DUSP3: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Dual specificity protein phosphatase 3''' is an [[enzyme]] that in humans is encoded by the ''DUSP3'' [[gene]].<ref name="pmid7829094">{{cite journal | vauthors = Folander K, Douglass J, Swanson R | title = 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 | journal = Genomics | volume = 23 | issue = 1 | pages = 295–6 |date=Feb 1995 | pmid = 7829094 | pmc =  | doi = 10.1006/geno.1994.1500 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DUSP3 dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1845| accessdate = }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_DUSP3_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1j4x.
| PDB = {{PDB2|1j4x}}, {{PDB2|1vhr}}
| Name = Dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)
| HGNCid = 3069
| Symbol = DUSP3
| AltSymbols =; VHR
| OMIM = 600183
| ECnumber =
| Homologene = 20870
| MGIid = 1919599
  | GeneAtlas_image1 = PBB_GE_DUSP3_201536_at_tn.png
| GeneAtlas_image2 = PBB_GE_DUSP3_201537_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_DUSP3_201538_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004725 |text = protein tyrosine phosphatase activity}} {{GNF_GO|id=GO:0008138 |text = protein tyrosine/serine/threonine phosphatase activity}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component =
| Process = {{GNF_GO|id=GO:0006470 |text = protein amino acid dephosphorylation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1845
    | Hs_Ensembl = ENSG00000108861
    | Hs_RefseqProtein = NP_004081
    | Hs_RefseqmRNA = NM_004090
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 39199016
    | Hs_GenLoc_end = 39211872
    | Hs_Uniprot = P51452
    | Mm_EntrezGene = 72349
    | Mm_Ensembl = ENSMUSG00000003518
    | Mm_RefseqmRNA = NM_028207
    | Mm_RefseqProtein = NP_082483
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 101790249
    | Mm_GenLoc_end = 101800860
    | Mm_Uniprot = Q3V2Y9
  }}
}}
'''Dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)''', also known as '''DUSP3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DUSP3 dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1845| accessdate = }}</ref>


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{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =  
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: DUSP3 dual specificity phosphatase 3 (vaccinia virus phosphatase VH1-related)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1845| accessdate = }}</ref>
| summary_text = 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.<ref name="entrez" />
}}
}}
==Model organisms==
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Dusp3'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#C40000"|Abnormal<ref name="DEXA">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBVF/body-composition-dexa/ |title=DEXA data for Dusp3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Radiography]] || bgcolor="#C40000"|Abnormal<ref name="Radiography">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBVF/x-ray-imaging/ |title=Radiography data for Dusp3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal<ref name="Haematology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBVF/haematology-cbc/ |title=Haematology data for Dusp3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Skin Histopathology || bgcolor="#488ED3"|Normal
|-
| Brain histopathology || bgcolor="#C40000"|Abnormal
|-
| ''[[Salmonella]]'' infection || bgcolor="#C40000"|Abnormal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBVF/salmonella-challenge/ |title=''Salmonella'' infection data for Dusp3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBVF/citrobacter-challenge/ |title=''Citrobacter'' infection data for Dusp3 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages =  925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of DUSP3 function. A conditional [[knockout mouse]] line, called ''Dusp3<sup>tm1a(KOMP)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Dusp3 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4365004 |title=Mouse Genome Informatics}}</ref> 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.<ref name="pmid21677750">{{Cite journal
| last1 = Skarnes |first1 =W. C.
| doi = 10.1038/nature10163
| last2 = Rosen | first2 = B.
| last3 = West | first3 = A. P.
| last4 = Koutsourakis | first4 = M.
| last5 = Bushell | first5 = W.
| last6 = Iyer | first6 = V.
| last7 = Mujica | first7 = A. O.
| last8 = Thomas | first8 = M.
| last9 = Harrow | first9 = J.
| last10 = Cox | first10 = T.
| last11 = Jackson | first11 = D.
| last12 = Severin | first12 = J.
| last13 = Biggs | first13 = P.
| last14 = Fu | first14 = J.
| last15 = Nefedov | first15 = M.
| last16 = De Jong | first16 = P. J.
| last17 = Stewart | first17 = A. F.
| last18 = Bradley | first18 = A.
| title = A conditional knockout resource for the genome-wide study of mouse gene function
| journal = Nature
| volume = 474
| issue = 7351
| pages = 337–342
| year = 2011
| pmid = 21677750
| pmc =3572410
}}</ref><ref name="mouse_library">{{cite journal | doi = 10.1038/474262a | title = Mouse library set to be knockout | year = 2011 | author = Dolgin E | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | pmid = 21677718 }}</ref><ref name="mouse_for_all_reasons">{{cite journal | doi = 10.1016/j.cell.2006.12.018 | title = A Mouse for All Reasons | year = 2007 | journal = Cell | volume = 128 | pages = 9–13 | pmid = 17218247 |vauthors=Collins FS, Rossant J, Wurst W| issue = 1 }}</ref>
Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal| vauthors=van der Weyden L, White JK, Adams DJ, Logan DW| title=The mouse genetics toolkit: revealing function and mechanism. | journal=Genome Biol | year= 2011 | volume= 12 | issue= 6 | pages= 224 | pmid=21722353 | doi=10.1186/gb-2011-12-6-224  | pmc=3218837}}</ref> Twenty five tests were carried out on [[mutant]] mice and four significant abnormalities were observed.<ref name="mgp_reference" /> [[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.<ref name="mgp_reference" />
==Interactions==
DUSP3 has been shown to [[Protein-protein interaction|interact]] with [[MAPK3]]<ref name=pmid10224087>{{cite journal |last=Todd |first=J L |author2=Tanner K G |author3=Denu J M  |date=May 1999 |title=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 |journal=J. Biol. Chem. |volume=274 |issue=19 |pages=13271–80 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 10224087 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |doi=10.1074/jbc.274.19.13271 }}</ref> and [[MAPK1]].<ref name=pmid10224087/>


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Ishibashi T, Bottaro DP, Chan A, ''et al.'' |title=Expression cloning of a human dual-specificity phosphatase. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 24 |pages= 12170-4 |year= 1993 |pmid= 1281549 |doi=  }}
*{{cite journal  | vauthors=Ishibashi T, Bottaro DP, Chan A |title=Expression cloning of a human dual-specificity phosphatase |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 24 |pages= 12170–4 |year= 1993 |pmid= 1281549 |doi=10.1073/pnas.89.24.12170  | pmc=50720 |display-authors=etal|bibcode=1992PNAS...8912170I}}
*{{cite journal  | author=Kamb A, Futreal PA, Rosenthal J, ''et al.'' |title=Localization of the VHR phosphatase gene and its analysis as a candidate for BRCA1. |journal=Genomics |volume=23 |issue= 1 |pages= 163-7 |year= 1995 |pmid= 7829067 |doi=  }}
*{{cite journal  | vauthors=Kamb A, Futreal PA, Rosenthal J |title=Localization of the VHR phosphatase gene and its analysis as a candidate for BRCA1 |journal=Genomics |volume=23 |issue= 1 |pages= 163–7 |year= 1995 |pmid= 7829067 |doi=10.1006/geno.1994.1473  |display-authors=etal}}
*{{cite journal  | author=Folander K, Douglass J, Swanson R |title=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. |journal=Genomics |volume=23 |issue= 1 |pages= 295-6 |year= 1995 |pmid= 7829094 |doi= 10.1006/geno.1994.1500 }}
*{{cite journal  | vauthors=Jones KA, Black DM, Brown MA |title=The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase |journal=Hum. Mol. Genet. |volume=3 |issue= 11 |pages= 1927–34 |year= 1995 |pmid= 7874108 |doi=10.1093/hmg/3.11.1927 |display-authors=etal}}
*{{cite journal  | author=Jones KA, Black DM, Brown MA, ''et al.'' |title=The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase. |journal=Hum. Mol. Genet. |volume=3 |issue= 11 |pages= 1927-34 |year= 1995 |pmid= 7874108 |doi=  }}
*{{cite journal  | vauthors=Yuvaniyama J, Denu JM, Dixon JE, Saper MA |title=Crystal structure of the dual specificity protein phosphatase VHR |journal=Science |volume=272 |issue= 5266 |pages= 1328–31 |year= 1996 |pmid= 8650541 |doi=10.1126/science.272.5266.1328 |bibcode=1996Sci...272.1328Y }}
*{{cite journal  | author=Yuvaniyama J, Denu JM, Dixon JE, Saper MA |title=Crystal structure of the dual specificity protein phosphatase VHR. |journal=Science |volume=272 |issue= 5266 |pages= 1328-31 |year= 1996 |pmid= 8650541 |doi=  }}
*{{cite journal  | vauthors=Todd JL, Tanner KG, Denu JM |title=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 |journal=J. Biol. Chem. |volume=274 |issue= 19 |pages= 13271–80 |year= 1999 |pmid= 10224087 |doi=10.1074/jbc.274.19.13271 }}
*{{cite journal  | author=Todd JL, Tanner KG, Denu JM |title=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. |journal=J. Biol. Chem. |volume=274 |issue= 19 |pages= 13271-80 |year= 1999 |pmid= 10224087 |doi=  }}
*{{cite journal  | vauthors=Alonso A, Saxena M, Williams S, Mustelin T |title=Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation |journal=J. Biol. Chem. |volume=276 |issue= 7 |pages= 4766–71 |year= 2001 |pmid= 11085983 |doi= 10.1074/jbc.M006497200 }}
*{{cite journal  | author=Alonso A, Saxena M, Williams S, Mustelin T |title=Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation. |journal=J. Biol. Chem. |volume=276 |issue= 7 |pages= 4766-71 |year= 2001 |pmid= 11085983 |doi= 10.1074/jbc.M006497200 }}
*{{cite journal  | vauthors=Najarro P, Traktman P, Lewis JA |title=Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses Stat1 activation |journal=J. Virol. |volume=75 |issue= 7 |pages= 3185–96 |year= 2001 |pmid= 11238845 |doi= 10.1128/JVI.75.7.3185-3196.2001 | pmc=114112 }}
*{{cite journal  | author=Najarro P, Traktman P, Lewis JA |title=Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses Stat1 activation. |journal=J. Virol. |volume=75 |issue= 7 |pages= 3185-96 |year= 2001 |pmid= 11238845 |doi= 10.1128/JVI.75.7.3185-3196.2001 }}
*{{cite journal  | vauthors=Alonso A, Rahmouni S, Williams S |title=Tyrosine phosphorylation of VHR phosphatase by ZAP-70 |journal=Nat. Immunol. |volume=4 |issue= 1 |pages= 44–8 |year= 2003 |pmid= 12447358 |doi= 10.1038/ni856 |display-authors=etal}}
*{{cite journal  | author=Alonso A, Rahmouni S, Williams S, ''et al.'' |title=Tyrosine phosphorylation of VHR phosphatase by ZAP-70. |journal=Nat. Immunol. |volume=4 |issue= 1 |pages= 44-8 |year= 2003 |pmid= 12447358 |doi= 10.1038/ni856 }}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal|bibcode=2002PNAS...9916899M }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | vauthors=Kim HS, Song MC, Kwak IH |title=Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence |journal=J. Biol. Chem. |volume=278 |issue= 39 |pages= 37497–510 |year= 2003 |pmid= 12840032 |doi= 10.1074/jbc.M211739200 |display-authors=etal}}
*{{cite journal  | author=Kim HS, Song MC, Kwak IH, ''et al.'' |title=Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence. |journal=J. Biol. Chem. |volume=278 |issue= 39 |pages= 37497-510 |year= 2003 |pmid= 12840032 |doi= 10.1074/jbc.M211739200 }}
*{{cite journal  | vauthors=Ota T, Suzuki Y, Nishikawa T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |display-authors=etal}}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | vauthors=Rual JF, Venkatesan K, Hao T |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |display-authors=etal|bibcode=2005Natur.437.1173R }}
*{{cite journal  | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal  | vauthors=Rahmouni S, Cerignoli F, Alonso A |title=Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence |journal=Nat. Cell Biol. |volume=8 |issue= 5 |pages= 524–31 |year= 2006 |pmid= 16604064 |doi= 10.1038/ncb1398 |display-authors=etal}}
*{{cite journal  | author=Rahmouni S, Cerignoli F, Alonso A, ''et al.'' |title=Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence. |journal=Nat. Cell Biol. |volume=8 |issue= 5 |pages= 524-31 |year= 2006 |pmid= 16604064 |doi= 10.1038/ncb1398 }}
*{{cite journal  | vauthors=Hao L, ElShamy WM |title=BRCA1-IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR |journal=Int. J. Cancer |volume=121 |issue= 1 |pages= 39–46 |year= 2007 |pmid= 17278098 |doi= 10.1002/ijc.22597 }}
*{{cite journal  | author=Hao L, ElShamy WM |title=BRCA1-IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR. |journal=Int. J. Cancer |volume=121 |issue= 1 |pages= 39-46 |year= 2007 |pmid= 17278098 |doi= 10.1002/ijc.22597 }}
*{{cite journal  | vauthors=Hoyt R, Zhu W, Cerignoli F |title=Cutting edge: selective tyrosine dephosphorylation of interferon-activated nuclear STAT5 by the VHR phosphatase |journal=J. Immunol. |volume=179 |issue= 6 |pages= 3402–6 |year= 2007 |pmid= 17785772 |doi=  10.4049/jimmunol.179.6.3402| pmc=2770724  |display-authors=etal}}
*{{cite journal  | author=Hoyt R, Zhu W, Cerignoli F, ''et al.'' |title=Cutting edge: selective tyrosine dephosphorylation of interferon-activated nuclear STAT5 by the VHR phosphatase. |journal=J. Immunol. |volume=179 |issue= 6 |pages= 3402-6 |year= 2007 |pmid= 17785772 |doi=  }}
}}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=1845}}
{{Protein tyrosine phosphatases}}
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{{protein-stub}}
[[Category:Genes mutated in mice]]
{{WikiDoc Sources}}

Latest revision as of 07:30, 23 June 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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View/Edit Human

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

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

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

References

  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. ↑ 2.0 2.1 "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. ↑ 8.0 8.1 8.2 8.3 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.
  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. ↑ 16.0 16.1 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

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