ID PTN18_HUMAN Reviewed; 460 AA. AC Q99952; B4E1E6; Q53P42; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 24-JUL-2024, entry version 193. DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 18; DE EC=3.1.3.48; DE AltName: Full=Brain-derived phosphatase; GN Name=PTPN18; Synonyms=BDP1; 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] (ISOFORM 1), TISSUE SPECIFICITY, AND RP CHARACTERIZATION. RC TISSUE=Brain; RX PubMed=8950995; RA Kim Y.W., Wang H.-Y., Sures I., Lammers R., Martell K.J., Ullrich A.; RT "Characterization of the PEST family protein tyrosine phosphatase BDP1."; RL Oncogene 13:2275-2279(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Liver; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] 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 [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-393, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 (1.5 ANGSTROMS) OF 6-299. RX PubMed=19167335; DOI=10.1016/j.cell.2008.11.038; RA Barr A.J., Ugochukwu E., Lee W.H., King O.N.F., Filippakopoulos P., RA Alfano I., Savitsky P., Burgess-Brown N.A., Mueller S., Knapp S.; RT "Large-scale structural analysis of the classical human protein tyrosine RT phosphatome."; RL Cell 136:352-363(2009). CC -!- FUNCTION: Differentially dephosphorylate autophosphorylated tyrosine CC kinases which are known to be overexpressed in tumor tissues. 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 -!- SUBUNIT: Interacts with PSTPIP1. {ECO:0000250}. CC -!- INTERACTION: CC Q99952; Q9Y297: BTRC; NbExp=2; IntAct=EBI-1384210, EBI-307461; CC Q99952; P04626: ERBB2; NbExp=6; IntAct=EBI-1384210, EBI-641062; CC Q99952; O43586: PSTPIP1; NbExp=5; IntAct=EBI-1384210, EBI-1050964; CC Q99952-1; Q9Y297: BTRC; NbExp=2; IntAct=EBI-12739708, EBI-307461; CC Q99952-1; P04626: ERBB2; NbExp=5; IntAct=EBI-12739708, EBI-641062; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q99952-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99952-2; Sequence=VSP_043073; CC -!- TISSUE SPECIFICITY: Expressed in brain, colon and several tumor-derived CC cell lines. {ECO:0000269|PubMed:8950995}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non- CC receptor class 4 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; X79568; CAA56105.1; -; mRNA. DR EMBL; AK303804; BAG64758.1; -; mRNA. DR EMBL; AC132479; AAY24077.1; -; Genomic_DNA. DR EMBL; CH471263; EAW55618.1; -; Genomic_DNA. DR EMBL; CH471263; EAW55619.1; -; Genomic_DNA. DR CCDS; CCDS2161.1; -. [Q99952-1] DR CCDS; CCDS46410.1; -. [Q99952-2] DR RefSeq; NP_001135842.1; NM_001142370.1. [Q99952-2] DR RefSeq; NP_055184.2; NM_014369.3. [Q99952-1] DR PDB; 2OC3; X-ray; 1.50 A; A=6-299. DR PDB; 4GFU; X-ray; 2.00 A; A=6-300. DR PDB; 4GFV; X-ray; 2.10 A; A/B=6-300. DR PDB; 4NND; X-ray; 2.50 A; A/B/D/G=6-295. DR PDBsum; 2OC3; -. DR PDBsum; 4GFU; -. DR PDBsum; 4GFV; -. DR PDBsum; 4NND; -. DR AlphaFoldDB; Q99952; -. DR SMR; Q99952; -. DR BioGRID; 117693; 57. DR IntAct; Q99952; 26. DR MINT; Q99952; -. DR STRING; 9606.ENSP00000175756; -. DR BindingDB; Q99952; -. DR ChEMBL; CHEMBL3351197; -. DR DEPOD; PTPN18; -. DR iPTMnet; Q99952; -. DR PhosphoSitePlus; Q99952; -. DR BioMuta; PTPN18; -. DR DMDM; 215273871; -. DR jPOST; Q99952; -. DR MassIVE; Q99952; -. DR PaxDb; 9606-ENSP00000175756; -. DR PeptideAtlas; Q99952; -. DR ProteomicsDB; 78538; -. [Q99952-1] DR ProteomicsDB; 78539; -. [Q99952-2] DR Pumba; Q99952; -. DR Antibodypedia; 33499; 134 antibodies from 25 providers. DR DNASU; 26469; -. DR Ensembl; ENST00000175756.10; ENSP00000175756.5; ENSG00000072135.13. [Q99952-1] DR Ensembl; ENST00000347849.7; ENSP00000310092.5; ENSG00000072135.13. [Q99952-2] DR GeneID; 26469; -. DR KEGG; hsa:26469; -. DR MANE-Select; ENST00000175756.10; ENSP00000175756.5; NM_014369.4; NP_055184.2. DR UCSC; uc002trb.4; human. [Q99952-1] DR AGR; HGNC:9649; -. DR CTD; 26469; -. DR DisGeNET; 26469; -. DR GeneCards; PTPN18; -. DR HGNC; HGNC:9649; PTPN18. DR HPA; ENSG00000072135; Low tissue specificity. DR MIM; 606587; gene. DR neXtProt; NX_Q99952; -. DR OpenTargets; ENSG00000072135; -. DR PharmGKB; PA33991; -. DR VEuPathDB; HostDB:ENSG00000072135; -. DR eggNOG; KOG0789; Eukaryota. DR GeneTree; ENSGT00940000162860; -. DR HOGENOM; CLU_015557_0_0_1; -. DR InParanoid; Q99952; -. DR OMA; WEFRVKV; -. DR OrthoDB; 5489271at2759; -. DR PhylomeDB; Q99952; -. DR TreeFam; TF351977; -. DR BRENDA; 3.1.3.48; 2681. DR PathwayCommons; Q99952; -. DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-HSA-9008059; Interleukin-37 signaling. DR SignaLink; Q99952; -. DR SIGNOR; Q99952; -. DR BioGRID-ORCS; 26469; 11 hits in 1172 CRISPR screens. DR ChiTaRS; PTPN18; human. DR EvolutionaryTrace; Q99952; -. DR GeneWiki; PTPN18; -. DR GenomeRNAi; 26469; -. DR Pharos; Q99952; Tbio. DR PRO; PR:Q99952; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q99952; Protein. DR Bgee; ENSG00000072135; Expressed in granulocyte and 194 other cell types or tissues. DR ExpressionAtlas; Q99952; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; TAS:ProtInc. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; EXP:Reactome. DR GO; GO:0001825; P:blastocyst formation; IEA:Ensembl. DR GO; GO:1901185; P:negative regulation of ERBB signaling pathway; TAS:Reactome. DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc. DR CDD; cd14603; PTPc-N18; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR IDEAL; IID00581; -. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR047170; PTN12/18/22. DR InterPro; IPR047254; PTN18_cat. DR InterPro; IPR000242; PTP_cat. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; Tyr_Pase_dom. DR PANTHER; PTHR45983; TYROSINE PHOSPHATSE N18, PUTATIVE-RELATED; 1. DR PANTHER; PTHR45983:SF4; TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 18; 1. DR Pfam; PF00102; Y_phosphatase; 1. DR PRINTS; PR00700; PRTYPHPHTASE. DR SMART; SM00194; PTPc; 1. DR SMART; SM00404; PTPc_motif; 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; PS50055; TYR_PHOSPHATASE_PTP; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Nucleus; KW Phosphoprotein; Protein phosphatase; Reference proteome. FT CHAIN 1..460 FT /note="Tyrosine-protein phosphatase non-receptor type 18" FT /id="PRO_0000094773" FT DOMAIN 26..291 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 361..460 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 365..379 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 229 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000255|PROSITE-ProRule:PRU10044" FT BINDING 197 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 229..235 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 276 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 389 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q61152" FT MOD_RES 393 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 426 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q61152" FT VAR_SEQ 32..138 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043073" FT VARIANT 193 FT /note="M -> V (in dbSNP:rs3739124)" FT /id="VAR_047651" FT CONFLICT 356..357 FT /note="VV -> EE (in Ref. 1; CAA56105)" FT /evidence="ECO:0000305" FT CONFLICT 378..379 FT /note="Missing (in Ref. 1; CAA56105)" FT /evidence="ECO:0000305" FT HELIX 11..14 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 20..22 FT /evidence="ECO:0007829|PDB:4GFV" FT HELIX 25..43 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 49..52 FT /evidence="ECO:0007829|PDB:2OC3" FT TURN 54..56 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 57..59 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 69..71 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 85..93 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 97..104 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 112..121 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 157..168 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 171..180 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 183..192 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 197..199 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 205..218 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 220..222 FT /evidence="ECO:0007829|PDB:4NND" FT STRAND 225..228 FT /evidence="ECO:0007829|PDB:2OC3" FT STRAND 230..233 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 234..250 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 260..268 FT /evidence="ECO:0007829|PDB:2OC3" FT HELIX 278..292 FT /evidence="ECO:0007829|PDB:2OC3" SQ SEQUENCE 460 AA; 50482 MW; 67ED24A0504D1883 CRC64; MSRSLDSARS FLERLEARGG REGAVLAGEF SDIQACSAAW KADGVCSTVA GSRPENVRKN RYKDVLPYDQ TRVILSLLQE EGHSDYINGN FIRGVDGSLA YIATQGPLPH TLLDFWRLVW EFGVKVILMA CREIENGRKR CERYWAQEQE PLQTGLFCIT LIKEKWLNED IMLRTLKVTF QKESRSVYQL QYMSWPDRGV PSSPDHMLAM VEEARRLQGS GPEPLCVHCS AGCGRTGVLC TVDYVRQLLL TQMIPPDFSL FDVVLKMRKQ RPAAVQTEEQ YRFLYHTVAQ MFCSTLQNAS PHYQNIKENC APLYDDALFL RTPQALLAIP RPPGGVLRSI SVPGSPGHAM ADTYAVVQKR GAPAGAGSGT QTGTGTGTGA RSAEEAPLYS KVTPRAQRPG AHAEDARGTL PGRVPADQSP AGSGAYEDVA GGAQTGGLGF NLRIGRPKGP RDPPAEWTRV //