DUS8_HUMAN
ID DUS8_HUMAN Reviewed; 625 AA.
AC Q13202; Q86SS8;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Dual specificity protein phosphatase 8;
DE EC=3.1.3.16;
DE EC=3.1.3.48;
DE AltName: Full=Dual specificity protein phosphatase hVH-5;
GN Name=DUSP8; Synonyms=C11orf81, VH5;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=7561881; DOI=10.1046/j.1471-4159.1995.65041823.x;
RA Martell K.J., Seasholtz A.F., Kwak S.P., Clemens K.K., Dixon J.E.;
RT "hVH-5: a protein tyrosine phosphatase abundant in brain that inactivates
RT mitogen-activated protein kinase.";
RL J. Neurochem. 65:1823-1833(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Skin;
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 [4] {ECO:0007744|PDB:4JMK}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 160-310, AND SUBUNIT.
RX PubMed=24531476; DOI=10.1107/s1399004713029866;
RA Jeong D.G., Wei C.H., Ku B., Jeon T.J., Chien P.N., Kim J.K., Park S.Y.,
RA Hwang H.S., Ryu S.Y., Park H., Kim D.S., Kim S.J., Ryu S.E.;
RT "The family-wide structure and function of human dual-specificity protein
RT phosphatases.";
RL Acta Crystallogr. D 70:421-435(2014).
CC -!- FUNCTION: Has phosphatase activity with synthetic phosphatase
CC substrates and negatively regulates mitogen-activated protein kinase
CC activity, presumably by catalysing their dephosphorylation. Expected to
CC display protein phosphatase activity toward phosphotyrosine,
CC phosphoserine and phosphothreonine residues.
CC {ECO:0000250|UniProtKB:O09112}.
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};
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 -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24531476}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O09112}. Nucleus
CC {ECO:0000250|UniProtKB:O09112}.
CC -!- TISSUE SPECIFICITY: Abundant in brain, heart and skeletal muscle.
CC {ECO:0000269|PubMed:7561881}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; U27193; AAA83151.1; -; mRNA.
DR EMBL; AP006285; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038231; AAH38231.1; -; mRNA.
DR EMBL; BC045110; AAH45110.1; -; mRNA.
DR CCDS; CCDS7724.1; -.
DR RefSeq; NP_004411.2; NM_004420.2.
DR RefSeq; XP_011518234.1; XM_011519932.2.
DR RefSeq; XP_011518235.1; XM_011519933.2.
DR PDB; 4JMK; X-ray; 1.90 A; A/B=160-310.
DR PDBsum; 4JMK; -.
DR AlphaFoldDB; Q13202; -.
DR SMR; Q13202; -.
DR BioGRID; 108183; 40.
DR IntAct; Q13202; 3.
DR MINT; Q13202; -.
DR STRING; 9606.ENSP00000380530; -.
DR DEPOD; DUSP8; -.
DR iPTMnet; Q13202; -.
DR PhosphoSitePlus; Q13202; -.
DR BioMuta; DUSP8; -.
DR DMDM; 223590200; -.
DR jPOST; Q13202; -.
DR MassIVE; Q13202; -.
DR MaxQB; Q13202; -.
DR PaxDb; Q13202; -.
DR PeptideAtlas; Q13202; -.
DR PRIDE; Q13202; -.
DR ProteomicsDB; 59222; -.
DR Antibodypedia; 10181; 214 antibodies from 30 providers.
DR DNASU; 1850; -.
DR Ensembl; ENST00000331588.4; ENSP00000329539.4; ENSG00000184545.11.
DR Ensembl; ENST00000397374.8; ENSP00000380530.3; ENSG00000184545.11.
DR Ensembl; ENST00000610856.1; ENSP00000479946.1; ENSG00000278165.3.
DR Ensembl; ENST00000617829.1; ENSP00000481775.1; ENSG00000273793.3.
DR Ensembl; ENST00000625578.2; ENSP00000487017.1; ENSG00000273793.3.
DR Ensembl; ENST00000629053.2; ENSP00000487093.1; ENSG00000278165.3.
DR GeneID; 1850; -.
DR KEGG; hsa:1850; -.
DR MANE-Select; ENST00000397374.8; ENSP00000380530.3; NM_004420.3; NP_004411.2.
DR UCSC; uc001lts.3; human.
DR CTD; 1850; -.
DR DisGeNET; 1850; -.
DR GeneCards; DUSP8; -.
DR HGNC; HGNC:3074; DUSP8.
DR HPA; ENSG00000184545; Tissue enhanced (pituitary).
DR MIM; 602038; gene.
DR neXtProt; NX_Q13202; -.
DR OpenTargets; ENSG00000184545; -.
DR PharmGKB; PA27531; -.
DR VEuPathDB; HostDB:ENSG00000184545; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00940000160004; -.
DR HOGENOM; CLU_027074_16_0_1; -.
DR InParanoid; Q13202; -.
DR OMA; ICESHFM; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; Q13202; -.
DR TreeFam; TF105122; -.
DR PathwayCommons; Q13202; -.
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; Q13202; -.
DR SIGNOR; Q13202; -.
DR BioGRID-ORCS; 1850; 15 hits in 1080 CRISPR screens.
DR ChiTaRS; DUSP8; human.
DR GenomeRNAi; 1850; -.
DR Pharos; Q13202; Tbio.
DR PRO; PR:Q13202; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q13202; protein.
DR Bgee; ENSG00000184545; Expressed in mucosa of stomach and 96 other tissues.
DR Genevisible; Q13202; 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; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
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:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0016311; P:dephosphorylation; ISS:UniProtKB.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
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; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00782; DSPc; 1.
DR Pfam; PF00581; Rhodanese; 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; 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; Cytoplasm; Hydrolase; Nucleus; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1..625
FT /note="Dual specificity protein phosphatase 8"
FT /id="PRO_0000094810"
FT DOMAIN 23..138
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 160..302
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 306..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..335
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..522
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..586
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 246
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT CONFLICT 299
FT /note="S -> T (in Ref. 1; AAA83151)"
FT /evidence="ECO:0000305"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:4JMK"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 179..184
FT /evidence="ECO:0007829|PDB:4JMK"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:4JMK"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:4JMK"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:4JMK"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 225..237
FT /evidence="ECO:0007829|PDB:4JMK"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:4JMK"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 252..265
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 269..279
FT /evidence="ECO:0007829|PDB:4JMK"
FT HELIX 287..306
FT /evidence="ECO:0007829|PDB:4JMK"
SQ SEQUENCE 625 AA; 65827 MW; C7C808407B724FFC CRC64;
MAGDRLPRKV MDAKKLASLL RGGPGGPLVI DSRSFVEYNS WHVLSSVNIC CSKLVKRRLQ
QGKVTIAELI QPAARSQVEA TEPQDVVVYD QSTRDASVLA ADSFLSILLS KLDGCFDSVA
ILTGGFATFS SCFPGLCEGK PAALLPMSLS QPCLPVPSVG LTRILPHLYL GSQKDVLNKD
LMTQNGISYV LNASNSCPKP DFICESRFMR VPINDNYCEK LLPWLDKSIE FIDKAKLSSC
QVIVHCLAGI SRSATIAIAY IMKTMGMSSD DAYRFVKDRR PSISPNFNFL GQLLEYERSL
KLLAALQGDP GTPSGTPEPP PSPAAGAPLP RLPPPTSESA ATGNAAAREG GLSAGGEPPA
PPTPPATSAL QQGLRGLHLS SDRLQDTNRL KRSFSLDIKS AYAPSRRPDG PGPPDPGEAP
KLCKLDSPSG AALGLSSPSP DSPDAAPEAR PRPRRRPRPP AGSPARSPAH SLGLNFGDAA
RQTPRHGLSA LSAPGLPGPG QPAGPGAWAP PLDSPGTPSP DGPWCFSPEG AQGAGGVLFA
PFGRAGAPGP GGGSDLRRRE AARAEPRDAR TGWPEEPAPE TQFKRRSCQM EFEEGMVEGR
ARGEELAALG KQASFSGSVE VIEVS
