ZO3_HUMAN
ID ZO3_HUMAN Reviewed; 919 AA.
AC O95049; A6NFP3; B3KR73; B3KXZ0; B4E2W6; F5H2X0; F5H4S9; K7EK22; Q32N01;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 3.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Tight junction protein ZO-3;
DE AltName: Full=Tight junction protein 3;
DE AltName: Full=Zona occludens protein 3;
DE AltName: Full=Zonula occludens protein 3;
GN Name=TJP3; Synonyms=ZO3;
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 [LARGE SCALE MRNA] (ISOFORMS 4; 5 AND 6).
RC TISSUE=Stomach, Testis, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT THR-898.
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 [5]
RP FUNCTION.
RX PubMed=16129888; DOI=10.1242/jcs.02528;
RA Michel D., Arsanto J.P., Massey-Harroche D., Beclin C., Wijnholds J.,
RA Le Bivic A.;
RT "PATJ connects and stabilizes apical and lateral components of tight
RT junctions in human intestinal cells.";
RL J. Cell Sci. 118:4049-4057(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164; SER-905 AND SER-906, 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 [7]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP INDUCTION.
RX PubMed=20434232; DOI=10.1016/j.ejcb.2010.03.002;
RA Vikstroem E., Bui L., Konradsson P., Magnusson K.E.;
RT "Role of calcium signalling and phosphorylations in disruption of the
RT epithelial junctions by Pseudomonas aeruginosa quorum sensing molecule.";
RL Eur. J. Cell Biol. 89:584-597(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164; SER-905 AND SER-906, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CCND1.
RX PubMed=21411630; DOI=10.1091/mbc.e10-08-0677;
RA Capaldo C.T., Koch S., Kwon M., Laur O., Parkos C.A., Nusrat A.;
RT "Tight function zonula occludens-3 regulates cyclin D1-dependent cell
RT proliferation.";
RL Mol. Biol. Cell 22:1677-1685(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION BY
RP 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 [14]
RP INDUCTION.
RX PubMed=22354024; DOI=10.1128/iai.00001-12;
RA Kwak Y.K., Vikstroem E., Magnusson K.E., Vecsey-Semjen B.,
RA Colque-Navarro P., Moellby R.;
RT "The Staphylococcus aureus alpha-toxin perturbs the barrier function in
RT Caco-2 epithelial cell monolayers by altering junctional integrity.";
RL Infect. Immun. 80:1670-1680(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112; SER-164; SER-203;
RP SER-591 AND SER-856, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23608536; DOI=10.1128/mcb.01435-12;
RA Aschauer L., Gruber L.N., Pfaller W., Limonciel A., Athersuch T.J.,
RA Cavill R., Khan A., Gstraunthaler G., Grillari J., Grillari R., Hewitt P.,
RA Leonard M.O., Wilmes A., Jennings P.;
RT "Delineation of the key aspects in the regulation of epithelial monolayer
RT formation.";
RL Mol. Cell. Biol. 33:2535-2550(2013).
RN [17]
RP INDUCTION.
RX PubMed=24314862; DOI=10.1016/j.jnutbio.2013.08.011;
RA Kim C.Y., Kim K.H.;
RT "Curcumin prevents leptin-induced tight junction dysfunction in intestinal
RT Caco-2 BBe cells.";
RL J. Nutr. Biochem. 25:26-35(2014).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136; SER-319; THR-325;
RP SER-327; SER-371; SER-591 AND SER-906, AND IDENTIFICATION BY MASS
RP 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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 475-775.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the SH3-kinase fragment of tight junction protein 3
RT (TJP3) in apo-form.";
RL Submitted (NOV-2009) to the PDB data bank.
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:16129888). The tight junction acts to limit movement of
CC substances through the paracellular space and as a boundary between the
CC compositionally distinct apical and basolateral plasma membrane domains
CC of epithelial and endothelial cells. Binds and recruits PATJ to tight
CC junctions where it connects and stabilizes apical and lateral
CC components of tight junctions (PubMed:16129888). Promotes cell-cycle
CC progression through the sequestration of cyclin D1 (CCND1) at tight
CC junctions during mitosis which prevents CCND1 degradation during M-
CC phase and enables S-phase transition (PubMed:21411630). With TJP1 and
CC TJP2, participates in the junctional retention and stability of the
CC transcription factor DBPA, but is not involved in its shuttling to the
CC nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for
CC individual viability, embryonic development, epithelial
CC differentiation, and the establishment of TJs, at least in the
CC laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683,
CC ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888,
CC ECO:0000269|PubMed:21411630}.
CC -!- SUBUNIT: Interacts with occludin OCLN, claudins and TPJ1 (By
CC similarity). Interacts with PATJ (By similarity). Interacts with UBN1
CC (PubMed:20434232). Interacts with FASLG (PubMed:19807924). Interacts
CC with CCND1 (PubMed:21411630). {ECO:0000250|UniProtKB:O62683,
CC ECO:0000269|PubMed:18823282, ECO:0000269|PubMed:19807924,
CC ECO:0000269|PubMed:21411630}.
CC -!- INTERACTION:
CC O95049; K9N5R3: E; Xeno; NbExp=2; IntAct=EBI-1171427, EBI-26374535;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21411630};
CC Peripheral membrane protein {ECO:0000269|PubMed:21411630}; Cytoplasmic
CC side {ECO:0000269|PubMed:21411630}. Cell junction, tight junction
CC {ECO:0000269|PubMed:21411630, ECO:0000269|PubMed:23608536}. Nucleus
CC {ECO:0000269|PubMed:23608536}. Note=Exhibits predominant nuclear
CC expression in proliferating cells but is exclusively junctionally
CC expressed after confluence is reached (PubMed:23608536). Shows an
CC epithelial-specific tight junction localization in a TJP1/TJP2-
CC dependent fashion (By similarity). {ECO:0000250|UniProtKB:Q9QXY1,
CC ECO:0000269|PubMed:23608536}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=5;
CC IsoId=O95049-1; Sequence=Displayed;
CC Name=3;
CC IsoId=O95049-3; Sequence=VSP_040238;
CC Name=4;
CC IsoId=O95049-4; Sequence=VSP_047022;
CC Name=6;
CC IsoId=O95049-5; Sequence=VSP_053844;
CC -!- INDUCTION: Exhibits enhanced expression in matured epithelial layers
CC (PubMed:23608536). Apical leptin, Staphylococcus aureus alpha-toxin and
CC Pseudomonas aeruginosa acyl-homoserine lactone 3O-C12-HSl lower
CC expression levels, altering junctional integrity in intestinal cells
CC (PubMed:20434232, PubMed:22354024, PubMed:24314862).
CC {ECO:0000269|PubMed:20434232, ECO:0000269|PubMed:22354024,
CC ECO:0000269|PubMed:23608536, ECO:0000269|PubMed:24314862}.
CC -!- PTM: Phosphorylated (By similarity). {ECO:0000250|UniProtKB:O62683}.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC72274.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAW69293.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK091118; BAG52285.1; -; mRNA.
DR EMBL; AK128237; BAG54652.1; -; mRNA.
DR EMBL; AK304462; BAG65278.1; -; mRNA.
DR EMBL; AC005954; AAC72274.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC006125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69293.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC108906; AAI08907.1; -; mRNA.
DR CCDS; CCDS32873.2; -. [O95049-1]
DR CCDS; CCDS59332.1; -. [O95049-4]
DR RefSeq; NP_001254489.1; NM_001267560.1. [O95049-1]
DR RefSeq; NP_001254490.1; NM_001267561.1. [O95049-4]
DR PDB; 3KFV; X-ray; 2.80 A; A=475-775.
DR PDBsum; 3KFV; -.
DR AlphaFoldDB; O95049; -.
DR SMR; O95049; -.
DR BioGRID; 118025; 18.
DR IntAct; O95049; 6.
DR MINT; O95049; -.
DR STRING; 9606.ENSP00000465419; -.
DR GlyGen; O95049; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95049; -.
DR PhosphoSitePlus; O95049; -.
DR BioMuta; TJP3; -.
DR EPD; O95049; -.
DR jPOST; O95049; -.
DR MassIVE; O95049; -.
DR MaxQB; O95049; -.
DR PaxDb; O95049; -.
DR PeptideAtlas; O95049; -.
DR PRIDE; O95049; -.
DR ProteomicsDB; 26098; -.
DR ProteomicsDB; 26665; -.
DR ProteomicsDB; 50630; -. [O95049-1]
DR ProteomicsDB; 50632; -. [O95049-3]
DR Antibodypedia; 23311; 215 antibodies from 33 providers.
DR DNASU; 27134; -.
DR Ensembl; ENST00000539908.6; ENSP00000439991.1; ENSG00000105289.15. [O95049-5]
DR Ensembl; ENST00000541714.7; ENSP00000439278.1; ENSG00000105289.15. [O95049-1]
DR Ensembl; ENST00000587686.1; ENSP00000467864.1; ENSG00000105289.15. [O95049-3]
DR Ensembl; ENST00000589378.5; ENSP00000465419.1; ENSG00000105289.15. [O95049-4]
DR GeneID; 27134; -.
DR KEGG; hsa:27134; -.
DR MANE-Select; ENST00000541714.7; ENSP00000439278.1; NM_001267560.2; NP_001254489.1.
DR UCSC; uc010xhs.4; human. [O95049-1]
DR CTD; 27134; -.
DR DisGeNET; 27134; -.
DR GeneCards; TJP3; -.
DR HGNC; HGNC:11829; TJP3.
DR HPA; ENSG00000105289; Tissue enhanced (intestine, stomach).
DR MIM; 612689; gene.
DR neXtProt; NX_O95049; -.
DR OpenTargets; ENSG00000105289; -.
DR PharmGKB; PA36534; -.
DR VEuPathDB; HostDB:ENSG00000105289; -.
DR eggNOG; KOG3580; Eukaryota.
DR GeneTree; ENSGT00940000160036; -.
DR HOGENOM; CLU_006234_0_0_1; -.
DR InParanoid; O95049; -.
DR OMA; RKHSGHL; -.
DR OrthoDB; 1175136at2759; -.
DR TreeFam; TF315606; -.
DR PathwayCommons; O95049; -.
DR SignaLink; O95049; -.
DR BioGRID-ORCS; 27134; 15 hits in 1066 CRISPR screens.
DR ChiTaRS; TJP3; human.
DR EvolutionaryTrace; O95049; -.
DR GeneWiki; TJP3; -.
DR GenomeRNAi; 27134; -.
DR Pharos; O95049; Tbio.
DR PRO; PR:O95049; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O95049; protein.
DR Bgee; ENSG00000105289; Expressed in mucosa of transverse colon and 165 other tissues.
DR ExpressionAtlas; O95049; baseline and differential.
DR Genevisible; O95049; HS.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0045216; P:cell-cell junction organization; IBA:GO_Central.
DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; IBA:GO_Central.
DR GO; GO:0035633; P:maintenance of blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:1905605; P:positive regulation of blood-brain barrier permeability; IBA:GO_Central.
DR GO; GO:0150105; P:protein localization to cell-cell junction; IBA:GO_Central.
DR Gene3D; 2.30.42.10; -; 3.
DR Gene3D; 3.40.50.300; -; 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; IPR005420; ZO-3.
DR PANTHER; PTHR13865:SF11; PTHR13865:SF11; 1.
DR Pfam; PF00625; Guanylate_kin; 1.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR01597; ZONOCCLUDNS.
DR PRINTS; PR01600; ZONOCCLUDNS3.
DR SMART; SM00072; GuKc; 1.
DR SMART; SM00228; PDZ; 3.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 3.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR PROSITE; PS50106; PDZ; 3.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; SH3 domain;
KW Tight junction.
FT CHAIN 1..919
FT /note="Tight junction protein ZO-3"
FT /id="PRO_0000094546"
FT DOMAIN 11..93
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 195..272
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 380..446
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 475..549
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 580..761
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 92..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 279..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 791..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 899..919
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..302
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..359
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXY1"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 325
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 591
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 856
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 906
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..36
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053844"
FT VAR_SEQ 1
FT /note="M -> MNLCGLMPIFPAPLDQVADM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040238"
FT VAR_SEQ 1
FT /note="M -> MAVRFQVADM (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047022"
FT VARIANT 898
FT /note="M -> T (in dbSNP:rs1046268)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_056114"
FT CONFLICT 19
FT /note="R -> H (in Ref. 4; AAI08907)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="H -> L (in Ref. 1; BAG52285)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="L -> P (in Ref. 1; BAG54652)"
FT /evidence="ECO:0000305"
FT CONFLICT 802
FT /note="R -> H (in Ref. 1; BAG52285)"
FT /evidence="ECO:0000305"
FT CONFLICT 901
FT /note="H -> R (in Ref. 1; BAG52285)"
FT /evidence="ECO:0000305"
FT CONFLICT 917
FT /note="T -> M (in Ref. 1; BAG65278)"
FT /evidence="ECO:0000305"
FT STRAND 478..482
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 490..493
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 501..506
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 522..527
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 533..539
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 542..555
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 596..602
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 606..614
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 621..625
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 628..638
FT /evidence="ECO:0007829|PDB:3KFV"
FT TURN 640..642
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 643..645
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 661..669
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 673..676
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 680..688
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 694..701
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 703..713
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 721..735
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 736..738
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 740..745
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 747..749
FT /evidence="ECO:0007829|PDB:3KFV"
FT HELIX 751..763
FT /evidence="ECO:0007829|PDB:3KFV"
FT STRAND 766..771
FT /evidence="ECO:0007829|PDB:3KFV"
SQ SEQUENCE 919 AA; 101397 MW; D36EB684E7E4A6C8 CRC64;
MEELTIWEQH TATLSKDPRR GFGIAISGGR DRPGGSMVVS DVVPGGPAEG RLQTGDHIVM
VNGVSMENAT SAFAIQILKT CTKMANITVK RPRRIHLPAT KASPSSPGRQ DSDEDDGPQR
VEEVDQGRGY DGDSSSGSGR SWDERSRRPR PGRRGRAGSH GRRSPGGGSE ANGLALVSGF
KRLPRQDVQM KPVKSVLVKR RDSEEFGVKL GSQIFIKHIT DSGLAARHRG LQEGDLILQI
NGVSSQNLSL NDTRRLIEKS EGKLSLLVLR DRGQFLVNIP PAVSDSDSSP LEDISDLASE
LSQAPPSHIP PPPRHAQRSP EASQTDSPVE SPRLRRESSV DSRTISEPDE QRSELPRESS
YDIYRVPSSQ SMEDRGYSPD TRVVRFLKGK SIGLRLAGGN DVGIFVSGVQ AGSPADGQGI
QEGDQILQVN DVPFQNLTRE EAVQFLLGLP PGEEMELVTQ RKQDIFWKMV QSRVGDSFYI
RTHFELEPSP PSGLGFTRGD VFHVLDTLHP GPGQSHARGG HWLAVRMGRD LREQERGIIP
NQSRAEQLAS LEAAQRAVGV GPGSSAGSNA RAEFWRLRGL RRGAKKTTQR SREDLSALTR
QGRYPPYERV VLREASFKRP VVILGPVADI AMQKLTAEMP DQFEIAETVS RTDSPSKIIK
LDTVRVIAEK DKHALLDVTP SAIERLNYVQ YYPIVVFFIP ESRPALKALR QWLAPASRRS
TRRLYAQAQK LRKHSSHLFT ATIPLNGTSD TWYQELKAII REQQTRPIWT AEDQLDGSLE
DNLDLPHHGL ADSSADLSCD SRVNSDYETD GEGGAYTDGE GYTDGEGGPY TDVDDEPPAP
ALARSSEPVQ ADESQSPRDR GRISAHQGAQ VDSRHPQGQW RQDSMRTYER EALKKKFMRV
HDAESSDEDG YDWGPATDL
