PTN12_HUMAN
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 03-AUG-2022, entry version 204.
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=5; 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};
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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; 128.
DR IntAct; Q05209; 103.
DR MINT; Q05209; -.
DR STRING; 9606.ENSP00000248594; -.
DR BindingDB; Q05209; -.
DR ChEMBL; CHEMBL3236; -.
DR DrugBank; DB01133; Tiludronic acid.
DR DEPOD; PTPN12; -.
DR GlyGen; Q05209; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q05209; -.
DR PhosphoSitePlus; Q05209; -.
DR BioMuta; PTPN12; -.
DR DMDM; 317373522; -.
DR EPD; Q05209; -.
DR jPOST; Q05209; -.
DR MassIVE; Q05209; -.
DR MaxQB; Q05209; -.
DR PaxDb; Q05209; -.
DR PeptideAtlas; Q05209; -.
DR PRIDE; Q05209; -.
DR ProteomicsDB; 19279; -.
DR ProteomicsDB; 19894; -.
DR ProteomicsDB; 58316; -. [Q05209-1]
DR Antibodypedia; 2052; 225 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 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; PFHISCE; -.
DR OrthoDB; 411281at2759; -.
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; 25 hits in 1084 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 colonic epithelium and 204 other tissues.
DR ExpressionAtlas; Q05209; baseline and differential.
DR Genevisible; Q05209; HS.
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 Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR012266; Ptpn_12.
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 PIRSF; PIRSF000932; Tyr-Ptase_nr12; 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; 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
