Biology:NME4
 Generic protein structure example |
Non-metastatic cells 4, protein expressed in, also known as NME4, is a protein which in humans is encoded by the NME4 gene.[1][2]
Function
The nucleoside diphosphate (NDP) kinases (EC 2.7.4.6) are ubiquitous enzymes that catalyze transfer of gamma-phosphates, via a phosphohistidine intermediate, between nucleoside and dioxynucleoside tri- and diphosphates. The enzymes are products of the nm23 gene family, which includes NME4. The first nm23 gene, nm23-H1 (NME1), was isolated based on its reduced expression in a highly metastatic murine melanoma cell line and was proposed to be a metastasis suppressing gene. The human equivalent was obtained by cDNA library screening using the murine gene as a probe and found to be homologous to the Drosophila awd gene. A second human gene, nm23-H2 (NME2), encoding a protein 88% identical to nm23-H1, was subsequently isolated. Both genes were localized on 17q21.3 and their gene products were formerly identified as the A and B subunits of NDP kinases. In mammals, functional NDP kinases are heterohexamers of the A and B monomers, which can combine at variable ratios to form different types of hybrids.[2] These enzymes are highly expressed in tumors as compared with normal tissues. In some cell lines and in certain solid tumors, decreased expression of NME1 is associated with increased metastatic potential; moreover, when transfected into very aggressive cell lines, such as human breast carcinoma, NME1 decreased the metastatic potential. A third human gene, DR-nm23 (NME3), was identified and found to share high sequence similarity with the NME1 and NME2 genes. It is highly expressed in blast crisis transition of chronic myeloid leukemia. When overexpressed by transfection, NME3 suppressed granulocyte differentiation and induced apoptosis of myeloid precursor cells.[1]
Model organisms
Model organisms have been used in the study of NME4 function. A conditional knockout mouse line called Nme4tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[3] Male and female animals underwent a standardized phenotypic screen[4] to determine the effects of deletion.[5][6][7][8] Additional screens performed: - In-depth immunological phenotyping[9]
| Characteristic | Phenotype |
|---|---|
| All data available at.[4][9] | |
| Insulin | Normal |
| Homozygous viability at P14 | Normal |
| Homozygous Fertility | Normal |
| Body weight | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology 16 Weeks | Normal |
| Peripheral blood leukocytes 16 Weeks | Normal |
| Salmonella infection | Normal |
References
- ↑ 1.0 1.1 "Entrez Gene: NME4 non-metastatic cells 4, protein expressed in". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4833.
- ↑ 2.0 2.1 "nm23-H4, a new member of the family of human nm23/nucleoside diphosphate kinase genes localised on chromosome 16p13". Human Genetics 99 (4): 550–7. Apr 1997. doi:10.1007/s004390050405. PMID 9099850.
- ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ 4.0 4.1 "International Mouse Phenotyping Consortium". http://www.mousephenotype.org/data/search?q=Nme4#fq=*:*&facet=gene.
- ↑ "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. Jun 2011. doi:10.1038/nature10163. PMID 21677750.
- ↑ "Mouse library set to be knockout". Nature 474 (7351): 262–3. Jun 2011. doi:10.1038/474262a. PMID 21677718.
- ↑ "A mouse for all reasons". Cell 128 (1): 9–13. Jan 2007. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. Jul 2013. doi:10.1016/j.cell.2013.06.022. PMID 23870131.
- ↑ 9.0 9.1 "Infection and Immunity Immunophenotyping (3i) Consortium". http://www.immunophenotyping.org/data/search?keys=Nme4&field_gene_construct_tid=All.
Further reading
- "The mammalian Nm23/NDPK family: from metastasis control to cilia movement". Molecular and Cellular Biochemistry 329 (1–2): 51–62. Sep 2009. doi:10.1007/s11010-009-0120-7. PMID 19387795.
- "The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase". The Journal of Biological Chemistry 275 (19): 14264–72. May 2000. doi:10.1074/jbc.275.19.14264. PMID 10799505.
- "Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16". Human Molecular Genetics 10 (4): 339–52. Feb 2001. doi:10.1093/hmg/10.4.339. PMID 11157797.
- "Localization and characterization of the mitochondrial isoform of the nucleoside diphosphate kinase in the pancreatic beta cell: evidence for its complexation with mitochondrial succinyl-CoA synthetase". Archives of Biochemistry and Biophysics 398 (2): 160–9. Feb 2002. doi:10.1006/abbi.2001.2710. PMID 11831846.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. Oct 2005. doi:10.1038/nature04209. PMID 16189514.
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