DUS2_MOUSE
ID DUS2_MOUSE Reviewed; 318 AA.
AC Q05922; Q60640; Q80ZN1;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Dual specificity protein phosphatase 2 {ECO:0000305};
DE EC=3.1.3.16 {ECO:0000269|PubMed:16288922};
DE EC=3.1.3.48 {ECO:0000255|PROSITE-ProRule:PRU10044, ECO:0000269|PubMed:16288922};
DE AltName: Full=Dual specificity protein phosphatase PAC-1;
GN Name=Dusp2 {ECO:0000312|MGI:MGI:101911}; Synonyms=Pac-1, Pac1;
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 [MRNA] (ISOFORM 1).
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] (ISOFORM 2).
RC STRAIN=129;
RX PubMed=7896276; DOI=10.1006/geno.1994.1598;
RA Gerondakis S., Economou C., Grumont R.J.;
RT "Structure of the gene encoding the murine dual specificity tyrosine-
RT threonine phosphatase PAC1.";
RL Genomics 24:182-184(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Limb;
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, INTERACTION WITH MAPK14, AND MUTAGENESIS OF
RP ARG-60; ARG-61; ARG-62; ASP-230; CYS-261; LYS-292; ARG-294 AND ARG-295.
RX PubMed=16288922; DOI=10.1016/j.jmb.2005.10.006;
RA Zhang Q., Muller M., Chen C.H., Zeng L., Farooq A., Zhou M.M.;
RT "New insights into the catalytic activation of the MAPK phosphatase PAC-1
RT induced by its substrate MAPK ERK2 binding.";
RL J. Mol. Biol. 354:777-788(2005).
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:16288922). Can dephosphorylate MAPK1
CC (PubMed:16288922). {ECO:0000269|PubMed:16288922}.
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:16288922};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10685;
CC Evidence={ECO:0000305|PubMed:16288922};
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:16288922};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005;
CC Evidence={ECO:0000305|PubMed:16288922};
CC -!- SUBUNIT: Interacts with MAPK14; this interaction does not lead to
CC catalytic activation of DUSP2 and dephosphrylation of MAPK14.
CC {ECO:0000269|PubMed:16288922}.
CC -!- INTERACTION:
CC Q05922; P28482: MAPK1; Xeno; NbExp=2; IntAct=EBI-7898692, EBI-959949;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=Q05922-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q05922-2; Sequence=VSP_005135, VSP_005136;
CC -!- TISSUE SPECIFICITY: In hematopoietic tissues such as spleen and thymus.
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; L11330; AAA19666.1; -; mRNA.
DR EMBL; U09268; AAA85136.1; -; Genomic_DNA.
DR EMBL; AK134067; BAE21999.1; -; mRNA.
DR EMBL; AL845368; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC048696; AAH48696.1; -; mRNA.
DR CCDS; CCDS16699.1; -. [Q05922-1]
DR PIR; B57126; B57126.
DR RefSeq; NP_034220.2; NM_010090.2. [Q05922-1]
DR AlphaFoldDB; Q05922; -.
DR SMR; Q05922; -.
DR BioGRID; 199340; 3.
DR IntAct; Q05922; 2.
DR MINT; Q05922; -.
DR STRING; 10090.ENSMUSP00000028846; -.
DR iPTMnet; Q05922; -.
DR PhosphoSitePlus; Q05922; -.
DR MaxQB; Q05922; -.
DR PaxDb; Q05922; -.
DR PRIDE; Q05922; -.
DR ProteomicsDB; 275413; -. [Q05922-1]
DR Antibodypedia; 54258; 95 antibodies from 22 providers.
DR DNASU; 13537; -.
DR Ensembl; ENSMUST00000028846; ENSMUSP00000028846; ENSMUSG00000027368. [Q05922-1]
DR GeneID; 13537; -.
DR KEGG; mmu:13537; -.
DR UCSC; uc008mff.1; mouse. [Q05922-1]
DR CTD; 1844; -.
DR MGI; MGI:101911; Dusp2.
DR VEuPathDB; HostDB:ENSMUSG00000027368; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00940000161605; -.
DR HOGENOM; CLU_027074_0_2_1; -.
DR InParanoid; Q05922; -.
DR OMA; RTPRDQY; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; Q05922; -.
DR TreeFam; TF105122; -.
DR Reactome; R-MMU-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR BioGRID-ORCS; 13537; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Dusp2; mouse.
DR PRO; PR:Q05922; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q05922; protein.
DR Bgee; ENSMUSG00000027368; Expressed in peripheral lymph node and 111 other tissues.
DR Genevisible; Q05922; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; IPI: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: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; IDA:MGI.
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 Alternative splicing; Hydrolase; Nucleus; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1..318
FT /note="Dual specificity protein phosphatase 2"
FT /id="PRO_0000094794"
FT DOMAIN 27..148
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 176..317
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 261
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT VAR_SEQ 175..179
FT /note="GGPVE -> VSSDL (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005135"
FT VAR_SEQ 180..318
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005136"
FT MUTAGEN 60
FT /note="R->A: Does not affect interaction with MAPK1."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 61
FT /note="R->A: Does not affect interaction with MAPK1. Loss
FT of interaction with MAPK1; when associated with A-62."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 62
FT /note="R->A: Loss of interaction with MAPK1. Loss of
FT interaction with MAPK1; when associated with A-61."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 230
FT /note="D->A: Loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 261
FT /note="C->S: Loss of phosphatase activity. Does not affect
FT interaction with MAPK1."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 292
FT /note="K->A: Does not affect phosphatase activity. Loss of
FT phosphatase activity; when associated with A-294 and A-295.
FT Does not affect interaction with MAPK1."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 294
FT /note="R->A: Loss of phosphatase activity. Loss of
FT phosphatase activity; when associated with A-292 and A-295.
FT Does not affect interaction with MAPK1."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 294
FT /note="R->K: Loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 295
FT /note="R->A: Loss of phosphatase activity. Loss of
FT phosphatase activity; when associated with A-292 and A-294.
FT Does not affect interaction with MAPK1."
FT /evidence="ECO:0000269|PubMed:7681221"
FT MUTAGEN 295
FT /note="R->K: Loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:7681221"
FT CONFLICT 11..12
FT /note="CE -> WQ (in Ref. 2; AAA85136)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="A -> V (in Ref. 2; AAA85136)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="R -> P (in Ref. 1; AAA19666 and 2; AAA85136)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="A -> T (in Ref. 1; AAA19666 and 2; AAA85136)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="P -> A (in Ref. 2; AAA85136)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 318 AA; 34576 MW; AAB6A01BA598C5C9 CRC64;
MPIAMGLETA CELECAALGA LLREPREAER TLLLDCRPFL AFCRSHVRAA RPVPWNALLR
RRARGTPAAA LACLLPDRAL RARLGRGELA RAVVLDESSA SVAELPPDGP AHLLLAALQH
EMRGGPTTVC FLRGGFKSFQ TYCPDLCSEA PAQALPPAGA ENSNSDPRVP IYDQGGPVEI
LPYLYLGSCN HSSDLQGLQA CGITAVLNVS ASCPNHFEGL FHYKSIPVED NQMVEISAWF
QEAISFIDSV KNSGGRVLVH CQAGISRSAT ICLAYLIQSH RVRLDEAFDF VKQRRGVISP
NFSFMGQLLQ LETQVLCH
