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 24-JAN-2024, entry version 160. 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 iodoacetic 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}. 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; 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; 9606-ENSP00000333917; -. DR PeptideAtlas; Q8NEJ0; -. DR ProteomicsDB; 73168; -. DR Antibodypedia; 24819; 53 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 AGR; HGNC:18484; -. 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; NTHYEDI; -. DR OrthoDB; 127323at2759; -. DR PhylomeDB; Q8NEJ0; -. DR TreeFam; TF316009; -. DR PathwayCommons; Q8NEJ0; -. DR SignaLink; Q8NEJ0; -. DR BioGRID-ORCS; 150290; 9 hits in 1166 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 164 other cell types or tissues. DR ExpressionAtlas; Q8NEJ0; baseline and differential. 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 CDD; cd14573; DUSP18_21; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 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 PANTHER; PTHR46495:SF2; DUAL SPECIFICITY PROTEIN PHOSPHATASE 18; 1. DR PANTHER; PTHR46495; DUAL SPECIFICITY PROTEIN PHOSPHATASE 21; 1. DR Pfam; PF00782; DSPc; 1. DR PRINTS; PR01908; ADSPHPHTASE. DR PRINTS; PR01910; ADSPHPHTASEB. DR SMART; SM00195; DSPc; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1. DR Genevisible; Q8NEJ0; HS. 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 //