ID ZO1_HUMAN Reviewed; 1748 AA. AC Q07157; B4E3K1; Q2NKP3; Q4ZGJ6; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2006, sequence version 3. DT 27-MAR-2024, entry version 241. DE RecName: Full=Tight junction protein ZO-1; DE AltName: Full=Tight junction protein 1; DE AltName: Full=Zona occludens protein 1; DE AltName: Full=Zonula occludens protein 1; GN Name=TJP1; Synonyms=ZO1; 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], AND VARIANT VAL-790. RC TISSUE=Liver; RX PubMed=8395056; DOI=10.1073/pnas.90.16.7834; RA Willott E., Balda M.S., Fanning A.S., Jameson B., van Itallie C., RA Anderson J.M.; RT "The tight junction protein ZO-1 is homologous to the Drosophila discs- RT large tumor suppressor protein of septate junctions."; RL Proc. Natl. Acad. Sci. U.S.A. 90:7834-7838(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), AND VARIANT VAL-790. RC TISSUE=Uterus; 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 [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-471; VAL-790; LEU-930; RP ARG-1110; ALA-1347 AND SER-1605. RG NIEHS SNPs program; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). 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 SUBCELLULAR LOCATION, INTERACTION WITH OCLN, AND FUNCTION. RX PubMed=7798316; DOI=10.1083/jcb.127.6.1617; RA Furuse M., Itoh M., Hirase T., Nagafuchi A., Yonemura S., Tsukita S., RA Tsukita S.; RT "Direct association of occludin with ZO-1 and its possible involvement in RT the localization of occludin at tight junctions."; RL J. Cell Biol. 127:1617-1626(1994). RN [7] RP PHOSPHORYLATION. RX PubMed=7542259; DOI=10.1242/jcs.108.4.1735; RA Van Itallie C.M., Balda M.S., Anderson J.M.; RT "Epidermal growth factor induces tyrosine phosphorylation and RT reorganization of the tight junction protein ZO-1 in A431 cells."; RL J. Cell Sci. 108:1735-1742(1995). RN [8] RP FUNCTION, DOMAIN, AND INTERACTION WITH ACTIN; TJP2 AND OCLN. RX PubMed=9792688; DOI=10.1074/jbc.273.45.29745; RA Fanning A.S., Jameson B.J., Jesaitis L.A., Anderson J.M.; RT "The tight junction protein ZO-1 establishes a link between the RT transmembrane protein occludin and the actin cytoskeleton."; RL J. Biol. Chem. 273:29745-29753(1998). RN [9] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CXADR. RX PubMed=11734628; DOI=10.1073/pnas.261452898; RA Cohen C.J., Shieh J.T.C., Pickles R.J., Okegawa T., Hsieh J.-T., RA Bergelson J.M.; RT "The coxsackievirus and adenovirus receptor is a transmembrane component of RT the tight junction."; RL Proc. Natl. Acad. Sci. U.S.A. 98:15191-15196(2001). RN [10] RP DOMAIN, AND INTERACTION WITH ACTIN. RX PubMed=12354695; DOI=10.1096/fj.02-0121fje; RA Fanning A.S., Ma T.Y., Anderson J.M.; RT "Isolation and functional characterization of the actin binding region in RT the tight junction protein ZO-1."; RL FASEB J. 16:1835-1837(2002). RN [11] RP INTERACTION WITH CGN. RX PubMed=12023291; DOI=10.1074/jbc.m203717200; RA D'Atri F., Nadalutti F., Citi S.; RT "Evidence for a functional interaction between cingulin and ZO-1 in RT cultured cells."; RL J. Biol. Chem. 277:27757-27764(2002). RN [12] RP INTERACTION WITH GJD3. RX PubMed=12154091; DOI=10.1074/jbc.m205348200; RA Nielsen P.A., Beahm D.L., Giepmans B.N., Baruch A., Hall J.E., Kumar N.M.; RT "Molecular cloning, functional expression, and tissue distribution of a RT novel human gap junction-forming protein, connexin-31.9. Interaction with RT zona occludens protein-1."; RL J. Biol. Chem. 277:38272-38283(2002). RN [13] RP INTERACTION WITH GJA12. RX PubMed=15183511; DOI=10.1016/j.neuroscience.2004.03.063; RA Li X., Ionescu A.V., Lynn B.D., Lu S., Kamasawa N., Morita M., RA Davidson K.G.V., Yasumura T., Rash J.E., Nagy J.I.; RT "Connexin47, connexin29 and connexin32 co-expression in oligodendrocytes RT and Cx47 association with zonula occludens-1 (ZO-1) in mouse brain."; RL Neuroscience 126:611-630(2004). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337 AND SER-1366, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [15] RP INTERACTION WITH DNMBP. RX PubMed=17015620; DOI=10.1083/jcb.200605012; RA Otani T., Ichii T., Aono S., Takeichi M.; RT "Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial RT cells."; RL J. Cell Biol. 175:135-146(2006). RN [16] RP INTERACTION WITH TJP2. RX PubMed=17897942; DOI=10.1074/jbc.m703826200; RA Wu J., Yang Y., Zhang J., Ji P., Du W., Jiang P., Xie D., Huang H., Wu M., RA Zhang G., Wu J., Shi Y.; RT "Domain-swapped dimerization of the second PDZ domain of ZO2 may provide a RT structural basis for the polymerization of claudins."; RL J. Biol. Chem. 282:35988-35999(2007). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125 AND SER-912, 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-277; SER-329; RP SER-617; SER-912; SER-968 AND SER-1545, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-912 (ISOFORM SHORT), 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 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 [20] RP INTERACTION WITH UBN1. RX PubMed=18823282; DOI=10.1042/bc20080072; RA Aho S., Lupo J., Coly P.-A., Sabine A., Castellazzi M., Morand P., RA Sergeant A., Manet E., Boyer V., Gruffat H.; RT "Characterization of the ubinuclein protein as a new member of the nuclear RT and adhesion complex components (NACos)."; RL Biol. Cell 101:319-334(2009). RN [21] RP PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPRJ. RX PubMed=19332538; DOI=10.1074/jbc.m901901200; RA Sallee J.L., Burridge K.; RT "Density-enhanced phosphatase 1 regulates phosphorylation of tight junction RT proteins and enhances barrier function of epithelial cells."; RL J. Biol. Chem. 284:14997-15006(2009). RN [22] RP INTERACTION WITH MYZAP. RX PubMed=20093627; DOI=10.1161/circresaha.109.213256; RA Seeger T.S., Frank D., Rohr C., Will R., Just S., Grund C., Lyon R., RA Luedde M., Koegl M., Sheikh F., Rottbauer W., Franke W.W., Katus H.A., RA Olson E.N., Frey N.; RT "Myozap, a novel intercalated disc protein, activates serum response RT factor-dependent signaling and is required to maintain cardiac function in RT vivo."; RL Circ. Res. 106:880-890(2010). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-329; SER-337; SER-353; RP SER-617; SER-968; SER-1366 AND SER-1617, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-912 (ISOFORM SHORT), AND IDENTIFICATION BY MASS RP 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 [24] 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 [25] RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND ACTIN-BINDING. RX PubMed=20930113; DOI=10.1096/fj.10-155598; RA Kremerskothen J., Stoelting M., Wiesner C., Korb-Pap A., van Vliet V., RA Linder S., Huber T.B., Rottiers P., Reuzeau E., Genot E., Pavenstaedt H.; RT "Zona occludens proteins modulate podosome formation and function."; RL FASEB J. 25:505-514(2011). RN [26] RP INTERACTION WITH ANKRD2. RX PubMed=22016770; DOI=10.1371/journal.pone.0025519; RA Belgrano A., Rakicevic L., Mittempergher L., Campanaro S., Martinelli V.C., RA Mouly V., Valle G., Kojic S., Faulkner G.; RT "Multi-tasking role of the mechanosensing protein Ankrd2 in the signaling RT network of striated muscle."; RL PLoS ONE 6:E25519-E25519(2011). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-175; SER-178; RP SER-179; THR-185; SER-297; SER-300; SER-329; SER-334; SER-337; SER-617; RP SER-622 AND SER-1366, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-912 RP (ISOFORM SHORT), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-212; SER-329; RP THR-354; SER-617; SER-837; SER-912; SER-968; SER-1111; SER-1413 AND RP SER-1617, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-175; SER-179; RP THR-267; SER-275; SER-277; SER-280; SER-284; SER-290; SER-294; SER-297; RP SER-300; SER-617; THR-809; SER-821; THR-854; THR-861; THR-868; SER-912; RP SER-968 AND SER-1617, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-912 RP (ISOFORM SHORT), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [30] RP SUBCELLULAR LOCATION. RX PubMed=28169360; DOI=10.1038/srep42125; RA Liu J., Li J., Li P., Wang Y., Liang Z., Jiang Y., Li J., Feng C., Wang R., RA Chen H., Zhou C., Zhang J., Yang J., Liu P.; RT "Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo RT signaling pathway."; RL Sci. Rep. 7:42125-42125(2017). RN [31] RP INTERACTION WITH SPEF1, AND SUBCELLULAR LOCATION. RX PubMed=31473225; DOI=10.1053/j.gastro.2019.08.031; RA Tapia R., Perez-Yepez E.A., Carlino M.J., Karandikar U.C., Kralicek S.E., RA Estes M.K., Hecht G.A.; RT "Sperm Flagellar 1 Binds Actin in Intestinal Epithelial Cells and RT Contributes to Formation of Filopodia and Lamellipodia."; RL Gastroenterology 157:1544-1555(2019). RN [32] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 18-110, AND SUBUNIT. RX PubMed=16737969; DOI=10.1074/jbc.m602901200; RA Appleton B.A., Zhang Y., Wu P., Yin J.P., Hunziker W., Skelton N.J., RA Sidhu S.S., Wiesmann C.; RT "Comparative structural analysis of the erbin PDZ domain and the first PDZ RT domain of ZO-1. Insights into determinants of PDZ domain specificity."; RL J. Biol. Chem. 281:22312-22320(2006). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 185-264, AND SUBUNIT. RX PubMed=17928286; DOI=10.1074/jbc.m707255200; RA Fanning A.S., Lye M.F., Anderson J.M., Lavie A.; RT "Domain swapping within PDZ2 is responsible for dimerization of ZO RT proteins."; RL J. Biol. Chem. 282:37710-37716(2007). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 182-273 IN COMPLEX WITH GJA1 RP PEPTIDE, SUBUNIT, MUTAGENESIS OF ARG-201 AND LYS-209, SUBCELLULAR LOCATION, RP AND INTERACTION WITH GJA1. RX PubMed=18636092; DOI=10.1038/emboj.2008.138; RA Chen J., Pan L., Wei Z., Zhao Y., Zhang M.; RT "Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory RT connexin43-binding sites."; RL EMBO J. 27:2113-2123(2008). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 516-803, AND INTERACTION WITH RP CALM. RX PubMed=20200156; DOI=10.1074/jbc.m109.093674; RA Lye M.F., Fanning A.S., Su Y., Anderson J.M., Lavie A.; RT "Insights into regulated ligand binding sites from the structure of ZO-1 RT Src homology 3-guanylate kinase module."; RL J. Biol. Chem. 285:13907-13917(2010). RN [36] RP STRUCTURE BY NMR OF 1631-1748 OF MUTANT 1699-MET-CYS-1700 IN COMPLEX WITH RP MYZAP, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 1699-MET-CYS-1700 AND RP PHE-1748, AND INTERACTION WITH MYZAP AND CDC42BPB. RX PubMed=21240187; DOI=10.1038/emboj.2010.353; RA Huo L., Wen W., Wang R., Kam C., Xia J., Feng W., Zhang M.; RT "Cdc42-dependent formation of the ZO-1/MRCKbeta complex at the leading edge RT controls cell migration."; RL EMBO J. 30:665-678(2011). RN [37] RP STRUCTURE BY NMR OF 185-264. RX PubMed=21387411; DOI=10.1002/prot.22955; RA Ji P., Yang G., Zhang J., Wu J., Chen Z., Gong Q., Wu J., Shi Y.; RT "Solution structure of the second PDZ domain of Zonula Occludens 1."; RL Proteins 79:1342-1346(2011). CC -!- FUNCTION: TJP1, TJP2, and TJP3 are closely related scaffolding proteins CC that link tight junction (TJ) transmembrane proteins such as claudins, CC junctional adhesion molecules, and occludin to the actin cytoskeleton CC (PubMed:7798316, PubMed:9792688). The tight junction acts to limit CC movement of substances through the paracellular space and as a boundary CC between the compositionally distinct apical and basolateral plasma CC membrane domains of epithelial and endothelial cells. Necessary for CC lumenogenesis, and particularly efficient epithelial polarization and CC barrier formation (By similarity). Plays a role in the regulation of CC cell migration by targeting CDC42BPB to the leading edge of migrating CC cells (PubMed:21240187). Plays an important role in podosome formation CC and associated function, thus regulating cell adhesion and matrix CC remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the CC junctional retention and stability of the transcription factor DBPA, CC but is not involved in its shuttling to the nucleus (By similarity). CC {ECO:0000250|UniProtKB:O97758, ECO:0000269|PubMed:20930113, CC ECO:0000269|PubMed:21240187}. CC -!- SUBUNIT: Homodimer (PubMed:16737969, PubMed:17928286). Forms CC heterodimers TJP3 (By similarity). Forms a heterodimer (via PDZ2 CC domain) with TJP2/ZO2 (via PDZ2 domain) (PubMed:17897942, CC PubMed:9792688). Interacts with OCLN, CALM, claudins, CGN/cingulin, CC CXADR, GJA12, GJD3 and UBN1 (PubMed:7798316, PubMed:11734628, CC PubMed:12023291, PubMed:12154091, PubMed:15183511, PubMed:18823282, CC PubMed:20200156). Interacts (via ZU5 domain) with CDC42BPB and MYZAP CC (PubMed:20093627, PubMed:21240187). Interacts (via PDZ domain) with CC GJA1 (PubMed:18636092). Interacts (via PDZ domains) with ANKRD2 CC (PubMed:22016770). Interacts with BVES (via the C-terminus cytoplasmic CC tail) (By similarity). Interacts with HSPA4 and KIRREL1 (By CC similarity). Interacts with DLL1 (By similarity). Interacts with USP53 CC (via the C-terminal region) (By similarity). Interacts (via ABR region) CC with F-actin (PubMed:9792688, PubMed:12354695, PubMed:20930113). CC Interacts with DNMBP (via C-terminal domain); required for the apical CC cell-cell junction localization of DNMBP (PubMed:17015620). Interacts CC with SPEF1 (PubMed:31473225). Interacts (via N-terminus) with CTNNA1 CC (By similarity). Interacts with CLDN18 (By similarity). CC {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, CC ECO:0000269|PubMed:11734628, ECO:0000269|PubMed:12023291, CC ECO:0000269|PubMed:12154091, ECO:0000269|PubMed:12354695, CC ECO:0000269|PubMed:15183511, ECO:0000269|PubMed:16737969, CC ECO:0000269|PubMed:17015620, ECO:0000269|PubMed:17897942, CC ECO:0000269|PubMed:17928286, ECO:0000269|PubMed:18636092, CC ECO:0000269|PubMed:18823282, ECO:0000269|PubMed:20093627, CC ECO:0000269|PubMed:20200156, ECO:0000269|PubMed:20930113, CC ECO:0000269|PubMed:21240187, ECO:0000269|PubMed:22016770, CC ECO:0000269|PubMed:31473225, ECO:0000269|PubMed:9792688}. CC -!- INTERACTION: CC Q07157; O43707: ACTN4; NbExp=4; IntAct=EBI-79553, EBI-351526; CC Q07157; P17302: GJA1; NbExp=3; IntAct=EBI-79553, EBI-1103439; CC Q07157; Q8N144: GJD3; NbExp=2; IntAct=EBI-79553, EBI-2629520; CC Q07157; Q96J84: KIRREL1; NbExp=7; IntAct=EBI-79553, EBI-3988456; CC Q07157; Q9EPK5: Wwtr1; Xeno; NbExp=4; IntAct=EBI-79553, EBI-1211920; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7798316}; CC Peripheral membrane protein {ECO:0000269|PubMed:7798316}; Cytoplasmic CC side {ECO:0000269|PubMed:7798316}. Cell junction, tight junction CC {ECO:0000269|PubMed:7798316}. Cell junction CC {ECO:0000269|PubMed:28169360}. Cell junction, gap junction. Cell CC projection, podosome {ECO:0000269|PubMed:20930113}. Note=Moves from the CC cytoplasm to the cell membrane concurrently with cell-cell contact CC (PubMed:7798316). At podosomal sites, is predominantly localized in the CC ring structure surrounding the actin core (PubMed:20930113). CC Colocalizes with SPEF1 at sites of cell-cell contact in intestinal CC epithelial cells (PubMed:31473225). {ECO:0000269|PubMed:20930113, CC ECO:0000269|PubMed:31473225, ECO:0000269|PubMed:7798316}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q07157-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q07157-2; Sequence=VSP_003148; CC -!- TISSUE SPECIFICITY: The alpha-containing isoform is found in most CC epithelial cell junctions. The short isoform is found both in CC endothelial cells and the highly specialized epithelial junctions of CC renal glomeruli and Sertoli cells of the seminiferous tubules. CC -!- DOMAIN: The 244-aa domain between residues 633 and 876 is the primary CC occludin (OCLN)-binding site and is required for stable association CC with the tight junction (PubMed:9792688). {ECO:0000269|PubMed:9792688}. CC -!- DOMAIN: The C-terminal region (residues 1151-1372) is an actin-binding CC region (ABR) that interacts directly with F-actin and plays an CC important role in the localization of TJP1 at junctions CC (PubMed:9792688, PubMed:12354695, PubMed:20930113). The ABR is also CC required for the localization to puncta at the free edge of cells CC before initiation of cell-cell contact (PubMed:12354695). The ABR is CC also necessary for TJP1 recruitment to podosomes (PubMed:20930113). CC {ECO:0000269|PubMed:12354695, ECO:0000269|PubMed:20930113, CC ECO:0000269|PubMed:9792688}. CC -!- DOMAIN: The second PDZ domain (PDZ2) mediates homodimerization and CC heterodimerization with TJP2 and TJP3 (PubMed:9792688, CC PubMed:17928286). {ECO:0000269|PubMed:17928286, CC ECO:0000269|PubMed:9792688}. CC -!- PTM: Phosphorylated at tyrosine redidues in response to epidermal CC growth factor (EGF) (PubMed:19332538, PubMed:7542259). This response is CC dependent on an intact actin microfilament system (PubMed:7542259). CC Dephosphorylated by PTPRJ (PubMed:19332538). CC {ECO:0000269|PubMed:19332538, ECO:0000269|PubMed:7542259}. CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA02891.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/tjp1/"; 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; L14837; AAA02891.1; ALT_INIT; mRNA. DR EMBL; AK304758; BAG65513.1; -; mRNA. DR EMBL; DQ015919; AAY22179.1; -; Genomic_DNA. DR EMBL; AC022613; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC111712; AAI11713.1; -; mRNA. DR CCDS; CCDS42007.1; -. [Q07157-1] DR CCDS; CCDS45199.1; -. [Q07157-2] DR PIR; A47747; A47747. DR RefSeq; NP_003248.3; NM_003257.4. [Q07157-1] DR RefSeq; NP_783297.2; NM_175610.3. [Q07157-2] DR PDB; 2H2B; X-ray; 1.60 A; A=18-110. DR PDB; 2H2C; X-ray; 2.00 A; A=18-110. DR PDB; 2H3M; X-ray; 2.90 A; A=18-110. DR PDB; 2JWE; NMR; -; A/B=185-264. DR PDB; 2KXR; NMR; -; A=1631-1748. DR PDB; 2KXS; NMR; -; A=1631-1748. DR PDB; 2RCZ; X-ray; 1.70 A; A/B=186-264. DR PDB; 3CYY; X-ray; 2.40 A; A/B=182-273. DR PDB; 3LH5; X-ray; 2.60 A; A=516-803. DR PDB; 3SHU; X-ray; 2.75 A; A/B=421-512. DR PDB; 3SHW; X-ray; 2.90 A; A=421-888. DR PDB; 3TSV; X-ray; 1.99 A; A=417-516. DR PDB; 3TSW; X-ray; 2.85 A; A/B/C/D=417-803. DR PDB; 3TSZ; X-ray; 2.50 A; A=417-803. DR PDB; 4OEO; X-ray; 1.90 A; A/B/C=18-110. DR PDB; 4OEP; X-ray; 2.35 A; A/B=18-110. DR PDB; 4Q2Q; X-ray; 1.45 A; A=419-504. DR PDB; 4YYX; X-ray; 1.79 A; A/B=18-110. DR PDBsum; 2H2B; -. DR PDBsum; 2H2C; -. DR PDBsum; 2H3M; -. DR PDBsum; 2JWE; -. DR PDBsum; 2KXR; -. DR PDBsum; 2KXS; -. DR PDBsum; 2RCZ; -. DR PDBsum; 3CYY; -. DR PDBsum; 3LH5; -. DR PDBsum; 3SHU; -. DR PDBsum; 3SHW; -. DR PDBsum; 3TSV; -. DR PDBsum; 3TSW; -. DR PDBsum; 3TSZ; -. DR PDBsum; 4OEO; -. DR PDBsum; 4OEP; -. DR PDBsum; 4Q2Q; -. DR PDBsum; 4YYX; -. DR AlphaFoldDB; Q07157; -. DR BMRB; Q07157; -. DR SMR; Q07157; -. DR BioGRID; 112937; 317. DR CORUM; Q07157; -. DR ELM; Q07157; -. DR IntAct; Q07157; 98. DR MINT; Q07157; -. DR STRING; 9606.ENSP00000348416; -. DR ChEMBL; CHEMBL4296026; -. DR TCDB; 8.A.24.1.9; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family. DR GlyCosmos; Q07157; 4 sites, 2 glycans. DR GlyGen; Q07157; 9 sites, 2 O-linked glycans (9 sites). DR iPTMnet; Q07157; -. DR PhosphoSitePlus; Q07157; -. DR BioMuta; TJP1; -. DR DMDM; 85700443; -. DR EPD; Q07157; -. DR jPOST; Q07157; -. DR MassIVE; Q07157; -. DR MaxQB; Q07157; -. DR PaxDb; 9606-ENSP00000281537; -. DR PeptideAtlas; Q07157; -. DR ProteomicsDB; 58506; -. [Q07157-1] DR ProteomicsDB; 58507; -. [Q07157-2] DR Pumba; Q07157; -. DR Antibodypedia; 783; 551 antibodies from 41 providers. DR DNASU; 7082; -. DR Ensembl; ENST00000346128.10; ENSP00000281537.7; ENSG00000104067.17. [Q07157-1] DR Ensembl; ENST00000545208.6; ENSP00000441202.2; ENSG00000104067.17. [Q07157-2] DR Ensembl; ENST00000621049.4; ENSP00000484535.2; ENSG00000277401.4. DR GeneID; 7082; -. DR KEGG; hsa:7082; -. DR UCSC; uc001zcr.4; human. [Q07157-1] DR AGR; HGNC:11827; -. DR CTD; 7082; -. DR DisGeNET; 7082; -. DR GeneCards; TJP1; -. DR HGNC; HGNC:11827; TJP1. DR HPA; ENSG00000104067; Low tissue specificity. DR MIM; 601009; gene. DR neXtProt; NX_Q07157; -. DR OpenTargets; ENSG00000104067; -. DR PharmGKB; PA36532; -. DR VEuPathDB; HostDB:ENSG00000104067; -. DR eggNOG; KOG3580; Eukaryota. DR GeneTree; ENSGT00940000155164; -. DR InParanoid; Q07157; -. DR OrthoDB; 2904077at2759; -. DR PhylomeDB; Q07157; -. DR TreeFam; TF315957; -. DR PathwayCommons; Q07157; -. DR Reactome; R-HSA-191650; Regulation of gap junction activity. DR Reactome; R-HSA-2028269; Signaling by Hippo. DR Reactome; R-HSA-351906; Apoptotic cleavage of cell adhesion proteins. DR Reactome; R-HSA-8935964; RUNX1 regulates expression of components of tight junctions. DR Reactome; R-HSA-9705677; SARS-CoV-2 targets PDZ proteins in cell-cell junction. DR SignaLink; Q07157; -. DR SIGNOR; Q07157; -. DR BioGRID-ORCS; 7082; 19 hits in 1164 CRISPR screens. DR ChiTaRS; TJP1; human. DR EvolutionaryTrace; Q07157; -. DR GeneWiki; Tight_junction_protein_1; -. DR GenomeRNAi; 7082; -. DR Pharos; Q07157; Tbio. DR PRO; PR:Q07157; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q07157; Protein. DR Bgee; ENSG00000104067; Expressed in corpus callosum and 96 other cell types or tissues. DR ExpressionAtlas; Q07157; baseline and differential. DR GO; GO:0005912; C:adherens junction; TAS:ProtInc. DR GO; GO:0043296; C:apical junction complex; IDA:MGI. DR GO; GO:0045177; C:apical part of cell; IDA:MGI. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI. DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005921; C:gap junction; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL. DR GO; GO:0002102; C:podosome; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IDA:ARUK-UCL. DR GO; GO:0070160; C:tight junction; IDA:ARUK-UCL. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central. DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:ARUK-UCL. DR GO; GO:0031032; P:actomyosin structure organization; IMP:ARUK-UCL. DR GO; GO:0034334; P:adherens junction maintenance; IMP:ARUK-UCL. DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central. DR GO; GO:0007043; P:cell-cell junction assembly; TAS:ProtInc. DR GO; GO:0045216; P:cell-cell junction organization; IMP:ARUK-UCL. DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; IMP:UniProtKB. DR GO; GO:0035633; P:maintenance of blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ARUK-UCL. DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISS:ARUK-UCL. DR GO; GO:1905605; P:positive regulation of blood-brain barrier permeability; IMP:ARUK-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:ARUK-UCL. DR GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; IMP:ARUK-UCL. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IMP:ARUK-UCL. DR GO; GO:0071896; P:protein localization to adherens junction; IMP:ARUK-UCL. DR GO; GO:1902396; P:protein localization to bicellular tight junction; IMP:ARUK-UCL. DR GO; GO:0150105; P:protein localization to cell-cell junction; IMP:ARUK-UCL. DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IMP:ARUK-UCL. DR GO; GO:1901888; P:regulation of cell junction assembly; IMP:ARUK-UCL. DR GO; GO:0051493; P:regulation of cytoskeleton organization; IMP:ARUK-UCL. DR CDD; cd00992; PDZ_signaling; 3. DR CDD; cd12026; SH3_ZO-1; 1. DR Gene3D; 2.30.42.10; -; 3. DR Gene3D; 2.60.220.30; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR008145; GK/Ca_channel_bsu. DR InterPro; IPR008144; Guanylate_kin-like_dom. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR005417; ZO. DR InterPro; IPR005418; ZO-1. DR InterPro; IPR035597; ZO-1_SH3. DR InterPro; IPR000906; ZU5_dom. DR PANTHER; PTHR13865; TIGHT JUNCTION PROTEIN; 1. DR PANTHER; PTHR13865:SF25; TIGHT JUNCTION PROTEIN ZO-1; 1. DR Pfam; PF00625; Guanylate_kin; 1. DR Pfam; PF00595; PDZ; 3. DR Pfam; PF07653; SH3_2; 1. DR Pfam; PF00791; ZU5; 1. DR PRINTS; PR01597; ZONOCCLUDNS. DR PRINTS; PR01598; ZONOCCLUDNS1. DR SMART; SM00072; GuKc; 1. DR SMART; SM00228; PDZ; 3. DR SMART; SM00218; ZU5; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF50156; PDZ domain-like; 3. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1. DR PROSITE; PS50106; PDZ; 3. DR PROSITE; PS50002; SH3; 1. DR PROSITE; PS51145; ZU5; 1. DR Genevisible; Q07157; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calmodulin-binding; Cell junction; KW Cell membrane; Cell projection; Gap junction; Membrane; Phosphoprotein; KW Reference proteome; Repeat; SH3 domain; Tight junction. FT CHAIN 1..1748 FT /note="Tight junction protein ZO-1" FT /id="PRO_0000094540" FT DOMAIN 23..110 FT /note="PDZ 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 186..264 FT /note="PDZ 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 421..502 FT /note="PDZ 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 516..584 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 598..779 FT /note="Guanylate kinase-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100" FT DOMAIN 1634..1748 FT /note="ZU5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00485" FT REGION 102..189 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 295..396 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 633..876 FT /note="Occludin (OCLN)-binding region" FT /evidence="ECO:0000269|PubMed:9792688" FT REGION 825..1081 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1095..1587 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1151..1371 FT /note="Actin-binding region (ABR)" FT /evidence="ECO:0000269|PubMed:12354695" FT COMPBIAS 134..171 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 172..186 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 298..326 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 358..375 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 848..864 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 919..977 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 999..1013 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1056..1071 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1110..1129 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1191..1205 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1273..1289 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1338..1370 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1384..1401 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1422..1436 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1460..1474 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1508..1532 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1558..1577 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 125 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 132 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:A0A0G2K2P5" FT MOD_RES 175 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 178 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 179 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 185 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 212 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 241 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 267 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 275 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 280 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 284 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 290 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 294 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 297 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 300 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 323 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 329 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 334 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 337 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 353 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 354 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 617 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 622 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 809 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 810 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 821 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 822 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 824 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 828 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A0A0G2K2P5" FT MOD_RES 837 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 846 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:A0A0G2K2P5" FT MOD_RES 848 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 854 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 861 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 868 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 912 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 968 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 1071 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 1111 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1139 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 1140 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 1165 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 1354 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P39447" FT MOD_RES 1366 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 1413 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1545 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1617 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT VAR_SEQ 922..1001 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000305" FT /id="VSP_003148" FT VARIANT 471 FT /note="N -> S (in dbSNP:rs2229517)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025153" FT VARIANT 790 FT /note="I -> V (in dbSNP:rs2229515)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:8395056, ECO:0000269|Ref.3" FT /id="VAR_025154" FT VARIANT 930 FT /note="P -> L (in dbSNP:rs45529137)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025155" FT VARIANT 1110 FT /note="H -> R (in dbSNP:rs45567033)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025156" FT VARIANT 1347 FT /note="D -> A (in dbSNP:rs2291166)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025157" FT VARIANT 1605 FT /note="N -> S (in dbSNP:rs45578638)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_025158" FT MUTAGEN 201 FT /note="R->A: Strongly reduced interaction with GJA1." FT /evidence="ECO:0000269|PubMed:18636092" FT MUTAGEN 209 FT /note="K->A: Abolishes interaction with GJA1." FT /evidence="ECO:0000269|PubMed:18636092" FT MUTAGEN 1699..1700 FT /note="MC->AA: Abolishes interaction with CDC42BPB." FT /evidence="ECO:0000269|PubMed:21240187" FT MUTAGEN 1748 FT /note="Missing: Abolishes interaction with CDC42BPB and FT MYZAP." FT /evidence="ECO:0000269|PubMed:21240187" FT CONFLICT 394..417 FT /note="QPDVDLPVSPSDGVLPNSTHEDGI -> NQMWIYLSVHLMVSYLIQLMKMGF FT (in Ref. 1; AAA02891)" FT /evidence="ECO:0000305" FT CONFLICT 545 FT /note="V -> A (in Ref. 1; AAA02891)" FT /evidence="ECO:0000305" FT CONFLICT 688 FT /note="I -> Y (in Ref. 1; AAA02891)" FT /evidence="ECO:0000305" FT CONFLICT 762 FT /note="R -> A (in Ref. 1; AAA02891)" FT /evidence="ECO:0000305" FT STRAND 19..27 FT /evidence="ECO:0007829|PDB:2H2B" FT TURN 30..32 FT /evidence="ECO:0007829|PDB:2H2B" FT STRAND 36..40 FT /evidence="ECO:0007829|PDB:2H2B" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:2H2B" FT STRAND 54..59 FT /evidence="ECO:0007829|PDB:2H2B" FT TURN 64..68 FT /evidence="ECO:0007829|PDB:4YYX" FT STRAND 74..78 FT /evidence="ECO:0007829|PDB:2H2B" FT HELIX 88..96 FT /evidence="ECO:0007829|PDB:2H2B" FT STRAND 100..110 FT /evidence="ECO:0007829|PDB:2H2B" FT STRAND 186..190 FT /evidence="ECO:0007829|PDB:2RCZ" FT TURN 191..193 FT /evidence="ECO:0007829|PDB:2JWE" FT STRAND 194..196 FT /evidence="ECO:0007829|PDB:2JWE" FT STRAND 200..211 FT /evidence="ECO:0007829|PDB:2RCZ" FT HELIX 216..220 FT /evidence="ECO:0007829|PDB:2RCZ" FT STRAND 228..232 FT /evidence="ECO:0007829|PDB:2RCZ" FT HELIX 242..250 FT /evidence="ECO:0007829|PDB:2RCZ" FT TURN 251..254 FT /evidence="ECO:0007829|PDB:3CYY" FT STRAND 255..261 FT /evidence="ECO:0007829|PDB:2RCZ" FT STRAND 422..428 FT /evidence="ECO:0007829|PDB:4Q2Q" FT STRAND 435..439 FT /evidence="ECO:0007829|PDB:4Q2Q" FT STRAND 441..443 FT /evidence="ECO:0007829|PDB:4Q2Q" FT STRAND 445..450 FT /evidence="ECO:0007829|PDB:4Q2Q" FT STRAND 452..454 FT /evidence="ECO:0007829|PDB:3SHW" FT HELIX 455..458 FT /evidence="ECO:0007829|PDB:4Q2Q" FT STRAND 466..470 FT /evidence="ECO:0007829|PDB:4Q2Q" FT HELIX 480..489 FT /evidence="ECO:0007829|PDB:4Q2Q" FT STRAND 495..501 FT /evidence="ECO:0007829|PDB:4Q2Q" FT HELIX 504..510 FT /evidence="ECO:0007829|PDB:3TSV" FT STRAND 519..523 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 542..549 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 550..552 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 553..562 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 564..566 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 568..575 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 577..584 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 632..640 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 647..651 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 654..664 FT /evidence="ECO:0007829|PDB:3TSZ" FT TURN 666..668 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 669..671 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 679..681 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 691..698 FT /evidence="ECO:0007829|PDB:3TSZ" FT TURN 699..701 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 703..706 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 710..718 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 724..729 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 733..743 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 751..765 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 766..768 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 770..774 FT /evidence="ECO:0007829|PDB:3TSZ" FT HELIX 781..795 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 796..801 FT /evidence="ECO:0007829|PDB:3TSZ" FT STRAND 1633..1640 FT /evidence="ECO:0007829|PDB:2KXR" FT STRAND 1645..1648 FT /evidence="ECO:0007829|PDB:2KXR" FT TURN 1650..1652 FT /evidence="ECO:0007829|PDB:2KXR" FT STRAND 1655..1658 FT /evidence="ECO:0007829|PDB:2KXR" FT STRAND 1669..1677 FT /evidence="ECO:0007829|PDB:2KXR" FT STRAND 1679..1681 FT /evidence="ECO:0007829|PDB:2KXR" FT TURN 1687..1689 FT /evidence="ECO:0007829|PDB:2KXR" FT STRAND 1701..1703 FT /evidence="ECO:0007829|PDB:2KXR" FT STRAND 1706..1715 FT /evidence="ECO:0007829|PDB:2KXR" FT HELIX 1720..1723 FT /evidence="ECO:0007829|PDB:2KXS" FT HELIX 1732..1734 FT /evidence="ECO:0007829|PDB:2KXR" FT TURN 1735..1737 FT /evidence="ECO:0007829|PDB:2KXR" FT STRAND 1738..1747 FT /evidence="ECO:0007829|PDB:2KXR" FT MOD_RES Q07157-2:912 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" SQ SEQUENCE 1748 AA; 195459 MW; 189E31617084C0CC CRC64; MSARAAAAKS TAMEETAIWE QHTVTLHRAP GFGFGIAISG GRDNPHFQSG ETSIVISDVL KGGPAEGQLQ ENDRVAMVNG VSMDNVEHAF AVQQLRKSGK NAKITIRRKK KVQIPVSRPD PEPVSDNEED SYDEEIHDPR SGRSGVVNRR SEKIWPRDRS ASRERSLSPR SDRRSVASSQ PAKPTKVTLV KSRKNEEYGL RLASHIFVKE ISQDSLAARD GNIQEGDVVL KINGTVTENM SLTDAKTLIE RSKGKLKMVV QRDERATLLN VPDLSDSIHS ANASERDDIS EIQSLASDHS GRSHDRPPRR SRSRSPDQRS EPSDHSRHSP QQPSNGSLRS RDEERISKPG AVSTPVKHAD DHTPKTVEEV TVERNEKQTP SLPEPKPVYA QVGQPDVDLP VSPSDGVLPN STHEDGILRP SMKLVKFRKG DSVGLRLAGG NDVGIFVAGV LEDSPAAKEG LEEGDQILRV NNVDFTNIIR EEAVLFLLDL PKGEEVTILA QKKKDVYRRI VESDVGDSFY IRTHFEYEKE SPYGLSFNKG EVFRVVDTLY NGKLGSWLAI RIGKNHKEVE RGIIPNKNRA EQLASVQYTL PKTAGGDRAD FWRFRGLRSS KRNLRKSRED LSAQPVQTKF PAYERVVLRE AGFLRPVTIF GPIADVAREK LAREEPDIYQ IAKSEPRDAG TDQRSSGIIR LHTIKQIIDQ DKHALLDVTP NAVDRLNYAQ WYPIVVFLNP DSKQGVKTMR MRLCPESRKS ARKLYERSHK LRKNNHHLFT TTINLNSMND GWYGALKEAI QQQQNQLVWV SEGKADGATS DDLDLHDDRL SYLSAPGSEY SMYSTDSRHT SDYEDTDTEG GAYTDQELDE TLNDEVGTPP ESAITRSSEP VREDSSGMHH ENQTYPPYSP QAQPQPIHRI DSPGFKPASQ QKAEASSPVP YLSPETNPAS STSAVNHNVN LTNVRLEEPT PAPSTSYSPQ ADSLRTPSTE AAHIMLRDQE PSLSSHVDPT KVYRKDPYPE EMMRQNHVLK QPAVSHPGHR PDKEPNLTYE PQLPYVEKQA SRDLEQPTYR YESSSYTDQF SRNYEHRLRY EDRVPMYEEQ WSYYDDKQPY PSRPPFDNQH SQDLDSRQHP EESSERGYFP RFEEPAPLSY DSRPRYEQAP RASALRHEEQ PAPGYDTHGR LRPEAQPHPS AGPKPAESKQ YFEQYSRSYE QVPPQGFTSR AGHFEPLHGA AAVPPLIPSS QHKPEALPSN TKPLPPPPTQ TEEEEDPAMK PQSVLTRVKM FENKRSASLE TKKDVNDTGS FKPPEVASKP SGAPIIGPKP TSQNQFSEHD KTLYRIPEPQ KPQLKPPEDI VRSNHYDPEE DEEYYRKQLS YFDRRSFENK PPAHIAASHL SEPAKPAHSQ NQSNFSSYSS KGKPPEADGV DRSFGEKRYE PIQATPPPPP LPSQYAQPSQ PVTSASLHIH SKGAHGEGNS VSLDFQNSLV SKPDPPPSQN KPATFRPPNR EDTAQAAFYP QKSFPDKAPV NGTEQTQKTV TPAYNRFTPK PYTSSARPFE RKFESPKFNH NLLPSETAHK PDLSSKTPTS PKTLVKSHSL AQPPEFDSGV ETFSIHAEKP KYQINNISTV PKAIPVSPSA VEEDEDEDGH TVVATARGIF NSNGGVLSSI ETGVSIIIPQ GAIPEGVEQE IYFKVCRDNS ILPPLDKEKG ETLLSPLVMC GPHGLKFLKP VELRLPHCDP KTWQNKCLPG DPNYLVGANC VSVLIDHF //