DUS18_HUMAN
ID DUS18_HUMAN Reviewed; 188 AA.
AC Q8NEJ0; B3KPA4;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Dual specificity protein phosphatase 18;
DE EC=3.1.3.16 {ECO:0000269|PubMed:12408986, ECO:0000269|PubMed:12591617};
DE EC=3.1.3.48 {ECO:0000269|PubMed:12408986, ECO:0000269|PubMed:12591617};
DE AltName: Full=Low molecular weight dual specificity phosphatase 20 {ECO:0000303|PubMed:12408986};
DE Short=LMW-DSP20;
GN Name=DUSP18; Synonyms=LMWDSP20;
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], CHARACTERIZATION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Colon tumor;
RX PubMed=12408986; DOI=10.1016/s0006-291x(02)02488-9;
RA Hood K.L., Tobin J.F., Yoon C.;
RT "Identification and characterization of two novel low-molecular-weight dual
RT specificity phosphatases.";
RL Biochem. Biophys. Res. Commun. 298:545-551(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, FUNCTION, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF ASP-73; LEU-102; CYS-104; ARG-110 AND SER-111.
RC TISSUE=Fetal brain;
RX PubMed=12591617; DOI=10.1016/s0167-4781(02)00629-2;
RA Wu Q., Gu S., Dai J., Dai J., Wang L., Li Y., Zeng L., Xu J., Ye X.,
RA Zhao W., Ji C., Xie Y., Mao Y.;
RT "Molecular cloning and characterization of a novel dual-specificity
RT phosphatase18 gene from human fetal brain.";
RL Biochim. Biophys. Acta 1625:296-304(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [7]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=16699184; DOI=10.1107/s0907444906010109;
RA Jeong D.G., Cho Y.H., Yoon T.S., Kim J.H., Son J.H., Ryu S.E., Kim S.J.;
RT "Structure of human DSP18, a member of the dual-specificity protein
RT tyrosine phosphatase family.";
RL Acta Crystallogr. D 62:582-588(2006).
CC -!- FUNCTION: Can dephosphorylate single and diphosphorylated synthetic
CC MAPK peptides, with preference for the phosphotyrosine and
CC diphosphorylated forms over phosphothreonine. In vitro,
CC dephosphorylates p-nitrophenyl phosphate (pNPP).
CC {ECO:0000269|PubMed:12408986, ECO:0000269|PubMed:12591617}.
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:12408986,
CC ECO:0000269|PubMed:12591617};
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:12408986, ECO:0000269|PubMed:12591617};
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:12408986, ECO:0000269|PubMed:12591617};
CC -!- ACTIVITY REGULATION: Activated by manganese ions, inhibited by
CC iodoaretic acid. {ECO:0000269|PubMed:12591617}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.0. {ECO:0000269|PubMed:12591617};
CC Temperature dependence:
CC Optimum temperature is 55 degrees Celsius.
CC {ECO:0000269|PubMed:12591617};
CC -!- INTERACTION:
CC Q8NEJ0; P06213: INSR; NbExp=2; IntAct=EBI-10698945, EBI-475899;
CC Q8NEJ0; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-10698945, EBI-1055254;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12408986}. Nucleus
CC {ECO:0000269|PubMed:12408986}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q8VE01}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8VE01}; Intermembrane side
CC {ECO:0000250|UniProtKB:Q8VE01}. Note=Translocates to cytoplasm in
CC response to apoptotic stimuli such as staurosporine treatment.
CC {ECO:0000250|UniProtKB:Q8VE01}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in liver,
CC brain, ovary and testis. {ECO:0000269|PubMed:12408986,
CC ECO:0000269|PubMed:12591617}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; AF533017; AAN59787.1; -; mRNA.
DR EMBL; AF461689; AAN77931.1; -; mRNA.
DR EMBL; CR456406; CAG30292.1; -; mRNA.
DR EMBL; AK056074; BAG51616.1; -; mRNA.
DR EMBL; CH471095; EAW59913.1; -; Genomic_DNA.
DR EMBL; BC030987; AAH30987.1; -; mRNA.
DR CCDS; CCDS13883.1; -.
DR RefSeq; NP_001291723.1; NM_001304794.1.
DR RefSeq; NP_001291724.1; NM_001304795.1.
DR RefSeq; NP_689724.3; NM_152511.4.
DR RefSeq; XP_005261425.1; XM_005261368.4.
DR RefSeq; XP_006724211.1; XM_006724148.3.
DR RefSeq; XP_011528222.1; XM_011529920.2.
DR RefSeq; XP_011528223.1; XM_011529921.2.
DR RefSeq; XP_016884116.1; XM_017028627.1.
DR RefSeq; XP_016884117.1; XM_017028628.1.
DR PDB; 2ESB; X-ray; 2.00 A; A=1-188.
DR PDBsum; 2ESB; -.
DR AlphaFoldDB; Q8NEJ0; -.
DR SMR; Q8NEJ0; -.
DR BioGRID; 127280; 21.
DR IntAct; Q8NEJ0; 20.
DR MINT; Q8NEJ0; -.
DR STRING; 9606.ENSP00000333917; -.
DR DEPOD; DUSP18; -.
DR PhosphoSitePlus; Q8NEJ0; -.
DR BioMuta; DUSP18; -.
DR DMDM; 29840768; -.
DR MassIVE; Q8NEJ0; -.
DR MaxQB; Q8NEJ0; -.
DR PaxDb; Q8NEJ0; -.
DR PeptideAtlas; Q8NEJ0; -.
DR PRIDE; Q8NEJ0; -.
DR ProteomicsDB; 73168; -.
DR Antibodypedia; 24819; 41 antibodies from 13 providers.
DR DNASU; 150290; -.
DR Ensembl; ENST00000334679.4; ENSP00000333917.3; ENSG00000167065.14.
DR Ensembl; ENST00000377087.3; ENSP00000366291.3; ENSG00000167065.14.
DR Ensembl; ENST00000404885.5; ENSP00000385463.1; ENSG00000167065.14.
DR Ensembl; ENST00000407308.1; ENSP00000386063.1; ENSG00000167065.14.
DR GeneID; 150290; -.
DR KEGG; hsa:150290; -.
DR MANE-Select; ENST00000334679.4; ENSP00000333917.3; NM_152511.5; NP_689724.3.
DR UCSC; uc003aiu.4; human.
DR CTD; 150290; -.
DR GeneCards; DUSP18; -.
DR HGNC; HGNC:18484; DUSP18.
DR HPA; ENSG00000167065; Low tissue specificity.
DR MIM; 611446; gene.
DR neXtProt; NX_Q8NEJ0; -.
DR OpenTargets; ENSG00000167065; -.
DR PharmGKB; PA134928498; -.
DR VEuPathDB; HostDB:ENSG00000167065; -.
DR eggNOG; KOG1718; Eukaryota.
DR GeneTree; ENSGT00940000161186; -.
DR InParanoid; Q8NEJ0; -.
DR OMA; PEYRAME; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; Q8NEJ0; -.
DR TreeFam; TF316009; -.
DR PathwayCommons; Q8NEJ0; -.
DR SignaLink; Q8NEJ0; -.
DR BioGRID-ORCS; 150290; 7 hits in 1073 CRISPR screens.
DR ChiTaRS; DUSP18; human.
DR EvolutionaryTrace; Q8NEJ0; -.
DR GeneWiki; DUSP18; -.
DR GenomeRNAi; 150290; -.
DR Pharos; Q8NEJ0; Tbio.
DR PRO; PR:Q8NEJ0; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q8NEJ0; protein.
DR Bgee; ENSG00000167065; Expressed in secondary oocyte and 162 other tissues.
DR ExpressionAtlas; Q8NEJ0; baseline and differential.
DR Genevisible; Q8NEJ0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; IDA:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR020420; Atypical_DUSP_subfamB.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
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 PRINTS; PR01910; ADSPHPHTASEB.
DR SMART; SM00195; DSPc; 1.
DR SUPFAM; SSF52799; SSF52799; 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; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleus; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1..188
FT /note="Dual specificity protein phosphatase 18"
FT /id="PRO_0000094828"
FT DOMAIN 19..160
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 104
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT MUTAGEN 73
FT /note="D->A: Abolishes most of in vitro phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:12591617"
FT MUTAGEN 102
FT /note="L->V: No effect on in vitro phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12591617"
FT MUTAGEN 104
FT /note="C->S: Abolishes most of in vitro phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:12591617"
FT MUTAGEN 110
FT /note="R->K: Abolishes most of in vitro phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:12591617"
FT MUTAGEN 111
FT /note="S->A: Abolishes most of in vitro phosphatase
FT activity."
FT /evidence="ECO:0000269|PubMed:12591617"
FT CONFLICT 2
FT /note="T -> A (in Ref. 2; AAN77931)"
FT /evidence="ECO:0000305"
FT STRAND 21..24
FT /evidence="ECO:0007829|PDB:2ESB"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 38..43
FT /evidence="ECO:0007829|PDB:2ESB"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:2ESB"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 79..82
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 83..95
FT /evidence="ECO:0007829|PDB:2ESB"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:2ESB"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 110..122
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 127..137
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 145..159
FT /evidence="ECO:0007829|PDB:2ESB"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:2ESB"
SQ SEQUENCE 188 AA; 21066 MW; A6EDECC3624F570F CRC64;
MTAPSCAFPV QFRQPSVSGL SQITKSLYIS NGVAANNKLM LSSNQITMVI NVSVEVVNTL
YEDIQYMQVP VADSPNSRLC DFFDPIADHI HSVEMKQGRT LLHCAAGVSR SAALCLAYLM
KYHAMSLLDA HTWTKSCRPI IRPNSGFWEQ LIHYEFQLFG KNTVHMVSSP VGMIPDIYEK
EVRLMIPL
