PTN18_HUMAN
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 03-AUG-2022, entry version 182.
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=4; 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}.
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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 EPD; Q99952; -.
DR jPOST; Q99952; -.
DR MassIVE; Q99952; -.
DR MaxQB; Q99952; -.
DR PaxDb; Q99952; -.
DR PeptideAtlas; Q99952; -.
DR PRIDE; Q99952; -.
DR ProteomicsDB; 78538; -. [Q99952-1]
DR ProteomicsDB; 78539; -. [Q99952-2]
DR Antibodypedia; 33499; 124 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 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; LVWEFRV; -.
DR OrthoDB; 411281at2759; -.
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 1079 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 192 other tissues.
DR ExpressionAtlas; Q99952; baseline and differential.
DR Genevisible; Q99952; HS.
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; IBA:GO_Central.
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:0035335; P:peptidyl-tyrosine dephosphorylation; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc.
DR Gene3D; 3.90.190.10; -; 1.
DR IDEAL; IID00581; -.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 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
