ID TENS4_HUMAN Reviewed; 715 AA. AC Q8IZW8; A6NMJ7; Q71RB7; Q8WV64; Q96JV4; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 3. DT 24-JAN-2024, entry version 158. DE RecName: Full=Tensin-4; DE AltName: Full=C-terminal tensin-like protein; DE Flags: Precursor; GN Name=TNS4; Synonyms=CTEN; ORFNames=PP14434; 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], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP VARIANTS PRO-179 AND ASN-498. RX PubMed=12154022; RA Lo S.H., Lo T.B.; RT "Cten, a COOH-terminal tensin-like protein with prostate restricted RT expression, is down-regulated in prostate cancer."; RL Cancer Res. 62:4217-4221(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-498. RC TISSUE=Placenta; 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 GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [6] RP CLEAVAGE BY CASPASE-3, AND MUTAGENESIS OF ASP-506 AND ASP-570. RX PubMed=15806167; DOI=10.1038/sj.onc.1208571; RA Lo S.-S., Lo S.H., Lo S.H.; RT "Cleavage of cten by caspase-3 during apoptosis."; RL Oncogene 24:4311-4314(2005). RN [7] RP INTERACTION WITH DLC1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-474. RX PubMed=17190795; DOI=10.1083/jcb.200608015; RA Liao Y.C., Si L., deVere White R.W., Lo S.H.; RT "The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of RT cten regulates focal adhesion localization and growth suppression activity RT of DLC-1."; RL J. Cell Biol. 176:43-49(2007). RN [8] RP FUNCTION, INTERACTION WITH ITGB1, SUBCELLULAR LOCATION, INDUCTION, AND RP MUTAGENESIS OF ARG-650. 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82 AND SER-248, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [10] RP TISSUE SPECIFICITY, AND ROLE IN COLON CANCER CELLS. RX PubMed=19487278; DOI=10.1158/0008-5472.can-09-0117; RA Liao Y.C., Chen N.T., Shih Y.P., Dong Y., Lo S.H.; RT "Up-regulation of C-terminal tensin-like molecule promotes the RT tumorigenicity of colon cancer through beta-catenin."; RL Cancer Res. 69:4563-4566(2009). RN [11] RP TISSUE SPECIFICITY, AND ROLE IN COLORECTAL CANCER CELLS. RX PubMed=19214987; DOI=10.1002/path.2508; RA Albasri A., Seth R., Jackson D., Benhasouna A., Crook S., Nateri A.S., RA Chapman R., Ilyas M.; RT "C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility RT possibly through repression of E-cadherin in colorectal cancer."; RL J. Pathol. 218:57-65(2009). RN [12] 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 [13] RP FUNCTION, INTERACTION WITH CBL, AND MUTAGENESIS OF ARG-474 AND ARG-650. RX PubMed=23774213; DOI=10.1158/0008-5472.can-12-4441; RA Hong S.Y., Shih Y.P., Li T., Carraway K.L. III, Lo S.H.; RT "CTEN prolongs signaling by EGFR through reducing its ligand-induced RT degradation."; RL Cancer Res. 73:5266-5276(2013). RN [14] RP FUNCTION, INTERACTION WITH MET AND ITGB1, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF ARG-474. 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 [15] RP ERRATUM OF PUBMED:24814316. RX PubMed=28898622; DOI=10.1016/j.devcel.2014.05.018; RA Muharram G., Sahgal P., Korpela T., De Franceschi N., Kaukonen R., RA Clark K., Tulasne D., Carpen O., Ivaska J.; RL Dev. Cell 29:629-630(2014). RN [16] RP ROLE IN COLORECTAL CANCER CELLS. RX PubMed=28691764; DOI=10.1002/mc.22704; RA Thorpe H., Asiri A., Akhlaq M., Ilyas M.; RT "Cten promotes epithelial-mesenchymal transition through the post- RT transcriptional stabilization of Snail."; RL Mol. Carcinog. 56:2601-2609(2017). RN [17] RP ROLE IN CANCER CELLS. RX PubMed=30321615; DOI=10.1016/j.bbamcr.2018.10.008; RA Hong S.Y., Shih Y.P., Lo A., Lo S.H.; RT "Identification of subcellular targeting sequences of Cten reveals its role RT in cell proliferation."; RL Biochim. Biophys. Acta 1866:450-458(2019). RN [18] RP VARIANT [LARGE SCALE ANALYSIS] CYS-642. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Promotes EGF-induced cell migration by displacing tensin TNS3 CC from the cytoplasmic tail of integrin ITGB1 which results in CC dissociation of TNS3 from focal adhesions, disassembly of actin stress CC fibers and initiation of cell migration (PubMed:17643115). Suppresses CC ligand-induced degradation of EGFR by reducing EGFR ubiquitination in CC the presence of EGF (PubMed:23774213). Increases MET protein stability CC by inhibiting MET endocytosis and subsequent lysosomal degradation CC which leads to increased cell survival, proliferation and migration CC (PubMed:24814316). {ECO:0000269|PubMed:17643115, CC ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:24814316}. CC -!- SUBUNIT: Interacts (via SH2 domain) with Rho GTPase-activating protein CC DLC1 (via C-terminus); the interaction is independent of DLC1 tyrosine CC phosphorylation (PubMed:17190795). Interacts with integrin ITGB1; the CC interaction displaces tensin TNS3 from the ITGB1 cytoplasmic tail and CC promotes ITGB1 stability (PubMed:17643115, PubMed:24814316). Interacts CC (via SH2 domain) with E3 ubiquitin-protein ligase CBL (phosphorylated CC on 'Tyr-774'); the interaction is enhanced in the presence of EGF and CC reduces interaction of CBL with EGFR (PubMed:23774213). Interacts (via CC SH2 domain) with receptor tyrosine kinase MET (when phosphorylated); CC the interaction increases MET protein stability (PubMed:24814316). CC {ECO:0000269|PubMed:17190795, ECO:0000269|PubMed:17643115, CC ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:24814316}. CC -!- INTERACTION: CC Q8IZW8; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-7543499, EBI-11530605; CC Q8IZW8; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-7543499, EBI-3867333; CC Q8IZW8; P00533: EGFR; NbExp=2; IntAct=EBI-7543499, EBI-297353; CC Q8IZW8; O75031: HSF2BP; NbExp=3; IntAct=EBI-7543499, EBI-7116203; CC Q8IZW8; Q674X7-2: KAZN; NbExp=3; IntAct=EBI-7543499, EBI-12024294; CC Q8IZW8; Q9NWS0: PIH1D1; NbExp=3; IntAct=EBI-7543499, EBI-357318; CC Q8IZW8; Q08209-2: PPP3CA; NbExp=5; IntAct=EBI-7543499, EBI-11959013; CC Q8IZW8; Q15276: RABEP1; NbExp=3; IntAct=EBI-7543499, EBI-447043; CC Q8IZW8; P19474: TRIM21; NbExp=3; IntAct=EBI-7543499, EBI-81290; CC Q8IZW8; P14373: TRIM27; NbExp=3; IntAct=EBI-7543499, EBI-719493; CC Q8IZW8; P42681: TXK; NbExp=3; IntAct=EBI-7543499, EBI-7877438; CC Q8IZW8; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-7543499, EBI-527853; CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion CC {ECO:0000269|PubMed:12154022, ECO:0000269|PubMed:17190795, CC ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:24814316}. Cytoplasm, CC cytoskeleton {ECO:0000269|PubMed:12154022}. CC -!- TISSUE SPECIFICITY: Expressed at low levels in colon (at protein level) CC (PubMed:19214987, PubMed:19487278). Expressed in prostate and placenta CC (PubMed:12154022). {ECO:0000269|PubMed:12154022, CC ECO:0000269|PubMed:19214987, ECO:0000269|PubMed:19487278}. CC -!- INDUCTION: By EGF. {ECO:0000269|PubMed:17643115}. CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis. CC {ECO:0000269|PubMed:15806167}. CC -!- MISCELLANEOUS: Expression is up-regulated in tumors from a variety of CC tissues including lung, breast, colon, pancreas, stomach and ovary but CC is down-regulated in prostate cancer (PubMed:23774213, PubMed:12154022, CC PubMed:19487278, PubMed:24814316). In colorectal cancer cells, induces CC epithelial-mesenchymal transition (EMT) accompanied by down-regulation CC of CDH1/E-cadherin protein levels and increased cell migration CC (PubMed:19214987). Contributes to cell motility in colorectal cancer CC cells by promoting EMT through its role in the post-transcriptional CC stabilization of SNAIL in an SH2-dependent manner which leads to CC increased cell migration (PubMed:28691764). Detected in the nucleus in CC colon cancer cells where it interacts with CTNNB1/beta-catenin and CC modulates colony formation, anchorage-independent growth and cell CC invasiveness (PubMed:19487278, PubMed:30321615). Also detected in the CC nucleus in other cancer cells such as lung and cervical cancer cells CC where it promotes cell proliferation (PubMed:30321615). CC {ECO:0000269|PubMed:12154022, ECO:0000269|PubMed:19214987, CC ECO:0000269|PubMed:19487278, ECO:0000269|PubMed:23774213, CC ECO:0000269|PubMed:24814316, ECO:0000269|PubMed:28691764, CC ECO:0000269|PubMed:30321615}. CC -!- SIMILARITY: Belongs to the PTEN phosphatase protein family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ15257.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40190/TNS4"; 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; AF417488; AAN32666.1; -; mRNA. DR EMBL; AF370421; AAQ15257.1; ALT_FRAME; mRNA. DR EMBL; AK027856; BAB55413.1; -; mRNA. DR EMBL; AC018629; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC018706; AAH18706.1; -; mRNA. DR CCDS; CCDS11368.1; -. DR RefSeq; NP_116254.4; NM_032865.5. DR AlphaFoldDB; Q8IZW8; -. DR SMR; Q8IZW8; -. DR BioGRID; 124383; 44. DR IntAct; Q8IZW8; 23. DR MINT; Q8IZW8; -. DR STRING; 9606.ENSP00000254051; -. DR GlyGen; Q8IZW8; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q8IZW8; -. DR PhosphoSitePlus; Q8IZW8; -. DR BioMuta; TNS4; -. DR DMDM; 229463025; -. DR EPD; Q8IZW8; -. DR jPOST; Q8IZW8; -. DR MassIVE; Q8IZW8; -. DR MaxQB; Q8IZW8; -. DR PaxDb; 9606-ENSP00000254051; -. DR PeptideAtlas; Q8IZW8; -. DR ProteomicsDB; 71438; -. DR Pumba; Q8IZW8; -. DR Antibodypedia; 16494; 280 antibodies from 27 providers. DR DNASU; 84951; -. DR Ensembl; ENST00000254051.11; ENSP00000254051.6; ENSG00000131746.13. DR GeneID; 84951; -. DR KEGG; hsa:84951; -. DR MANE-Select; ENST00000254051.11; ENSP00000254051.6; NM_032865.6; NP_116254.4. DR UCSC; uc010cxb.4; human. DR AGR; HGNC:24352; -. DR CTD; 84951; -. DR DisGeNET; 84951; -. DR GeneCards; TNS4; -. DR HGNC; HGNC:24352; TNS4. DR HPA; ENSG00000131746; Tissue enhanced (skin, vagina). DR MIM; 608385; gene. DR neXtProt; NX_Q8IZW8; -. DR OpenTargets; ENSG00000131746; -. DR PharmGKB; PA142670717; -. DR VEuPathDB; HostDB:ENSG00000131746; -. DR eggNOG; KOG1930; Eukaryota. DR GeneTree; ENSGT00940000160142; -. DR HOGENOM; CLU_398985_0_0_1; -. DR InParanoid; Q8IZW8; -. DR OMA; SQPSMKF; -. DR OrthoDB; 3439226at2759; -. DR PhylomeDB; Q8IZW8; -. DR TreeFam; TF315996; -. DR PathwayCommons; Q8IZW8; -. DR Reactome; R-HSA-8875513; MET interacts with TNS proteins. DR SignaLink; Q8IZW8; -. DR BioGRID-ORCS; 84951; 11 hits in 1150 CRISPR screens. DR ChiTaRS; TNS4; human. DR GeneWiki; TNS4; -. DR GenomeRNAi; 84951; -. DR Pharos; Q8IZW8; Tbio. DR PRO; PR:Q8IZW8; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q8IZW8; Protein. DR Bgee; ENSG00000131746; Expressed in skin of abdomen and 146 other cell types or tissues. DR ExpressionAtlas; Q8IZW8; baseline and differential. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW. DR GO; GO:0008104; P:protein localization; IDA:UniProtKB. DR CDD; cd01213; PTB_tensin; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR013625; PTB. DR InterPro; IPR006020; PTB/PI_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR033929; Tensin_PTB. DR PANTHER; PTHR45734; TENSIN; 1. DR PANTHER; PTHR45734:SF6; TENSIN-4; 1. DR Pfam; PF08416; PTB; 1. DR Pfam; PF00017; SH2; 1. DR SMART; SM00462; PTB; 1. DR SMART; SM00252; SH2; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; Q8IZW8; HS. PE 1: Evidence at protein level; KW Actin-binding; Cell junction; Cytoplasm; Cytoskeleton; Phosphoprotein; KW Reference proteome; SH2 domain; Signal. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..715 FT /note="Tensin-4" FT /id="PRO_0000248213" FT DOMAIN 449..556 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 582..705 FT /note="PTB" FT /evidence="ECO:0000255" FT REGION 159..183 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 195..251 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 291..364 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 376..435 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 161..176 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 291..346 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 389..424 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 570..571 FT /note="Cleavage; by caspase-3" FT /evidence="ECO:0000269|PubMed:15806167" FT MOD_RES 82 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 248 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT VARIANT 179 FT /note="L -> P (in dbSNP:rs3764424)" FT /evidence="ECO:0000269|PubMed:12154022" FT /id="VAR_027264" FT VARIANT 327 FT /note="T -> K (in dbSNP:rs33923045)" FT /id="VAR_055292" FT VARIANT 498 FT /note="S -> N (in dbSNP:rs2290207)" FT /evidence="ECO:0000269|PubMed:12154022, FT ECO:0000269|PubMed:14702039" FT /id="VAR_027265" FT VARIANT 642 FT /note="R -> C (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs148022611)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036515" FT MUTAGEN 100..118 FT /note="Missing: Abolishes focal adhesion localization; when FT associated with A-474." FT /evidence="ECO:0000269|PubMed:30321615" FT MUTAGEN 474 FT /note="R->A: Abolishes interaction with DLC1. Abolishes FT interaction with CBL following EGF stimulation. Loss of FT ability to reduce ubiquitination of activated EGFR. FT Significant decrease in interaction with MET, faster MET FT trafficking to the lysosome and significant increase in MET FT turnover. Significant inhibition of basal and FT HGF-stimulated cell migration. No effect on focal adhesion FT localization. Abolishes focal adhesion localization; when FT associated with 100-F--L-118 DEL." FT /evidence="ECO:0000269|PubMed:17190795, FT ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:24814316, FT ECO:0000269|PubMed:30321615" FT MUTAGEN 506 FT /note="D->A: No effect on cleavage by caspase-3." FT /evidence="ECO:0000269|PubMed:15806167" FT MUTAGEN 570 FT /note="D->A: Abolishes cleavage by caspase-3." FT /evidence="ECO:0000269|PubMed:15806167" FT MUTAGEN 650 FT /note="R->A: Abolishes interaction with ITGB1. Does not FT affect interaction with CBL following EGF stimulation." FT /evidence="ECO:0000269|PubMed:17643115, FT ECO:0000269|PubMed:23774213" FT CONFLICT 163 FT /note="G -> W (in Ref. 1; AAN32666)" FT /evidence="ECO:0000305" FT CONFLICT 360 FT /note="S -> I (in Ref. 1; AAN32666 and 3; BAB55413)" FT /evidence="ECO:0000305" FT CONFLICT 623 FT /note="K -> E (in Ref. 1; AAN32666 and 3; BAB55413)" FT /evidence="ECO:0000305" SQ SEQUENCE 715 AA; 76764 MW; E6AD7CB6B6DDA5D2 CRC64; MSQVMSSPLL AGGHAVSLAP CDEPRRTLHP APSPSLPPQC SYYTTEGWGA QALMAPVPCM GPPGRLQQAP QVEAKATCFL PSPGEKALGT PEDLDSYIDF SLESLNQMIL ELDPTFQLLP PGTGGSQAEL AQSTMSMRKK EESEALDIKY IEVTSARSRC HDGPQHCSSP SVTPPFGSLR SGGLLLSRDV PRETRSSSES LIFSGNQGRG HQRPLPPSEG LSPRPPNSPS ISIPCMGSKA SSPHGLGSPL VASPRLEKRL GGLAPQRGSR ISVLSASPVS DVSYMFGSSQ SLLHSSNSSH QSSSRSLESP ANSSSSLHSL GSVSLCTRPS DFQAPRNPTL TMGQPRTPHS PPLAKEHASS CPPSITNSMV DIPIVLINGC PEPGSSPPQR TPGHQNSVQP GAASPSNPCP ATRSNSQTLS DAPFTTCPEG PARDMQPTMK FVMDTSKYWF KPNITREQAI ELLRKEEPGA FVIRDSSSYR GSFGLALKVQ EVPASAQSRP GEDSNDLIRH FLIESSAKGV HLKGADEEPY FGSLSAFVCQ HSIMALALPC KLTIPQRELG GADGASDSTD SPASCQKKSA GCHTLYLSSV SVETLTGALA VQKAISTTFE RDILPTPTVV HFKVTEQGIT LTDVQRKVFF RRHYPLTTLR FCGMDPEQRK WQKYCKPSWI FGFVAKSQTE PQENVCHLFA EYDMVQPASQ VIGLVTALLQ DAERM //