ZO2_HUMAN
ID ZO2_HUMAN Reviewed; 1190 AA.
AC Q9UDY2; A2A3H9; B7Z2R8; B7Z7T6; F5H301; F5H886; Q15883; Q5VXL0; Q5VXL1;
AC Q8N756; Q8NI14; Q99839; Q9UDY0; Q9UDY1;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Tight junction protein ZO-2;
DE AltName: Full=Tight junction protein 2;
DE AltName: Full=Zona occludens protein 2;
DE AltName: Full=Zonula occludens protein 2;
GN Name=TJP2; Synonyms=X104, ZO2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A1), AND VARIANTS GLU-482; ASN-822 AND
RP ASP-829.
RC TISSUE=Brain;
RX PubMed=7951235; DOI=10.1093/hmg/3.6.909;
RA Duclos F., Rodius F., Wrogemann K., Mandel J.-L., Koenig M.;
RT "The Friedreich ataxia region: characterization of two novel genes and
RT reduction of the critical region to 300 kb.";
RL Hum. Mol. Genet. 3:909-914(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A1; C1; A2 AND C2), TISSUE
RP SPECIFICITY, ALTERNATIVE PROMOTER USAGE, AND VARIANT GLU-482.
RC TISSUE=Pancreas;
RX PubMed=11018256; DOI=10.1016/s0167-4781(00)00185-8;
RA Chlenski A., Ketels K.V., Korovaitseva G.I., Talamonti M.S., Oyasu R.,
RA Scarpelli D.G.;
RT "Organization and expression of the human zo-2 gene (tjp-2) in normal and
RT neoplastic tissues.";
RL Biochim. Biophys. Acta 1493:319-324(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A3), AND VARIANT GLU-482.
RA Yan H.H., Rong L., Qiang S., Jian W., Peng Z., Hua H., Hui Z.W.;
RT "LIM protein KyoT2 interacts with human tight junction protein ZO-2-i3.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 7), AND VARIANTS
RP GLU-482 AND ILE-668.
RC TISSUE=Brain, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A1).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-166 (ISOFORMS A1/A2/A3), AND NUCLEOTIDE
RP SEQUENCE [MRNA] OF 1-119 (ISOFORMS C1/C2).
RC TISSUE=Pancreas;
RX PubMed=10360833;
RX DOI=10.1002/(sici)1097-0215(19990702)82:1<137::aid-ijc23>3.0.co;2-f;
RA Chlenski A., Ketels K.V., Tsao M.-S., Talamonti M.S., Anderson M.R.,
RA Oyasu R., Scarpelli D.G.;
RT "Tight junction protein ZO-2 is differentially expressed in normal
RT pancreatic ducts compared to human pancreatic adenocarcinoma.";
RL Int. J. Cancer 82:137-144(1999).
RN [8]
RP PARTIAL NUCLEOTIDE SEQUENCE (ISOFORMS A1 AND C1), AND ALTERNATIVE PROMOTER
RP USAGE.
RC TISSUE=Pancreas;
RX PubMed=10495427;
RX DOI=10.1002/(sici)1097-0215(19991029)83:3<349::aid-ijc10>3.0.co;2-c;
RA Chlenski A., Ketels K.V., Engeriser J.L., Talamonti M.S., Tsao M.-S.,
RA Koutnikova H., Oyasu R., Scarpelli D.G.;
RT "Zo-2 gene alternative promoters in normal and neoplastic human pancreatic
RT duct cells.";
RL Int. J. Cancer 83:349-358(1999).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1047-1167.
RC TISSUE=Aortic smooth muscle;
RA Adams L.D., Werny I., Schwartz S.M.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP INTERACTION WITH SCRIB.
RX PubMed=15975580; DOI=10.1016/j.febslet.2005.05.062;
RA Metais J.-Y., Navarro C., Santoni M.-J., Audebert S., Borg J.-P.;
RT "hScrib interacts with ZO-2 at the cell-cell junctions of epithelial
RT cells.";
RL FEBS Lett. 579:3725-3730(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION BY
RP 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174; SER-244; SER-702;
RP SER-966 AND SER-986, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; SER-174; SER-244;
RP SER-266; SER-400; THR-455; SER-920; THR-925; THR-933; SER-978; SER-986;
RP SER-1067; SER-1068; THR-1131 AND SER-1159, 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [15]
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 [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244 AND SER-1159, AND
RP IDENTIFICATION BY 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-170; SER-174;
RP SER-244; SER-920; THR-925; SER-986 AND SER-1159, 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-153; SER-168;
RP SER-174; SER-200; SER-220; SER-244; SER-430; SER-978; SER-986; SER-1067;
RP SER-1068; SER-1147 AND SER-1159, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-130; SER-150;
RP SER-170; SER-174; SER-232; SER-244; SER-266; SER-415; SER-424; SER-430;
RP SER-431; THR-455; SER-499; SER-913; SER-966; SER-978; SER-986; SER-1067;
RP TYR-1118 AND SER-1159, 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-325; SER-406;
RP SER-431; SER-702; SER-966; SER-978; SER-986 AND SER-1159, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP INVOLVEMENT IN PFIC4.
RX PubMed=24614073; DOI=10.1038/ng.2918;
RA Sambrotta M., Strautnieks S., Papouli E., Rushton P., Clark B.E.,
RA Parry D.A., Logan C.V., Newbury L.J., Kamath B.M., Ling S.,
RA Grammatikopoulos T., Wagner B.E., Magee J.C., Sokol R.J., Mieli-Vergani G.,
RA Smith J.D., Johnson C.A., McClean P., Simpson M.A., Knisely A.S.,
RA Bull L.N., Thompson R.J.;
RT "Mutations in TJP2 cause progressive cholestatic liver disease.";
RL Nat. Genet. 46:326-328(2014).
RN [23]
RP STRUCTURE BY NMR OF 306-385, HOMODIMERIZATION, AND INTERACTION WITH TJP1.
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 [24]
RP VARIANT FHCA1 ALA-48, CHARACTERIZATION OF VARIANT FHCA1 ALA-48, AND
RP INTERACTION WITH CLDN1; CLDN2; CLDN3; CLDN5 AND CLDN7.
RX PubMed=12704386; DOI=10.1038/ng1147;
RA Carlton V.E.H., Harris B.Z., Puffenberger E.G., Batta A.K., Knisely A.S.,
RA Robinson D.L., Strauss K.A., Shneider B.L., Lim W.A., Salen G.,
RA Morton D.H., Bull L.N.;
RT "Complex inheritance of familial hypercholanemia with associated mutations
RT in TJP2 and BAAT.";
RL Nat. Genet. 34:91-96(2003).
RN [25]
RP VARIANT [LARGE SCALE ANALYSIS] GLU-482, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: Plays a role in tight junctions and adherens junctions.
CC -!- SUBUNIT: Homodimer (PubMed:17897942). Interacts with TJP1/ZO1
CC (PubMed:17897942). Interacts with occludin, SAFB and UBN1. Interaction
CC with SAFB occurs in the nucleus. Interacts with SCRIB. Interacts with
CC USP53 (via the C-terminal region) (By similarity). Interacts with
CC claudins, including CLDN1, CLDN2, CLDN3, CLDN5 and CLDN7
CC (PubMed:12704386). {ECO:0000250|UniProtKB:Q9Z0U1,
CC ECO:0000269|PubMed:12704386, ECO:0000269|PubMed:15975580,
CC ECO:0000269|PubMed:17897942, ECO:0000269|PubMed:18823282}.
CC -!- INTERACTION:
CC Q9UDY2; Q14847: LASP1; NbExp=9; IntAct=EBI-1042602, EBI-742828;
CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}. Cell junction, tight junction
CC {ECO:0000250|UniProtKB:Q9Z0U1}. Nucleus {ECO:0000250}. Note=Also
CC nuclear under environmental stress conditions and in migratory
CC endothelial cells and subconfluent epithelial cell cultures.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=7;
CC Name=A1;
CC IsoId=Q9UDY2-1; Sequence=Displayed;
CC Name=A2;
CC IsoId=Q9UDY2-2; Sequence=VSP_003149;
CC Name=A3;
CC IsoId=Q9UDY2-5; Sequence=VSP_007835, VSP_007836;
CC Name=C1;
CC IsoId=Q9UDY2-3; Sequence=VSP_006953;
CC Name=C2;
CC IsoId=Q9UDY2-4; Sequence=VSP_006953, VSP_003149;
CC Name=6;
CC IsoId=Q9UDY2-6; Sequence=VSP_046115, VSP_046116;
CC Name=7;
CC IsoId=Q9UDY2-7; Sequence=VSP_046114;
CC -!- TISSUE SPECIFICITY: This protein is found in epithelial cell junctions.
CC Isoform A1 is abundant in the heart and brain. Detected in brain and
CC skeletal muscle. It is present almost exclusively in normal tissues.
CC Isoform C1 is expressed at high level in the kidney, pancreas, heart
CC and placenta. Not detected in brain and skeletal muscle. Found in
CC normal as well as in most neoplastic tissues.
CC {ECO:0000269|PubMed:11018256}.
CC -!- DISEASE: Hypercholanemia, familial, 1 (FHCA1) [MIM:607748]: A disorder
CC characterized by elevated serum bile acid concentrations, itching, and
CC fat malabsorption. {ECO:0000269|PubMed:12704386}. Note=The disease may
CC be caused by variants affecting distinct genetic loci, including the
CC gene represented in this entry.
CC -!- DISEASE: Cholestasis, progressive familial intrahepatic, 4 (PFIC4)
CC [MIM:615878]: A disorder characterized by early onset of cholestasis
CC that progresses to hepatic fibrosis, cirrhosis, and end-stage liver
CC disease before adulthood. PFIC4 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:24614073}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform A1]: Produced by alternative promoter usage.
CC -!- MISCELLANEOUS: [Isoform A2]: Produced by alternative splicing of
CC isoform A1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform A3]: Produced by alternative splicing of
CC isoform A1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform C1]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform C2]: Produced by alternative splicing of
CC isoform C1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA61300.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TJP2ID44347ch9q21.html";
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DR EMBL; L27476; AAA61300.1; ALT_FRAME; mRNA.
DR EMBL; AF177533; AAD20387.2; -; Genomic_DNA.
DR EMBL; AF043195; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF043196; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF043197; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177518; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177519; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177520; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177521; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177522; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177523; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177524; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177525; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177526; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177527; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177528; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177529; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177530; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177531; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177532; AAD20387.2; JOINED; Genomic_DNA.
DR EMBL; AF177533; AAC02527.2; -; Genomic_DNA.
DR EMBL; AF043196; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF043197; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177518; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177519; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177520; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177521; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177522; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177523; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177524; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177525; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177526; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177527; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177528; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177529; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177530; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177531; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177532; AAC02527.2; JOINED; Genomic_DNA.
DR EMBL; AF177533; AAD56218.2; -; Genomic_DNA.
DR EMBL; AF043195; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF043196; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF043197; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177518; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177519; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177520; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177521; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177522; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177523; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177524; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177525; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177526; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177527; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177528; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177529; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177532; AAD56218.2; JOINED; Genomic_DNA.
DR EMBL; AF177533; AAD56219.2; -; Genomic_DNA.
DR EMBL; AF043196; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF043197; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177518; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177519; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177520; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177521; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177522; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177523; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177524; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177525; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177526; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177527; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177528; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177529; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF177532; AAD56219.2; JOINED; Genomic_DNA.
DR EMBL; AF489824; AAM28524.1; -; mRNA.
DR EMBL; AK295034; BAH11954.1; -; mRNA.
DR EMBL; AK302483; BAH13722.1; -; mRNA.
DR EMBL; AL162730; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL358113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027592; AAH27592.1; -; mRNA.
DR EMBL; AF083892; AAC33121.1; -; mRNA.
DR EMBL; AF083893; AAC33122.1; -; mRNA.
DR EMBL; U84581; AAB41794.1; -; mRNA.
DR CCDS; CCDS55315.1; -. [Q9UDY2-6]
DR CCDS; CCDS55316.1; -. [Q9UDY2-7]
DR CCDS; CCDS55317.1; -. [Q9UDY2-4]
DR CCDS; CCDS6627.1; -. [Q9UDY2-1]
DR CCDS; CCDS6628.1; -. [Q9UDY2-2]
DR PIR; I54378; I54378.
DR RefSeq; NP_001163886.1; NM_001170415.1. [Q9UDY2-6]
DR RefSeq; NP_001163887.1; NM_001170416.1. [Q9UDY2-7]
DR RefSeq; NP_004808.2; NM_004817.3. [Q9UDY2-1]
DR RefSeq; XP_011517508.1; XM_011519206.2. [Q9UDY2-3]
DR RefSeq; XP_011517509.1; XM_011519207.2. [Q9UDY2-3]
DR RefSeq; XP_011517510.1; XM_011519208.2. [Q9UDY2-3]
DR RefSeq; XP_011517511.1; XM_011519209.2. [Q9UDY2-3]
DR PDB; 2OSG; NMR; -; A/B=306-385.
DR PDB; 3E17; X-ray; 1.75 A; A/B=306-384.
DR PDBsum; 2OSG; -.
DR PDBsum; 3E17; -.
DR AlphaFoldDB; Q9UDY2; -.
DR BMRB; Q9UDY2; -.
DR SMR; Q9UDY2; -.
DR BioGRID; 114809; 249.
DR ELM; Q9UDY2; -.
DR IntAct; Q9UDY2; 68.
DR MINT; Q9UDY2; -.
DR STRING; 9606.ENSP00000438262; -.
DR GlyGen; Q9UDY2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UDY2; -.
DR MetOSite; Q9UDY2; -.
DR PhosphoSitePlus; Q9UDY2; -.
DR BioMuta; TJP2; -.
DR DMDM; 317373313; -.
DR EPD; Q9UDY2; -.
DR jPOST; Q9UDY2; -.
DR MassIVE; Q9UDY2; -.
DR MaxQB; Q9UDY2; -.
DR PaxDb; Q9UDY2; -.
DR PeptideAtlas; Q9UDY2; -.
DR PRIDE; Q9UDY2; -.
DR ProteomicsDB; 26127; -.
DR ProteomicsDB; 27714; -.
DR ProteomicsDB; 84127; -. [Q9UDY2-1]
DR ProteomicsDB; 84128; -. [Q9UDY2-2]
DR ProteomicsDB; 84129; -. [Q9UDY2-3]
DR ProteomicsDB; 84130; -. [Q9UDY2-4]
DR ProteomicsDB; 84131; -. [Q9UDY2-5]
DR Antibodypedia; 784; 413 antibodies from 37 providers.
DR DNASU; 9414; -.
DR Ensembl; ENST00000348208.9; ENSP00000345893.4; ENSG00000119139.21. [Q9UDY2-2]
DR Ensembl; ENST00000377245.9; ENSP00000366453.4; ENSG00000119139.21. [Q9UDY2-1]
DR Ensembl; ENST00000535702.6; ENSP00000442090.1; ENSG00000119139.21. [Q9UDY2-6]
DR Ensembl; ENST00000539225.2; ENSP00000438262.1; ENSG00000119139.21. [Q9UDY2-7]
DR GeneID; 9414; -.
DR KEGG; hsa:9414; -.
DR MANE-Select; ENST00000377245.9; ENSP00000366453.4; NM_004817.4; NP_004808.2.
DR UCSC; uc004ahd.4; human. [Q9UDY2-1]
DR CTD; 9414; -.
DR DisGeNET; 9414; -.
DR GeneCards; TJP2; -.
DR HGNC; HGNC:11828; TJP2.
DR HPA; ENSG00000119139; Low tissue specificity.
DR MalaCards; TJP2; -.
DR MIM; 607709; gene.
DR MIM; 607748; phenotype.
DR MIM; 615878; phenotype.
DR neXtProt; NX_Q9UDY2; -.
DR OpenTargets; ENSG00000119139; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR Orphanet; 238475; Familial hypercholanemia.
DR Orphanet; 480483; Progressive familial intrahepatic cholestasis type 4.
DR PharmGKB; PA36533; -.
DR VEuPathDB; HostDB:ENSG00000119139; -.
DR eggNOG; KOG3580; Eukaryota.
DR GeneTree; ENSGT00940000158634; -.
DR HOGENOM; CLU_006234_1_0_1; -.
DR InParanoid; Q9UDY2; -.
DR OrthoDB; 1175136at2759; -.
DR PhylomeDB; Q9UDY2; -.
DR TreeFam; TF315957; -.
DR PathwayCommons; Q9UDY2; -.
DR Reactome; R-HSA-2028269; Signaling by Hippo.
DR Reactome; R-HSA-351906; Apoptotic cleavage of cell adhesion proteins.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR SignaLink; Q9UDY2; -.
DR SIGNOR; Q9UDY2; -.
DR BioGRID-ORCS; 9414; 15 hits in 1081 CRISPR screens.
DR ChiTaRS; TJP2; human.
DR EvolutionaryTrace; Q9UDY2; -.
DR GeneWiki; Tight_junction_protein_2; -.
DR GenomeRNAi; 9414; -.
DR Pharos; Q9UDY2; Tbio.
DR PRO; PR:Q9UDY2; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9UDY2; protein.
DR Bgee; ENSG00000119139; Expressed in corpus callosum and 94 other tissues.
DR ExpressionAtlas; Q9UDY2; baseline and differential.
DR Genevisible; Q9UDY2; HS.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0044291; C:cell-cell contact zone; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central.
DR GO; GO:0004385; F:guanylate kinase activity; TAS:ProtInc.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:ARUK-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0034109; P:homotypic cell-cell adhesion; IDA:ARUK-UCL.
DR GO; GO:0050892; P:intestinal absorption; IMP:UniProtKB.
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; IMP:ARUK-UCL.
DR GO; GO:0150105; P:protein localization to cell-cell junction; IBA:GO_Central.
DR GO; GO:0090559; P:regulation of membrane permeability; IMP:UniProtKB.
DR CDD; cd12027; SH3_ZO-2; 1.
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; IPR005419; ZO-2.
DR InterPro; IPR035598; ZO-2_SH3.
DR Pfam; PF00625; Guanylate_kin; 1.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR01597; ZONOCCLUDNS.
DR PRINTS; PR01599; ZONOCCLUDNS2.
DR SMART; SM00072; GuKc; 1.
DR SMART; SM00228; PDZ; 3.
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 promoter usage; Alternative splicing;
KW Cell junction; Cell membrane; Disease variant; Intrahepatic cholestasis;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Repeat; SH3 domain;
KW Tight junction.
FT CHAIN 1..1190
FT /note="Tight junction protein ZO-2"
FT /id="PRO_0000094543"
FT DOMAIN 33..120
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 307..385
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 509..590
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 604..669
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 678..876
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 152..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 408..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 920..1079
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1105..1190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1188..1190
FT /note="Interaction with SCRIB"
FT /evidence="ECO:0000269|PubMed:15975580"
FT COMPBIAS 162..296
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..445
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 927..941
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 956..970
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 997..1011
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1012..1027
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1157..1172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0U1"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0U1"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 406
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 455
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 574
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0U1"
FT MOD_RES 702
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 902
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0U1"
FT MOD_RES 905
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0U1"
FT MOD_RES 913
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 925
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 933
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 966
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 978
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 986
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1006
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0U1"
FT MOD_RES 1067
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1068
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1118
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1131
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1147
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1159
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 ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform C1 and isoform C2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006953"
FT VAR_SEQ 1..20
FT /note="MPVRGDRGFPPRRELSGWLR -> MKTAQALHRMWIQAVKKLRRWKGRVSPS
FT ASSPLVFPNLSSWEGEGSKTILT (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046114"
FT VAR_SEQ 1..19
FT /note="MPVRGDRGFPPRRELSGWL -> MKTAQALHRMWIQAVKKLRRWKG (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046115"
FT VAR_SEQ 961..1107
FT /note="Missing (in isoform A2 and isoform C2)"
FT /evidence="ECO:0000305"
FT /id="VSP_003149"
FT VAR_SEQ 961..997
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046116"
FT VAR_SEQ 961..993
FT /note="SIRKPSPEPRAQMRRAASSDQLRDNSPPPAFKP -> VRRGRPRAGTGEPGV
FT FLALSWTAVCSGCCGRHS (in isoform A3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_007835"
FT VAR_SEQ 994..1190
FT /note="Missing (in isoform A3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_007836"
FT VARIANT 48
FT /note="V -> A (in FHCA1; affects the interaction with
FT claudins; dbSNP:rs121918299)"
FT /evidence="ECO:0000269|PubMed:12704386"
FT /id="VAR_016004"
FT VARIANT 482
FT /note="D -> E (in dbSNP:rs2309428)"
FT /evidence="ECO:0000269|PubMed:11018256,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:7951235,
FT ECO:0000269|Ref.3, ECO:0007744|PubMed:21269460"
FT /id="VAR_030798"
FT VARIANT 668
FT /note="M -> I (in dbSNP:rs34774441)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_046675"
FT VARIANT 711
FT /note="S -> P (in dbSNP:rs35797487)"
FT /id="VAR_046676"
FT VARIANT 822
FT /note="K -> N (in dbSNP:rs1049624)"
FT /evidence="ECO:0000269|PubMed:7951235"
FT /id="VAR_046677"
FT VARIANT 829
FT /note="N -> D (in dbSNP:rs1049625)"
FT /evidence="ECO:0000269|PubMed:7951235"
FT /id="VAR_046678"
FT CONFLICT 411
FT /note="N -> T (in Ref. 1; AAA61300 and 3; AAM28524)"
FT /evidence="ECO:0000305"
FT CONFLICT 718
FT /note="A -> V (in Ref. 4; BAH13722)"
FT /evidence="ECO:0000305"
FT CONFLICT 782
FT /note="I -> V (in Ref. 1; AAA61300 and 3; AAM28524)"
FT /evidence="ECO:0000305"
FT CONFLICT 808
FT /note="P -> S (in Ref. 1; AAA61300)"
FT /evidence="ECO:0000305"
FT CONFLICT 812..814
FT /note="FFN -> SFT (in Ref. 1; AAA61300)"
FT /evidence="ECO:0000305"
FT CONFLICT 834
FT /note="K -> N (in Ref. 1; AAA61300)"
FT /evidence="ECO:0000305"
FT CONFLICT 842
FT /note="Q -> H (in Ref. 1; AAA61300)"
FT /evidence="ECO:0000305"
FT CONFLICT 996
FT /note="P -> S (in Ref. 1; AAA61300)"
FT /evidence="ECO:0000305"
FT CONFLICT 1093
FT /note="R -> G (in Ref. 1; AAA61300)"
FT /evidence="ECO:0000305"
FT CONFLICT 1110
FT /note="I -> L (in Ref. 4; BAH13722)"
FT /evidence="ECO:0000305"
FT CONFLICT 1136
FT /note="S -> N (in Ref. 9; AAB41794)"
FT /evidence="ECO:0000305"
FT CONFLICT 1155..1158
FT /note="GSYG -> RSFC (in Ref. 9; AAB41794)"
FT /evidence="ECO:0000305"
FT CONFLICT 1165..1167
FT /note="EYR -> IRS (in Ref. 9; AAB41794)"
FT /evidence="ECO:0000305"
FT STRAND 306..311
FT /evidence="ECO:0007829|PDB:3E17"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:2OSG"
FT STRAND 321..332
FT /evidence="ECO:0007829|PDB:3E17"
FT HELIX 337..341
FT /evidence="ECO:0007829|PDB:3E17"
FT STRAND 349..353
FT /evidence="ECO:0007829|PDB:3E17"
FT HELIX 363..372
FT /evidence="ECO:0007829|PDB:3E17"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:3E17"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:3E17"
SQ SEQUENCE 1190 AA; 133958 MW; 27305B723043BF6C CRC64;
MPVRGDRGFP PRRELSGWLR APGMEELIWE QYTVTLQKDS KRGFGIAVSG GRDNPHFENG
ETSIVISDVL PGGPADGLLQ ENDRVVMVNG TPMEDVLHSF AVQQLRKSGK VAAIVVKRPR
KVQVAALQAS PPLDQDDRAF EVMDEFDGRS FRSGYSERSR LNSHGGRSRS WEDSPERGRP
HERARSRERD LSRDRSRGRS LERGLDQDHA RTRDRSRGRS LERGLDHDFG PSRDRDRDRS
RGRSIDQDYE RAYHRAYDPD YERAYSPEYR RGARHDARSR GPRSRSREHP HSRSPSPEPR
GRPGPIGVLL MKSRANEEYG LRLGSQIFVK EMTRTGLATK DGNLHEGDII LKINGTVTEN
MSLTDARKLI EKSRGKLQLV VLRDSQQTLI NIPSLNDSDS EIEDISEIES NRSFSPEERR
HQYSDYDYHS SSEKLKERPS SREDTPSRLS RMGATPTPFK STGDIAGTVV PETNKEPRYQ
EDPPAPQPKA APRTFLRPSP EDEAIYGPNT KMVRFKKGDS VGLRLAGGND VGIFVAGIQE
GTSAEQEGLQ EGDQILKVNT QDFRGLVRED AVLYLLEIPK GEMVTILAQS RADVYRDILA
CGRGDSFFIR SHFECEKETP QSLAFTRGEV FRVVDTLYDG KLGNWLAVRI GNELEKGLIP
NKSRAEQMAS VQNAQRDNAG DRADFWRMRG QRSGVKKNLR KSREDLTAVV SVSTKFPAYE
RVLLREAGFK RPVVLFGPIA DIAMEKLANE LPDWFQTAKT EPKDAGSEKS TGVVRLNTVR
QIIEQDKHAL LDVTPKAVDL LNYTQWFPIV IFFNPDSRQG VKTMRQRLNP TSNKSSRKLF
DQANKLKKTC AHLFTATINL NSANDSWFGS LKDTIQHQQG EAVWVSEGKM EGMDDDPEDR
MSYLTAMGAD YLSCDSRLIS DFEDTDGEGG AYTDNELDEP AEEPLVSSIT RSSEPVQHEE
SIRKPSPEPR AQMRRAASSD QLRDNSPPPA FKPEPPKAKT QNKEESYDFS KSYEYKSNPS
AVAGNETPGA STKGYPPPVA AKPTFGRSIL KPSTPIPPQE GEEVGESSEE QDNAPKSVLG
KVKIFEKMDH KARLQRMQEL QEAQNARIEI AQKHPDIYAV PIKTHKPDPG TPQHTSSRPP
EPQKAPSRPY QDTRGSYGSD AEEEEYRQQL SEHSKRGYYG QSARYRDTEL
