DUS3_HUMAN
ID DUS3_HUMAN Reviewed; 185 AA.
AC P51452; D3DX45; Q5U0J1; Q8IYJ9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Dual specificity protein phosphatase 3;
DE EC=3.1.3.16;
DE EC=3.1.3.48;
DE AltName: Full=Dual specificity protein phosphatase VHR;
DE AltName: Full=Vaccinia H1-related phosphatase;
DE Short=VHR;
GN Name=DUSP3; Synonyms=VHR;
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] (ISOFORM 1).
RX PubMed=1281549; DOI=10.1073/pnas.89.24.12170;
RA Ishibashi T., Bottaro D.P., Chan A., Miki T., Aaronson S.A.;
RT "Expression cloning of a human dual-specificity phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:12170-12174(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
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] (ISOFORMS 1 AND 2).
RC TISSUE=Duodenum, and Uterus;
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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10224087; DOI=10.1074/jbc.274.19.13271;
RA Todd J.L., Tanner K.G., Denu J.M.;
RT "Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates
RT for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in
RT down-regulating the ERK pathway.";
RL J. Biol. Chem. 274:13271-13280(1999).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=8650541; DOI=10.1126/science.272.5266.1328;
RA Yuvaniyama J., Denu J.M., Dixon J.E., Saper M.A.;
RT "Crystal structure of the dual specificity protein phosphatase VHR.";
RL Science 272:1328-1331(1996).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 2-185, AND FUNCTION.
RX PubMed=11863439; DOI=10.1021/bi015799l;
RA Schumacher M.A., Todd J.L., Rice A.E., Tanner K.G., Denu J.M.;
RT "Structural basis for the recognition of a bisphosphorylated MAP kinase
RT peptide by human VHR protein Phosphatase.";
RL Biochemistry 41:3009-3017(2002).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 3-185.
RX PubMed=19888758; DOI=10.1021/jm901016k;
RA Wu S., Vossius S., Rahmouni S., Miletic A.V., Vang T.,
RA Vazquez-Rodriguez J., Cerignoli F., Arimura Y., Williams S., Hayes T.,
RA Moutschen M., Vasile S., Pellecchia M., Mustelin T., Tautz L.;
RT "Multidentate small-molecule inhibitors of vaccinia H1-related (VHR)
RT phosphatase decrease proliferation of cervix cancer cells.";
RL J. Med. Chem. 52:6716-6723(2009).
CC -!- FUNCTION: Shows activity both for tyrosine-protein phosphate and
CC serine-protein phosphate, but displays a strong preference toward
CC phosphotyrosines. Specifically dephosphorylates and inactivates ERK1
CC and ERK2. {ECO:0000269|PubMed:10224087, ECO:0000269|PubMed:11863439}.
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};
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 VRK3, which seems to activate it's phosphatase
CC activity. {ECO:0000250}.
CC -!- INTERACTION:
CC P51452; P50221: MEOX1; NbExp=3; IntAct=EBI-1049755, EBI-2864512;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10224087}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P51452-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51452-2; Sequence=VSP_056284;
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; L05147; AAA35777.1; -; mRNA.
DR EMBL; BT019522; AAV38329.1; -; mRNA.
DR EMBL; CH471178; EAW51667.1; -; Genomic_DNA.
DR EMBL; CH471178; EAW51668.1; -; Genomic_DNA.
DR EMBL; BC002682; AAH02682.1; -; mRNA.
DR EMBL; BC035701; AAH35701.1; -; mRNA.
DR EMBL; AC003098; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC055813; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS11469.1; -. [P51452-1]
DR PIR; A47196; A47196.
DR RefSeq; NP_004081.1; NM_004090.3. [P51452-1]
DR PDB; 1J4X; X-ray; 2.75 A; A=2-185.
DR PDB; 1VHR; X-ray; 2.10 A; A/B=2-185.
DR PDB; 3F81; X-ray; 1.90 A; A/B=3-185.
DR PDBsum; 1J4X; -.
DR PDBsum; 1VHR; -.
DR PDBsum; 3F81; -.
DR AlphaFoldDB; P51452; -.
DR SMR; P51452; -.
DR BioGRID; 108178; 65.
DR IntAct; P51452; 32.
DR MINT; P51452; -.
DR STRING; 9606.ENSP00000226004; -.
DR BindingDB; P51452; -.
DR ChEMBL; CHEMBL2635; -.
DR DEPOD; DUSP3; -.
DR GlyGen; P51452; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51452; -.
DR PhosphoSitePlus; P51452; -.
DR BioMuta; DUSP3; -.
DR DMDM; 1718191; -.
DR UCD-2DPAGE; P51452; -.
DR EPD; P51452; -.
DR jPOST; P51452; -.
DR MassIVE; P51452; -.
DR MaxQB; P51452; -.
DR PaxDb; P51452; -.
DR PeptideAtlas; P51452; -.
DR PRIDE; P51452; -.
DR ProteomicsDB; 56308; -. [P51452-1]
DR ProteomicsDB; 71190; -.
DR Antibodypedia; 29589; 318 antibodies from 32 providers.
DR DNASU; 1845; -.
DR Ensembl; ENST00000226004.8; ENSP00000226004.2; ENSG00000108861.9. [P51452-1]
DR GeneID; 1845; -.
DR KEGG; hsa:1845; -.
DR MANE-Select; ENST00000226004.8; ENSP00000226004.2; NM_004090.4; NP_004081.1.
DR UCSC; uc002ied.5; human. [P51452-1]
DR CTD; 1845; -.
DR DisGeNET; 1845; -.
DR GeneCards; DUSP3; -.
DR HGNC; HGNC:3069; DUSP3.
DR HPA; ENSG00000108861; Tissue enhanced (skeletal).
DR MIM; 600183; gene.
DR neXtProt; NX_P51452; -.
DR OpenTargets; ENSG00000108861; -.
DR PharmGKB; PA27526; -.
DR VEuPathDB; HostDB:ENSG00000108861; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00940000163612; -.
DR HOGENOM; CLU_027074_11_3_1; -.
DR InParanoid; P51452; -.
DR OMA; RQKMDVR; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; P51452; -.
DR TreeFam; TF105128; -.
DR BRENDA; 3.1.3.16; 2681.
DR BRENDA; 3.1.3.48; 2681.
DR PathwayCommons; P51452; -.
DR Reactome; R-HSA-202670; ERKs are inactivated.
DR SignaLink; P51452; -.
DR SIGNOR; P51452; -.
DR BioGRID-ORCS; 1845; 11 hits in 1085 CRISPR screens.
DR ChiTaRS; DUSP3; human.
DR EvolutionaryTrace; P51452; -.
DR GeneWiki; DUSP3; -.
DR GenomeRNAi; 1845; -.
DR Pharos; P51452; Tchem.
DR PRO; PR:P51452; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P51452; protein.
DR Bgee; ENSG00000108861; Expressed in skeletal muscle tissue of rectus abdominis and 212 other tissues.
DR ExpressionAtlas; P51452; baseline and differential.
DR Genevisible; P51452; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; IPI:BHF-UCL.
DR GO; GO:0033549; F:MAP kinase phosphatase activity; IMP:UniProtKB.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:MGI.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:BHF-UCL.
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:0030971; F:receptor tyrosine kinase binding; IPI:BHF-UCL.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:0050922; P:negative regulation of chemotaxis; IMP:BHF-UCL.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:UniProtKB.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR GO; GO:1990264; P:peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity; ISS:BHF-UCL.
DR GO; GO:0120183; P:positive regulation of focal adhesion disassembly; IMP:BHF-UCL.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; IMP:BHF-UCL.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR020405; Atypical_DUSP_subfamA.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR PANTHER; PTHR45682; PTHR45682; 1.
DR Pfam; PF00782; DSPc; 1.
DR PRINTS; PR01909; ADSPHPHTASEA.
DR SMART; SM00195; DSPc; 1.
DR SUPFAM; SSF52799; SSF52799; 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; Alternative splicing; Hydrolase; Nucleus;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1..185
FT /note="Dual specificity protein phosphatase 3"
FT /id="PRO_0000094795"
FT DOMAIN 28..179
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 124
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT VAR_SEQ 1..42
FT /note="MSGSFELSVQDLNDLLSDGSGCYSLPSQPCNEVTPRIYVGNA -> M (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056284"
FT HELIX 8..16
FT /evidence="ECO:0007829|PDB:3F81"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:3F81"
FT STRAND 27..34
FT /evidence="ECO:0007829|PDB:3F81"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:3F81"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:3F81"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:3F81"
FT TURN 79..82
FT /evidence="ECO:0007829|PDB:3F81"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 98..101
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 102..114
FT /evidence="ECO:0007829|PDB:3F81"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:1J4X"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:3F81"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 130..143
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:3F81"
FT HELIX 164..179
FT /evidence="ECO:0007829|PDB:3F81"
SQ SEQUENCE 185 AA; 20478 MW; C1045DD9B226FD94 CRC64;
MSGSFELSVQ DLNDLLSDGS GCYSLPSQPC NEVTPRIYVG NASVAQDIPK LQKLGITHVL
NAAEGRSFMH VNTNANFYKD SGITYLGIKA NDTQEFNLSA YFERAADFID QALAQKNGRV
LVHCREGYSR SPTLVIAYLM MRQKMDVKSA LSIVRQNREI GPNDGFLAQL CQLNDRLAKE
GKLKP
