DUS4_RAT
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 03-AUG-2022, entry version 148.
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}.
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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; Q62767; -.
DR GeneID; 60587; -.
DR KEGG; rno:60587; -.
DR CTD; 1846; -.
DR RGD; 620625; Dusp4.
DR eggNOG; KOG1716; Eukaryota.
DR InParanoid; Q62767; -.
DR OrthoDB; 1576308at2759; -.
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: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:0004721; F:phosphoprotein phosphatase activity; IBA:GO_Central.
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 GO; GO:0006470; P:protein dephosphorylation; IDA:RGD.
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 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
