODIFY to GO:0044183 is appropriate. Reason: GO:0051082 is scheduled for obsolescence (go-ontology#30962). The obsoletion notice specifies that annotations should be redirected to either GO:0044183 (protein folding chaperone, i.e. foldase) or to a holdase chaperone term. PMID:10211837 demonstrates that NPM1 has both holdase activity (preventing aggregation of multiple substrates) and foldase activity (promoting restoration of LADH activity after guanidine-HCl denaturation). Since GO:0044183 captures the foldase/refolding function and NPM1 clearly promotes refolding, this is the most appropriate replacement. Additionally, the histone chaperone function of NPM1 (PMID:11602260, PMID:16107701) is a distinct activity best captured by GO:0140713, which should be proposed as a NEW annotation. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:10211837 Protein B23 inhibited the aggregation of the Rev protein, with the amount of inhibition proportional to the concentration of B23 added. This activity was saturable with nearly complete inhibition when the molar ratio of B23:Rev was slightly above one. PMID:10211837 Protein B23 also protected liver alcohol dehydrogenase (LADH), carboxypeptidase A, citrate synthase, and rhodanese from aggregation during thermal denaturation and preserved the enzyme activity of LADH under these conditions. PMID:10211837 In addition, protein B23 was able to promote the restoration of activity of LADH previously denatured with guanidine-HCl. PMID:10211837 Protein B23 preferentially bound denatured substrates and exposed hydrophobic regions when complexed with denatured proteins. Thus, by several criteria, protein B23 behaves like a molecular chaperone; these activities may be related to its role in ribosome biogenesis. PMID:11602260 Nucleophosmin/B23 was shown to bind to histones, preferentially to histone H3, to mediate formation of nucleosome, and to decondense sperm chromatin. These activities of B23 were dependent on its acidic regions as other histone chaperones, suggesting that B23/nucleophosmin is a member of histone chaperone proteins. |
| GO:0051059 NF-kappaB binding | IDA PMID:15087454 Identification of nucleophosmin as an NF-kappaB co-activator... | KEEP AS NON CORE | Summary: PMID:15087454 demonstrated physical interaction between NPM and NF-kappaB using co-immunoprecipitation and NF-kappaB affinity chromatography. NPM was the most abundant protein in the NF-kappaB-bound fraction. Reason: NF-kappaB binding is demonstrated but is part of NPM1 non-core transcription coactivator function. Not a core molecular function. Supporting Evidence: PMID:15087454 Co-immunoprecipitation studies suggest a physical interaction between NPM and NF-kappaB proteins. |
| GO:0003713 transcription coactivator activity | IDA PMID:15087454 Identification of nucleophosmin as an NF-kappaB co-activator... | KEEP AS NON CORE | Summary: PMID:15087454 showed NPM1 acts as NF-kappaB coactivator for SOD2 induction. Increasing NPM expression increased SOD2 transcription dose-dependently. Reason: Transcription coactivator activity is a non-core function. Redundant with annotation from PMID:19160485. Supporting Evidence: PMID:15087454 The results indicate that an increase NPM expression leads to increased MnSOD gene transcription in a dose-dependent manner. |
| GO:0005813 centrosome | IDA PMID:11051553 Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome... | ACCEPT | Summary: PMID:11051553 showed NPM1 associates specifically with unduplicated centrosomes and dissociates upon CDK2/cyclin E phosphorylation to initiate centrosome duplication. Reason: Centrosome localization is a core feature of NPM1, directly demonstrated by IDA in a landmark study. Supporting Evidence: PMID:11051553 NPM/B23 associates specifically with unduplicated centrosomes, and NPM/B23 dissociates from centrosomes by CDK2/cyclin E-mediated phosphorylation. |
| GO:0007098 centrosome cycle | IMP PMID:11051553 Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome... | ACCEPT | Summary: PMID:11051553 demonstrated NPM1 is a CDK2/cyclin E substrate in centrosome duplication. NPM1 phosphorylation triggers centrosome duplication initiation. Reason: Centrosome cycle regulation is a core function of NPM1. Landmark study demonstrating direct involvement. Supporting Evidence: PMID:11051553 We identified nucleophosmin (NPM/B23) as a substrate of CDK2/cyclin E in centrosome duplication. |
| GO:0005515 protein binding | IPI PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | REMOVE | Summary: Protein binding (GO:0005515) is uninformative and does not capture the specific molecular function of the interaction. NPM1 interacts with many proteins as part of its diverse functions. This annotation from PMID:12080348 should be replaced with more specific MF terms. Reason: Per curation guidelines, protein binding is too vague to be informative. More specific molecular function terms (e.g. histone chaperone activity, protein folding chaperone, ribosomal subunit binding) better capture NPM1 activities. |
| GO:0005634 nucleus | IDA PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | ACCEPT | Summary: IDA annotation for nucleus from PMID:12080348 which studied NPM1 regulation of p53. NPM1 is a nuclear protein. Consistent with all other evidence. Reason: Nuclear localization is fundamental to NPM1 function. Well-established. |
| GO:0005730 nucleolus | IDA PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | ACCEPT | Summary: IDA annotation for nucleolus from PMID:12080348. NPM1 is one of the most abundant nucleolar proteins. Its nucleolar localization is a core feature. Reason: Nucleolus is the primary localization of NPM1. Well-established across many independent studies. |
| GO:0005737 cytoplasm | IDA PMID:9121481 Role of the nucleophosmin (NPM) portion of the non-Hodgkin's... | ACCEPT | Summary: IDA annotation for cytoplasm from PMID:9121481 which studied the NPM-ALK fusion oncogene. NPM1 was shown to shuttle between nucleus and cytoplasm. Reason: Cytoplasmic localization confirmed by IDA. NPM1 is a nucleocytoplasmic shuttling protein. Supporting Evidence: PMID:9121481 Cell fractionation studies of the t(2;5) translocation-containing lymphoma cell line SUP-M2 showed NPM-ALK to be localized within both the cytoplasmic and nuclear compartments. |
| GO:0006886 intracellular protein transport | TAS PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | ACCEPT | Summary: TAS annotation for intracellular protein transport. NPM1 functions as a nucleocytoplasmic shuttle for ribosomal subunits and other cargo proteins. PMID:12080348 discusses NPM1 shuttling. Reason: Intracellular protein transport is a core function of NPM1. It acts as a nuclear export chaperone for ribosomes and import adaptor for various proteins. |
| GO:0006913 nucleocytoplasmic transport | TAS PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | ACCEPT | Summary: TAS annotation for nucleocytoplasmic transport from PMID:12080348. NPM1 is a well-established nucleocytoplasmic shuttling protein. Reason: Nucleocytoplasmic transport is a core function of NPM1. It shuttles between nucleus and cytoplasm to export ribosomal subunits. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | KEEP AS NON CORE | Summary: PMID:12080348 showed NPM1 stabilizes p53 and can suppress cell growth. However, NPM1 also has pro-proliferative roles through ribosome biogenesis and ATF5 degradation. The negative regulation may reflect specific contexts. Reason: NPM1 has context-dependent effects on proliferation. The negative regulation is through p53 stabilization in certain conditions. Not a core defining function. |
| GO:0042255 ribosome assembly | TAS PMID:12080348 Nucleophosmin regulates the stability and transcriptional ac... | ACCEPT | Summary: TAS annotation for ribosome assembly. NPM1 is essential for ribosome biogenesis including assembly, processing, and export (PMID:18809582, PMID:16648475). Reason: Ribosome assembly is a core function of NPM1. Well-supported by multiple direct studies. |
| GO:0042803 protein homodimerization activity | IDA PMID:9121481 Role of the nucleophosmin (NPM) portion of the non-Hodgkin's... | ACCEPT | Summary: IDA annotation for protein homodimerization from PMID:9121481. NPM1 forms pentamers and decamers. Consistent with IPI from PMID:24106084 and structural data. Reason: NPM1 oligomerization is a fundamental structural property. Forms pentamers/decamers essential for function. |
| GO:0140713 histone chaperone activity | IDA PMID:11602260 Function of nucleophosmin/B23, a nucleolar acidic protein, a... | NEW | Summary: NPM1 functions as a histone chaperone for core histones H3, H2B, and H4. PMID:11602260 demonstrated NPM1 binds histones (preferentially H3), mediates nucleosome formation, and decondenses sperm chromatin. These activities depend on its acidic regions, as in other histone chaperones. PMID:16107701 showed NPM1 enhances acetylation-dependent chromatin transcription, disrupting nucleosomal structure. UniProt classifies NPM1 as a chaperonin for core histones. GO:0140713 (histone chaperone activity) is the appropriate specific term for this well-documented function that is not currently annotated with this precise GO term. Reason: Histone chaperone activity is a core molecular function of NPM1 that is well-supported by multiple experimental studies but is not captured by any existing annotation at this level of specificity. The existing annotations cover histone binding (GO:0042393) and chromatin remodeling (GO:0006338) but not the specific chaperone activity. Supporting Evidence: PMID:11602260 Nucleophosmin/B23 was shown to bind to histones, preferentially to histone H3, to mediate formation of nucleosome, and to decondense sperm chromatin. These activities of B23 were dependent on its acidic regions as other histone chaperones, suggesting that B23/nucleophosmin is a member of histone chaperone proteins. PMID:16107701 Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin transcription. |
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