ID DUS4_RAT Reviewed; 395 AA. AC Q62767; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 08-NOV-2023, entry version 152. DE RecName: Full=Dual specificity protein phosphatase 4; DE EC=3.1.3.16; DE EC=3.1.3.48 {ECO:0000269|PubMed:7782322}; DE AltName: Full=Mitogen-activated protein kinase phosphatase 2; DE Short=MAP kinase phosphatase 2; DE Short=MKP-2; GN Name=Dusp4; Synonyms=Mkp2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND FUNCTION. RC TISSUE=Pheochromocytoma; RX PubMed=7782322; DOI=10.1074/jbc.270.24.14587; RA Misra-Press A., Rim C.S., Yao H., Roberson M.S., Stork P.J.S.; RT "A novel mitogen-activated protein kinase phosphatase. Structure, RT expression, and regulation."; RL J. Biol. Chem. 270:14587-14596(1995). CC -!- FUNCTION: Regulates mitogenic signal transduction by dephosphorylating CC both Thr and Tyr residues on MAP kinases ERK1 and ERK2. CC {ECO:0000269|PubMed:7782322}. 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:7782322}; 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:Q13115}; 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:Q13115}; CC -!- SUBUNIT: Hollow spherical complex composed of 24 subunits with CC pseudooctahedral symmetry, has a tetramer as the basic unit. CC {ECO:0000250|UniProtKB:Q13115}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13115}. CC -!- TISSUE SPECIFICITY: Expressed at moderate levels in nearly all tissues CC and cells including brain, spleen, and testes with the higher CC expression in the heart and lung and lower expression in skeletal CC muscle and kidney. Undetectable in liver. Expressed in many areas of CC the brain with very strong expression in the hippocampus, piriform CC cortex, and the suprachiasmatic nucleus. CC -!- INDUCTION: By mitogens and by stress. CC -!- PTM: Phosphorylation in the C-terminus by ERK1/2 inhibits proteasomal CC degradation and stabilizes the protein. {ECO:0000250|UniProtKB:Q13115}. 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; U23438; AAC52493.1; -; mRNA. DR RefSeq; NP_071535.1; NM_022199.1. DR AlphaFoldDB; Q62767; -. DR SMR; Q62767; -. DR STRING; 10116.ENSRNOP00000016328; -. DR iPTMnet; Q62767; -. DR PhosphoSitePlus; Q62767; -. DR PaxDb; 10116-ENSRNOP00000016328; -. DR GeneID; 60587; -. DR KEGG; rno:60587; -. DR AGR; RGD:620625; -. DR CTD; 1846; -. DR RGD; 620625; Dusp4. DR eggNOG; KOG1716; Eukaryota. DR InParanoid; Q62767; -. DR OrthoDB; 2901840at2759; -. DR PhylomeDB; Q62767; -. DR Reactome; R-RNO-112409; RAF-independent MAPK1/3 activation. DR Reactome; R-RNO-202670; ERKs are inactivated. DR Reactome; R-RNO-5675221; Negative regulation of MAPK pathway. DR PRO; PR:Q62767; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:1990439; F:MAP kinase serine/threonine phosphatase activity; ISS:UniProtKB. 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; IDA:RGD. DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0016791; F:phosphatase activity; ISO:RGD. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISS:UniProtKB. DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IDA:RGD. DR GO; GO:0016311; P:dephosphorylation; ISO:RGD. DR GO; GO:0001706; P:endoderm formation; IBA:GO_Central. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central. DR CDD; cd14640; DSP_DUSP4; 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:SF111; DUAL SPECIFICITY PROTEIN PHOSPHATASE 4; 1. 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; (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. PE 1: Evidence at protein level; KW Acetylation; Hydrolase; Nucleus; Phosphoprotein; Protein phosphatase; KW Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q13115" FT CHAIN 2..395 FT /note="Dual specificity protein phosphatase 4" FT /id="PRO_0000094800" FT DOMAIN 42..160 FT /note="Rhodanese" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173" FT DOMAIN 196..337 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT ACT_SITE 281 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT MOD_RES 2 FT /note="N-acetylvaline" FT /evidence="ECO:0000250|UniProtKB:Q13115" FT MOD_RES 387 FT /note="Phosphoserine; by MAPK" FT /evidence="ECO:0000250|UniProtKB:Q13115" FT MOD_RES 392 FT /note="Phosphoserine; by MAPK" FT /evidence="ECO:0000250|UniProtKB:Q13115" SQ SEQUENCE 395 AA; 43187 MW; A90EFFD378A050FD CRC64; MVTMEELREM DCSVLKRLMN RDENGGTAGS SGGSHGALGL LSGGKCLLLD CRPFLAHSAG YIRGSVNVRC NTIVRRRAKG SVSLEQILPA EEEVRARLRS GLYSAVIVYD ERSPRAESLR EDSTVSLVVQ ALRRNAERTD ICLLKGGYER FSSEYPEFCS KTKALAAIPP PVPPSTNESL DLGCSSCGTP LHDQGGPVEI LPFLYLGSAY HAARRDMLDA LGITALLNVS SDCPNHFEGH YQYKCIPVED NHKADISSWF MEAIEYIDAV KDCRGRVLVH CQAGISRSAT ICLAYLMMKK RVRLEEAFEF VKQRRSIISP NFSFMGQLLQ FESQVLTTSC AAEAASPSGP LRERGKATPT PTSQFVFSFP VSVGVHAAPS NLPYLHSPIT TSPSC //