ID PTN12_HUMAN Reviewed; 780 AA. AC Q05209; A4D1C5; B4DKY2; E9PBR5; E9PEH9; Q16130; Q59FD6; Q75MN8; Q86XU4; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 27-MAR-2024, entry version 213. DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 12; DE EC=3.1.3.48 {ECO:0000269|PubMed:27134172, ECO:0000269|PubMed:8454633}; DE AltName: Full=PTP-PEST {ECO:0000303|PubMed:8454633}; DE AltName: Full=Protein-tyrosine phosphatase G1; DE Short=PTPG1; GN Name=PTPN12; 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), AND VARIANT ILE-322. RC TISSUE=Colon; RX PubMed=1472029; DOI=10.1016/0006-291x(92)92335-u; RA Takekawa M., Itoh F., Hinoda Y., Arimura Y., Toyota M., Sekiya M., RA Adachi M., Imai K., Yachi A.; RT "Cloning and characterization of a human cDNA encoding a novel putative RT cytoplasmic protein-tyrosine-phosphatase."; RL Biochem. Biophys. Res. Commun. 189:1223-1230(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CATALYTIC ACTIVITY. RX PubMed=8454633; DOI=10.1016/s0021-9258(18)53296-8; RA Yang Q., Co D., Sommercorn J., Tonks N.K.; RT "Cloning and expression of PTP-PEST. A novel, human, nontransmembrane RT protein tyrosine phosphatase."; RL J. Biol. Chem. 268:6622-6628(1993). RN [3] RP ERRATUM OF PUBMED:8454633, AND SEQUENCE REVISION TO 495-517 AND 526-780. RX PubMed=8349645; DOI=10.1016/s0021-9258(19)85383-8; RA Yang Q., Co D., Sommercorn J., Tonks N.K.; RL J. Biol. Chem. 268:17650-17650(1993). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP ILE-322 AND ALA-573. RC TISSUE=Cerebellum, and Tongue; 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 MRNA] (ISOFORM 1), AND VARIANT ILE-322. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [9] RP PROTEIN SEQUENCE OF 1-8, AND ACETYLATION AT MET-1. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 59-136 (ISOFORM 1), AND VARIANT COLON CANCER RP ARG-61. RX PubMed=7509295; DOI=10.1016/0014-5793(94)80420-6; RA Takekawa M., Itoh F., Hinoda Y., Adachi M., Ariyama T., Inazawa J., RA Imai K., Yachi A.; RT "Chromosomal localization of the protein tyrosine phosphatase G1 gene and RT characterization of the aberrant transcripts in human colon cancer cells."; RL FEBS Lett. 339:222-228(1994). RN [11] RP INTERACTION WITH PSTPIP1. RX PubMed=9857189; DOI=10.1093/emboj/17.24.7320; RA Li J., Nishizawa K., An W., Hussey R.E., Lialios F.E., Salgia R., RA Sunder-Plassmann R., Reinherz E.L.; RT "A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic RT domain and regulates CD2-triggered adhesion."; RL EMBO J. 17:7320-7336(1998). RN [12] RP PHOSPHORYLATION BY STK24. RX PubMed=17046825; DOI=10.1074/jbc.m605035200; RA Lu T.J., Lai W.Y., Huang C.Y., Hsieh W.J., Yu J.S., Hsieh Y.J., Chang W.T., RA Leu T.H., Chang W.C., Chuang W.J., Tang M.J., Chen T.Y., Lu T.L., Lai M.D.; RT "Inhibition of cell migration by autophosphorylated mammalian sterile 20- RT like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase- RT PEST."; RL J. Biol. Chem. 281:38405-38417(2006). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-673, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [14] RP INTERACTION WITH PTK2B/PYK2, AND FUNCTION. RX PubMed=17329398; DOI=10.1152/ajpcell.00503.2006; RA Sahu S.N., Nunez S., Bai G., Gupta A.; RT "Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells."; RL Am. J. Physiol. 292:C2288-C2296(2007). RN [15] RP INTERACTION WITH SORBS2, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=18559503; DOI=10.1158/0008-5472.can-08-0958; RA Taieb D., Roignot J., Andre F., Garcia S., Masson B., Pierres A., RA Iovanna J.L., Soubeyran P.; RT "ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, RT and tumorigenicity."; RL Cancer Res. 68:4588-4596(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-689 AND THR-693, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-603 AND SER-673, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332; SER-468; THR-519; RP SER-567; THR-569; SER-571; SER-603; SER-606; SER-608; SER-613; SER-689 AND RP THR-693, VARIANT [LARGE SCALE ANALYSIS] ILE-322, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-435; SER-449 AND RP SER-673, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332; SER-435; SER-449; RP SER-603; SER-606 AND SER-673, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-332; SER-435; RP SER-449; THR-509; SER-571; SER-606 AND SER-673, VARIANT [LARGE SCALE RP ANALYSIS] ILE-322, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332; SER-606 AND SER-673, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] {ECO:0007744|PDB:5J8R} RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 1-305, FUNCTION, CATALYTIC RP ACTIVITY, MUTAGENESIS OF SER-19; ARG-36; ARG-63; TYR-64; ASP-66; ASP-199; RP HIS-200; ARG-270 AND GLN-278, AND PHOSPHORYLATION AT SER-19. RX PubMed=27134172; DOI=10.1016/j.celrep.2016.04.016; RA Li H., Yang F., Liu C., Xiao P., Xu Y., Liang Z., Liu C., Wang H., Wang W., RA Zheng W., Zhang W., Ma X., He D., Song X., Cui F., Xu Z., Yi F., Sun J.P., RA Yu X.; RT "Crystal structure and substrate specificity of PTPN12."; RL Cell Rep. 15:1345-1358(2016). CC -!- FUNCTION: Dephosphorylates a range of proteins, and thereby regulates CC cellular signaling cascades (PubMed:18559503). Dephosphorylates CC cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby CC regulates signaling via ERBB2 and PTK2B/PYK2 (PubMed:17329398, CC PubMed:27134172). Selectively dephosphorylates ERBB2 phosphorylated at CC 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248' (PubMed:27134172). CC {ECO:0000269|PubMed:17329398, ECO:0000269|PubMed:18559503, CC ECO:0000269|PubMed:27134172}. 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:27134172, CC ECO:0000269|PubMed:8454633}; CC -!- SUBUNIT: Interacts with TGFB1I1 (By similarity). Interacts with PSTPIP1 CC (PubMed:9857189). Interacts with PTK2B/PYK2 (PubMed:17329398). CC Interacts with LPXN (By similarity). Interacts with SORBS2; this CC interaction greatly enhances WASF1 dephosphorylation and might mediate CC partial translocation to focal adhesion sites (PubMed:18559503). CC {ECO:0000250|UniProtKB:P35831, ECO:0000269|PubMed:17329398, CC ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:9857189}. CC -!- INTERACTION: CC Q05209; P56945: BCAR1; NbExp=5; IntAct=EBI-2266035, EBI-702093; CC Q05209; P00533: EGFR; NbExp=5; IntAct=EBI-2266035, EBI-297353; CC Q05209; P04626: ERBB2; NbExp=4; IntAct=EBI-2266035, EBI-641062; CC Q05209; P09619: PDGFRB; NbExp=3; IntAct=EBI-2266035, EBI-641237; CC Q05209; O43586: PSTPIP1; NbExp=6; IntAct=EBI-2266035, EBI-1050964; CC Q05209; P49023: PXN; NbExp=2; IntAct=EBI-2266035, EBI-702209; CC Q05209; P29353: SHC1; NbExp=8; IntAct=EBI-2266035, EBI-78835; CC Q05209; Q02763: TEK; NbExp=2; IntAct=EBI-2266035, EBI-2257090; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P35831}. Cell CC junction, focal adhesion {ECO:0000269|PubMed:18559503}. Cell CC projection, podosome {ECO:0000250|UniProtKB:P35831}. Note=Partial CC translocation to focal adhesion sites may be mediated by interaction CC with SORBS2. {ECO:0000269|PubMed:18559503}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q05209-1; Sequence=Displayed; CC Name=2; CC IsoId=Q05209-2; Sequence=VSP_046274; CC Name=3; CC IsoId=Q05209-3; Sequence=VSP_054168; CC -!- PTM: Phosphorylated by STK24/MST3 and this results in inhibition of its CC activity. {ECO:0000269|PubMed:17046825}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non- CC receptor class 4 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92761.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; D13380; BAA02648.1; -; mRNA. DR EMBL; M93425; AAA36529.1; -; mRNA. DR EMBL; AK289573; BAF82262.1; -; mRNA. DR EMBL; AK296764; BAG59344.1; -; mRNA. DR EMBL; AB209524; BAD92761.1; ALT_INIT; mRNA. DR EMBL; AC006451; AAQ96881.1; -; Genomic_DNA. DR EMBL; CH236949; EAL24198.1; -; Genomic_DNA. DR EMBL; CH471091; EAW77036.1; -; Genomic_DNA. DR EMBL; CH471091; EAW77037.1; -; Genomic_DNA. DR EMBL; BC050008; AAH50008.2; -; mRNA. DR EMBL; S69184; AAB30047.2; -; mRNA. DR CCDS; CCDS47619.1; -. [Q05209-3] DR CCDS; CCDS47620.1; -. [Q05209-2] DR CCDS; CCDS5592.1; -. [Q05209-1] DR PIR; JC1368; JC1368. DR RefSeq; NP_001124480.1; NM_001131008.1. [Q05209-3] DR RefSeq; NP_001124481.1; NM_001131009.1. [Q05209-2] DR RefSeq; NP_002826.3; NM_002835.3. [Q05209-1] DR PDB; 5HDE; X-ray; 1.62 A; A=1-301. DR PDB; 5J8R; X-ray; 2.04 A; A/B/C/D=1-305. DR PDB; 5O2P; NMR; -; A=328-344. DR PDBsum; 5HDE; -. DR PDBsum; 5J8R; -. DR PDBsum; 5O2P; -. DR AlphaFoldDB; Q05209; -. DR SMR; Q05209; -. DR BioGRID; 111746; 137. DR IntAct; Q05209; 102. DR MINT; Q05209; -. DR STRING; 9606.ENSP00000248594; -. DR BindingDB; Q05209; -. DR ChEMBL; CHEMBL3236; -. DR DrugBank; DB01133; Tiludronic acid. DR DEPOD; PTPN12; -. DR GlyGen; Q05209; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; Q05209; -. DR PhosphoSitePlus; Q05209; -. DR SwissPalm; Q05209; -. DR BioMuta; PTPN12; -. DR DMDM; 317373522; -. DR EPD; Q05209; -. DR jPOST; Q05209; -. DR MassIVE; Q05209; -. DR MaxQB; Q05209; -. DR PaxDb; 9606-ENSP00000248594; -. DR PeptideAtlas; Q05209; -. DR ProteomicsDB; 19279; -. DR ProteomicsDB; 19894; -. DR ProteomicsDB; 58316; -. [Q05209-1] DR Pumba; Q05209; -. DR Antibodypedia; 2052; 268 antibodies from 33 providers. DR DNASU; 5782; -. DR Ensembl; ENST00000248594.11; ENSP00000248594.6; ENSG00000127947.16. [Q05209-1] DR Ensembl; ENST00000415482.6; ENSP00000392429.2; ENSG00000127947.16. [Q05209-3] DR Ensembl; ENST00000435495.6; ENSP00000397991.2; ENSG00000127947.16. [Q05209-2] DR GeneID; 5782; -. DR KEGG; hsa:5782; -. DR MANE-Select; ENST00000248594.11; ENSP00000248594.6; NM_002835.4; NP_002826.3. DR UCSC; uc003ugh.3; human. [Q05209-1] DR AGR; HGNC:9645; -. DR CTD; 5782; -. DR DisGeNET; 5782; -. DR GeneCards; PTPN12; -. DR HGNC; HGNC:9645; PTPN12. DR HPA; ENSG00000127947; Low tissue specificity. DR MalaCards; PTPN12; -. DR MIM; 600079; gene. DR neXtProt; NX_Q05209; -. DR OpenTargets; ENSG00000127947; -. DR PharmGKB; PA33987; -. DR VEuPathDB; HostDB:ENSG00000127947; -. DR eggNOG; KOG0789; Eukaryota. DR GeneTree; ENSGT00940000156909; -. DR HOGENOM; CLU_015557_2_0_1; -. DR InParanoid; Q05209; -. DR OMA; GPFHISC; -. DR OrthoDB; 5489271at2759; -. DR PhylomeDB; Q05209; -. DR TreeFam; TF351977; -. DR BRENDA; 3.1.3.16; 2681. DR BRENDA; 3.1.3.48; 2681. DR PathwayCommons; Q05209; -. DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling. DR Reactome; R-HSA-182971; EGFR downregulation. DR Reactome; R-HSA-186797; Signaling by PDGF. DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-HSA-9008059; Interleukin-37 signaling. DR Reactome; R-HSA-9634285; Constitutive Signaling by Overexpressed ERBB2. DR SignaLink; Q05209; -. DR SIGNOR; Q05209; -. DR BioGRID-ORCS; 5782; 34 hits in 1181 CRISPR screens. DR ChiTaRS; PTPN12; human. DR GeneWiki; PTPN12; -. DR GenomeRNAi; 5782; -. DR Pharos; Q05209; Tchem. DR PRO; PR:Q05209; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q05209; Protein. DR Bgee; ENSG00000127947; Expressed in primordial germ cell in gonad and 206 other cell types or tissues. DR ExpressionAtlas; Q05209; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell. DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; EXP:Reactome. DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:UniProtKB. DR GO; GO:1901185; P:negative regulation of ERBB signaling pathway; TAS:Reactome. DR GO; GO:2000587; P:negative regulation of platelet-derived growth factor receptor-beta signaling pathway; TAS:Reactome. DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB. DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB. DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0042246; P:tissue regeneration; IEA:Ensembl. DR CDD; cd14604; PTPc-N12; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR012266; PTN12. DR InterPro; IPR047170; PTN12/18/22. DR InterPro; IPR047251; PTN12_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:SF3; TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 12; 1. DR Pfam; PF00102; Y_phosphatase; 1. DR PIRSF; PIRSF000932; Tyr-Ptase_nr12; 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. DR Genevisible; Q05209; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell junction; KW Cell projection; Cytoplasm; Direct protein sequencing; Disease variant; KW Hydrolase; Phosphoprotein; Protein phosphatase; Reference proteome. FT CHAIN 1..780 FT /note="Tyrosine-protein phosphatase non-receptor type 12" FT /id="PRO_0000094771" FT DOMAIN 28..293 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 345..438 FT /note="Interaction with TGFB1I1" FT /evidence="ECO:0000250" FT REGION 502..639 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 657..725 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 744..780 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 549..582 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 615..639 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 686..701 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 702..725 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 231 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000255|PROSITE-ProRule:PRU10044" FT BINDING 36 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:27134172" FT BINDING 63..67 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:27134172" FT BINDING 199 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:27134172" FT BINDING 231..237 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 278 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:27134172" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:27134172, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 332 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 435 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 449 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 468 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 509 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 519 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 567 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 569 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 571 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 596 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35831" FT MOD_RES 598 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P35831" FT MOD_RES 603 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692" FT MOD_RES 606 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 608 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 613 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 673 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 689 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648" FT MOD_RES 693 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648" FT VAR_SEQ 1..130 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046274" FT VAR_SEQ 1..119 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_054168" FT VARIANT 61 FT /note="K -> R (in colon cancer; dbSNP:rs121434623)" FT /evidence="ECO:0000269|PubMed:7509295" FT /id="VAR_006385" FT VARIANT 322 FT /note="V -> I (in dbSNP:rs9640663)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:1472029, ECO:0000269|Ref.5, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT /id="VAR_019512" FT VARIANT 573 FT /note="T -> A (in dbSNP:rs3750050)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_020297" FT VARIANT 706 FT /note="E -> K (in dbSNP:rs2230602)" FT /id="VAR_057129" FT MUTAGEN 19 FT /note="S->E: Loss of phosphorylation site." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 36 FT /note="R->A: Decreases enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 63 FT /note="R->A: Decreases enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 64 FT /note="Y->A: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 66 FT /note="D->A: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 67 FT /note="I->A: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 199 FT /note="D->A: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 200 FT /note="H->A: Decreases enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 270 FT /note="R->A: Decreases enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT MUTAGEN 278 FT /note="Q->A: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:27134172" FT CONFLICT 121 FT /note="I -> V (in Ref. 1; BAA02648 and 10; AAB30047)" FT /evidence="ECO:0000305" FT CONFLICT 612 FT /note="N -> D (in Ref. 4; BAG59344)" FT /evidence="ECO:0000305" FT HELIX 3..17 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 27..42 FT /evidence="ECO:0007829|PDB:5HDE" FT TURN 43..46 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 51..54 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 56..61 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 71..73 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:5J8R" FT STRAND 90..94 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 102..106 FT /evidence="ECO:0007829|PDB:5HDE" FT TURN 111..113 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 114..123 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 128..131 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 135..137 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 160..170 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 173..182 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 185..194 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 207..219 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 222..225 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 227..230 FT /evidence="ECO:0007829|PDB:5HDE" FT STRAND 232..235 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 236..252 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 262..269 FT /evidence="ECO:0007829|PDB:5HDE" FT TURN 270..272 FT /evidence="ECO:0007829|PDB:5HDE" FT HELIX 280..298 FT /evidence="ECO:0007829|PDB:5HDE" SQ SEQUENCE 780 AA; 88106 MW; 663DB3E5176FD7FD CRC64; MEQVEILRKF IQRVQAMKSP DHNGEDNFAR DFMRLRRLST KYRTEKIYPT ATGEKEENVK KNRYKDILPF DHSRVKLTLK TPSQDSDYIN ANFIKGVYGP KAYVATQGPL ANTVIDFWRM IWEYNVVIIV MACREFEMGR KKCERYWPLY GEDPITFAPF KISCEDEQAR TDYFIRTLLL EFQNESRRLY QFHYVNWPDH DVPSSFDSIL DMISLMRKYQ EHEDVPICIH CSAGCGRTGA ICAIDYTWNL LKAGKIPEEF NVFNLIQEMR TQRHSAVQTK EQYELVHRAI AQLFEKQLQL YEIHGAQKIA DGVNEINTEN MVSSIEPEKQ DSPPPKPPRT RSCLVEGDAK EEILQPPEPH PVPPILTPSP PSAFPTVTTV WQDNDRYHPK PVLHMVSSEQ HSADLNRNYS KSTELPGKNE STIEQIDKKL ERNLSFEIKK VPLQEGPKSF DGNTLLNRGH AIKIKSASPC IADKISKPQE LSSDLNVGDT SQNSCVDCSV TQSNKVSVTP PEESQNSDTP PRPDRLPLDE KGHVTWSFHG PENAIPIPDL SEGNSSDINY QTRKTVSLTP SPTTQVETPD LVDHDNTSPL FRTPLSFTNP LHSDDSDSDE RNSDGAVTQN KTNISTASAT VSAATSTESI STRKVLPMSI ARHNIAGTTH SGAEKDVDVS EDSPPPLPER TPESFVLASE HNTPVRSEWS ELQSQERSEQ KKSEGLITSE NEKCDHPAGG IHYEMCIECP PTFSDKREQI SENPTEATDI GFGNRCGKPK GPRDPPSEWT //