DUS9_HUMAN
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 03-AUG-2022, entry version 182.
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}.
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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; 92.
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; Q99956; -.
DR PeptideAtlas; Q99956; -.
DR PRIDE; Q99956; -.
DR ProteomicsDB; 78541; -.
DR Antibodypedia; 519; 291 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 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; DIHYKQI; -.
DR OrthoDB; 1576308at2759; -.
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 703 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 79 other tissues.
DR Genevisible; Q99956; HS.
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: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; IBA:GO_Central.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
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:0070373; P:negative regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR GO; GO:0060420; P:regulation of heart growth; IBA:GO_Central.
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; 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; SM00450; RHOD; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF52821; SSF52821; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
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
