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 02-SEP-2026, entry version 208. 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=O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10044, ECO:0000269|PubMed:7961985}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-phospho-L-seryl-[protein] + H2O = 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=O-phospho-L-threonyl-[protein] + H2O = 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; Q02410: APBA1; NbExp=2; IntAct=EBI-7487376, EBI-368690; CC Q16690; Q99767: APBA2; NbExp=2; IntAct=EBI-7487376, EBI-81711; CC Q16690; Q12959: DLG1; NbExp=3; IntAct=EBI-7487376, EBI-357481; CC Q16690; Q92796: DLG3; NbExp=3; IntAct=EBI-7487376, EBI-80440; CC Q16690; P78352: DLG4; NbExp=3; IntAct=EBI-7487376, EBI-80389; CC Q16690; Q68DX3: FRMPD2; NbExp=3; IntAct=EBI-7487376, EBI-53993476; CC Q16690; Q9Y3R0: GRIP1; NbExp=5; IntAct=EBI-7487376, EBI-5349621; CC Q16690; Q9C0E4: GRIP2; NbExp=5; IntAct=EBI-7487376, EBI-949557; CC Q16690; Q14005: IL16; NbExp=3; IntAct=EBI-7487376, EBI-2831580; CC Q16690; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-7487376, EBI-739832; CC Q16690; Q96QZ7: MAGI1; NbExp=2; IntAct=EBI-7487376, EBI-924464; CC Q16690; Q86UL8: MAGI2; NbExp=5; IntAct=EBI-7487376, EBI-311035; CC Q16690; P28482: MAPK1; NbExp=3; IntAct=EBI-7487376, EBI-959949; CC Q16690; O75970: MPDZ; NbExp=3; IntAct=EBI-7487376, EBI-821405; CC Q16690; Q86UT5: NHERF4; NbExp=2; IntAct=EBI-7487376, EBI-8744528; CC Q16690; Q8NI35: PATJ; NbExp=9; IntAct=EBI-7487376, EBI-724390; CC Q16690; Q5T2W1: PDZK1; NbExp=2; IntAct=EBI-7487376, EBI-349819; CC Q16690; Q14160: SCRIB; NbExp=2; IntAct=EBI-7487376, EBI-357345; CC Q16690; Q07157: TJP1; NbExp=2; IntAct=EBI-7487376, EBI-79553; CC Q16690; Q9P202: WHRN; NbExp=3; IntAct=EBI-7487376, EBI-310886; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. 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; 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_004419.4. DR PDB; 2G6Z; X-ray; 2.70 A; A/B/C=178-384. DR AlphaFoldDB; Q16690; -. DR SMR; Q16690; -. DR BioGRID; 108180; 54. DR FunCoup; Q16690; 2051. DR IntAct; Q16690; 88. DR MINT; Q16690; -. DR NDEx; IQUERY-CP-DUSP5; 5 NDEx IQuery Curated Pathways. 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 MassIVE; Q16690; -. DR PaxDb; 9606-ENSP00000358596; -. DR PeptideAtlas; Q16690; -. DR ProteomicsDB; 61034; -. DR Antibodypedia; 18355; 306 antibodies from 29 providers. DR DNASU; 1847; -. DR Ensembl; ENST00000369583.4; ENSP00000358596.3; ENSG00000138166.7. 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 AGR; HGNC:3071; -. DR ClinPGx; PA27528; -. DR CTD; 1847; -. DR DisGeNET; 1847; -. DR GeneCards; DUSP5; -. DR HGNC; HGNC:3071; DUSP5. DR HPA; ENSG00000138166; Tissue enhanced (urinary). DR MIM; 603069; gene. DR OpenTargets; ENSG00000138166; -. DR VEuPathDB; HostDB:ENSG00000138166; -. DR eggNOG; KOG1716; Eukaryota. DR GeneTree; ENSGT00940000159529; -. DR HOGENOM; CLU_027074_0_2_1; -. DR InParanoid; Q16690; -. DR OMA; CRPYLSY; -. DR OrthoDB; 165342at2759; -. DR PAN-GO; Q16690; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q16690; -. DR BRENDA; 3.1.3.16; 2681. DR BRENDA; 3.1.3.48; 2681. 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 Agora; ENSG00000138166; -. DR BioGRID-ORCS; 1847; 20 hits in 1170 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 184 other cell types or tissues. 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; IEA:InterPro. DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; EXP:UniProtKB. 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: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: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 CDD; cd14639; DSP_DUSP5; 1. DR CDD; cd01446; DSP_MapKP; 1. DR FunFam; 3.90.190.10:FF:000057; Dual specificity phosphatase 5; 1. DR FunFam; 3.40.250.10:FF:000023; Dual specificity protein phosphatase; 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:SF40; DUAL SPECIFICITY PROTEIN PHOSPHATASE 5; 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. DR PDBsum; 2G6Z; -. PE 1: Evidence at protein level; KW 3D-structure; Hydrolase; Nucleus; Protein phosphatase; KW Proteomics identification; 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 //