CADH1_HUMAN
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 03-AUG-2022, entry version 254.
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 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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47] {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 [48]
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 [49] {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 [50] {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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
RP VARIANTS HDGC 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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
RP VARIANT HDGC 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 [65]
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 [66]
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 [67]
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). {ECO:0000250,
CC ECO:0000250|UniProtKB:P09803, ECO:0000250|UniProtKB:Q9R0T4,
CC ECO:0000269|PubMed:11226248, ECO:0000269|PubMed:11856755,
CC ECO:0000269|PubMed:12526809, ECO:0000269|PubMed:14595118,
CC ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15240885,
CC ECO:0000269|PubMed:16126725, ECO:0000269|PubMed:17261850,
CC ECO:0000269|PubMed:18093941, ECO:0000269|PubMed:19604491,
CC ECO:0000269|PubMed:20116244, ECO:0000269|PubMed:20432435,
CC ECO:0000269|PubMed:31473225, 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=6; IntAct=EBI-727477, EBI-701918;
CC P12830; P35222: CTNNB1; NbExp=14; 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; Q9BQ29: THAP4; NbExp=3; IntAct=EBI-727477, EBI-22013570;
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; 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 -!- DISEASE: Hereditary diffuse gastric cancer (HDGC) [MIM:137215]: A
CC cancer predisposition syndrome with increased susceptibility to diffuse
CC gastric cancer. Diffuse gastric cancer is a malignant disease
CC characterized by poorly differentiated infiltrating lesions resulting
CC in thickening of the stomach. Malignant tumors start in the stomach,
CC can spread to the esophagus or the small intestine, and can extend
CC through the stomach wall to nearby lymph nodes and organs. It also can
CC metastasize to other parts of the body. {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="http://atlasgeneticsoncology.org/Genes/CDH1ID166ch16q22.html";
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";
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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 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 AlphaFoldDB; P12830; -.
DR SMR; P12830; -.
DR BioGRID; 107434; 696.
DR CORUM; P12830; -.
DR DIP; DIP-477N; -.
DR ELM; P12830; -.
DR IntAct; P12830; 111.
DR MINT; P12830; -.
DR STRING; 9606.ENSP00000261769; -.
DR ChEMBL; CHEMBL2321609; -.
DR GlyGen; P12830; 14 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P12830; -.
DR PhosphoSitePlus; P12830; -.
DR BioMuta; CDH1; -.
DR DMDM; 399166; -.
DR CPTAC; CPTAC-1599; -.
DR EPD; P12830; -.
DR jPOST; P12830; -.
DR MassIVE; P12830; -.
DR MaxQB; P12830; -.
DR PaxDb; P12830; -.
DR PeptideAtlas; P12830; -.
DR PRIDE; P12830; -.
DR ProteomicsDB; 52879; -. [P12830-1]
DR ProteomicsDB; 84533; -.
DR TopDownProteomics; P12830-2; -. [P12830-2]
DR ABCD; P12830; 29 sequenced antibodies.
DR Antibodypedia; 1347; 3058 antibodies from 58 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 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; 182239at2759; -.
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 SignaLink; P12830; -.
DR SIGNOR; P12830; -.
DR BioGRID-ORCS; 999; 44 hits in 1076 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 156 other tissues.
DR ExpressionAtlas; P12830; baseline and differential.
DR Genevisible; P12830; HS.
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:0005737; C:cytoplasm; IBA:GO_Central.
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:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016328; C:lateral plasma 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:0098609; P:cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; 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: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:0042307; P:positive regulation of protein import into nucleus; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; 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 Gene3D; 4.10.900.10; -; 1.
DR InterPro; IPR039808; Cadherin.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR000233; Cadherin_cytoplasmic-dom.
DR InterPro; IPR014868; Cadherin_pro_dom.
DR InterPro; IPR027397; Catenin-bd_sf.
DR InterPro; IPR030049; CDH1.
DR PANTHER; PTHR24027; PTHR24027; 1.
DR PANTHER; PTHR24027:SF319; PTHR24027:SF319; 1.
DR Pfam; PF00028; Cadherin; 5.
DR Pfam; PF01049; Cadherin_C; 1.
DR Pfam; PF08758; Cadherin_pro; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 4.
DR SMART; SM01055; Cadherin_pro; 1.
DR SUPFAM; SSF49313; SSF49313; 6.
DR PROSITE; PS00232; CADHERIN_1; 3.
DR PROSITE; PS50268; CADHERIN_2; 5.
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 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 /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 HDGC; 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 /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 HDGC)"
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 /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 HDGC; 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:4ZT1"
FT STRAND 265..272
FT /evidence="ECO:0007829|PDB:4ZT1"
FT STRAND 279..283
FT /evidence="ECO:0007829|PDB:4ZT1"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:4ZT1"
FT STRAND 301..309
FT /evidence="ECO:0007829|PDB:4ZT1"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:4ZT1"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:4ZT1"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:4ZT1"
FT TURN 335..337
FT /evidence="ECO:0007829|PDB:4ZT1"
FT STRAND 340..349
FT /evidence="ECO:0007829|PDB:4ZT1"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:4ZT1"
FT STRAND 356..366
FT /evidence="ECO:0007829|PDB:4ZT1"
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
