DUS6_RAT
ID DUS6_RAT Reviewed; 381 AA.
AC Q64346;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Neuron;
RX PubMed=8626780; DOI=10.1074/jbc.271.8.4319;
RA Muda M., Boschert U., Dickinson R., Martinou J.-C., Martinou I., Camps M.,
RA Schlegel W., Arkinstall S.;
RT "MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a
RT new class of mitogen-activated protein kinase phosphatase.";
RL J. Biol. Chem. 271:4319-4326(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8631996; DOI=10.1074/jbc.271.7.3795;
RA Mourey R.J., Vega Q.C., Campbell J.S., Wenderoth M.P., Hauschka S.D.,
RA Krebs E.G., Dixon J.E.;
RT "A novel cytoplasmic dual specificity protein tyrosine phosphatase
RT implicated in muscle and neuronal differentiation.";
RL J. Biol. Chem. 271:3795-3802(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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).
CC -!- FUNCTION: Inactivates MAP kinases. Has a specificity for the ERK family
CC (PubMed:8626780). Implicated in muscle and neuronal differentiation
CC (PubMed:8631996). Plays an important role in alleviating chronic
CC postoperative pain. Necessary for the normal dephosphorylation of the
CC long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38
CC induced by peripheral surgery, which drives the resolution of acute
CC postoperative allodynia (By similarity). Also important for
CC dephosphorylation of MAPK1/3 in local wound tissue, which further
CC contributes to resolution of acute pain (By similarity).
CC {ECO:0000250|UniProtKB:Q9DBB1, ECO:0000269|PubMed:8626780,
CC ECO:0000269|PubMed:8631996}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8626780}.
CC -!- TISSUE SPECIFICITY: Expressed in lung, heart, brain, and kidney, but
CC not significantly in skeletal muscle or testis.
CC {ECO:0000269|PubMed:8626780}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; X94185; CAA63895.1; -; mRNA.
DR EMBL; U42627; AAB06202.1; -; mRNA.
DR EMBL; BC087003; AAH87003.1; -; mRNA.
DR RefSeq; NP_446335.1; NM_053883.2.
DR PDB; 2FYS; X-ray; 2.50 A; C/D=60-76.
DR PDBsum; 2FYS; -.
DR AlphaFoldDB; Q64346; -.
DR SMR; Q64346; -.
DR DIP; DIP-61143N; -.
DR IntAct; Q64346; 1.
DR STRING; 10116.ENSRNOP00000032969; -.
DR BindingDB; Q64346; -.
DR ChEMBL; CHEMBL5511; -.
DR DrugCentral; Q64346; -.
DR iPTMnet; Q64346; -.
DR PhosphoSitePlus; Q64346; -.
DR PaxDb; Q64346; -.
DR Ensembl; ENSRNOT00000111909; ENSRNOP00000087245; ENSRNOG00000023896.
DR GeneID; 116663; -.
DR KEGG; rno:116663; -.
DR UCSC; RGD:70978; rat.
DR CTD; 1848; -.
DR RGD; 70978; Dusp6.
DR eggNOG; KOG1717; Eukaryota.
DR GeneTree; ENSGT00940000158342; -.
DR HOGENOM; CLU_027074_0_0_1; -.
DR InParanoid; Q64346; -.
DR OMA; IEFDRWA; -.
DR OrthoDB; 911920at2759; -.
DR PhylomeDB; Q64346; -.
DR TreeFam; TF105122; -.
DR Reactome; R-RNO-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-RNO-202670; ERKs are inactivated.
DR Reactome; R-RNO-5675221; Negative regulation of MAPK pathway.
DR EvolutionaryTrace; Q64346; -.
DR PRO; PR:Q64346; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000023896; Expressed in lung and 20 other tissues.
DR Genevisible; Q64346; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; ISO:RGD.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISO:RGD.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IDA:RGD.
DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEP:RGD.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:RGD.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; ISO:RGD.
DR GO; GO:0060420; P:regulation of heart growth; ISO:RGD.
DR GO; GO:0070848; P:response to growth factor; IEP:RGD.
DR GO; GO:0051409; P:response to nitrosative stress; ISO:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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 3D-structure; Cytoplasm; Hydrolase; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1..381
FT /note="Dual specificity protein phosphatase 6"
FT /id="PRO_0000094806"
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"
SQ SEQUENCE 381 AA; 42319 MW; C511E00CB68F2888 CRC64;
MIDTLRPVPF ASEMAISKTV AWLNEQLELG NEQLLLMDCR 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 SPCDNRVPAQ
QLYFTAPSNQ NVYQVDSLQS T
