DUS1_HUMAN
ID DUS1_HUMAN Reviewed; 367 AA.
AC P28562; D3DQL9; Q2V508;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 3.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Dual specificity protein phosphatase 1 {ECO:0000305};
DE EC=3.1.3.16 {ECO:0000250|UniProtKB:P28563};
DE EC=3.1.3.48 {ECO:0000269|PubMed:1406996};
DE AltName: Full=Dual specificity protein phosphatase hVH1 {ECO:0000303|PubMed:8106404};
DE AltName: Full=Mitogen-activated protein kinase phosphatase 1;
DE Short=MAP kinase phosphatase 1;
DE Short=MKP-1;
DE AltName: Full=Protein-tyrosine phosphatase CL100 {ECO:0000303|PubMed:1406996};
GN Name=DUSP1 {ECO:0000312|HGNC:HGNC:3064};
GN Synonyms=CL100 {ECO:0000303|PubMed:1406996}, MKP1,
GN PTPN10 {ECO:0000312|HGNC:HGNC:3064}, VH1 {ECO:0000303|PubMed:8106404};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND INDUCTION.
RC TISSUE=Foreskin;
RX PubMed=1406996; DOI=10.1038/359644a0;
RA Keyes S.M., Emslie E.A.;
RT "Oxidative stress and heat shock induce a human gene encoding a protein-
RT tyrosine phosphatase.";
RL Nature 359:644-647(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8106404; DOI=10.1016/s0021-9258(17)41905-3;
RA Kwak S.P., Hakes D.J., Martell K.J., Dixon J.E.;
RT "Isolation and characterization of a human dual specificity protein-
RT tyrosine phosphatase gene.";
RL J. Biol. Chem. 269:3596-3604(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-56 AND HIS-187.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [7] {ECO:0007744|PDB:6APX}
RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 172-314 OF MUTANT SER-258, AND
RP MUTAGENESIS OF CYS-258.
RX PubMed=29052270; DOI=10.1002/pro.3328;
RA Gumpena R., Lountos G.T., Raran-Kurussi S., Tropea J.E., Cherry S.,
RA Waugh D.S.;
RT "Crystal structure of the human dual specificity phosphatase 1 catalytic
RT domain.";
RL Protein Sci. 27:561-567(2018).
CC -!- FUNCTION: Dual specificity phosphatase that dephosphorylates MAP kinase
CC MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity
CC during the meiotic cell cycle. {ECO:0000250|UniProtKB:P28563}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044, ECO:0000269|PubMed:1406996};
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 Evidence={ECO:0000250|UniProtKB:P28563};
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 Evidence={ECO:0000250|UniProtKB:P28563};
CC -!- INTERACTION:
CC P28562; P28482: MAPK1; NbExp=3; IntAct=EBI-975493, EBI-959949;
CC P28562; Q16539: MAPK14; NbExp=4; IntAct=EBI-975493, EBI-73946;
CC P28562; P27361: MAPK3; NbExp=3; IntAct=EBI-975493, EBI-73995;
CC P28562; Q13309: SKP2; NbExp=3; IntAct=EBI-975493, EBI-456291;
CC P28562; P0CG47: UBB; NbExp=2; IntAct=EBI-975493, EBI-413034;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q91790}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the lung, liver
CC placenta and pancreas. Moderate levels seen in the heart and skeletal
CC muscle. Lower levels found in the brain and kidney.
CC {ECO:0000269|PubMed:8106404}.
CC -!- INDUCTION: By oxidative stress and heat shock.
CC {ECO:0000269|PubMed:1406996}.
CC -!- PTM: Phosphorylation at Ser-359 and Ser-364 by MAPK1/ERK2 and
CC MAPK3/ERK1 reduces its rate of degradation.
CC {ECO:0000250|UniProtKB:P28563}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/dusp1/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DUSP1ID40371ch5q35.html";
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DR EMBL; X68277; CAA48338.1; -; mRNA.
DR EMBL; DQ301957; ABB96250.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61425.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61426.1; -; Genomic_DNA.
DR EMBL; BC022463; AAH22463.1; -; mRNA.
DR CCDS; CCDS4380.1; -.
DR PIR; S29090; S29090.
DR RefSeq; NP_004408.1; NM_004417.3.
DR PDB; 6APX; X-ray; 2.49 A; A=172-314.
DR PDB; 6D65; X-ray; 2.35 A; A/C=172-314.
DR PDB; 6D66; X-ray; 2.23 A; A=172-314.
DR PDB; 6D67; X-ray; 2.55 A; A=172-314.
DR PDBsum; 6APX; -.
DR PDBsum; 6D65; -.
DR PDBsum; 6D66; -.
DR PDBsum; 6D67; -.
DR AlphaFoldDB; P28562; -.
DR SMR; P28562; -.
DR BioGRID; 108176; 92.
DR IntAct; P28562; 61.
DR MINT; P28562; -.
DR STRING; 9606.ENSP00000239223; -.
DR BindingDB; P28562; -.
DR ChEMBL; CHEMBL6026; -.
DR DEPOD; DUSP1; -.
DR iPTMnet; P28562; -.
DR PhosphoSitePlus; P28562; -.
DR BioMuta; DUSP1; -.
DR DMDM; 1346900; -.
DR CPTAC; CPTAC-1758; -.
DR EPD; P28562; -.
DR MassIVE; P28562; -.
DR MaxQB; P28562; -.
DR PaxDb; P28562; -.
DR PeptideAtlas; P28562; -.
DR PRIDE; P28562; -.
DR ProteomicsDB; 54489; -.
DR Antibodypedia; 4343; 597 antibodies from 39 providers.
DR DNASU; 1843; -.
DR Ensembl; ENST00000239223.4; ENSP00000239223.3; ENSG00000120129.6.
DR GeneID; 1843; -.
DR KEGG; hsa:1843; -.
DR MANE-Select; ENST00000239223.4; ENSP00000239223.3; NM_004417.4; NP_004408.1.
DR UCSC; uc003mbv.3; human.
DR CTD; 1843; -.
DR DisGeNET; 1843; -.
DR GeneCards; DUSP1; -.
DR HGNC; HGNC:3064; DUSP1.
DR HPA; ENSG00000120129; Low tissue specificity.
DR MIM; 600714; gene.
DR neXtProt; NX_P28562; -.
DR OpenTargets; ENSG00000120129; -.
DR PharmGKB; PA27519; -.
DR VEuPathDB; HostDB:ENSG00000120129; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00940000159044; -.
DR HOGENOM; CLU_027074_0_2_1; -.
DR InParanoid; P28562; -.
DR OMA; PSCSPCN; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; P28562; -.
DR TreeFam; TF105122; -.
DR BRENDA; 3.1.3.16; 2681.
DR PathwayCommons; P28562; -.
DR Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR SABIO-RK; P28562; -.
DR SignaLink; P28562; -.
DR SIGNOR; P28562; -.
DR BioGRID-ORCS; 1843; 21 hits in 1081 CRISPR screens.
DR ChiTaRS; DUSP1; human.
DR GeneWiki; DUSP1; -.
DR GenomeRNAi; 1843; -.
DR Pharos; P28562; Tchem.
DR PRO; PR:P28562; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P28562; protein.
DR Bgee; ENSG00000120129; Expressed in vena cava and 206 other tissues.
DR Genevisible; P28562; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISS:UniProtKB.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IBA:GO_Central.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:BHF-UCL.
DR GO; GO:0001706; P:endoderm formation; IBA:GO_Central.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IMP:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0051447; P:negative regulation of meiotic cell cycle; ISS:UniProtKB.
DR GO; GO:0090027; P:negative regulation of monocyte chemotaxis; IMP:BHF-UCL.
DR GO; GO:1903753; P:negative regulation of p38MAPK cascade; IMP:BHF-UCL.
DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; ISS:UniProtKB.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; ISS:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR GO; GO:0090266; P:regulation of mitotic cell cycle spindle assembly checkpoint; ISS:UniProtKB.
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; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
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; SM00404; PTPc_motif; 1.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF52821; SSF52821; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Hydrolase; Nucleus; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Stress response.
FT CHAIN 1..367
FT /note="Dual specificity protein phosphatase 1"
FT /id="PRO_0000094790"
FT DOMAIN 20..137
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 173..314
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 258
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT MOD_RES 359
FT /note="Phosphoserine; by MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:P28563"
FT MOD_RES 364
FT /note="Phosphoserine; by MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:P28563"
FT VARIANT 56
FT /note="A -> T (in dbSNP:rs34013988)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025201"
FT VARIANT 187
FT /note="Y -> H (in dbSNP:rs34471628)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025202"
FT MUTAGEN 258
FT /note="C->S: Loss of phosphatase activity."
FT /evidence="ECO:0000305|PubMed:29052270"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:6D66"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:6D66"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:6D66"
FT HELIX 192..197
FT /evidence="ECO:0007829|PDB:6D66"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:6D66"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:6D66"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:6D65"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:6D66"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:6D66"
FT HELIX 237..249
FT /evidence="ECO:0007829|PDB:6D66"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:6D66"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:6D66"
FT HELIX 264..277
FT /evidence="ECO:0007829|PDB:6D66"
FT HELIX 281..291
FT /evidence="ECO:0007829|PDB:6D66"
FT HELIX 299..312
FT /evidence="ECO:0007829|PDB:6D66"
SQ SEQUENCE 367 AA; 39298 MW; 11BD1D39A9FCD51F CRC64;
MVMEVGTLDA GGLRALLGER AAQCLLLDCR SFFAFNAGHI AGSVNVRFST IVRRRAKGAM
GLEHIVPNAE LRGRLLAGAY HAVVLLDERS AALDGAKRDG TLALAAGALC REARAAQVFF
LKGGYEAFSA SCPELCSKQS TPMGLSLPLS TSVPDSAESG CSSCSTPLYD QGGPVEILPF
LYLGSAYHAS RKDMLDALGI TALINVSANC PNHFEGHYQY KSIPVEDNHK ADISSWFNEA
IDFIDSIKNA GGRVFVHCQA GISRSATICL AYLMRTNRVK LDEAFEFVKQ RRSIISPNFS
FMGQLLQFES QVLAPHCSAE AGSPAMAVLD RGTSTTTVFN FPVSIPVHST NSALSYLQSP
ITTSPSC
