NPM1
Nucleophosmin
Also known as: B23, NPM, NPM_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P06748
- Gene
- NPM1
- Ensembl
- ENSG00000181163
- Chromosome
- 5
- Canonical length
- 294 aa
- Protein class
- Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nucleoli rim
OverviewNCBI Gene
The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified. [provided by RefSeq, Aug 2017]
Canonical amino-acid sequenceUniProt
294 residues, UniProt reviewed canonical sequence.
>P06748|NPM1
1 MEDSMDMDMS PLRPQNYLFG CELKADKDYH FKVDNDENEH QLSLRTVSLG AGAKDELHIV
61 EAEAMNYEGS PIKVTLATLK MSVQPTVSLG GFEITPPVVL RLKCGSGPVH ISGQHLVAVE
121 EDAESEDEEE EDVKLLSISG KRSAPGGGSK VPQKKVKLAA DEDDDDDDEE DDDEDDDDDD
181 FDDEEAEEKA PVKKSIRDTP AKNAQKSNQN GKDSKPSSTP RSKGQESFKK QEKTPKTPKG
241 PSSVEDIKAK MQASIEKGGS LPKVEAKFIN YVKNCFRMTD QEAIQDLWQW RKSLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against NPM1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.5
- Highest tissue expression
- 1,213 nTPM
Expression across tissuesHPA
Tissue
- ovary: 1,213 nTPM
- bone marrow: 744 nTPM
- pancreas: 733 nTPM
- lymph node: 725 nTPM
- tonsil: 713 nTPM
- thymus: 637 nTPM
Single-cell type
- migrating cytotrophoblasts: 1,912 nCPM
- esophageal basal cells: 1,540 nCPM
- extravillous trophoblasts: 1,466 nCPM
- fallopian secretory cells: 1,428 nCPM
- epididymal efferent duct absorptive cells: 1,321 nCPM
- cytotrophoblasts: 1,276 nCPM
Immune cell
- naive CD4 T-cell: 1,192 nTPM
- total PBMC: 1,073 nTPM
- naive CD8 T-cell: 975 nTPM
- memory B-cell: 850 nTPM
- MAIT T-cell: 835 nTPM
- memory CD4 T-cell: 834 nTPM
Brain region
- spinal cord: 222 nTPM
- hypothalamus: 214 nTPM
- medulla oblongata: 203 nTPM
- white matter: 198 nTPM
- choroid plexus: 180 nTPM
- pons: 168 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about NPM1.
Disease | GeneticClinVar
8 pathogenic / likely-pathogenic of 90 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Acute myeloid leukemia
- Myelodysplastic syndrome progressed to acute myeloid leukemia
- NPM1-related disorder
- Acute myeloid leukemia with NPM1 somatic mutations
- Acute myeloid leukemia with multilineage dysplasia
Disease | ImmuneIEDB
Conditions an epitope on NPM1 was assayed in.
- rheumatoid arthritis T cell
ReferencesPubMed · IEDB
Publications for NPM1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
10 publications
- Immune response to the ALK oncogenic tyrosine kinase in patients with anaplastic large-cell lymphoma.
2000 · Blood · RCR 1.5 · 86 citations - Autoantibodies against B23, a nucleolar phosphoprotein, occur in scleroderma and are associated with pulmonary hypertension.
2003 · Arthritis Rheum · RCR 1.2 · 53 citations - Identification and evaluation of novel serum autoantibody biomarkers for early diagnosis of gastric cancer and precancerous lesion.
2023 · J Cancer Res Clin Oncol · RCR 1.1 · 9 citations - Antibodies in scleroderma: direct pathogenicity and phenotypic associations.
2004 · Curr Rheumatol Rep · RCR 1 · 46 citations - Using Serological Proteome Analysis to Identify Serum Anti-Nucleophosmin 1 Autoantibody as a Potential Biomarker in European-American and African-American Patients With Prostate Cancer.
2016 · Prostate · RCR 1 · 32 citations
Show 5 more
- Autoantibodies to the nuclear phosphoprotein nucleophosmin in breast cancer patients.
1998 · Cancer Epidemiol Biomarkers Prev · RCR 1 · 42 citations - Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma.
2017 · World J Gastroenterol · RCR 0.9 · 21 citations - Autoantibodies to the major nucleolar phosphoprotein B23 define a novel subset of patients with anticardiolipin antibodies.
1989 · Arthritis Rheum · RCR 0.5 · 18 citations - Humoral autoimmune response to nucleophosmin in the immunodiagnosis of hepatocellular carcinoma.
2015 · Oncol Rep · RCR 0.4 · 10 citations - Association between anti-nucleophosmin and anti-cardiolipin antibodies in (NZW x BXSB)F1 mice and human systemic lupus erythematosus.
2005 · Arthritis Res Ther · RCR 0.3 · 11 citations
Reference: B cellIEDB
1 publication
- Peptide microarray-based characterization of antibody responses to host proteins after bacille Calmette-Guérin vaccination.
2017 · Int J Infect Dis · RCR 0.7 · 19 citations
Reference: T cellIEDB
2 publications
- Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides.
2021 · Cell Rep · RCR 0.9 · 19 citations - Immune responses to citrullinated and homocitrullinated peptides in healthy donors are not restricted to the HLA SE shared allele and can be selected into the memory pool.
2023 · Immunology · RCR 0.8 · 6 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.16
- gnomAD pLI
- 1
- gnomAD missense Z
- 1.95
- DepMap mean gene effect
- -0.8
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell volume homeostasis
- cellular response to UV
- cellular senescence
- centrosome cycle
- chromatin remodeling
- DNA repair
- intracellular protein localization
- intracellular protein transport
- macrophage differentiation
- negative regulation of apoptotic process
- negative regulation of cell population proliferation
- negative regulation of centrosome duplication
- negative regulation of mRNA splicing, via spliceosome
- negative regulation of protein kinase activity by regulation of protein phosphorylation
- nucleocytoplasmic transport
- nucleosome assembly
- positive regulation of cell cycle G2/M phase transition
- positive regulation of cell population proliferation
- positive regulation of centrosome duplication
- positive regulation of DNA-templated transcription
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of protein localization to nucleolus
- positive regulation of protein ubiquitination
- positive regulation of transcription by RNA polymerase II
- positive regulation of translation
- protein import into nucleus
- protein stabilization
- regulation of cell growth
- regulation of centriole replication
- regulation of centrosome duplication
- regulation of DNA damage response, signal transduction by p53 class mediator
- ribosomal large subunit biogenesis
- ribosomal large subunit export from nucleus
- ribosomal small subunit biogenesis
- ribosomal small subunit export from nucleus
- ribosome assembly
- signal transduction
- regulation of eIF2 alpha phosphorylation by dsRNA
- regulation of mRNA stability involved in cellular response to UV
Molecular functions
- chromatin binding
- core promoter sequence-specific DNA binding
- DNA-binding transcription factor binding
- histone binding
- molecular adaptor activity
- NF-kappaB binding
- protein homodimerization activity
- protein kinase binding
- protein kinase inhibitor activity
- ribosomal large subunit binding
- ribosomal small subunit binding
- RNA binding
- rRNA binding
- Tat protein binding
- transcription coactivator activity
- unfolded protein binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Nucleoplasmin family
- Nucleoplasmin core domain
- Nucleoplasmin core domain superfamily
- Nucleoplasmin/nucleophosmin domain
- Nucleophosmin, C-terminal
- Nucleophosmin C-terminal domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of NPM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads NPM1 as an antibody target. Whether an autoantibody or antibody against NPM1 could matter depends on whether native NPM1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NPM1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label NPM1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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