ID TENS3_HUMAN Reviewed; 1445 AA. AC Q68CZ2; B2RNV1; Q6IPQ2; Q8IZW7; Q8NAD0; Q96PE0; Q96S48; DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2007, sequence version 2. DT 27-MAR-2024, entry version 160. DE RecName: Full=Tensin-3; DE EC=3.1.3.- {ECO:0000305}; DE AltName: Full=Tensin-like SH2 domain-containing protein 1; DE AltName: Full=Tumor endothelial marker 6; GN Name=TNS3; Synonyms=TEM6, TENS1, TPP; 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 2), AND TISSUE SPECIFICITY. RX PubMed=11559528; RA Carson-Walter E.B., Watkins D.N., Nanda A., Vogelstein B., Kinzler K.W., RA St Croix B.; RT "Cell surface tumor endothelial markers are conserved in mice and humans."; RL Cancer Res. 61:6649-6655(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, INDUCTION, INTERACTION WITH EGFR; PTK2/FAK1 AND BCAR1, AND RP PHOSPHORYLATION. RX PubMed=15140944; RA Cui Y., Liao Y.-C., Lo S.H.; RT "Epidermal growth factor modulates tyrosine phosphorylation of a novel RT tensin family member, tensin3."; RL Mol. Cancer Res. 2:225-232(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Spleen; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Amygdala; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [5] 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 [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Brain, and Kidney; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 749-1445, AND TISSUE SPECIFICITY. RX PubMed=16461921; DOI=10.1677/jme.1.01913; RA Maeda I., Takano T., Yoshida H., Matsuzuka F., Amino N., Miyauchi A.; RT "Tensin3 is a novel thyroid-specific gene."; RL J. Mol. Endocrinol. 36:R1-R8(2006). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND KNOCKDOWN IN MCF10A CELLS. RX PubMed=17643115; DOI=10.1038/ncb1622; RA Katz M., Amit I., Citri A., Shay T., Carvalho S., Lavi S., Milanezi F., RA Lyass L., Amariglio N., Jacob-Hirsch J., Ben-Chetrit N., Tarcic G., RA Lindzen M., Avraham R., Liao Y.C., Trusk P., Lyass A., Rechavi G., RA Spector N.L., Lo S.H., Schmitt F., Bacus S.S., Yarden Y.; RT "A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell RT migration."; RL Nat. Cell Biol. 9:961-969(2007). RN [10] 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332; THR-632; SER-660; RP SER-776; SER-866; SER-901; SER-1149; SER-1154 AND SER-1293, AND RP IDENTIFICATION BY MASS 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 [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=20069572; DOI=10.1002/jcb.22460; RA Clark K., Howe J.D., Pullar C.E., Green J.A., Artym V.V., Yamada K.M., RA Critchley D.R.; RT "Tensin 2 modulates cell contractility in 3D collagen gels through the RT RhoGAP DLC1."; RL J. Cell. Biochem. 109:808-817(2010). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-660; SER-735; RP SER-776; TYR-780; SER-811; SER-1149 AND SER-1154, AND IDENTIFICATION BY RP 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 [15] 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 [16] RP IDENTIFICATION BY MASS SPECTROMETRY [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 [17] RP IDENTIFICATION BY MASS 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-660; SER-776; SER-1149 AND RP SER-1441, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [19] RP INTERACTION WITH MET. RX PubMed=24814316; DOI=10.1016/j.devcel.2014.03.024; RA Muharram G., Sahgal P., Korpela T., De Franceschi N., Kaukonen R., RA Clark K., Tulasne D., Carpen O., Ivaska J.; RT "Tensin-4-dependent MET stabilization is essential for survival and RT proliferation in carcinoma cells."; RL Dev. Cell 29:421-436(2014). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361; SER-440; SER-516; RP SER-776; SER-811; SER-901; SER-1149 AND SER-1154, AND IDENTIFICATION BY RP 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 [21] RP FUNCTION. RX PubMed=26427649; DOI=10.1016/j.bbamcr.2015.09.028; RA Shih Y.P., Sun P., Wang A., Lo S.H.; RT "Tensin1 positively regulates RhoA activity through its interaction with RT DLC1."; RL Biochim. Biophys. Acta 1853:3258-3265(2015). RN [22] RP ERRATUM OF PUBMED:26427649. RX PubMed=29866430; DOI=10.1016/j.bbamcr.2018.05.016; RA Shih Y.P., Sun P., Wang A., Lo S.H.; RL Biochim. Biophys. Acta 1865:1383-1383(2018). RN [23] RP FUNCTION, INTERACTION WITH DLC1 AND PI3K, PHOSPHORYLATION AT THR-323, AND RP MUTAGENESIS OF TYR-321 AND THR-323. RX PubMed=26166433; DOI=10.1038/ncomms8721; RA Cao X., Kaneko T., Li J.S., Liu A.D., Voss C., Li S.S.; RT "A phosphorylation switch controls the spatiotemporal activation of Rho RT GTPases in directional cell migration."; RL Nat. Commun. 6:7721-7721(2015). RN [24] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=31905841; DOI=10.3390/cells9010089; RA Park G.C., Kim H.S., Park H.Y., Seo Y., Kim J.M., Shin S.C., Kwon H.K., RA Sung E.S., Lee J.C., Lee B.J.; RT "Tensin-3 Regulates Integrin-Mediated Proliferation and Differentiation of RT Tonsil-Derived Mesenchymal Stem Cells."; RL Cells 9:0-0(2019). RN [25] RP FUNCTION, INTERACTION WITH ITGB1; ITGB3; ITGB5 AND PEAK1, SUBCELLULAR RP LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-1173; TYR-1206 AND RP TYR-1256. RX PubMed=35687021; DOI=10.1083/jcb.202108027; RA Zuidema A., Atherton P., Kreft M., Hoekman L., Bleijerveld O.B., RA Nagaraj N., Chen N., Faessler R., Sonnenberg A.; RT "PEAK1 Y635 phosphorylation regulates cell migration through association RT with Tensin3 and integrins."; RL J. Cell Biol. 221:0-0(2022). CC -!- FUNCTION: May act as a protein phosphatase and/or a lipid phosphatase CC (Probable). Involved in the dissociation of the integrin-tensin-actin CC complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 CC which results in capping the tail of ITGB1 (PubMed:17643115). Increases CC DOCK5 guanine nucleotide exchange activity towards Rac and plays a role CC in osteoclast podosome organization (By similarity). Enhances RHOA CC activation in the presence of DLC1 (PubMed:26427649). Required for CC growth factor-induced epithelial cell migration; growth factor CC stimulation induces TNS3 phosphorylation which changes its binding CC preference from DLC1 to the p85 regulatory subunit of the PI3K kinase CC complex, displacing PI3K inhibitor PTEN and resulting in translocation CC of the TNS3-p85 complex to the leading edge of migrating cells to CC promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches CC binding preference from p85 to DLC1 and the PTEN-DLC1 complex CC translocates to the posterior of migrating cells to activate RHOA CC (PubMed:26166433). Acts as an adapter protein by bridging the CC association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 CC and ITGB5 which contributes to the promotion of cell migration CC (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell CC proliferation and differentiation by regulating the activity of CC integrin ITGB1 (PubMed:31905841). {ECO:0000250|UniProtKB:Q5SSZ5, CC ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:26166433, CC ECO:0000269|PubMed:26427649, ECO:0000269|PubMed:31905841, CC ECO:0000269|PubMed:35687021, ECO:0000305}. CC -!- SUBUNIT: Interacts with EGFR; EGF promotes the interaction with EGFR CC (PubMed:15140944). Interacts with PTK2/FAK1 and BCAR1 CC (PubMed:15140944). Tyrosine phosphorylation is critical for these CC interactions (PubMed:15140944). Interacts with Rho GTPase-activating CC protein DLC1 and with the regulatory p85 subunit of the PI3K kinase CC complex; in resting cells, interacts (via C2 tensin-type domain) with CC DLC1 but, following growth factor stimulation, TNS3 is phosphorylated CC which leads to weakened interaction with DLC1 and enhanced interaction CC (via C2 tensin-type domain) with p85 while DLC1 interaction with PTEN CC increases (PubMed:26166433). Interacts (when phosphorylated on the SH2 CC domain) with integrins ITGB1, ITGB3 and ITGB5 and with scaffolding CC protein PEAK1 (phosphorylated on 'Tyr-635'); mediates the association CC of PEAK1 with ITGB1, ITGB3 and ITGB5 (PubMed:35687021). Interacts (via CC N-terminus) with DOCK5 (via N-terminus); the interaction increases CC DOCK5 guanine nucleotide exchange activity towards Rac (By similarity). CC Interacts with receptor tyrosine kinase MET (PubMed:24814316). CC {ECO:0000250|UniProtKB:Q5SSZ5, ECO:0000269|PubMed:15140944, CC ECO:0000269|PubMed:24814316, ECO:0000269|PubMed:26166433, CC ECO:0000269|PubMed:35687021}. CC -!- INTERACTION: CC Q68CZ2; P56945: BCAR1; NbExp=8; IntAct=EBI-1220488, EBI-702093; CC Q68CZ2; P12830: CDH1; NbExp=2; IntAct=EBI-1220488, EBI-727477; CC Q68CZ2; P00533: EGFR; NbExp=5; IntAct=EBI-1220488, EBI-297353; CC Q68CZ2; P04626: ERBB2; NbExp=2; IntAct=EBI-1220488, EBI-641062; CC Q68CZ2; P21860: ERBB3; NbExp=2; IntAct=EBI-1220488, EBI-720706; CC Q68CZ2; P10721: KIT; NbExp=5; IntAct=EBI-1220488, EBI-1379503; CC Q68CZ2; P08581: MET; NbExp=3; IntAct=EBI-1220488, EBI-1039152; CC Q68CZ2; Q05397: PTK2; NbExp=3; IntAct=EBI-1220488, EBI-702142; CC Q68CZ2; P12931: SRC; NbExp=13; IntAct=EBI-1220488, EBI-621482; CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion CC {ECO:0000269|PubMed:15140944, ECO:0000269|PubMed:17643115, CC ECO:0000269|PubMed:20069572, ECO:0000269|PubMed:35687021}. Cell CC projection, podosome {ECO:0000250|UniProtKB:Q5SSZ5}. Note=Localizes to CC both focal and fibrillar adhesions but is mostly found in fibrillar CC adhesions. {ECO:0000269|PubMed:20069572}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q68CZ2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q68CZ2-2; Sequence=VSP_027123; CC Name=3; CC IsoId=Q68CZ2-3; Sequence=VSP_027126, VSP_027127; CC Name=4; CC IsoId=Q68CZ2-4; Sequence=VSP_027124, VSP_027125; CC -!- TISSUE SPECIFICITY: Expressed in umbilical vein endothelial cells, CC epithelial cells, and fibroblasts cells (at protein level). Highly CC expressed in thyroid, kidney and placenta. Low expression in heart, CC skeletal muscle, spleen, liver, and lung. Expressed at higher levels in CC tonsil-derived mesenchymal stem cells (MSCs) than in adipose tissue- CC derived MSCs or bone marrow-derived MSCs (PubMed:31905841). Expressed CC in tumor endothelial cells. Expression seems to be down-regulated in CC thyroid tumor tissues and in anaplastic carcinomas. CC {ECO:0000269|PubMed:11559528, ECO:0000269|PubMed:15140944, CC ECO:0000269|PubMed:16461921, ECO:0000269|PubMed:31905841}. CC -!- INDUCTION: Down-regulated by EGF. {ECO:0000269|PubMed:15140944, CC ECO:0000269|PubMed:17643115}. CC -!- PTM: Phosphorylated on Ser/Thr and Tyr residues (PubMed:26166433). CC Phosphorylated on Thr-323 in the C2-type tensin domain following EGF CC stimulation which changes its binding preference from DLC1 to the p85 CC regulatory subunit of the PI3K kinase complex (PubMed:26166433). EGF CC induces tyrosine phosphorylation in a time- and dose-dependent manner CC (PubMed:15140944). Phosphorylation of the SH2 domain enhances CC interaction with PEAK1 (PubMed:35687021). {ECO:0000269|PubMed:15140944, CC ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:35687021}. CC -!- SIMILARITY: Belongs to the PTEN phosphatase protein family. CC {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; AF378756; AAL11993.1; -; mRNA. DR EMBL; AF417489; AAN32667.1; -; mRNA. DR EMBL; AK092864; BAC03993.1; -; mRNA. DR EMBL; CR749644; CAH18438.1; -; mRNA. DR EMBL; AC073341; AAQ96841.1; -; Genomic_DNA. DR EMBL; CH471128; EAW61011.1; -; Genomic_DNA. DR EMBL; BC071791; AAH71791.1; -; mRNA. DR EMBL; BC137133; AAI37134.1; -; mRNA. DR EMBL; BC137134; AAI37135.1; -; mRNA. DR EMBL; AB062750; BAB60681.1; -; mRNA. DR CCDS; CCDS5506.2; -. [Q68CZ2-1] DR RefSeq; NP_073585.8; NM_022748.11. [Q68CZ2-1] DR RefSeq; XP_011513782.1; XM_011515480.2. [Q68CZ2-1] DR RefSeq; XP_011513783.1; XM_011515481.2. [Q68CZ2-1] DR RefSeq; XP_011513784.1; XM_011515482.2. DR RefSeq; XP_011513785.1; XM_011515483.2. [Q68CZ2-1] DR RefSeq; XP_016868028.1; XM_017012539.1. DR AlphaFoldDB; Q68CZ2; -. DR SMR; Q68CZ2; -. DR BioGRID; 122272; 77. DR IntAct; Q68CZ2; 148. DR MINT; Q68CZ2; -. DR STRING; 9606.ENSP00000312143; -. DR ChEMBL; CHEMBL4295861; -. DR DEPOD; TNS3; -. DR GlyGen; Q68CZ2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q68CZ2; -. DR MetOSite; Q68CZ2; -. DR PhosphoSitePlus; Q68CZ2; -. DR SwissPalm; Q68CZ2; -. DR BioMuta; TNS3; -. DR DMDM; 156637424; -. DR EPD; Q68CZ2; -. DR jPOST; Q68CZ2; -. DR MassIVE; Q68CZ2; -. DR MaxQB; Q68CZ2; -. DR PaxDb; 9606-ENSP00000312143; -. DR PeptideAtlas; Q68CZ2; -. DR ProteomicsDB; 66036; -. [Q68CZ2-1] DR ProteomicsDB; 66037; -. [Q68CZ2-2] DR ProteomicsDB; 66038; -. [Q68CZ2-3] DR ProteomicsDB; 66039; -. [Q68CZ2-4] DR Pumba; Q68CZ2; -. DR Antibodypedia; 1019; 155 antibodies from 26 providers. DR DNASU; 64759; -. DR Ensembl; ENST00000311160.14; ENSP00000312143.9; ENSG00000136205.18. [Q68CZ2-1] DR Ensembl; ENST00000442536.6; ENSP00000389285.2; ENSG00000136205.18. [Q68CZ2-4] DR GeneID; 64759; -. DR KEGG; hsa:64759; -. DR MANE-Select; ENST00000311160.14; ENSP00000312143.9; NM_022748.12; NP_073585.8. DR UCSC; uc003tnw.3; human. [Q68CZ2-1] DR AGR; HGNC:21616; -. DR CTD; 64759; -. DR DisGeNET; 64759; -. DR GeneCards; TNS3; -. DR HGNC; HGNC:21616; TNS3. DR HPA; ENSG00000136205; Low tissue specificity. DR MIM; 606825; gene. DR neXtProt; NX_Q68CZ2; -. DR OpenTargets; ENSG00000136205; -. DR PharmGKB; PA134888115; -. DR VEuPathDB; HostDB:ENSG00000136205; -. DR eggNOG; KOG1930; Eukaryota. DR eggNOG; KOG2283; Eukaryota. DR GeneTree; ENSGT00940000156328; -. DR HOGENOM; CLU_002189_1_0_1; -. DR InParanoid; Q68CZ2; -. DR OMA; QGSEHLH; -. DR OrthoDB; 3439226at2759; -. DR PhylomeDB; Q68CZ2; -. DR TreeFam; TF315996; -. DR PathwayCommons; Q68CZ2; -. DR Reactome; R-HSA-8875513; MET interacts with TNS proteins. DR SignaLink; Q68CZ2; -. DR SIGNOR; Q68CZ2; -. DR BioGRID-ORCS; 64759; 83 hits in 1155 CRISPR screens. DR ChiTaRS; TNS3; human. DR GenomeRNAi; 64759; -. DR Pharos; Q68CZ2; Tbio. DR PRO; PR:Q68CZ2; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q68CZ2; Protein. DR Bgee; ENSG00000136205; Expressed in renal glomerulus and 204 other cell types or tissues. DR ExpressionAtlas; Q68CZ2; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IDA:HPA. DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IEA:UniProtKB-KW. DR GO; GO:0016311; P:dephosphorylation; IEA:InterPro. DR CDD; cd01213; PTB_tensin; 1. DR CDD; cd14561; PTP_tensin-3; 1. DR CDD; cd09927; SH2_Tensin_like; 1. DR Gene3D; 2.60.40.1110; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR013625; PTB. DR InterPro; IPR006020; PTB/PI_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR035012; Tensin-like_SH2. DR InterPro; IPR014020; Tensin_C2-dom. DR InterPro; IPR029023; Tensin_phosphatase. DR InterPro; IPR033929; Tensin_PTB. DR InterPro; IPR003595; Tyr_Pase_cat. DR InterPro; IPR000387; Tyr_Pase_dom. DR PANTHER; PTHR45734; TENSIN; 1. DR PANTHER; PTHR45734:SF5; TENSIN-3; 1. DR Pfam; PF08416; PTB; 1. DR Pfam; PF10409; PTEN_C2; 1. DR Pfam; PF00017; SH2; 1. DR SMART; SM00462; PTB; 1. DR SMART; SM01326; PTEN_C2; 1. DR SMART; SM00404; PTPc_motif; 1. DR SMART; SM00252; SH2; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS51182; C2_TENSIN; 1. DR PROSITE; PS51181; PPASE_TENSIN; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; Q68CZ2; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell junction; Cell projection; Hydrolase; KW Phosphoprotein; Protein phosphatase; Reference proteome; SH2 domain. FT CHAIN 1..1445 FT /note="Tensin-3" FT /id="PRO_0000295915" FT DOMAIN 1..170 FT /note="Phosphatase tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT DOMAIN 175..301 FT /note="C2 tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589" FT DOMAIN 1172..1282 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 1310..1444 FT /note="PTB" FT /evidence="ECO:0000255" FT REGION 358..421 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 538..568 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 618..695 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 717..769 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 859..981 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1076..1127 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 376..398 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 630..644 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 719..733 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 910..950 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1110..1127 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 323 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:26166433" FT MOD_RES 332 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 361 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 440 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 516 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 571 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5SSZ5" FT MOD_RES 632 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 649 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 660 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 687 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5SSZ5" FT MOD_RES 690 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5SSZ5" FT MOD_RES 735 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 776 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 780 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 811 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:24275569" FT MOD_RES 866 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 901 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1149 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1154 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569" FT MOD_RES 1293 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1441 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 241..480 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11559528" FT /id="VSP_027123" FT VAR_SEQ 243..250 FT /note="KCYHKKYR -> MNYNIANI (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_027124" FT VAR_SEQ 251..1445 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_027125" FT VAR_SEQ 381..391 FT /note="DHSDHTLSVSS -> ANVLFELIGQV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_027126" FT VAR_SEQ 392..1445 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_027127" FT VARIANT 600 FT /note="Q -> H (in dbSNP:rs2293362)" FT /id="VAR_034593" FT VARIANT 679 FT /note="G -> S (in dbSNP:rs7808646)" FT /id="VAR_034594" FT VARIANT 1034 FT /note="E -> K (in dbSNP:rs3807590)" FT /id="VAR_052548" FT MUTAGEN 321 FT /note="Y->T: Constitutive interaction with p85 and FT interaction with DLC1 after EGF stimulation." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 323 FT /note="T->A: Abolishes phosphorylation. Abolishes FT interaction with DLC1 and p85." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 323 FT /note="T->E: Constitutive interaction with p85." FT /evidence="ECO:0000269|PubMed:26166433" FT MUTAGEN 1173 FT /note="Y->F: Significantly reduced interaction with PEAK1; FT when associated with F-1206 and F-1256." FT /evidence="ECO:0000269|PubMed:35687021" FT MUTAGEN 1206 FT /note="Y->F: Significantly reduced interaction with PEAK1; FT when associated with F-1173 and F-1256." FT /evidence="ECO:0000269|PubMed:35687021" FT MUTAGEN 1256 FT /note="Y->F: Significantly reduced interaction with PEAK1; FT when associated with F-1173 and F-1206." FT /evidence="ECO:0000269|PubMed:35687021" FT CONFLICT 31 FT /note="L -> P (in Ref. 2; AAN32667)" FT /evidence="ECO:0000305" FT CONFLICT 458 FT /note="V -> A (in Ref. 4; CAH18438)" FT /evidence="ECO:0000305" FT CONFLICT 505 FT /note="A -> V (in Ref. 2; AAN32667)" FT /evidence="ECO:0000305" FT CONFLICT 917 FT /note="T -> A (in Ref. 4; CAH18438)" FT /evidence="ECO:0000305" FT CONFLICT 1047 FT /note="A -> T (in Ref. 4; CAH18438)" FT /evidence="ECO:0000305" SQ SEQUENCE 1445 AA; 155266 MW; 40B02C6269899320 CRC64; MEEGHGLDLT YITERIIAVS FPAGCSEESY LHNLQEVTRM LKSKHGDNYL VLNLSEKRYD LTKLNPKIMD VGWPELHAPP LDKMCTICKA QESWLNSNLQ HVVVIHCRGG KGRIGVVISS YMHFTNVSAS ADQALDRFAM KKFYDDKVSA LMQPSQKRYV QFLSGLLSGS VKMNASPLFL HFVILHGTPN FDTGGVCRPF LKLYQAMQPV YTSGIYNVGP ENPSRICIVI EPAQLLKGDV MVKCYHKKYR SATRDVIFRL QFHTGAVQGY GLVFGKEDLD NASKDDRFPD YGKVELVFSA TPEKIQGSEH LYNDHGVIVD YNTTDPLIRW DSYENLSADG EVLHTQGPVD GSLYAKVRKK SSSDPGIPGG PQAIPATNSP DHSDHTLSVS SDSGHSTASA RTDKTEERLA PGTRRGLSAQ EKAELDQLLS GFGLEDPGSS LKEMTDARSK YSGTRHVVPA QVHVNGDAAL KDRETDILDD EMPHHDLHSV DSLGTLSSSE GPQSAHLGPF TCHKSSQNSL LSDGFGSNVG EDPQGTLVPD LGLGMDGPYE RERTFGSREP KQPQPLLRKP SVSAQMQAYG QSSYSTQTWV RQQQMVVAHQ YSFAPDGEAR LVSRCPADNP GLVQAQPRVP LTPTRGTSSR VAVQRGVGSG PHPPDTQQPS PSKAFKPRFP GDQVVNGAGP ELSTGPSPGS PTLDIDQSIE QLNRLILELD PTFEPIPTHM NALGSQANGS VSPDSVGGGL RASSRLPDTG EGPSRATGRQ GSSAEQPLGG RLRKLSLGQY DNDAGGQLPF SKCAWGKAGV DYAPNLPPFP SPADVKETMT PGYPQDLDII DGRILSSKES MCSTPAFPVS PETPYVKTAL RHPPFSPPEP PLSSPASQHK GGREPRSCPE TLTHAVGMSE SPIGPKSTML RADASSTPSF QQAFASSCTI SSNGPGQRRE SSSSAERQWV ESSPKPMVSL LGSGRPTGSP LSAEFSGTRK DSPVLSCFPP SELQAPFHSH ELSLAEPPDS LAPPSSQAFL GFGTAPVGSG LPPEEDLGAL LANSHGASPT PSIPLTATGA ADNGFLSHNF LTVAPGHSSH HSPGLQGQGV TLPGQPPLPE KKRASEGDRS LGSVSPSSSG FSSPHSGSTI SIPFPNVLPD FSKASEAASP LPDSPGDKLV IVKFVQDTSK FWYKADISRE QAIAMLKDKE PGSFIVRDSH SFRGAYGLAM KVATPPPSVL QLNKKAGDLA NELVRHFLIE CTPKGVRLKG CSNEPYFGSL TALVCQHSIT PLALPCKLLI PERDPLEEIA ESSPQTAANS AAELLKQGAA CNVWYLNSVE MESLTGHQAI QKALSITLVQ EPPPVSTVVH FKVSAQGITL TDNQRKLFFR RHYPVNSVIF CALDPQDRKW IKDGPSSKVF GFVARKQGSA TDNVCHLFAE HDPEQPASAI VNFVSKVMIG SPKKV //