DUSP5

Function

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1/2, is expressed in a variety of tissues with the highest levels in pancreas and brain, and is localized in the nucleus.[6]

Model organisms

Model organisms have been used in the study of DUSP5 function. A conditional knockout mouse line called Dusp5tm1a(KOMP)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]

Dusp5 knockout mouse phenotype[8][13]
CharacteristicPhenotype
InsulinNormal
Homozygous viability at P14Normal
Homozygous FertilityNormal
Body weightNormal
Neurological assessmentNormal
Grip strengthNormal
DysmorphologyNormal
Indirect calorimetryNormal
Glucose tolerance testNormal
Auditory brainstem responseNormal
DEXANormal
RadiographyNormal
Eye morphologyNormal
Clinical chemistryNormal
Haematology 16 WeeksNormal
Peripheral blood leukocytes 16 WeeksNormal
Heart weightNormal
Salmonella infectionNormal
Spleen ImmunophenotypingNormal
Epidermal Immune CompositionNormal

References
  1. GRCh38: Ensembl release 89: ENSG00000138166 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000034765 - Ensembl, 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. Martell KJ, Kwak S, Hakes DJ, Dixon JE, Trent JM (Jul 1994). "Chromosomal localization of four human VH1-like protein-tyrosine phosphatases". Genomics. 22 (2): 462–4. doi:10.1006/geno.1994.1411. hdl:2027.42/31442. PMID 7806236.
  6. "Entrez Gene: DUSP5 dual specificity phosphatase 5".
  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. "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. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading
  • Overview of all the structural information available in the PDB for UniProt: Q16690 (Dual specificity protein phosphatase 5) at the PDBe-KB.


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