ID CADH1_HUMAN Reviewed; 882 AA. AC P12830; A8K1U7; Q13799; Q14216; Q15855; Q16194; Q4PJ14; Q9UII8; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 3. DT 27-MAR-2024, entry version 263. DE RecName: Full=Cadherin-1; DE AltName: Full=CAM 120/80; DE AltName: Full=Epithelial cadherin; DE Short=E-cadherin; DE AltName: Full=Uvomorulin; DE AltName: CD_antigen=CD324; DE Contains: DE RecName: Full=E-Cad/CTF1; DE Contains: DE RecName: Full=E-Cad/CTF2; DE Contains: DE RecName: Full=E-Cad/CTF3; DE Flags: Precursor; GN Name=CDH1; Synonyms=CDHE, UVO; 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 1). RC TISSUE=Pancreas; RX PubMed=8459805; DOI=10.1007/bf00996219; RA Bussemakers M.J.G., Mees S.G.M., van Bokhoven A., Debruyne F.M.J., RA Schalken J.A.; RT "Molecular cloning and characterization of the human E-cadherin cDNA."; RL Mol. Biol. Rep. 17:123-128(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT 274-GLY--PRO-277 DEL. RX PubMed=8127895; DOI=10.1073/pnas.91.5.1858; RA Oda T., Kanai Y., Oyama T., Yoshiura K., Shimoyama Y., Birchmeier W., RA Sugimura T., Hirohashi S.; RT "E-cadherin gene mutations in human gastric carcinoma cell lines."; RL Proc. Natl. Acad. Sci. U.S.A. 91:1858-1862(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=8185635; DOI=10.1006/bbrc.1994.1656; RA Rimm D.L., Morrow J.S.; RT "Molecular cloning of human E-cadherin suggests a novel subdivision of the RT cadherin superfamily."; RL Biochem. Biophys. Res. Commun. 200:1754-1761(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 586-591, RP PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION. RC TISSUE=Epidermal carcinoma; RX PubMed=10597309; DOI=10.1038/sj.onc.1203191; RA Ito K., Okamoto I., Araki N., Kawano Y., Nakao M., Fujiyama S., Tomita K., RA Mimori T., Saya H.; RT "Calcium influx triggers the sequential proteolysis of extracellular and RT cytoplasmic domains of E-cadherin, leading to loss of beta-catenin from RT cell-cell contacts."; RL Oncogene 18:7080-7090(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Shibamoto S., Fukudome Y., Yanagihara K.; RT "Mutant E-cadherin."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Hippocampus, 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-478; THR-617; MET-832 RP AND LYS-880. RG NIEHS SNPs program; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. RX PubMed=8093045; DOI=10.1006/bbrc.1994.2321; RA Bussemakers M.J.G., Giroldi L.A., van Bokhoven A., Schalken J.A.; RT "Transcriptional regulation of the human E-cadherin gene in human prostate RT cancer cell lines: characterization of the human E-cadherin gene RT promoter."; RL Biochem. Biophys. Res. Commun. 203:1284-1290(1994). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. RC TISSUE=Placenta; RX PubMed=7543680; DOI=10.1073/pnas.92.16.7416; RA Yoshiura K., Kanai Y., Ochiai A., Shimoyama Y., Sugimura T., Hirohashi S.; RT "Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in RT human carcinomas."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7416-7419(1995). RN [12] RP INTERACTION WITH CTNNB1 AND PKP2. RX PubMed=11790773; DOI=10.1074/jbc.m108765200; RA Chen X., Bonne S., Hatzfeld M., van Roy F., Green K.J.; RT "Protein binding and functional characterization of plakophilin 2. Evidence RT for its diverse roles in desmosomes and beta -catenin signaling."; RL J. Biol. Chem. 277:10512-10522(2002). RN [13] RP INTERACTION WITH PIP5K1C. RX PubMed=17261850; DOI=10.1083/jcb.200606023; RA Ling K., Bairstow S.F., Carbonara C., Turbin D.A., Huntsman D.G., RA Anderson R.A.; RT "Type I gamma phosphatidylinositol phosphate kinase modulates adherens RT junction and E-cadherin trafficking via a direct interaction with mu 1B RT adaptin."; RL J. Cell Biol. 176:343-353(2007). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-882. RC TISSUE=Placenta; RX PubMed=7601454; DOI=10.1016/0888-7543(95)80212-5; RA Berx G., Staes K., van Hengel J., Molemans F., Bussemakers M.J.G., RA van Bokhoven A., van Roy F.; RT "Cloning and characterization of the human invasion suppressor gene E- RT cadherin (CDH1)."; RL Genomics 26:281-289(1995). RN [15] RP PROTEIN SEQUENCE OF 155-174, AND FUNCTION AS L.MONOCYTOGENES RECEPTOR RP (MICROBIAL INFECTION). RX PubMed=8601315; DOI=10.1016/s0092-8674(00)81070-3; RA Mengaud J., Ohayon H., Gounon P., Mege R.M., Cossart P.; RT "E-cadherin is the receptor for internalin, a surface protein required for RT entry of L. monocytogenes into epithelial cells."; RL Cell 84:923-932(1996). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 172-311 (ISOFORM 1/2). RC TISSUE=Liver; RX PubMed=3263290; DOI=10.1111/j.1432-0436.1988.tb00593.x; RA Mansouri A., Spurr N., Goodfellow P.N., Kemler R.; RT "Characterization and chromosomal localization of the gene encoding the RT human cell adhesion molecule uvomorulin."; RL Differentiation 38:67-71(1988). RN [17] RP NUCLEOTIDE SEQUENCE [MRNA] OF 265-392 (ISOFORM 1). RC TISSUE=Liver; RA Frixen U.H.; RL Submitted (MAR-1990) to the EMBL/GenBank/DDBJ databases. RN [18] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 337-476, AND VARIANTS ALA-370 AND RP ASP-473. RX PubMed=8033105; RA Becker K.-F., Atkinson M.J., Reich U., Becker I., Nekarda H., Siewert J.R., RA Hoefler H.; RT "E-cadherin gene mutations provide clues to diffuse type gastric RT carcinomas."; RL Cancer Res. 54:3845-3852(1994). RN [19] RP PROTEIN SEQUENCE OF 701-714 AND 732-742, PROTEOLYTIC PROCESSING BY RP GAMMA-SECRETASE/PS1 AND A MEMBRANE-BOUND METALLOPROTEINASE, AND MUTAGENESIS RP OF 759-GLY--GLY-761. RX PubMed=11953314; DOI=10.1093/emboj/21.8.1948; RA Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V., RA Baki L., Wen P., Efthimiopoulos S., Shao Z., Wisniewski T., Robakis N.K.; RT "A presenilin-1/gamma-secretase cleavage releases the E-cadherin RT intracellular domain and regulates disassembly of adherens junctions."; RL EMBO J. 21:1948-1956(2002). RN [20] RP PARTIAL PROTEIN SEQUENCE, AND PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION). RX PubMed=23532847; DOI=10.1074/jbc.m113.459875; RA Sumitomo T., Nakata M., Higashino M., Terao Y., Kawabata S.; RT "Group A streptococcal cysteine protease cleaves epithelial junctions and RT contributes to bacterial translocation."; RL J. Biol. Chem. 288:13317-13324(2013). RN [21] RP DOMAIN CATENIN-BINDING. RX PubMed=2349235; DOI=10.1073/pnas.87.11.4246; RA Ozawa M., Ringwald M., Kemler R.; RT "Uvomorulin-catenin complex formation is regulated by a specific domain in RT the cytoplasmic region of the cell adhesion molecule."; RL Proc. Natl. Acad. Sci. U.S.A. 87:4246-4250(1990). RN [22] RP IDENTIFICATION IN AN E-CADHERIN/CATENIN ADHESION COMPLEX. RX PubMed=7982500; DOI=10.1016/0014-5793(94)01205-9; RA Butz S., Kemler R.; RT "Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell RT adhesion."; RL FEBS Lett. 355:195-200(1994). RN [23] RP FUNCTION AS L.MONOCYTOGENES RECEPTOR (MICROBIAL INFECTION), AND MUTAGENESIS RP OF PRO-170. RX PubMed=10406800; DOI=10.1093/emboj/18.14.3956; RA Lecuit M., Dramsi S., Gottardi C., Fedor-Chaiken M., Gumbiner B., RA Cossart P.; RT "A single amino acid in E-cadherin responsible for host specificity towards RT the human pathogen Listeria monocytogenes."; RL EMBO J. 18:3956-3963(1999). RN [24] RP PROTEOLYTIC PROCESSING. RX PubMed=11076937; DOI=10.1074/jbc.m006102200; RA Steinhusen U., Weiske J., Badock V., Tauber R., Bommert K., Huber O.; RT "Cleavage and shedding of E-cadherin after induction of apoptosis."; RL J. Biol. Chem. 276:4972-4980(2001). RN [25] RP INTERACTION WITH PSEN1. RX PubMed=11226248; DOI=10.1073/pnas.041603398; RA Baki L., Marambaud P., Efthimiopoulos S., Georgakopoulos A., Wen P., RA Cui W., Shioi J., Koo E., Ozawa M., Friedrich V.L., Robakis N.K.; RT "Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 RT association, and regulates stability and function of the cadherin/catenin RT adhesion complex."; RL Proc. Natl. Acad. Sci. U.S.A. 98:2381-2386(2001). RN [26] RP INTERCHAIN DISULFIDE BOND. RX PubMed=11856755; DOI=10.1074/jbc.m200916200; RA Makagiansar I.T., Nguyen P.D., Ikesue A., Kuczera K., Dentler W., RA Urbauer J.L., Galeva N., Alterman M., Siahaan T.J.; RT "Disulfide bond formation promotes the cis- and trans-dimerization of the RT E-cadherin-derived first repeat."; RL J. Biol. Chem. 277:16002-16010(2002). RN [27] RP FUNCTION. RX PubMed=11976333; DOI=10.1074/jbc.m201984200; RA Meigs T.E., Fedor-Chaiken M., Kaplan D.D., Brackenbury R., Casey P.J.; RT "Galpha12 and Galpha13 negatively regulate the adhesive functions of RT cadherin."; RL J. Biol. Chem. 277:24594-24600(2002). RN [28] RP INTERACTION WITH DLGAP5, AND SUBCELLULAR LOCATION. RX PubMed=14699157; DOI=10.1074/jbc.m309843200; RA Laprise P., Viel A., Rivard N.; RT "Human homolog of disc-large is required for adherens junction assembly and RT differentiation of human intestinal epithelial cells."; RL J. Biol. Chem. 279:10157-10166(2004). RN [29] RP INTERACTION WITH AJAP1. RC TISSUE=Brain; RX PubMed=14595118; DOI=10.1091/mbc.e03-05-0281; RA Bharti S., Handrow-Metzmacher H., Zickenheiner S., Zeitvogel A., RA Baumann R., Starzinski-Powitz A.; RT "Novel membrane protein shrew-1 targets to cadherin-mediated junctions in RT polarized epithelial cells."; RL Mol. Biol. Cell 15:397-406(2004). RN [30] RP INTERACTION WITH CTNND1. RX PubMed=15240885; DOI=10.1073/pnas.0401366101; RA Krakstad B.F., Ardawatia V.V., Aragay A.M.; RT "A role for Galpha12/Galpha13 in p120ctn regulation."; RL Proc. Natl. Acad. Sci. U.S.A. 101:10314-10319(2004). RN [31] RP INTERACTION WITH PSEN1 AND CTNNB1, AND MUTAGENESIS OF 759-GLY--GLY-761. RX PubMed=16126725; DOI=10.1074/jbc.m507503200; RA Serban G., Kouchi Z., Baki L., Georgakopoulos A., Litterst C.M., Shioi J., RA Robakis N.K.; RT "Cadherins mediate both the association between PS1 and beta-catenin and RT the effects of PS1 on beta-catenin stability."; RL J. Biol. Chem. 280:36007-36012(2005). RN [32] RP SUBCELLULAR LOCATION. RX PubMed=15689490; DOI=10.1091/mbc.e04-10-0867; RA Lock J.G., Stow J.L.; RT "Rab11 in recycling endosomes regulates the sorting and basolateral RT transport of E-cadherin."; RL Mol. Biol. Cell 16:1744-1755(2005). RN [33] RP FUNCTION OF E-CAD/CTF2. RX PubMed=16417575; DOI=10.1111/j.1471-4159.2005.03616.x; RA Agiostratidou G., Muros R.M., Shioi J., Marambaud P., Robakis N.K.; RT "The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic RT degradation of A beta precursors."; RL J. Neurochem. 96:1182-1188(2006). RN [34] RP INDUCTION. RX PubMed=17893710; DOI=10.1038/cr.2007.79; RA Meng Y.G., Han W.-D., Zhao Y.-L., Huang K., Si Y.-L., Wu Z.-Q., Mu Y.-M.; RT "Induction of the LRP16 gene by estrogen promotes the invasive growth of RT Ishikawa human endometrial cancer cells through the downregulation of E- RT cadherin."; RL Cell Res. 17:869-880(2007). RN [35] RP INVOLVEMENT IN LBC. RX PubMed=17660459; DOI=10.1136/jmg.2007.051268; RA Masciari S., Larsson N., Senz J., Boyd N., Kaurah P., Kandel M.J., RA Harris L.N., Pinheiro H.C., Troussard A., Miron P., Tung N., Oliveira C., RA Collins L., Schnitt S., Garber J.E., Huntsman D.; RT "Germline E-cadherin mutations in familial lobular breast cancer."; RL J. Med. Genet. 44:726-731(2007). RN [36] RP GLYCOSYLATION AT ASN-558; ASN-570; ASN-622 AND ASN-637, AND MUTAGENESIS OF RP ASN-637. RX PubMed=18491227; DOI=10.1007/s10719-008-9133-9; RA Zhou F., Su J., Fu L., Yang Y., Zhang L., Wang L., Zhao H., Zhang D., RA Li Z., Zha X.; RT "Unglycosylation at Asn-633 made extracellular domain of E-cadherin folded RT incorrectly and arrested in endoplasmic reticulum, then sequentially RT degraded by ERAD."; RL Glycoconj. J. 25:727-740(2008). RN [37] RP INTERACTION WITH LIMA1. RX PubMed=18093941; DOI=10.1073/pnas.0710504105; RA Abe K., Takeichi M.; RT "EPLIN mediates linkage of the cadherin catenin complex to F-actin and RT stabilizes the circumferential actin belt."; RL Proc. Natl. Acad. Sci. U.S.A. 105:13-19(2008). RN [38] RP REVIEW ON CADHERINS. RX PubMed=20066110; DOI=10.1101/cshperspect.a003053; RA Shapiro L., Weis W.I.; RT "Structure and biochemistry of cadherins and catenins."; RL Cold Spring Harb. Perspect. Biol. 1:A3053-A3053(2009). RN [39] RP SUBCELLULAR LOCATION, AND GLYCOSYLATION. RX PubMed=19403558; DOI=10.1093/hmg/ddp194; RA Pinho S.S., Reis C.A., Paredes J., Magalhaes A.M., Ferreira A.C., RA Figueiredo J., Xiaogang W., Carneiro F., Gaertner F., Seruca R.; RT "The role of N-acetylglucosaminyltransferase III and V in the post- RT transcriptional modifications of E-cadherin."; RL Hum. Mol. Genet. 18:2599-2608(2009). RN [40] RP INTERACTION WITH TBC1D2. RX PubMed=20116244; DOI=10.1016/j.cub.2009.12.053; RA Frasa M.A., Maximiano F.C., Smolarczyk K., Francis R.E., Betson M.E., RA Lozano E., Goldenring J., Seabra M.C., Rak A., Ahmadian M.R., Braga V.M.; RT "Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin RT degradation."; RL Curr. Biol. 20:198-208(2010). RN [41] RP SUBCELLULAR LOCATION, AND INTERACTION WITH DDR1. RX PubMed=20432435; DOI=10.1002/jcp.22134; RA Eswaramoorthy R., Wang C.K., Chen W.C., Tang M.J., Ho M.L., Hwang C.C., RA Wang H.M., Wang C.Z.; RT "DDR1 regulates the stabilization of cell surface E-cadherin and E- RT cadherin-mediated cell aggregation."; RL J. Cell. Physiol. 224:387-397(2010). RN [42] 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 [43] RP UBIQUITINATION BY CBLL1. RX PubMed=21283129; DOI=10.1038/cr.2011.17; RA Zhou W.J., Geng Z.H., Chi S., Zhang W., Niu X.F., Lan S.J., Ma L., Yang X., RA Wang L.J., Ding Y.Q., Geng J.G.; RT "Slit-Robo signaling induces malignant transformation through Hakai- RT mediated E-cadherin degradation during colorectal epithelial cell RT carcinogenesis."; RL Cell Res. 21:609-626(2011). RN [44] RP UBIQUITINATION BY A SKP2-CONTAINING SCF COMPLEX, AND PHOSPHORYLATION BY RP CSNK1A1. RX PubMed=22770219; DOI=10.1016/j.cell.2012.05.038; RA Inuzuka H., Gao D., Finley L.W., Yang W., Wan L., Fukushima H., Chin Y.R., RA Zhai B., Shaik S., Lau A.W., Wang Z., Gygi S.P., Nakayama K., RA Teruya-Feldstein J., Toker A., Haigis M.C., Pandolfi P.P., Wei W.; RT "Acetylation-dependent regulation of Skp2 function."; RL Cell 150:179-193(2012). RN [45] RP PHOSPHORYLATION AT TYR-753; TYR-754 AND TYR-755, AND MUTAGENESIS OF RP TYR-754. RX PubMed=22252131; DOI=10.1038/emboj.2011.496; RA Mukherjee M., Chow S.Y., Yusoff P., Seetharaman J., Ng C., Sinniah S., RA Koh X.W., Asgar N.F., Li D., Yim D., Jackson R.A., Yew J., Qian J., Iyu A., RA Lim Y.P., Zhou X., Sze S.K., Guy G.R., Sivaraman J.; RT "Structure of a novel phosphotyrosine-binding domain in Hakai that targets RT E-cadherin."; RL EMBO J. 31:1308-1319(2012). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-770 AND SER-793, 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 [47] 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 [48] RP INTERACTION WITH SPEF1. 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 [49] {ECO:0007744|PDB:1O6S} RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 156-255 IN COMPLEX WITH RP L.MONOCYTOGENES INLA, FUNCTION (MICROBIAL INFECTION), SUBUNIT (MICROBIAL RP INFECTION), AND MUTAGENESIS OF TRP-156 AND PRO-170. RX PubMed=12526809; DOI=10.1016/s0092-8674(02)01136-4; RA Schubert W.-D., Urbanke C., Ziehm T., Beier V., Machner M.P., Domann E., RA Wehland J., Chakraborty T., Heinz D.W.; RT "Structure of internalin, a major invasion protein of Listeria RT monocytogenes, in complex with its human receptor E-cadherin."; RL Cell 111:825-836(2002). RN [50] RP REVIEW ON VARIANTS. RX PubMed=9744472; RX DOI=10.1002/(sici)1098-1004(1998)12:4<226::aid-humu2>3.0.co;2-d; RA Berx G., Becker K.-F., Hoefler H., van Roy F.; RT "Mutations of the human E-cadherin (CDH1) gene."; RL Hum. Mutat. 12:226-237(1998). RN [51] {ECO:0007744|PDB:2OMV, ECO:0007744|PDB:2OMY} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 156-255 IN COMPLEX WITH RP L.MONOCYTOGENES INLA, FUNCTION (MICROBIAL INFECTION), AND SUBUNIT RP (MICROBIAL INFECTION). RX PubMed=17540170; DOI=10.1016/j.cell.2007.03.049; RA Wollert T., Pasche B., Rochon M., Deppenmeier S., van den Heuvel J., RA Gruber A.D., Heinz D.W., Lengeling A., Schubert W.D.; RT "Extending the host range of Listeria monocytogenes by rational protein RT design."; RL Cell 129:891-902(2007). RN [52] {ECO:0007744|PDB:2OMU, ECO:0007744|PDB:2OMZ} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 156-255 IN COMPLEX WITH RP L.MONOCYTOGENES INLA, AND SUBUNIT (MICROBIAL INFECTION). RX PubMed=17715295; DOI=10.1073/pnas.0702199104; RA Wollert T., Heinz D.W., Schubert W.D.; RT "Thermodynamically reengineering the listerial invasion complex InlA/E- RT cadherin."; RL Proc. Natl. Acad. Sci. U.S.A. 104:13960-13965(2007). RN [53] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 155-367, AND CALCIUM-BINDING RP SITES. RX PubMed=17850815; DOI=10.1016/j.jmb.2007.08.011; RA Parisini E., Higgins J.M., Liu J.H., Brenner M.B., Wang J.H.; RT "The crystal structure of human E-cadherin domains 1 and 2, and comparison RT with other cadherins in the context of adhesion mechanism."; RL J. Mol. Biol. 373:401-411(2007). RN [54] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 155-253 IN COMPLEX WITH KLRG1. RX PubMed=19604491; DOI=10.1016/j.immuni.2009.04.019; RA Li Y., Hofmann M., Wang Q., Teng L., Chlewicki L.K., Pircher H., RA Mariuzza R.A.; RT "Structure of natural killer cell receptor KLRG1 bound to E-cadherin RT reveals basis for MHC-independent missing self recognition."; RL Immunity 31:35-46(2009). RN [55] RP VARIANT LOBULAR BREAST CARCINOMA SER-315. RX PubMed=7961105; DOI=10.1111/j.1349-7006.1994.tb02902.x; RA Kanai Y., Oda T., Tsuda H., Ochiai A., Hirohashi S.; RT "Point mutation of the E-cadherin gene in invasive lobular carcinoma of the RT breast."; RL Jpn. J. Cancer Res. 85:1035-1039(1994). RN [56] RP VARIANTS THR-617 AND VAL-711, AND VARIANT OVARIAN CANCER GLY-838. RX PubMed=8075649; DOI=10.1038/ng0594-98; RA Risinger J.I., Berchuck A., Kohler M.F., Boyd J.; RT "Mutations of the E-cadherin gene in human gynecologic cancers."; RL Nat. Genet. 7:98-102(1994). RN [57] RP VARIANT PRO-193. RX PubMed=8797891; DOI=10.1111/j.1349-7006.1996.tb02109.x; RA Muta H., Noguchi M., Kanai Y., Ochiai A., Nawata H., Hirohashi S.; RT "E-cadherin gene mutations in signet ring cell carcinoma of the stomach."; RL Jpn. J. Cancer Res. 87:843-848(1996). RN [58] RP VARIANTS ASP-400 DEL AND 418-ASP--PHE-423 DEL. RX PubMed=9045944; DOI=10.1111/j.1349-7006.1996.tb03125.x; RA Tamura G., Sakata K., Nishizuka S., Maesawa C., Suzuki Y., Iwaya T., RA Terashima M., Saito K., Satodate R.; RT "Inactivation of the E-cadherin gene in primary gastric carcinomas and RT gastric carcinoma cell lines."; RL Jpn. J. Cancer Res. 87:1153-1159(1996). RN [59] RP VARIANT THYROID CANCER THR-592. RX PubMed=8985087; RX DOI=10.1002/(sici)1097-0215(19970106)70:1<32::aid-ijc5>3.0.co;2-7; RA Soares P., Berx G., van Roy F., Sobrinho-Simoes M.; RT "E-cadherin gene alterations are rare events in thyroid tumors."; RL Int. J. Cancer 70:32-38(1997). RN [60] RP VARIANTS ASP-336 AND ILE-470. RX PubMed=9537325; DOI=10.1038/32918; RA Guilford P.J., Hopkins J.B.W., Harraway J., McLeod M., McLeod N., RA Harawira P., Taite H., Scoular R., Miller A., Reeve A.E.; RT "E-cadherin germline mutations in familial gastric cancer."; RL Nature 392:402-405(1998). RN [61] RP VARIANTS DGLBC GLY-244 AND ALA-487. RX PubMed=10319582; DOI=10.1007/s100380050137; RA Yoon K.-A., Ku J.-L., Yang H.-K., Kim W.H., Park S.Y., Park J.-G.; RT "Germline mutations of E-cadherin gene in Korean familial gastric cancer RT patients."; RL J. Hum. Genet. 44:177-180(1999). RN [62] RP VARIANT ALA-340. RX PubMed=10896919; DOI=10.1136/gut.47.2.262; RA Kim H.C., Wheeler J.M.D., Kim J.C., Ilyas M., Beck N.E., Kim B.S., RA Park K.C., Bodmer W.F.; RT "The E-cadherin gene (CDH1) variants T340A and L599V in gastric and RT colorectal cancer patients in Korea."; RL Gut 47:262-267(2000). RN [63] RP VARIANT ALA-270. RX PubMed=11705864; RA Ikonen T., Matikainen M., Mononen N., Hyytinen E.R., Helin H.J., RA Tommola S., Tammela T.L., Pukkala E., Schleutker J., Kallioniemi O.-P., RA Koivisto P.A.; RT "Association of E-cadherin germ-line alterations with prostate cancer."; RL Clin. Cancer Res. 7:3465-3471(2001). RN [64] RP VARIANT THR-592. RX PubMed=11562785; DOI=10.3892/ijmm.8.4.439; RA Salahshor S., Hou H., Diep C.B., Loukola A., Zhang H., Liu T., Chen J., RA Iselius L., Rubio C., Lothe R.A., Aaltonen L., Sun X.F., Lindmark G., RA Lindblom A.; RT "A germline E-cadherin mutation in a family with gastric and colon RT cancer."; RL Int. J. Mol. Med. 8:439-443(2001). RN [65] RP VARIANT ALA-340. RX PubMed=11968083; DOI=10.1002/humu.10068; RA Oliveira C., Bordin M.C., Grehan N., Huntsman D., Suriano G., Machado J.C., RA Kiviluoto T., Aaltonen L., Jackson C.E., Seruca R., Caldas C.; RT "Screening E-cadherin in gastric cancer families reveals germline mutations RT only in hereditary diffuse gastric cancer kindred."; RL Hum. Mutat. 19:510-517(2002). RN [66] RP VARIANT DGLBC MET-832. RX PubMed=12216071; DOI=10.1002/ijc.10633; RA Yabuta T., Shinmura K., Tani M., Yamaguchi S., Yoshimura K., Katai H., RA Nakajima T., Mochiki E., Tsujinaka T., Takami M., Hirose K., Yamaguchi A., RA Takenoshita S., Yokota J.; RT "E-cadherin gene variants in gastric cancer families whose probands are RT diagnosed with diffuse gastric cancer."; RL Int. J. Cancer 101:434-441(2002). RN [67] RP VARIANTS THR-617 AND VAL-634, AND CHARACTERIZATION OF VARIANTS ALA-340; RP THR-617 AND VAL-634. RX PubMed=12588804; DOI=10.1093/hmg/ddg048; RA Suriano G., Oliveira C., Ferreira P., Machado J.C., Bordin M.C., RA De Wever O., Bruyneel E.A., Moguilevsky N., Grehan N., Porter T.R., RA Richards F.M., Hruban R.H., Roviello F., Huntsman D., Mareel M., RA Carneiro F., Caldas C., Seruca R.; RT "Identification of CDH1 germline missense mutations associated with RT functional inactivation of the E-cadherin protein in young gastric cancer RT probands."; RL Hum. Mol. Genet. 12:575-582(2003). RN [68] RP VARIANTS ILE-282 AND ASN-777. RX PubMed=17224074; DOI=10.1186/bcr1637; RA Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., RA Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., RA Boerresen-Dale A.-L.; RT "Somatic sequence alterations in twenty-one genes selected by expression RT profile analysis of breast carcinomas."; RL Breast Cancer Res. 9:R5-R5(2007). RN [69] RP INVOLVEMENT IN BCDS1, VARIANTS BCDS1 TYR-254; VAL-257 AND VAL-454 DEL, RP CHARACTERIZATION OF VARIANTS BCDS1 TYR-254; VAL-257 AND VAL-454 DEL, AND RP SUBCELLULAR LOCATION. RX PubMed=28301459; DOI=10.1038/gim.2017.11; RA Ghoumid J., Stichelbout M., Jourdain A.S., Frenois F., Lejeune-Dumoulin S., RA Alex-Cordier M.P., Lebrun M., Guerreschi P., Duquennoy-Martinot V., RA Vinchon M., Ferri J., Jung M., Vicaire S., Vanlerberghe C., Escande F., RA Petit F., Manouvrier-Hanu S.; RT "Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to RT mutations in CDH1 and CTNND1."; RL Genet. Med. 19:1013-1021(2017). CC -!- FUNCTION: Cadherins are calcium-dependent cell adhesion proteins CC (PubMed:11976333). They preferentially interact with themselves in a CC homophilic manner in connecting cells; cadherins may thus contribute to CC the sorting of heterogeneous cell types. CDH1 is involved in mechanisms CC regulating cell-cell adhesions, mobility and proliferation of CC epithelial cells (PubMed:11976333). Has a potent invasive suppressor CC role. It is a ligand for integrin alpha-E/beta-7. CC {ECO:0000269|PubMed:11976333, ECO:0000269|PubMed:16417575}. CC -!- FUNCTION: E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta CC precursors. Has a strong inhibitory effect on APP C99 and C83 CC production. {ECO:0000269|PubMed:16417575}. CC -!- FUNCTION: (Microbial infection) Serves as a receptor for Listeria CC monocytogenes; internalin A (InlA) binds to this protein and promotes CC uptake of the bacteria. {ECO:0000269|PubMed:10406800, CC ECO:0000269|PubMed:17540170, ECO:0000269|PubMed:8601315}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:11856755). Component of an CC E-cadherin/ catenin adhesion complex composed of at least E- CC cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP, and CC potentially alpha-catenin/CTNNA1; the complex is located to adherens CC junctions (PubMed:16126725, PubMed:7982500). Interacts with the TRPV4 CC and CTNNB1 complex (By similarity). Interacts with CTNND1 CC (PubMed:15240885). The stable association of CTNNA1 is controversial as CC CTNNA1 was shown not to bind to F-actin when assembled in the complex CC (By similarity). Alternatively, the CTNNA1-containing complex may be CC linked to F-actin by other proteins such as LIMA1 (By similarity). CC Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of CC cadherin-based adherens junctions (CAJs) (PubMed:11226248, CC PubMed:16126725). Interacts with AJAP1 and DLGAP5 (PubMed:14699157, CC PubMed:14595118). Interacts with TBC1D2 (PubMed:20116244). Interacts CC with LIMA1 (PubMed:18093941). Interacts with CAV1. Interacts with CC PIP5K1C (PubMed:17261850). Interacts with RAB8B (By similarity). CC Interacts with RAPGEF2 (By similarity). Interacts with DDR1; this CC stabilizes CDH1 at the cell surface and inhibits its internalization CC (PubMed:20432435). Interacts with KLRG1 (PubMed:19604491). Forms a CC ternary complex composed of ADAM10, CADH1 and EPHA4; within the CC complex, CADH1 is cleaved by ADAM10 which disrupts adherens junctions CC (By similarity). Interacts with SPEF1 (PubMed:31473225). Interacts with CC CTNNB1 and PKP2 (PubMed:11790773). {ECO:0000250, CC ECO:0000250|UniProtKB:P09803, ECO:0000250|UniProtKB:Q9R0T4, CC ECO:0000269|PubMed:11226248, ECO:0000269|PubMed:11790773, CC ECO:0000269|PubMed:11856755, ECO:0000269|PubMed:12526809, CC ECO:0000269|PubMed:14595118, ECO:0000269|PubMed:14699157, CC ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:16126725, CC ECO:0000269|PubMed:17261850, ECO:0000269|PubMed:18093941, CC ECO:0000269|PubMed:19604491, ECO:0000269|PubMed:20116244, CC ECO:0000269|PubMed:20432435, ECO:0000269|PubMed:31473225, CC ECO:0000269|PubMed:7982500}. CC -!- SUBUNIT: (Microbial infection) Interacts with L.monocytogenes InlA CC (PubMed:12526809, PubMed:17540170, PubMed:17715295). The formation of CC the complex between InlA and cadherin-1 is calcium-dependent CC (PubMed:12526809). {ECO:0000269|PubMed:12526809, CC ECO:0000269|PubMed:17540170, ECO:0000269|PubMed:17715295}. CC -!- INTERACTION: CC P12830; O94983-5: CAMTA2; NbExp=3; IntAct=EBI-727477, EBI-10176008; CC P12830; P30260: CDC27; NbExp=2; IntAct=EBI-727477, EBI-994813; CC P12830; P12830: CDH1; NbExp=7; IntAct=EBI-727477, EBI-727477; CC P12830; Q6UXH1-2: CRELD2; NbExp=3; IntAct=EBI-727477, EBI-21670927; CC P12830; P35221: CTNNA1; NbExp=8; IntAct=EBI-727477, EBI-701918; CC P12830; P35222: CTNNB1; NbExp=17; IntAct=EBI-727477, EBI-491549; CC P12830; P49184: DNASE1L1; NbExp=3; IntAct=EBI-727477, EBI-20894690; CC P12830; Q9H8V3: ECT2; NbExp=3; IntAct=EBI-727477, EBI-1054039; CC P12830; P00533: EGFR; NbExp=4; IntAct=EBI-727477, EBI-297353; CC P12830; P16422: EPCAM; NbExp=3; IntAct=EBI-727477, EBI-1171184; CC P12830; P11362: FGFR1; NbExp=3; IntAct=EBI-727477, EBI-1028277; CC P12830; Q7Z6Z7-2: HUWE1; NbExp=3; IntAct=EBI-727477, EBI-10975491; CC P12830; Q9UHB6: LIMA1; NbExp=2; IntAct=EBI-727477, EBI-351479; CC P12830; P43356: MAGEA2B; NbExp=3; IntAct=EBI-727477, EBI-5650739; CC P12830; Q7Z434: MAVS; NbExp=3; IntAct=EBI-727477, EBI-995373; CC P12830; Q8NCR3: MFI; NbExp=3; IntAct=EBI-727477, EBI-744790; CC P12830; Q8TB02: MGC39372; NbExp=3; IntAct=EBI-727477, EBI-25834188; CC P12830; Q9NPC7: MYNN; NbExp=3; IntAct=EBI-727477, EBI-3446748; CC P12830; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-727477, EBI-11750983; CC P12830; Q8N323: NXPE1; NbExp=3; IntAct=EBI-727477, EBI-25834085; CC P12830; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-727477, EBI-473160; CC P12830; Q8NBT0: POC1A; NbExp=3; IntAct=EBI-727477, EBI-2557132; CC P12830; P62136: PPP1CA; NbExp=2; IntAct=EBI-727477, EBI-357253; CC P12830; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-727477, EBI-2860740; CC P12830; P17612: PRKACA; NbExp=3; IntAct=EBI-727477, EBI-476586; CC P12830; Q15139: PRKD1; NbExp=7; IntAct=EBI-727477, EBI-1181072; CC P12830; Q9Y617: PSAT1; NbExp=3; IntAct=EBI-727477, EBI-709652; CC P12830; P50454: SERPINH1; NbExp=3; IntAct=EBI-727477, EBI-350723; CC P12830; Q02978: SLC25A11; NbExp=3; IntAct=EBI-727477, EBI-359174; CC P12830; P12931: SRC; NbExp=2; IntAct=EBI-727477, EBI-621482; CC P12830; P48775: TDO2; NbExp=3; IntAct=EBI-727477, EBI-743494; CC P12830; P37173: TGFBR2; NbExp=3; IntAct=EBI-727477, EBI-296151; CC P12830; Q9BT49: THAP7; NbExp=3; IntAct=EBI-727477, EBI-741350; CC P12830; Q68CZ2: TNS3; NbExp=2; IntAct=EBI-727477, EBI-1220488; CC P12830; Q9ULW0: TPX2; NbExp=3; IntAct=EBI-727477, EBI-1037322; CC P12830; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-727477, EBI-25830993; CC P12830; Q9BQ29; NbExp=3; IntAct=EBI-727477, EBI-22013570; CC P12830; Q9JIY2: Cbll1; Xeno; NbExp=21; IntAct=EBI-727477, EBI-7644904; CC P12830; P0DJM0: inlA; Xeno; NbExp=3; IntAct=EBI-727477, EBI-1035388; CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction CC {ECO:0000269|PubMed:28169360}. Cell membrane CC {ECO:0000269|PubMed:19403558, ECO:0000269|PubMed:28301459}; Single-pass CC type I membrane protein. Endosome. Golgi apparatus, trans-Golgi CC network. Note=Colocalizes with DLGAP5 at sites of cell-cell contact in CC intestinal epithelial cells. Anchored to actin microfilaments through CC association with alpha-, beta- and gamma-catenin. Sequential CC proteolysis induced by apoptosis or calcium influx, results in CC translocation from sites of cell-cell contact to the cytoplasm. CC Colocalizes with RAB11A endosomes during its transport from the Golgi CC apparatus to the plasma membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P12830-1; Sequence=Displayed; CC Name=2; CC IsoId=P12830-2; Sequence=VSP_055586; CC -!- TISSUE SPECIFICITY: Non-neural epithelial tissues. CC -!- INDUCTION: Expression is repressed by MACROD1. CC {ECO:0000269|PubMed:17893710}. CC -!- DOMAIN: Three calcium ions are usually bound at the interface of each CC cadherin domain and rigidify the connections, imparting a strong CC curvature to the full-length ectodomain. {ECO:0000269|PubMed:2349235}. CC -!- PTM: During apoptosis or with calcium influx, cleaved by a membrane- CC bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 CC (PubMed:11076937, PubMed:11953314, PubMed:10597309). Processing by the CC metalloproteinase, induced by calcium influx, causes disruption of CC cell-cell adhesion and the subsequent release of beta-catenin into the CC cytoplasm (PubMed:10597309). The residual membrane-tethered cleavage CC product is rapidly degraded via an intracellular proteolytic pathway CC (PubMed:10597309). Cleavage by caspase-3 releases the cytoplasmic tail CC resulting in disintegration of the actin microfilament system CC (PubMed:11076937). The gamma-secretase-mediated cleavage promotes CC disassembly of adherens junctions (PubMed:11953314). During development CC of the cochlear organ of Corti, cleavage by ADAM10 at adherens CC junctions promotes pillar cell separation (By similarity). CC {ECO:0000250|UniProtKB:P09803, ECO:0000269|PubMed:10597309, CC ECO:0000269|PubMed:11076937, ECO:0000269|PubMed:11953314}. CC -!- PTM: N-glycosylation at Asn-637 is essential for expression, folding CC and trafficking. Addition of bisecting N-acetylglucosamine by MGAT3 CC modulates its cell membrane location (PubMed:19403558). CC {ECO:0000269|PubMed:18491227, ECO:0000269|PubMed:19403558}. CC -!- PTM: Ubiquitinated by a SCF complex containing SKP2, which requires CC prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI, CC requires prior phosphorylation at Tyr-754. CC {ECO:0000269|PubMed:21283129, ECO:0000269|PubMed:22252131, CC ECO:0000269|PubMed:22770219}. CC -!- PTM: O-glycosylated. O-manosylated by TMTC1, TMTC2, TMTC3 or TMTC4. CC Thr-285 and Thr-509 are O-mannosylated by TMTC2 or TMTC4 but not TMTC1 CC or TMTC3. {ECO:0000250|UniProtKB:P09803}. CC -!- PTM: (Microbial infection) Cleaved by S.pyogenes SpeB protease; leading CC to its degradation (PubMed:23532847). Degradation by SpeB promotes CC bacterial translocation across the host epithelial barrier CC (PubMed:23532847). {ECO:0000269|PubMed:23532847}. CC -!- DISEASE: Diffuse gastric and lobular breast cancer syndrome (DGLBC) CC [MIM:137215]: A cancer predisposition syndrome with increased CC susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a CC malignant disease characterized by poorly differentiated infiltrating CC lesions resulting in thickening of the stomach. Malignant tumors start CC in the stomach, can spread to the esophagus or the small intestine, and CC can extend through the stomach wall to nearby lymph nodes and organs. CC It also can metastasize to other parts of the body. In addition to CC gastric cancer, most female mutation carriers develop lobular carcinoma CC of the breast. {ECO:0000269|PubMed:10319582, CC ECO:0000269|PubMed:12216071}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC Heterozygous CDH1 germline mutations are responsible for familial cases CC of diffuse gastric cancer. Somatic mutations has also been found in CC patients with sporadic diffuse gastric cancer and lobular breast CC cancer. CC -!- DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of CC endometrium, the mucous lining of the uterus. Most endometrial cancers CC are adenocarcinomas, cancers that begin in cells that make and release CC mucus and other fluids. Note=Disease susceptibility is associated with CC variants affecting the gene represented in this entry. CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer CC defines malignancies originating from ovarian tissue. Although many CC histologic types of ovarian tumors have been described, epithelial CC ovarian carcinoma is the most common form. Ovarian cancers are often CC asymptomatic and the recognized signs and symptoms, even of late-stage CC disease, are vague. Consequently, most patients are diagnosed with CC advanced disease. {ECO:0000269|PubMed:8075649}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Breast cancer, lobular (LBC) [MIM:137215]: A type of breast CC cancer that begins in the milk-producing glands (lobules) of the CC breast. {ECO:0000269|PubMed:17660459}. Note=The gene represented in CC this entry may be involved in disease pathogenesis. CC -!- DISEASE: Blepharocheilodontic syndrome 1 (BCDS1) [MIM:119580]: A form CC of blepharocheilodontic syndrome, a rare autosomal dominant disorder. CC It is characterized by lower eyelid ectropion, upper eyelid CC distichiasis, euryblepharon, bilateral cleft lip and palate, and CC features of ectodermal dysplasia, including hair anomalies, conical CC teeth and tooth agenesis. An additional rare manifestation is CC imperforate anus. There is considerable phenotypic variability among CC affected individuals. {ECO:0000269|PubMed:28301459}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAA61259.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/166/CDH1"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cdh1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=E-cadherin entry; CC URL="https://en.wikipedia.org/wiki/E-cadherin"; 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; Z13009; CAA78353.1; -; mRNA. DR EMBL; Z18923; CAA79356.1; -; mRNA. DR EMBL; L08599; AAA61259.1; ALT_FRAME; mRNA. DR EMBL; AB025105; BAA88956.1; -; mRNA. DR EMBL; AK290012; BAF82701.1; -; mRNA. DR EMBL; AK312551; BAG35448.1; -; mRNA. DR EMBL; DQ090940; AAY68225.1; -; Genomic_DNA. DR EMBL; AC099314; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471092; EAW83243.1; -; Genomic_DNA. DR EMBL; CH471092; EAW83244.1; -; Genomic_DNA. DR EMBL; L34545; AAA21764.1; -; Genomic_DNA. DR EMBL; D49685; BAA08537.1; -; Genomic_DNA. DR EMBL; Z35402; CAA84586.1; -; Genomic_DNA. DR EMBL; Z35403; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35404; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35405; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35406; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35407; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35408; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35409; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35410; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35411; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35412; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35413; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35414; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; Z35415; CAA84586.1; JOINED; Genomic_DNA. DR EMBL; X12790; CAA31279.1; -; mRNA. DR EMBL; X52279; CAA36522.1; -; mRNA. DR EMBL; S72492; AAD14108.1; -; Genomic_DNA. DR EMBL; S72397; AAD14108.1; JOINED; Genomic_DNA. DR EMBL; S72491; AAD14108.1; JOINED; Genomic_DNA. DR CCDS; CCDS10869.1; -. [P12830-1] DR CCDS; CCDS82005.1; -. [P12830-2] DR PIR; S37654; IJHUCE. DR RefSeq; NP_001304113.1; NM_001317184.1. [P12830-2] DR RefSeq; NP_001304114.1; NM_001317185.1. DR RefSeq; NP_001304115.1; NM_001317186.1. DR RefSeq; NP_004351.1; NM_004360.4. [P12830-1] DR PDB; 1O6S; X-ray; 1.80 A; B=156-255. DR PDB; 2O72; X-ray; 2.00 A; A=155-367. DR PDB; 2OMT; X-ray; 2.00 A; B=156-255. DR PDB; 2OMU; X-ray; 1.80 A; B=156-255. DR PDB; 2OMV; X-ray; 1.90 A; B=156-255. DR PDB; 2OMX; X-ray; 1.70 A; B=156-258. DR PDB; 2OMY; X-ray; 1.70 A; B=156-254. DR PDB; 2OMZ; X-ray; 1.60 A; B=156-254. DR PDB; 3FF7; X-ray; 1.80 A; A/B=155-253. DR PDB; 3FF8; X-ray; 2.00 A; A/B=155-254. DR PDB; 3L6X; X-ray; 2.40 A; B=756-773. DR PDB; 3L6Y; X-ray; 3.00 A; B/D/F=756-773. DR PDB; 4ZT1; X-ray; 1.92 A; A/B=157-367. DR PDB; 4ZTE; X-ray; 2.13 A; A/B=157-367. DR PDB; 6CXY; X-ray; 2.20 A; C=155-371. DR PDB; 6OLE; EM; 3.10 A; y=693-730. DR PDB; 6OLF; EM; 3.90 A; y=693-730. DR PDB; 6OLG; EM; 3.40 A; A=693-730. DR PDB; 6VEL; X-ray; 2.65 A; C=155-371. DR PDB; 7STZ; X-ray; 2.95 A; C/D=155-698. DR PDB; 8H62; X-ray; 1.91 A; B=155-367. DR PDBsum; 1O6S; -. DR PDBsum; 2O72; -. DR PDBsum; 2OMT; -. DR PDBsum; 2OMU; -. DR PDBsum; 2OMV; -. DR PDBsum; 2OMX; -. DR PDBsum; 2OMY; -. DR PDBsum; 2OMZ; -. DR PDBsum; 3FF7; -. DR PDBsum; 3FF8; -. DR PDBsum; 3L6X; -. DR PDBsum; 3L6Y; -. DR PDBsum; 4ZT1; -. DR PDBsum; 4ZTE; -. DR PDBsum; 6CXY; -. DR PDBsum; 6OLE; -. DR PDBsum; 6OLF; -. DR PDBsum; 6OLG; -. DR PDBsum; 6VEL; -. DR PDBsum; 7STZ; -. DR PDBsum; 8H62; -. DR AlphaFoldDB; P12830; -. DR EMDB; EMD-25883; -. DR EMDB; EMD-25884; -. DR EMDB; EMD-25886; -. DR EMDB; EMD-25892; -. DR SMR; P12830; -. DR BioGRID; 107434; 766. DR CORUM; P12830; -. DR DIP; DIP-477N; -. DR ELM; P12830; -. DR IntAct; P12830; 126. DR MINT; P12830; -. DR STRING; 9606.ENSP00000261769; -. DR BindingDB; P12830; -. DR ChEMBL; CHEMBL2321609; -. DR TCDB; 8.A.204.1.1; the cadhesin (cdh) family. DR UniLectin; P12830; -. DR GlyCosmos; P12830; 13 sites, No reported glycans. DR GlyGen; P12830; 16 sites, 2 O-linked glycans (3 sites). DR iPTMnet; P12830; -. DR PhosphoSitePlus; P12830; -. DR SwissPalm; P12830; -. DR BioMuta; CDH1; -. DR DMDM; 399166; -. DR CPTAC; CPTAC-1599; -. DR CPTAC; CPTAC-5772; -. DR CPTAC; CPTAC-5773; -. DR CPTAC; non-CPTAC-5366; -. DR CPTAC; non-CPTAC-5367; -. DR CPTAC; non-CPTAC-5370; -. DR CPTAC; non-CPTAC-5541; -. DR CPTAC; non-CPTAC-5542; -. DR EPD; P12830; -. DR jPOST; P12830; -. DR MassIVE; P12830; -. DR MaxQB; P12830; -. DR PaxDb; 9606-ENSP00000261769; -. DR PeptideAtlas; P12830; -. DR ProteomicsDB; 52879; -. [P12830-1] DR ProteomicsDB; 84533; -. DR Pumba; P12830; -. DR TopDownProteomics; P12830-2; -. [P12830-2] DR ABCD; P12830; 29 sequenced antibodies. DR Antibodypedia; 1347; 3447 antibodies from 59 providers. DR CPTC; P12830; 4 antibodies. DR DNASU; 999; -. DR Ensembl; ENST00000261769.10; ENSP00000261769.4; ENSG00000039068.20. [P12830-1] DR Ensembl; ENST00000422392.6; ENSP00000414946.2; ENSG00000039068.20. [P12830-2] DR GeneID; 999; -. DR KEGG; hsa:999; -. DR MANE-Select; ENST00000261769.10; ENSP00000261769.4; NM_004360.5; NP_004351.1. DR UCSC; uc002ewg.2; human. [P12830-1] DR AGR; HGNC:1748; -. DR CTD; 999; -. DR DisGeNET; 999; -. DR GeneCards; CDH1; -. DR GeneReviews; CDH1; -. DR HGNC; HGNC:1748; CDH1. DR HPA; ENSG00000039068; Tissue enhanced (parathyroid). DR MalaCards; CDH1; -. DR MIM; 119580; phenotype. DR MIM; 137215; phenotype. DR MIM; 167000; phenotype. DR MIM; 192090; gene. DR MIM; 608089; phenotype. DR neXtProt; NX_P12830; -. DR OpenTargets; ENSG00000039068; -. DR Orphanet; 1997; Blepharo-cheilo-odontic syndrome. DR Orphanet; 199306; Cleft lip/palate. DR Orphanet; 1331; Familial prostate cancer. DR Orphanet; 227535; Hereditary breast cancer. DR Orphanet; 26106; Hereditary diffuse gastric cancer. DR PharmGKB; PA26282; -. DR VEuPathDB; HostDB:ENSG00000039068; -. DR eggNOG; KOG3594; Eukaryota. DR GeneTree; ENSGT00940000157175; -. DR HOGENOM; CLU_005284_2_1_1; -. DR InParanoid; P12830; -. DR OrthoDB; 5306553at2759; -. DR PhylomeDB; P12830; -. DR TreeFam; TF316817; -. DR PathwayCommons; P12830; -. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-351906; Apoptotic cleavage of cell adhesion proteins. DR Reactome; R-HSA-418990; Adherens junctions interactions. DR Reactome; R-HSA-5626467; RHO GTPases activate IQGAPs. DR Reactome; R-HSA-8876493; InlA-mediated entry of Listeria monocytogenes into host cells. DR Reactome; R-HSA-9823730; Formation of definitive endoderm. DR SignaLink; P12830; -. DR SIGNOR; P12830; -. DR BioGRID-ORCS; 999; 47 hits in 1173 CRISPR screens. DR ChiTaRS; CDH1; human. DR EvolutionaryTrace; P12830; -. DR GeneWiki; CDH1_(gene); -. DR GenomeRNAi; 999; -. DR Pharos; P12830; Tbio. DR PRO; PR:P12830; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P12830; Protein. DR Bgee; ENSG00000039068; Expressed in jejunal mucosa and 158 other cell types or tissues. DR ExpressionAtlas; P12830; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:BHF-UCL. DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB. DR GO; GO:0043296; C:apical junction complex; IDA:UniProtKB. DR GO; GO:0016342; C:catenin complex; IDA:BHF-UCL. DR GO; GO:0030054; C:cell junction; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0016600; C:flotillin complex; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0016328; C:lateral plasma membrane; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IEA:Ensembl. DR GO; GO:0005802; C:trans-Golgi network; IMP:BHF-UCL. DR GO; GO:0030506; F:ankyrin binding; IPI:BHF-UCL. DR GO; GO:0008013; F:beta-catenin binding; IDA:BHF-UCL. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:UniProtKB. DR GO; GO:0045295; F:gamma-catenin binding; IPI:BHF-UCL. DR GO; GO:0032794; F:GTPase activating protein binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:1990782; F:protein tyrosine kinase binding; IEA:Ensembl. DR GO; GO:0034332; P:adherens junction organization; IMP:UniProtKB. DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IBA:GO_Central. DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central. DR GO; GO:0098609; P:cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; IBA:GO_Central. DR GO; GO:0007043; P:cell-cell junction assembly; IBA:GO_Central. DR GO; GO:0071681; P:cellular response to indole-3-methanol; IDA:UniProtKB. DR GO; GO:0071285; P:cellular response to lithium ion; IDA:UniProtKB. DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; NAS:UniProtKB. DR GO; GO:0030517; P:negative regulation of axon extension; IEA:Ensembl. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:ARUK-UCL. DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl. DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:BHF-UCL. DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:BHF-UCL. DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB. DR GO; GO:0099576; P:regulation of protein catabolic process at postsynapse, modulating synaptic transmission; IEA:Ensembl. DR GO; GO:0140459; P:response to Gram-positive bacterium; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007416; P:synapse assembly; IBA:GO_Central. DR CDD; cd00031; CA_like; 1. DR CDD; cd11304; Cadherin_repeat; 3. DR Gene3D; 2.60.40.60; Cadherins; 6. DR Gene3D; 4.10.900.10; TCF3-CBD (Catenin binding domain); 1. DR InterPro; IPR039808; Cadherin. DR InterPro; IPR002126; Cadherin-like_dom. DR InterPro; IPR015919; Cadherin-like_sf. DR InterPro; IPR020894; Cadherin_CS. DR InterPro; IPR014868; Cadherin_pro_dom. DR InterPro; IPR000233; Cadherin_Y-type_LIR. DR InterPro; IPR027397; Catenin-bd_sf. DR PANTHER; PTHR24027:SF319; CADHERIN-1; 1. DR PANTHER; PTHR24027; CADHERIN-23; 1. DR Pfam; PF01049; CADH_Y-type_LIR; 1. DR Pfam; PF00028; Cadherin; 5. DR Pfam; PF08758; Cadherin_pro; 1. DR PRINTS; PR00205; CADHERIN. DR SMART; SM00112; CA; 4. DR SMART; SM01055; Cadherin_pro; 1. DR SUPFAM; SSF49313; Cadherin-like; 6. DR PROSITE; PS00232; CADHERIN_1; 3. DR PROSITE; PS50268; CADHERIN_2; 5. DR Genevisible; P12830; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell adhesion; Cell junction; KW Cell membrane; Cleavage on pair of basic residues; KW Direct protein sequencing; Disease variant; Disulfide bond; KW Ectodermal dysplasia; Endosome; Glycoprotein; Golgi apparatus; Membrane; KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix; Ubl conjugation. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT PROPEP 23..154 FT /evidence="ECO:0000255" FT /id="PRO_0000003715" FT CHAIN 155..882 FT /note="Cadherin-1" FT /id="PRO_0000003716" FT CHAIN 701..882 FT /note="E-Cad/CTF1" FT /id="PRO_0000236067" FT CHAIN 732..882 FT /note="E-Cad/CTF2" FT /id="PRO_0000236068" FT CHAIN 751..882 FT /note="E-Cad/CTF3" FT /id="PRO_0000236069" FT TOPO_DOM 155..709 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 710..730 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 731..882 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 155..262 FT /note="Cadherin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 263..375 FT /note="Cadherin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 376..486 FT /note="Cadherin 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 487..593 FT /note="Cadherin 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 594..697 FT /note="Cadherin 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT REGION 747..767 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 758..769 FT /note="Required for binding CTNND1 and PSEN1" FT REGION 811..882 FT /note="Required for binding alpha, beta and gamma catenins" FT BINDING 257 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT BINDING 257 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT BINDING 288 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT SITE 364..365 FT /note="Cleavage; by S.pyogenes SpeB" FT /evidence="ECO:0000269|PubMed:23532847" FT SITE 700..701 FT /note="Cleavage; by a metalloproteinase" FT SITE 731..732 FT /note="Cleavage; by gamma-secretase/PS1" FT SITE 750..751 FT /note="Cleavage; by caspase-3" FT MOD_RES 753 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:22252131" FT MOD_RES 754 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:22252131" FT MOD_RES 755 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:22252131" FT MOD_RES 770 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 793 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 838 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT MOD_RES 840 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT MOD_RES 846 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 280 FT /note="O-linked (Man...) serine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 285 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 358 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 470 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 472 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 509 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 558 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:18491227" FT CARBOHYD 570 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:18491227" FT CARBOHYD 576 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 578 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 580 FT /note="O-linked (Man...) threonine" FT /evidence="ECO:0000250|UniProtKB:P09803" FT CARBOHYD 622 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:18491227" FT CARBOHYD 637 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:18491227" FT DISULFID 163 FT /note="Interchain" FT VAR_SEQ 380..440 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_055586" FT VARIANT 72 FT /note="D -> N (in dbSNP:rs35606263)" FT /id="VAR_048500" FT VARIANT 123 FT /note="H -> Y (in a gastric cancer sample)" FT /evidence="ECO:0000269|PubMed:9744472" FT /id="VAR_001306" FT VARIANT 193 FT /note="T -> P (in a diffuse gastric cancer sample)" FT /evidence="ECO:0000269|PubMed:8797891" FT /id="VAR_001307" FT VARIANT 244 FT /note="D -> G (in DGLBC; dbSNP:rs1064794231)" FT /evidence="ECO:0000269|PubMed:10319582" FT /id="VAR_008712" FT VARIANT 254 FT /note="D -> Y (in BCDS1; abolishes protein abundance; loss FT of cell membrane localization; dbSNP:rs1555515445)" FT /evidence="ECO:0000269|PubMed:28301459" FT /id="VAR_079392" FT VARIANT 257 FT /note="D -> V (in BCDS1; slightly decreases protein FT abundance; loss of cell membrane localization)" FT /evidence="ECO:0000269|PubMed:28301459" FT /id="VAR_079393" FT VARIANT 270 FT /note="S -> A (may contribute to prostate cancer; FT dbSNP:rs587776399)" FT /evidence="ECO:0000269|PubMed:11705864" FT /id="VAR_013970" FT VARIANT 274..277 FT /note="Missing (found in gastric carcinoma cell lines)" FT /evidence="ECO:0000269|PubMed:8127895" FT /id="VAR_001308" FT VARIANT 282 FT /note="M -> I (in a breast cancer sample; somatic mutation; FT dbSNP:rs200932258)" FT /evidence="ECO:0000269|PubMed:17224074" FT /id="VAR_033026" FT VARIANT 315 FT /note="N -> S (in lobular breast carcinoma)" FT /evidence="ECO:0000269|PubMed:7961105" FT /id="VAR_001309" FT VARIANT 336 FT /note="E -> D (in dbSNP:rs267606712)" FT /evidence="ECO:0000269|PubMed:9537325" FT /id="VAR_001310" FT VARIANT 340 FT /note="T -> A (found in gastric and colorectal cancer FT samples; cells exhibited decreased aggregation increased FT invasiveness and non-uniform migration in vitro compared to FT cells transfected with wild-type sequence; FT dbSNP:rs116093741)" FT /evidence="ECO:0000269|PubMed:10896919, FT ECO:0000269|PubMed:11968083, ECO:0000269|PubMed:12588804" FT /id="VAR_013971" FT VARIANT 370 FT /note="D -> A (in a diffuse gastric cancer sample)" FT /evidence="ECO:0000269|PubMed:8033105" FT /id="VAR_001311" FT VARIANT 393 FT /note="I -> N (in dbSNP:rs34466743)" FT /id="VAR_048501" FT VARIANT 400 FT /note="Missing (in a gastric carcinoma sample; loss of FT heterozygosity)" FT /evidence="ECO:0000269|PubMed:9045944" FT /id="VAR_001312" FT VARIANT 418..423 FT /note="Missing (in a gastric carcinoma sample)" FT /evidence="ECO:0000269|PubMed:9045944" FT /id="VAR_001313" FT VARIANT 454 FT /note="Missing (in BCDS1; decreases protein abundance; loss FT of cell membrane localization)" FT /evidence="ECO:0000269|PubMed:28301459" FT /id="VAR_079394" FT VARIANT 463 FT /note="E -> Q (in a gastric carcinoma sample)" FT /evidence="ECO:0000269|PubMed:9744472" FT /id="VAR_001314" FT VARIANT 470 FT /note="T -> I (in dbSNP:rs370864592)" FT /evidence="ECO:0000269|PubMed:9537325" FT /id="VAR_001315" FT VARIANT 473 FT /note="V -> D (in a diffuse gastric cancer sample)" FT /evidence="ECO:0000269|PubMed:8033105" FT /id="VAR_001317" FT VARIANT 473 FT /note="V -> I (in dbSNP:rs36087757)" FT /id="VAR_048502" FT VARIANT 478 FT /note="L -> P (in dbSNP:rs35520415)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_023357" FT VARIANT 487 FT /note="V -> A (in DGLBC)" FT /evidence="ECO:0000269|PubMed:10319582" FT /id="VAR_008713" FT VARIANT 592 FT /note="A -> T (in a thyroid cancer sample; may play a role FT in colorectal carcinogenesis; dbSNP:rs35187787)" FT /evidence="ECO:0000269|PubMed:11562785, FT ECO:0000269|PubMed:8985087" FT /id="VAR_001318" FT VARIANT 598 FT /note="R -> Q (in a gastric cancer sample; FT dbSNP:rs780759537)" FT /evidence="ECO:0000269|PubMed:9744472" FT /id="VAR_001319" FT VARIANT 617 FT /note="A -> T (detected in an endometrial cancer sample; FT loss of heterozygosity; cells exhibited an intermediate FT phenotype concerning aggregation invasiveness and migration FT in vitro compared to cells transfected with wild-type FT sequence; dbSNP:rs33935154)" FT /evidence="ECO:0000269|PubMed:12588804, FT ECO:0000269|PubMed:8075649, ECO:0000269|Ref.7" FT /id="VAR_001320" FT VARIANT 630 FT /note="L -> V (in dbSNP:rs2276331)" FT /id="VAR_021868" FT VARIANT 634 FT /note="A -> V (found in a gastric cancer sample; cells FT exhibited decreased aggregation increased invasiveness and FT non-uniform migration in vitro compared to cells FT transfected with wild-type sequence; dbSNP:rs121964878)" FT /evidence="ECO:0000269|PubMed:12588804" FT /id="VAR_055431" FT VARIANT 695 FT /note="C -> R (in dbSNP:rs9282655)" FT /id="VAR_021869" FT VARIANT 711 FT /note="L -> V (detected in an endometrial cancer sample; FT dbSNP:rs121964871)" FT /evidence="ECO:0000269|PubMed:8075649" FT /id="VAR_001321" FT VARIANT 777 FT /note="D -> N (in a breast cancer sample; somatic mutation; FT dbSNP:rs372989292)" FT /evidence="ECO:0000269|PubMed:17224074" FT /id="VAR_033027" FT VARIANT 832 FT /note="V -> M (in DGLBC; dbSNP:rs35572355)" FT /evidence="ECO:0000269|PubMed:12216071, ECO:0000269|Ref.7" FT /id="VAR_023358" FT VARIANT 838 FT /note="S -> G (in an ovarian carcinoma sample; somatic FT mutation; loss of heterozygosity; dbSNP:rs121964872)" FT /evidence="ECO:0000269|PubMed:8075649" FT /id="VAR_001322" FT VARIANT 880 FT /note="E -> K (in dbSNP:rs34507583)" FT /evidence="ECO:0000269|Ref.7" FT /id="VAR_023359" FT MUTAGEN 156 FT /note="W->A,S: No longer binds L.monocytogenes InlA." FT /evidence="ECO:0000269|PubMed:12526809" FT MUTAGEN 156 FT /note="W->D: Protein is partially unfolded, no longer binds FT L.monocytogenes InlA." FT /evidence="ECO:0000269|PubMed:12526809" FT MUTAGEN 170 FT /note="P->A,E,V: No longer binds L.monocytogenes InlA." FT /evidence="ECO:0000269|PubMed:12526809" FT MUTAGEN 170 FT /note="P->E: No longer adheres to L.monocytogenes InlA FT coated beads, nor do cells take up InlA coated beads." FT /evidence="ECO:0000269|PubMed:10406800" FT MUTAGEN 637 FT /note="N->Q: CDH1 becomes a substrate for ERAD and is FT retro-translocated from ER to cytoplasm." FT /evidence="ECO:0000269|PubMed:18491227" FT MUTAGEN 754 FT /note="Y->F: Abolishes binding to CBLL1." FT /evidence="ECO:0000269|PubMed:22252131" FT MUTAGEN 759..761 FT /note="GGG->AAA: Binds to CTNNB1 but abolishes interaction FT of CTNNB1 with PSEN1. Abolishes gamma-secretase cleavage." FT /evidence="ECO:0000269|PubMed:11953314, FT ECO:0000269|PubMed:16126725" FT CONFLICT 10 FT /note="A -> G (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 29 FT /note="H -> L (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 47 FT /note="E -> R (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 70..71 FT /note="SL -> P (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 483 FT /note="A -> G (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 530 FT /note="A -> R (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 543 FT /note="S -> F (in Ref. 2; CAA79356)" FT /evidence="ECO:0000305" FT CONFLICT 615 FT /note="I -> H (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 634..636 FT /note="ASA -> RVP (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 868 FT /note="R -> P (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT CONFLICT 882 FT /note="D -> H (in Ref. 3; AAA61259)" FT /evidence="ECO:0000305" FT STRAND 163..166 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 169..177 FT /evidence="ECO:0007829|PDB:2OMZ" FT HELIX 181..184 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 189..195 FT /evidence="ECO:0007829|PDB:2OMZ" FT TURN 196..198 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 199..201 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 204..207 FT /evidence="ECO:0007829|PDB:2OMZ" FT TURN 209..211 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:2OMZ" FT TURN 222..224 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 227..235 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 241..243 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 246..253 FT /evidence="ECO:0007829|PDB:2OMZ" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 265..272 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 280..283 FT /evidence="ECO:0007829|PDB:8H62" FT TURN 292..294 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 301..309 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 316..319 FT /evidence="ECO:0007829|PDB:8H62" FT TURN 321..323 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 325..328 FT /evidence="ECO:0007829|PDB:8H62" FT TURN 335..337 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 340..348 FT /evidence="ECO:0007829|PDB:8H62" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 356..366 FT /evidence="ECO:0007829|PDB:8H62" FT STRAND 374..384 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 394..396 FT /evidence="ECO:0007829|PDB:7STZ" FT TURN 407..409 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 410..417 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 423..428 FT /evidence="ECO:0007829|PDB:7STZ" FT TURN 429..432 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 433..440 FT /evidence="ECO:0007829|PDB:7STZ" FT TURN 444..446 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 448..460 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 470..477 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 485..498 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 504..507 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 522..527 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 533..535 FT /evidence="ECO:0007829|PDB:7STZ" FT TURN 537..539 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 541..544 FT /evidence="ECO:0007829|PDB:7STZ" FT TURN 553..555 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 557..568 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 571..573 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 576..586 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 594..596 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 599..607 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 610..615 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 622..625 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 627..633 FT /evidence="ECO:0007829|PDB:7STZ" FT TURN 635..637 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 638..644 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 648..656 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 660..673 FT /evidence="ECO:0007829|PDB:7STZ" FT STRAND 675..691 FT /evidence="ECO:0007829|PDB:7STZ" FT HELIX 769..771 FT /evidence="ECO:0007829|PDB:3L6X" SQ SEQUENCE 882 AA; 97456 MW; E427118043A13C67 CRC64; MGPWSRSLSA LLLLLQVSSW LCQEPEPCHP GFDAESYTFT VPRRHLERGR VLGRVNFEDC TGRQRTAYFS LDTRFKVGTD GVITVKRPLR FHNPQIHFLV YAWDSTYRKF STKVTLNTVG HHHRPPPHQA SVSGIQAELL TFPNSSPGLR RQKRDWVIPP ISCPENEKGP FPKNLVQIKS NKDKEGKVFY SITGQGADTP PVGVFIIERE TGWLKVTEPL DRERIATYTL FSHAVSSNGN AVEDPMEILI TVTDQNDNKP EFTQEVFKGS VMEGALPGTS VMEVTATDAD DDVNTYNAAI AYTILSQDPE LPDKNMFTIN RNTGVISVVT TGLDRESFPT YTLVVQAADL QGEGLSTTAT AVITVTDTND NPPIFNPTTY KGQVPENEAN VVITTLKVTD ADAPNTPAWE AVYTILNDDG GQFVVTTNPV NNDGILKTAK GLDFEAKQQY ILHVAVTNVV PFEVSLTTST ATVTVDVLDV NEAPIFVPPE KRVEVSEDFG VGQEITSYTA QEPDTFMEQK ITYRIWRDTA NWLEINPDTG AISTRAELDR EDFEHVKNST YTALIIATDN GSPVATGTGT LLLILSDVND NAPIPEPRTI FFCERNPKPQ VINIIDADLP PNTSPFTAEL THGASANWTI QYNDPTQESI ILKPKMALEV GDYKINLKLM DNQNKDQVTT LEVSVCDCEG AAGVCRKAQP VEAGLQIPAI LGILGGILAL LILILLLLLF LRRRAVVKEP LLPPEDDTRD NVYYYDEEGG GEEDQDFDLS QLHRGLDARP EVTRNDVAPT LMSVPRYLPR PANPDEIGNF IDENLKAADT DPTAPPYDSL LVFDYEGSGS EAASLSSLNS SESDKDQDYD YLNEWGNRFK KLADMYGGGE DD //