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 27-MAR-2024, entry version 182. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000028846; -. DR ProteomicsDB; 275413; -. [Q05922-1] DR Antibodypedia; 54258; 122 antibodies from 23 providers. DR DNASU; 13537; -. DR Ensembl; ENSMUST00000028846.7; ENSMUSP00000028846.7; ENSMUSG00000027368.7. [Q05922-1] DR GeneID; 13537; -. DR KEGG; mmu:13537; -. DR UCSC; uc008mff.1; mouse. [Q05922-1] DR AGR; MGI:101911; -. 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; RDQYTSA; -. DR OrthoDB; 2901840at2759; -. 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 79 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 114 other cell types or tissues. 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:0033550; F:MAP kinase tyrosine phosphatase activity; 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:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central. DR GO; GO:0016311; P:dephosphorylation; IEA:InterPro. DR GO; GO:0001706; P:endoderm formation; IBA:GO_Central. DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central. DR CDD; cd14641; DSP_DUSP2; 1. DR CDD; cd01446; DSP_MapKP; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 3.40.250.10; Rhodanese-like domain; 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 PANTHER; PTHR10159; DUAL SPECIFICITY PROTEIN PHOSPHATASE; 1. DR PANTHER; PTHR10159:SF109; DUAL SPECIFICITY PROTEIN PHOSPHATASE 2; 1. DR Pfam; PF00782; DSPc; 1. DR Pfam; PF00581; Rhodanese; 1. DR PIRSF; PIRSF000939; MAPK_Ptase; 1. DR PRINTS; PR01908; ADSPHPHTASE. DR PRINTS; PR01764; MAPKPHPHTASE. DR SMART; SM00195; DSPc; 1. DR SMART; SM00404; PTPc_motif; 1. DR SMART; SM00450; RHOD; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF52821; Rhodanese/Cell cycle control phosphatase; 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. DR Genevisible; Q05922; MM. 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 //