DUS5_HUMAN
ID DUS5_HUMAN Reviewed; 384 AA.
AC Q16690; Q12997; Q5T603;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Dual specificity protein phosphatase 5;
DE EC=3.1.3.16 {ECO:0000269|PubMed:7961985};
DE EC=3.1.3.48 {ECO:0000269|PubMed:7961985};
DE AltName: Full=Dual specificity protein phosphatase hVH3;
GN Name=DUSP5; Synonyms=VH3;
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], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Mammary gland;
RX PubMed=7961985; DOI=10.1016/s0021-9258(18)43965-8;
RA Ishibashi T., Bottaro D.P., Michieli P., Kelley C.A., Aaronson S.A.;
RT "A novel dual specificity phosphatase induced by serum stimulation and heat
RT shock.";
RL J. Biol. Chem. 269:29897-29902(1994).
RN [2]
RP SEQUENCE REVISION.
RA Bottaro D.P.;
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=7836374; DOI=10.1074/jbc.270.3.1156;
RA Kwak S.P., Dixon J.E.;
RT "Multiple dual specificity protein tyrosine phosphatases are expressed and
RT regulated differentially in liver cell lines.";
RL J. Biol. Chem. 270:1156-1160(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 178-384, AND ACTIVE SITE.
RX PubMed=17078075; DOI=10.1002/prot.21224;
RA Jeong D.G., Cho Y.H., Yoon T.S., Kim J.H., Ryu S.E., Kim S.J.;
RT "Crystal structure of the catalytic domain of human DUSP5, a dual
RT specificity MAP kinase protein phosphatase.";
RL Proteins 66:253-258(2007).
CC -!- FUNCTION: Dual specificity protein phosphatase; active with
CC phosphotyrosine, phosphoserine and phosphothreonine residues. The
CC highest relative activity is toward ERK1. {ECO:0000269|PubMed:7961985}.
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:7961985};
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:0000269|PubMed:7961985};
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:7961985};
CC -!- INTERACTION:
CC Q16690; P28482: MAPK1; NbExp=3; IntAct=EBI-7487376, EBI-959949;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; U15932; AAA64693.2; -; mRNA.
DR EMBL; U16996; AAB06261.1; -; mRNA.
DR EMBL; AL355512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062545; AAH62545.1; -; mRNA.
DR CCDS; CCDS7566.1; -.
DR PIR; I38890; I38890.
DR RefSeq; NP_004410.3; NM_004419.3.
DR PDB; 2G6Z; X-ray; 2.70 A; A/B/C=178-384.
DR PDBsum; 2G6Z; -.
DR AlphaFoldDB; Q16690; -.
DR SMR; Q16690; -.
DR BioGRID; 108180; 52.
DR IntAct; Q16690; 5.
DR MINT; Q16690; -.
DR STRING; 9606.ENSP00000358596; -.
DR BindingDB; Q16690; -.
DR ChEMBL; CHEMBL1250380; -.
DR DEPOD; DUSP5; -.
DR iPTMnet; Q16690; -.
DR PhosphoSitePlus; Q16690; -.
DR BioMuta; DUSP5; -.
DR DMDM; 215273975; -.
DR EPD; Q16690; -.
DR MassIVE; Q16690; -.
DR MaxQB; Q16690; -.
DR PaxDb; Q16690; -.
DR PeptideAtlas; Q16690; -.
DR PRIDE; Q16690; -.
DR ProteomicsDB; 61034; -.
DR Antibodypedia; 18355; 307 antibodies from 27 providers.
DR DNASU; 1847; -.
DR Ensembl; ENST00000369583.4; ENSP00000358596.3; ENSG00000138166.6.
DR GeneID; 1847; -.
DR KEGG; hsa:1847; -.
DR MANE-Select; ENST00000369583.4; ENSP00000358596.3; NM_004419.4; NP_004410.3.
DR UCSC; uc001kzd.4; human.
DR CTD; 1847; -.
DR DisGeNET; 1847; -.
DR GeneCards; DUSP5; -.
DR HGNC; HGNC:3071; DUSP5.
DR HPA; ENSG00000138166; Tissue enhanced (esophagus, urinary bladder).
DR MIM; 603069; gene.
DR neXtProt; NX_Q16690; -.
DR OpenTargets; ENSG00000138166; -.
DR PharmGKB; PA27528; -.
DR VEuPathDB; HostDB:ENSG00000138166; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00940000159529; -.
DR HOGENOM; CLU_027074_0_2_1; -.
DR InParanoid; Q16690; -.
DR OMA; SYCTFPT; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; Q16690; -.
DR TreeFam; TF105122; -.
DR PathwayCommons; Q16690; -.
DR Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR SignaLink; Q16690; -.
DR SIGNOR; Q16690; -.
DR BioGRID-ORCS; 1847; 18 hits in 1077 CRISPR screens.
DR ChiTaRS; DUSP5; human.
DR EvolutionaryTrace; Q16690; -.
DR GeneWiki; DUSP5; -.
DR GenomeRNAi; 1847; -.
DR Pharos; Q16690; Tchem.
DR PRO; PR:Q16690; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q16690; protein.
DR Bgee; ENSG00000138166; Expressed in lower esophagus mucosa and 182 other tissues.
DR Genevisible; Q16690; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB.
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:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0001706; P:endoderm formation; IBA:GO_Central.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; TAS:Reactome.
DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; IDA:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
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..384
FT /note="Dual specificity protein phosphatase 5"
FT /id="PRO_0000094802"
FT DOMAIN 19..141
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 178..319
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT MOTIF 53..74
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 263
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000269|PubMed:17078075"
FT VARIANT 154
FT /note="E -> D (in dbSNP:rs2282238)"
FT /id="VAR_020298"
FT VARIANT 220
FT /note="A -> T (in dbSNP:rs1889566)"
FT /id="VAR_059777"
FT VARIANT 220
FT /note="A -> V (in dbSNP:rs1889565)"
FT /id="VAR_059778"
FT VARIANT 322
FT /note="P -> L (in dbSNP:rs35101549)"
FT /id="VAR_047368"
FT CONFLICT 9..11
FT /note="RQL -> GHV (in Ref. 1; AAA64693)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="A -> R (in Ref. 1; AAA64693)"
FT /evidence="ECO:0000305"
FT CONFLICT 105..106
FT /note="AR -> F (in Ref. 1; AAA64693)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="A -> M (in Ref. 1; AAA64693, 3; AAB06261 and 5;
FT AAH62545)"
FT /evidence="ECO:0000305"
FT CONFLICT 382
FT /note="T -> Q (in Ref. 1; AAA64693)"
FT /evidence="ECO:0000305"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:2G6Z"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:2G6Z"
FT HELIX 191..194
FT /evidence="ECO:0007829|PDB:2G6Z"
FT HELIX 197..203
FT /evidence="ECO:0007829|PDB:2G6Z"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:2G6Z"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:2G6Z"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:2G6Z"
FT HELIX 242..254
FT /evidence="ECO:0007829|PDB:2G6Z"
FT STRAND 259..268
FT /evidence="ECO:0007829|PDB:2G6Z"
FT HELIX 269..282
FT /evidence="ECO:0007829|PDB:2G6Z"
FT HELIX 286..296
FT /evidence="ECO:0007829|PDB:2G6Z"
FT HELIX 304..317
FT /evidence="ECO:0007829|PDB:2G6Z"
SQ SEQUENCE 384 AA; 42047 MW; 2E4B2938F886CB4E CRC64;
MKVTSLDGRQ LRKMLRKEAA ARCVVLDCRP YLAFAASNVR GSLNVNLNSV VLRRARGGAV
SARYVLPDEA ARARLLQEGG GGVAAVVVLD QGSRHWQKLR EESAARVVLT SLLACLPAGP
RVYFLKGGYE TFYSEYPECC VDVKPISQEK IESERALISQ CGKPVVNVSY RPAYDQGGPV
EILPFLYLGS AYHASKCEFL ANLHITALLN VSRRTSEACA THLHYKWIPV EDSHTADISS
HFQEAIDFID CVREKGGKVL VHCEAGISRS PTICMAYLMK TKQFRLKEAF DYIKQRRSMV
SPNFGFMGQL LQYESEILPS TPNPQPPSCQ GEAAGSSLIG HLQTLSPDMQ GAYCTFPASV
LAPVPTHSTV SELSRSPVAT ATSC
