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 01-MAY-2013, entry version 114.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA 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.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA 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.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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 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
RT tyrosine phosphatome.";
RL Cell 136:352-363(2009).
CC -!- FUNCTION: Differentially dephosphorylate autophosphorylated
CC tyrosine kinases which are known to be overexpressed in tumor
CC tissues.
CC -!- CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein
CC tyrosine + phosphate.
CC -!- SUBUNIT: Interacts with PSTPIP1 (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By
CC similarity).
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 Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in brain, colon and several tumor-
CC derived cell lines.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC Non-receptor class 4 subfamily.
CC -!- SIMILARITY: Contains 1 tyrosine-protein phosphatase domain.
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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 IPI; IPI00152019; -.
DR IPI; IPI00219132; -.
DR RefSeq; NP_001135842.1; NM_001142370.1.
DR RefSeq; NP_055184.2; NM_014369.3.
DR UniGene; Hs.516390; -.
DR PDB; 2OC3; X-ray; 1.50 A; A=6-299.
DR PDBsum; 2OC3; -.
DR ProteinModelPortal; Q99952; -.
DR IntAct; Q99952; 1.
DR STRING; 9606.ENSP00000175756; -.
DR PhosphoSite; Q99952; -.
DR DMDM; 215273871; -.
DR PaxDb; Q99952; -.
DR PRIDE; Q99952; -.
DR DNASU; 26469; -.
DR Ensembl; ENST00000175756; ENSP00000175756; ENSG00000072135.
DR Ensembl; ENST00000347849; ENSP00000310092; ENSG00000072135.
DR GeneID; 26469; -.
DR KEGG; hsa:26469; -.
DR UCSC; uc002trc.3; human.
DR CTD; 26469; -.
DR GeneCards; GC02P131113; -.
DR HGNC; HGNC:9649; PTPN18.
DR HPA; CAB012174; -.
DR MIM; 606587; gene.
DR neXtProt; NX_Q99952; -.
DR PharmGKB; PA33991; -.
DR eggNOG; COG5599; -.
DR HOGENOM; HOG000115776; -.
DR HOVERGEN; HBG053419; -.
DR InParanoid; Q99952; -.
DR KO; K01104; -.
DR OMA; GLGFNLR; -.
DR OrthoDB; EOG4X0MSD; -.
DR PhylomeDB; Q99952; -.
DR ChiTaRS; PTPN18; human.
DR EvolutionaryTrace; Q99952; -.
DR GenomeRNAi; 26469; -.
DR NextBio; 48711; -.
DR ArrayExpress; Q99952; -.
DR Bgee; Q99952; -.
DR CleanEx; HS_BDP1; -.
DR CleanEx; HS_PTPN18; -.
DR Genevestigator; Q99952; -.
DR GermOnline; ENSG00000072135; Homo sapiens.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; TAS:ProtInc.
DR InterPro; IPR000387; Tyr/Dual-sp_Pase.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR000242; Tyr_Pase_rcpt/non-rcpt.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00194; PTPc; 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; Complete proteome; Cytoplasm;
KW Hydrolase; Nucleus; Phosphoprotein; Polymorphism; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1 460 Tyrosine-protein phosphatase non-receptor
FT type 18.
FT /FTId=PRO_0000094773.
FT DOMAIN 26 291 Tyrosine-protein phosphatase.
FT REGION 229 235 Substrate binding (By similarity).
FT ACT_SITE 229 229 Phosphocysteine intermediate (By
FT similarity).
FT BINDING 197 197 Substrate (By similarity).
FT BINDING 276 276 Substrate (By similarity).
FT MOD_RES 389 389 Phosphotyrosine (By similarity).
FT MOD_RES 426 426 Phosphotyrosine (By similarity).
FT VAR_SEQ 32 138 Missing (in isoform 2).
FT /FTId=VSP_043073.
FT VARIANT 193 193 M -> V (in dbSNP:rs3739124).
FT /FTId=VAR_047651.
FT CONFLICT 356 357 VV -> EE (in Ref. 1; CAA56105).
FT CONFLICT 378 379 Missing (in Ref. 1; CAA56105).
FT HELIX 11 14
FT HELIX 25 43
FT HELIX 49 52
FT TURN 54 56
FT HELIX 57 59
FT HELIX 69 71
FT STRAND 72 74
FT HELIX 79 81
FT STRAND 85 93
FT STRAND 97 104
FT HELIX 109 111
FT HELIX 112 121
FT STRAND 126 129
FT STRAND 133 135
FT STRAND 152 154
FT STRAND 157 168
FT STRAND 171 180
FT STRAND 183 192
FT STRAND 197 199
FT HELIX 205 218
FT STRAND 225 228
FT STRAND 230 233
FT HELIX 234 250
FT HELIX 260 268
FT HELIX 278 292
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
//