ID DUS9_HUMAN Reviewed; 384 AA. AC Q99956; D3DWU5; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 27-MAR-2024, entry version 191. DE RecName: Full=Dual specificity protein phosphatase 9; DE EC=3.1.3.16; DE EC=3.1.3.48; DE AltName: Full=Mitogen-activated protein kinase phosphatase 4; DE Short=MAP kinase phosphatase 4; DE Short=MKP-4; GN Name=DUSP9; Synonyms=MKP4; 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]. RC TISSUE=Placenta; RX PubMed=9030581; DOI=10.1074/jbc.272.8.5141; RA Muda M., Boschert U., Smith A., Antonsonn B., Gillieron C., Chabert C., RA Camps M., Martinou I., Ashworth A., Arkinstall S.; RT "Molecular cloning and functional characterization of a novel mitogen- RT activated protein kinase phosphatase, MKP-4."; RL J. Biol. Chem. 272:5141-5151(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-351, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16 AND SER-262, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 201-345. RX PubMed=18058037; DOI=10.1007/s10969-007-9036-1; RA Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P., RA Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S., RA Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y., RA Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R., Sali A., RA Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K.; RT "Structural genomics of protein phosphatases."; RL J. Struct. Funct. Genomics 8:121-140(2007). CC -!- FUNCTION: Inactivates MAP kinases. Has a specificity for the ERK CC family. 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; 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 -!- 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 -!- INTERACTION: CC Q99956; P28482: MAPK1; NbExp=4; IntAct=EBI-3906678, EBI-959949; CC Q99956; Q16539: MAPK14; NbExp=4; IntAct=EBI-3906678, EBI-73946; CC Q99956; P47811: Mapk14; Xeno; NbExp=2; IntAct=EBI-3906678, EBI-298727; CC -!- SUBCELLULAR LOCATION: Cytoplasm. 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; Y08302; CAA69610.1; -; mRNA. DR EMBL; U52111; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471172; EAW72847.1; -; Genomic_DNA. DR EMBL; CH471172; EAW72848.1; -; Genomic_DNA. DR EMBL; CH471172; EAW72849.1; -; Genomic_DNA. DR CCDS; CCDS14724.1; -. DR RefSeq; NP_001305432.1; NM_001318503.1. DR RefSeq; NP_001386.1; NM_001395.3. DR RefSeq; XP_011529426.1; XM_011531124.1. DR PDB; 2HXP; X-ray; 1.83 A; A=201-345. DR PDB; 3LJ8; X-ray; 2.70 A; A=202-347. DR PDBsum; 2HXP; -. DR PDBsum; 3LJ8; -. DR AlphaFoldDB; Q99956; -. DR SMR; Q99956; -. DR BioGRID; 108185; 94. DR IntAct; Q99956; 23. DR MINT; Q99956; -. DR STRING; 9606.ENSP00000345853; -. DR DEPOD; DUSP9; -. DR iPTMnet; Q99956; -. DR PhosphoSitePlus; Q99956; -. DR BioMuta; DUSP9; -. DR DMDM; 3913541; -. DR EPD; Q99956; -. DR jPOST; Q99956; -. DR MassIVE; Q99956; -. DR MaxQB; Q99956; -. DR PaxDb; 9606-ENSP00000345853; -. DR PeptideAtlas; Q99956; -. DR ProteomicsDB; 78541; -. DR Pumba; Q99956; -. DR Antibodypedia; 519; 324 antibodies from 32 providers. DR DNASU; 1852; -. DR Ensembl; ENST00000342782.4; ENSP00000345853.3; ENSG00000130829.18. DR Ensembl; ENST00000370167.8; ENSP00000359186.4; ENSG00000130829.18. DR GeneID; 1852; -. DR KEGG; hsa:1852; -. DR MANE-Select; ENST00000342782.4; ENSP00000345853.3; NM_001318503.2; NP_001305432.1. DR UCSC; uc004fhx.5; human. DR AGR; HGNC:3076; -. DR CTD; 1852; -. DR DisGeNET; 1852; -. DR GeneCards; DUSP9; -. DR HGNC; HGNC:3076; DUSP9. DR HPA; ENSG00000130829; Group enriched (kidney, placenta). DR MIM; 300134; gene. DR neXtProt; NX_Q99956; -. DR OpenTargets; ENSG00000130829; -. DR PharmGKB; PA27533; -. DR VEuPathDB; HostDB:ENSG00000130829; -. DR eggNOG; KOG1717; Eukaryota. DR GeneTree; ENSGT00940000161880; -. DR HOGENOM; CLU_027074_0_0_1; -. DR InParanoid; Q99956; -. DR OMA; DRDAMSC; -. DR OrthoDB; 2901840at2759; -. DR PhylomeDB; Q99956; -. DR TreeFam; TF105122; -. DR BRENDA; 3.1.3.48; 2681. DR PathwayCommons; Q99956; -. DR Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation. DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway. DR Reactome; R-HSA-9652817; Signaling by MAPK mutants. DR SignaLink; Q99956; -. DR SIGNOR; Q99956; -. DR BioGRID-ORCS; 1852; 18 hits in 791 CRISPR screens. DR ChiTaRS; DUSP9; human. DR EvolutionaryTrace; Q99956; -. DR GenomeRNAi; 1852; -. DR Pharos; Q99956; Tbio. DR PRO; PR:Q99956; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q99956; Protein. DR Bgee; ENSG00000130829; Expressed in placenta and 80 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. 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:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; TAS:ProtInc. DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; TAS:Reactome. DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; TAS:Reactome. DR GO; GO:0007254; P:JNK cascade; TAS:ProtInc. 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:0006470; P:protein dephosphorylation; TAS:ProtInc. DR CDD; cd14644; DSP_DUSP9; 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; IPR000387; Tyr_Pase_dom. DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom. DR PANTHER; PTHR10159; DUAL SPECIFICITY PROTEIN PHOSPHATASE; 1. DR PANTHER; PTHR10159:SF388; DUAL SPECIFICITY PROTEIN PHOSPHATASE 9; 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; 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; PS50056; TYR_PHOSPHATASE_2; 1. DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1. DR Genevisible; Q99956; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Hydrolase; Phosphoprotein; Protein phosphatase; KW Reference proteome. FT CHAIN 1..384 FT /note="Dual specificity protein phosphatase 9" FT /id="PRO_0000094812" FT DOMAIN 18..139 FT /note="Rhodanese" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173" FT DOMAIN 203..346 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 348..384 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 353..378 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 290 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 262 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 351 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT STRAND 205..208 FT /evidence="ECO:0007829|PDB:2HXP" FT STRAND 211..214 FT /evidence="ECO:0007829|PDB:2HXP" FT HELIX 218..220 FT /evidence="ECO:0007829|PDB:2HXP" FT HELIX 222..227 FT /evidence="ECO:0007829|PDB:2HXP" FT STRAND 230..235 FT /evidence="ECO:0007829|PDB:2HXP" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:2HXP" FT TURN 243..246 FT /evidence="ECO:0007829|PDB:2HXP" FT STRAND 251..254 FT /evidence="ECO:0007829|PDB:2HXP" FT HELIX 259..264 FT /evidence="ECO:0007829|PDB:2HXP" FT HELIX 265..281 FT /evidence="ECO:0007829|PDB:2HXP" FT STRAND 285..289 FT /evidence="ECO:0007829|PDB:2HXP" FT STRAND 291..295 FT /evidence="ECO:0007829|PDB:2HXP" FT HELIX 296..309 FT /evidence="ECO:0007829|PDB:2HXP" FT HELIX 313..323 FT /evidence="ECO:0007829|PDB:2HXP" FT HELIX 331..344 FT /evidence="ECO:0007829|PDB:2HXP" SQ SEQUENCE 384 AA; 41868 MW; F8598CA95AB379B7 CRC64; MEGLGRSCLW LRRELSPPRP RLLLLDCRSR ELYESARIGG ALSVALPALL LRRLRRGSLS VRALLPGPPL QPPPPAPVLL YDQGGGRRRR GEAEAEAEEW EAESVLGTLL QKLREEGYLA YYLQGGFSRF QAECPHLCET SLAGRAGSSM APVPGPVPVV GLGSLCLGSD CSDAESEADR DSMSCGLDSE GATPPPVGLR ASFPVQILPN LYLGSARDSA NLESLAKLGI RYILNVTPNL PNFFEKNGDF HYKQIPISDH WSQNLSRFFP EAIEFIDEAL SQNCGVLVHC LAGVSRSVTV TVAYLMQKLH LSLNDAYDLV KRKKSNISPN FNFMGQLLDF ERSLRLEERH SQEQGSGGQA SAASNPPSFF TTPTSDGAFE LAPT //