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NME4

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NME4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNME4, NDPK-D, NM23H4, nm23-H4, NME/NM23 nucleoside diphosphate kinase 4
External IDsOMIM: 601818; MGI: 1931148; HomoloGene: 3673; GeneCards: NME4; OMA:NME4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_019731

RefSeq (protein)

NP_062705

Location (UCSC)Chr 16: 0.4 – 0.41 MbChr 17: 26.31 – 26.31 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Non-metastatic cells 4, protein expressed in, also known as NME4, is a protein which in humans is encoded by the NME4 gene.[5][6]

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.[6] 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.[5]

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.[7] Male and female animals underwent a standardized phenotypic screen[8] to determine the effects of deletion.[9][10][11][12] Additional screens performed: - In-depth immunological phenotyping[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000103202Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024177Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: NME4 non-metastatic cells 4, protein expressed in".
  6. ^ a b Milon L, Rousseau-Merck MF, Munier A, Erent M, Lascu I, Capeau J, Lacombe ML (Apr 1997). "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. doi:10.1007/s004390050405. PMID 9099850. S2CID 8408840.
  7. ^ 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. S2CID 85911512.
  8. ^ a b "International Mouse Phenotyping Consortium".
  9. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  10. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  11. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  12. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  13. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading