DUS6_MOUSE
ID DUS6_MOUSE Reviewed; 381 AA.
AC Q9DBB1; Q542I5; Q9D7L4;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Dual specificity protein phosphatase 6;
DE EC=3.1.3.16;
DE EC=3.1.3.48;
DE AltName: Full=Mitogen-activated protein kinase phosphatase 3;
DE Short=MAP kinase phosphatase 3;
DE Short=MKP-3;
GN Name=Dusp6; Synonyms=Mkp3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Liver, Thymus, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24155322; DOI=10.1523/jneurosci.5605-12.2013;
RA Saha M., Skopelja S., Martinez E., Alvarez D.L., Liponis B.S.,
RA Romero-Sandoval E.A.;
RT "Spinal mitogen-activated protein kinase phosphatase-3 (MKP-3) is necessary
RT for the normal resolution of mechanical allodynia in a mouse model of acute
RT postoperative pain.";
RL J. Neurosci. 33:17182-17187(2013).
RN [4]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28405172; DOI=10.2147/jpr.s129826;
RA Skopelja-Gardner S., Saha M., Alvarado-Vazquez P.A., Liponis B.S.,
RA Martinez E., Romero-Sandoval E.A.;
RT "Mitogen-activated protein kinase phosphatase-3 (MKP-3) in the surgical
RT wound is necessary for the resolution of postoperative pain in mice.";
RL J. Pain Res. 10:763-774(2017).
CC -!- FUNCTION: Inactivates MAP kinases. Has a specificity for the ERK family
CC (By similarity). Plays an important role in alleviating acute
CC postoperative pain (PubMed:24155322, PubMed:28405172). Necessary for
CC the normal dephosphorylation of the long-lasting phosphorylated forms
CC of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery,
CC which drives the resolution of acute postoperative allodynia
CC (PubMed:24155322). Also important for dephosphorylation of MAPK1/3 in
CC local wound tissue, which further contributes to resolution of acute
CC pain (PubMed:28405172). {ECO:0000250|UniProtKB:Q16828,
CC ECO:0000269|PubMed:24155322, ECO:0000269|PubMed:28405172}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC -!- SUBUNIT: Interacts with MAPK1/ERK2. {ECO:0000250|UniProtKB:Q16828}.
CC -!- INTERACTION:
CC Q9DBB1; P63085: Mapk1; NbExp=2; IntAct=EBI-7812384, EBI-397697;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16828}.
CC -!- INDUCTION: Up-regulated in local wound tissue 5-7 days after surgical
CC incision. {ECO:0000269|PubMed:28405172}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit a persistent state of mechanical
CC allodynia following plantar incision (PubMed:24155322,
CC PubMed:28405172). This allodynia phenotype is concurrent with long-
CC lasting spinal phosphorylation of MAPK1/3 and MAP kinase p38
CC (PubMed:24155322). Tissue at the local incision site also shows
CC prolonged expression of phosphorylated MAPK1/3 which persists through
CC to post-operative day 12, although levels of phosphorylated MAP kinase
CC p38 are normal (PubMed:28405172). {ECO:0000269|PubMed:24155322,
CC ECO:0000269|PubMed:28405172}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; AK005062; BAB23786.1; -; mRNA.
DR EMBL; AK009131; BAB26093.1; -; mRNA.
DR EMBL; AK088468; BAC40372.1; -; mRNA.
DR EMBL; AK088665; BAC40489.1; -; mRNA.
DR EMBL; AK159146; BAE34853.1; -; mRNA.
DR EMBL; AK159502; BAE35135.1; -; mRNA.
DR EMBL; AK159900; BAE35465.1; -; mRNA.
DR EMBL; BC003869; AAH03869.1; -; mRNA.
DR CCDS; CCDS24147.1; -.
DR RefSeq; NP_080544.1; NM_026268.3.
DR AlphaFoldDB; Q9DBB1; -.
DR SMR; Q9DBB1; -.
DR BioGRID; 212304; 1.
DR CORUM; Q9DBB1; -.
DR IntAct; Q9DBB1; 1.
DR MINT; Q9DBB1; -.
DR STRING; 10090.ENSMUSP00000020118; -.
DR iPTMnet; Q9DBB1; -.
DR PhosphoSitePlus; Q9DBB1; -.
DR MaxQB; Q9DBB1; -.
DR PaxDb; Q9DBB1; -.
DR PRIDE; Q9DBB1; -.
DR ProteomicsDB; 279584; -.
DR Antibodypedia; 4315; 550 antibodies from 38 providers.
DR DNASU; 67603; -.
DR Ensembl; ENSMUST00000020118; ENSMUSP00000020118; ENSMUSG00000019960.
DR GeneID; 67603; -.
DR KEGG; mmu:67603; -.
DR UCSC; uc007gxk.2; mouse.
DR CTD; 1848; -.
DR MGI; MGI:1914853; Dusp6.
DR VEuPathDB; HostDB:ENSMUSG00000019960; -.
DR eggNOG; KOG1717; Eukaryota.
DR GeneTree; ENSGT00940000158342; -.
DR HOGENOM; CLU_027074_0_0_1; -.
DR InParanoid; Q9DBB1; -.
DR OMA; IEFDRWA; -.
DR OrthoDB; 911920at2759; -.
DR PhylomeDB; Q9DBB1; -.
DR TreeFam; TF105122; -.
DR Reactome; R-MMU-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-MMU-202670; ERKs are inactivated.
DR Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR BioGRID-ORCS; 67603; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Dusp6; mouse.
DR PRO; PR:Q9DBB1; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9DBB1; protein.
DR Bgee; ENSMUSG00000019960; Expressed in metanephric ureteric bud and 320 other tissues.
DR ExpressionAtlas; Q9DBB1; baseline and differential.
DR Genevisible; Q9DBB1; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:0060420; P:regulation of heart growth; IMP:MGI.
DR GO; GO:0070848; P:response to growth factor; IEA:Ensembl.
DR GO; GO:0051409; P:response to nitrosative stress; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR Gene3D; 3.40.250.10; -; 1.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR008343; MKP.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00782; DSPc; 1.
DR Pfam; PF00581; Rhodanese; 1.
DR PIRSF; PIRSF000939; MAPK_Ptase; 1.
DR PRINTS; PR01764; MAPKPHPHTASE.
DR SMART; SM00195; DSPc; 1.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF52821; SSF52821; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Protein phosphatase; Reference proteome.
FT CHAIN 1..381
FT /note="Dual specificity protein phosphatase 6"
FT /id="PRO_0000094805"
FT DOMAIN 30..148
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 206..349
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 176..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 293
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT CONFLICT 22
FT /note="W -> G (in Ref. 1; BAB26093)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="L -> F (in Ref. 1; BAB26093)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 381 AA; 42408 MW; 7EA1FB154F4AD2DA CRC64;
MIDTLRPVPF ASEMAICKTV SWLNEQLELG NERLLLMDCR PQELYESSHI ESAINVAIPG
IMLRRLQKGN LPVRALFTRC EDRDRFTRRC GTDTVVLYDE NSSDWNENTG GESVLGLLLK
KLKDEGCRAF YLEGGFSKFQ AEFALHCETN LDGSCSSSSP PLPVLGLGGL RISSDSSSDI
ESDLDRDPNS ATDSDGSPLS NSQPSFPVEI LPFLYLGCAK DSTNLDVLEE FGIKYILNVT
PNLPNLFENA GEFKYKQIPI SDHWSQNLSQ FFPEAISFID EARGKNCGVL VHCLAGISRS
VTVTVAYLMQ KLNLSMNDAY DIVKMKKSNI SPNFNFMGQL LDFERTLGLS SPCDNRVPTP
QLYFTTPSNQ NVYQVDSLQS T
