DUSP3

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Dual specificity phosphatase 3
Protein DUSP3 PDB 1j4x.png
PDB rendering based on 1j4x.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DUSP3 ; VHR
External IDs OMIM600183 MGI1919599 HomoloGene20870 ChEMBL: 2635 GeneCards: DUSP3 Gene
EC number 3.1.3.16, 3.1.3.48
RNA expression pattern
PBB GE DUSP3 201536 at tn.png
PBB GE DUSP3 201537 s at tn.png
PBB GE DUSP3 201538 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1845 72349
Ensembl ENSG00000108861 ENSMUSG00000003518
UniProt P51452 Q9D7X3
RefSeq (mRNA) NM_004090 NM_028207
RefSeq (protein) NP_004081 NP_082483
Location (UCSC) Chr 17:
41.84 – 41.86 Mb
Chr 11:
101.97 – 101.99 Mb
PubMed search [1] [2]

Dual specificity protein phosphatase 3 is an enzyme that in humans is encoded by the DUSP3 gene.[1][2]

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 maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1.[2]

Model organisms[edit]

Model organisms have been used in the study of DUSP3 function. A conditional knockout mouse line, called Dusp3tm1a(KOMP)Wtsi[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty five tests were carried out on mutant mice and four significant abnormalities were observed.[8] Homozygous mutants had an increased percent of body fat, abnormal humerus morphology and an increased susceptibility to bacterial infection. Corpus callosum area, hippocampus area and total brain section area was increased, while length of pyramidal cell layer was reduced.[8]

Interactions[edit]

DUSP3 has been shown to interact with MAPK3[16] and MAPK1.[16]

References[edit]

  1. ^ Folander K, Douglass J, Swanson R (Feb 1995). "Confirmation of the assignment of the gene encoding Kv1.3, a voltage-gated potassium channel (KCNA3) to the proximal short arm of human chromosome 1". Genomics 23 (1): 295–6. doi:10.1006/geno.1994.1500. PMID 7829094. 
  2. ^ a b "Entrez Gene: DUSP3 dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)". 
  3. ^ "DEXA data for Dusp3". Wellcome Trust Sanger Institute. 
  4. ^ "Radiography data for Dusp3". Wellcome Trust Sanger Institute. 
  5. ^ "Haematology data for Dusp3". Wellcome Trust Sanger Institute. 
  6. ^ "Salmonella infection data for Dusp3". Wellcome Trust Sanger Institute. 
  7. ^ "Citrobacter infection data for Dusp3". Wellcome Trust Sanger Institute. 
  8. ^ a b c d 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. 
  9. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  10. ^ "International Knockout Mouse Consortium". 
  11. ^ "Mouse Genome Informatics". 
  12. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  13. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  14. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  15. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  16. ^ a b Todd, J L; Tanner K G; Denu J M (May 1999). "Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway". J. Biol. Chem. (UNITED STATES) 274 (19): 13271–80. doi:10.1074/jbc.274.19.13271. ISSN 0021-9258. PMID 10224087. 

Further reading[edit]