DUS2_HUMAN
ID DUS2_HUMAN Reviewed; 314 AA.
AC Q05923; Q53T45;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Dual specificity protein phosphatase 2 {ECO:0000305};
DE EC=3.1.3.16 {ECO:0000269|PubMed:8107850};
DE EC=3.1.3.48 {ECO:0000255|PROSITE-ProRule:PRU10044, ECO:0000269|PubMed:8107850};
DE AltName: Full=Dual specificity protein phosphatase PAC-1;
GN Name=DUSP2 {ECO:0000312|HGNC:HGNC:3068}; Synonyms=PAC1;
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].
RX PubMed=7681221; DOI=10.1126/science.7681221;
RA Rohan P., Davis P., Moskaluk C.A., Kearns M., Krutzsch H., Siebenlist U.,
RA Kelly K.;
RT "PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase.";
RL Science 259:1763-1766(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7590752; DOI=10.1006/geno.1995.1110;
RA Yi H., Morton C.C., Weremowicz S., McBride O.W., Kelly K.;
RT "Genomic organization and chromosomal localization of the DUSP2 gene,
RT encoding a MAP kinase phosphatase, to human 2p11.2-q11.";
RL Genomics 28:92-96(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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=B-cell;
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, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-257.
RX PubMed=8107850; DOI=10.1038/367651a0;
RA Ward Y., Gupta S., Jensen P., Wartmann M., Davis R.J., Kelly K.;
RT "Control of MAP kinase activation by the mitogen-induced threonine/tyrosine
RT phosphatase PAC1.";
RL Nature 367:651-654(1994).
RN [7]
RP STRUCTURE BY NMR OF 170-314.
RX PubMed=12575935; DOI=10.1016/s0969-2126(02)00943-7;
RA Farooq A., Plotnikova O., Chaturvedi G., Yan S., Zeng L., Zhang Q.,
RA Zhou M.M.;
RT "Solution structure of the MAPK phosphatase PAC-1 catalytic domain.
RT Insights into substrate-induced enzymatic activation of MKP.";
RL Structure 11:155-164(2003).
CC -!- FUNCTION: Dephosphorylates both phosphorylated Thr and Tyr residues in
CC MAPK1, and dephosphorylation of phosphotyrosine is slightly faster than
CC that of phosphothreonine (PubMed:8107850). Can dephosphorylate MAPK1
CC (By similarity). {ECO:0000250|UniProtKB:Q05922,
CC ECO:0000269|PubMed:8107850}.
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:8107850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10685;
CC Evidence={ECO:0000269|PubMed:8107850};
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:0000269|PubMed:8107850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005;
CC Evidence={ECO:0000305|PubMed:8107850};
CC -!- SUBUNIT: Interacts with MAPK14; this interaction does not lead to
CC catalytic activation of DUSP2 and dephosphrylation of MAPK14.
CC {ECO:0000250|UniProtKB:Q05922}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Expressed in hematopoietic tissues.
CC -!- INDUCTION: By mitogens.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; L11329; AAA50779.1; -; mRNA.
DR EMBL; U23853; AAA86112.1; -; Genomic_DNA.
DR EMBL; AC012307; AAY24222.1; -; Genomic_DNA.
DR EMBL; CH471207; EAW71385.1; -; Genomic_DNA.
DR EMBL; BC007771; AAH07771.1; -; mRNA.
DR CCDS; CCDS2016.1; -.
DR PIR; A57126; A57126.
DR RefSeq; NP_004409.1; NM_004418.3.
DR PDB; 1M3G; NMR; -; A=170-314.
DR PDBsum; 1M3G; -.
DR AlphaFoldDB; Q05923; -.
DR BMRB; Q05923; -.
DR SMR; Q05923; -.
DR BioGRID; 108177; 78.
DR IntAct; Q05923; 2.
DR MINT; Q05923; -.
DR STRING; 9606.ENSP00000288943; -.
DR BindingDB; Q05923; -.
DR ChEMBL; CHEMBL2157858; -.
DR DEPOD; DUSP2; -.
DR iPTMnet; Q05923; -.
DR PhosphoSitePlus; Q05923; -.
DR BioMuta; DUSP2; -.
DR DMDM; 464334; -.
DR jPOST; Q05923; -.
DR MassIVE; Q05923; -.
DR PaxDb; Q05923; -.
DR PeptideAtlas; Q05923; -.
DR PRIDE; Q05923; -.
DR ProteomicsDB; 58356; -.
DR Antibodypedia; 54258; 95 antibodies from 22 providers.
DR DNASU; 1844; -.
DR Ensembl; ENST00000288943.5; ENSP00000288943.4; ENSG00000158050.5.
DR GeneID; 1844; -.
DR KEGG; hsa:1844; -.
DR MANE-Select; ENST00000288943.5; ENSP00000288943.4; NM_004418.4; NP_004409.1.
DR UCSC; uc002svk.5; human.
DR CTD; 1844; -.
DR DisGeNET; 1844; -.
DR GeneCards; DUSP2; -.
DR HGNC; HGNC:3068; DUSP2.
DR HPA; ENSG00000158050; Tissue enhanced (bone).
DR MIM; 603068; gene.
DR neXtProt; NX_Q05923; -.
DR OpenTargets; ENSG00000158050; -.
DR PharmGKB; PA27525; -.
DR VEuPathDB; HostDB:ENSG00000158050; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00940000161605; -.
DR HOGENOM; CLU_027074_0_2_1; -.
DR InParanoid; Q05923; -.
DR OMA; RTPRDQY; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; Q05923; -.
DR TreeFam; TF105122; -.
DR BRENDA; 3.1.3.16; 2681.
DR PathwayCommons; Q05923; -.
DR Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR SignaLink; Q05923; -.
DR SIGNOR; Q05923; -.
DR BioGRID-ORCS; 1844; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; DUSP2; human.
DR EvolutionaryTrace; Q05923; -.
DR GeneWiki; DUSP2; -.
DR GenomeRNAi; 1844; -.
DR Pharos; Q05923; Tbio.
DR PRO; PR:Q05923; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q05923; protein.
DR Bgee; ENSG00000158050; Expressed in seminal vesicle and 137 other tissues.
DR Genevisible; Q05923; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IEA:Ensembl.
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:0004725; F:protein tyrosine phosphatase activity; TAS:ProtInc.
DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0001706; P:endoderm formation; IBA:GO_Central.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
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; Hydrolase; Nucleus; Protein phosphatase; Reference proteome.
FT CHAIN 1..314
FT /note="Dual specificity protein phosphatase 2"
FT /id="PRO_0000094793"
FT DOMAIN 23..144
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 172..313
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 257
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT MUTAGEN 257
FT /note="C->S: Loss of tyrosine phosphatase activity."
FT /evidence="ECO:0000269|PubMed:8107850"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:1M3G"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:1M3G"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:1M3G"
FT HELIX 188..197
FT /evidence="ECO:0007829|PDB:1M3G"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:1M3G"
FT STRAND 206..213
FT /evidence="ECO:0007829|PDB:1M3G"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:1M3G"
FT HELIX 236..248
FT /evidence="ECO:0007829|PDB:1M3G"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:1M3G"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:1M3G"
FT HELIX 263..274
FT /evidence="ECO:0007829|PDB:1M3G"
FT HELIX 279..287
FT /evidence="ECO:0007829|PDB:1M3G"
FT HELIX 305..311
FT /evidence="ECO:0007829|PDB:1M3G"
SQ SEQUENCE 314 AA; 34400 MW; FDD3543C6DE10CA5 CRC64;
MGLEAARELE CAALGTLLRD PREAERTLLL DCRPFLAFCR RHVRAARPVP WNALLRRRAR
GPPAAVLACL LPDRALRTRL VRGELARAVV LDEGSASVAE LRPDSPAHVL LAALLHETRA
GPTAVYFLRG GFDGFQGCCP DLCSEAPAPA LPPTGDKTSR SDSRAPVYDQ GGPVEILPYL
FLGSCSHSSD LQGLQACGIT AVLNVSASCP NHFEGLFRYK SIPVEDNQMV EISAWFQEAI
GFIDWVKNSG GRVLVHCQAG ISRSATICLA YLMQSRRVRL DEAFDFVKQR RGVISPNFSF
MGQLLQFETQ VLCH
