Cancer Protein Description
This report provides a detailed description of a selected cancer protein with information collected from various sources, including UniProt, the Wellcome Trust Sanger Institute’s Catalogue of Somatic Mutations in Cancer (COSMIC), and the Atlas of Genetics and Cytogenetics in Oncology and Haematology.
| Protein Name: | NPM1 |
| Gene Name: | NPM1 |
| Protein Full Name: | Nucleophosmin |
| Alias: | B23; Nucleolar phosphoprotein B23; Nucleolar protein NO38; Nucleophosmin (Nucleolar phosphoprotein B23, numatrin); Nucleophosmin/B23.2; Numatrin |
| Mass (Da): | 32575 |
| Number AA: | 294 |
| UniProt ID: | P06748 |
| Locus ID: | 4869 |
| COSMIC ID: | NPM1 |
| Gene location on chromosome: | 5q35.1 |
| Cancer protein type: | OP |
| Effect of cancer mutation on protein: | UNCLEAR |
| Effect of active protein on cancer: | PROMOTES |
| Number of cancer specimens: | 41166 |
| Percent of cancer specimens with mutations: | 12.51 |
| General distribution of mutations: | Narrow |
| Location of most mutations: | One main region at AA 285-295 with point mutations, complex mutations, insertions and deletions. |
| Commonly recorded point mutations: | W288fs* (2398, Insertion - Frameshift); |
| Deregulated in translocations: | Large-cell lymphomas. Fusion partners include Alk. Acute non lymphocytic leukemia (ANLL), myelodysplasia (MDS), chronic myelogenous leukemia in blast crisis (BC-CML), fusion partner is MLF1. Promyelocytic ANLL, fusion partner is RARa. |
| Normal role description: | NPM1 is a nuclear localized RNA binding phosphoprotein required for ribosome assembly and shuttling of ribonucleoproteins between cellular compartments. NPM1 functions in regulating the assembly and trafficking of translational machinery. The NPM1 gene locus has been observed to participate in a translocation event ALK, a tyrosine kinase, to result in a fusion protein. The NPM1-ALK fusion protein has been implicated in 80% of all ALK-mediated Anaplasic large cell lymphomas. The fusion event causes a constitutively activated ALK which can activate STAT3 and STAT5A expression which leads to malignancies. The NPM1 locus may also be mutated by an insertional frameshift event which leads to aberrant localization of NPM1 from the nucleus to the cytoplasm. This mutation has been implicated in the development of leukemias. |
| Commentary on involvement of protein in cancer: | W288fs - W288A: Complete destabilization of the structure; when associated with A-290. AA243-294 appear to be required for nucleolar locaization. |