CADH2_HUMAN
ID CADH2_HUMAN Reviewed; 906 AA.
AC P19022; A8MWK3; B0YIY6; Q14923; Q8N173;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 4.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Cadherin-2;
DE AltName: Full=CDw325;
DE AltName: Full=Neural cadherin;
DE Short=N-cadherin {ECO:0000303|PubMed:2216790};
DE AltName: CD_antigen=CD325;
DE Flags: Precursor;
GN Name=CDH2; Synonyms=CDHN, NCAD;
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), AND VARIANT THR-196.
RX PubMed=2216790; DOI=10.1093/nar/18.19.5896;
RA Reid R.A., Hemperly J.J.;
RT "Human N-cadherin: nucleotide and deduced amino acid sequence.";
RL Nucleic Acids Res. 18:5896-5896(1990).
RN [2]
RP SEQUENCE REVISION TO 341; 699 AND 705.
RA Reid R.A.;
RL Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1500442; DOI=10.1242/jcs.102.1.7;
RA Salomon D., Ayalon O., Patel-King R., Hynes R.O., Geiger B.;
RT "Extrajunctional distribution of N-cadherin in cultured human endothelial
RT cells.";
RL J. Cell Sci. 102:7-17(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-454.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 160-906 (ISOFORM 1), AND VARIANT LEU-212.
RX PubMed=2384753; DOI=10.1111/j.1471-4159.1990.tb04563.x;
RA Walsh F.S., Barton C.H., Putt W., Moore S.E., Kelsell D., Spurr N.,
RA Goodfellow P.N.;
RT "N-cadherin gene maps to human chromosome 18 and is not linked to the E-
RT cadherin gene.";
RL J. Neurochem. 55:805-812(1990).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
RX PubMed=7959764; DOI=10.1006/geno.1994.1358;
RA Wallis J.A., Fox M., Walsh F.S.;
RT "Structure of the human N-cadherin gene: YAC analysis and fine chromosomal
RT mapping to 18q11.2.";
RL Genomics 22:172-179(1994).
RN [11]
RP INTERACTION WITH CDCP1.
RX PubMed=16007225; DOI=10.1038/sj.onc.1208582;
RA Bhatt A.S., Erdjument-Bromage H., Tempst P., Craik C.S., Moasser M.M.;
RT "Adhesion signaling by a novel mitotic substrate of src kinases.";
RL Oncogene 24:5333-5343(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-273; ASN-402; ASN-572 AND
RP ASN-692.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP PHOSPHORYLATION AT SER-96 AND SER-135.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [14]
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 [15]
RP INVOLVEMENT IN ARVD14, AND VARIANTS ARVD14 PRO-229 AND ASN-407.
RX PubMed=28280076; DOI=10.1161/circgenetics.116.001605;
RA Mayosi B.M., Fish M., Shaboodien G., Mastantuono E., Kraus S., Wieland T.,
RA Kotta M.C., Chin A., Laing N., Ntusi N.B., Chong M., Horsfall C.,
RA Pimstone S.N., Gentilini D., Parati G., Strom T.M., Meitinger T., Pare G.,
RA Schwartz P.J., Crotti L.;
RT "Identification of cadherin 2 (CDH2) mutations in arrhythmogenic right
RT ventricular cardiomyopathy.";
RL Circ. Cardiovasc. Genet. 10:0-0(2017).
RN [16]
RP INVOLVEMENT IN ARVD14, AND VARIANT ARVD14 ASN-407.
RX PubMed=28326674; DOI=10.1111/chd.12462;
RA Turkowski K.L., Tester D.J., Bos J.M., Haugaa K.H., Ackerman M.J.;
RT "Whole exome sequencing with genomic triangulation implicates CDH2-encoded
RT N-cadherin as a novel pathogenic substrate for arrhythmogenic
RT cardiomyopathy.";
RL Congenit. Heart Dis. 12:226-235(2017).
RN [17]
RP INVOLVEMENT IN ACOGS, FUNCTION, VARIANTS ACOGS ASN-353; ASN-597; TYR-597;
RP THR-601; TRP-613; GLY-627 AND CYS-676, AND CHARACTERIZATION OF VARIANTS
RP ACOGS ASN-353; ASN-597; THR-601; TRP-613; GLY-627 AND CYS-676.
RX PubMed=31585109; DOI=10.1016/j.ajhg.2019.09.005;
RG Undiagnosed Diseases Network;
RA Accogli A., Calabretta S., St-Onge J., Boudrahem-Addour N.,
RA Dionne-Laporte A., Joset P., Azzarello-Burri S., Rauch A., Krier J.,
RA Fieg E., Pallais J.C., McConkie-Rosell A., McDonald M., Freedman S.F.,
RA Riviere J.B., Lafond-Lapalme J., Simpson B.N., Hopkin R.J., Trimouille A.,
RA Van-Gils J., Begtrup A., McWalter K., Delphine H., Keren B., Genevieve D.,
RA Argilli E., Sherr E.H., Severino M., Rouleau G.A., Yam P.T., Charron F.,
RA Srour M.;
RT "De novo pathogenic variants in N-cadherin cause a syndromic
RT neurodevelopmental disorder with corpus collosum, axon, cardiac, ocular,
RT and genital defects.";
RL Am. J. Hum. Genet. 105:854-868(2019).
RN [18]
RP INVOLVEMENT IN ACOGS, AND VARIANTS ACOGS ASP-162; GLY-525 AND SER-603.
RX PubMed=31650526; DOI=10.1111/cge.13660;
RA Reis L.M., Houssin N.S., Zamora C., Abdul-Rahman O., Kalish J.M.,
RA Zackai E.H., Plageman T.F. Jr., Semina E.V.;
RT "Novel variants in CDH2 are associated with a new syndrome including Peters
RT anomaly.";
RL Clin. Genet. 97:502-508(2020).
CC -!- FUNCTION: Calcium-dependent cell adhesion protein; preferentially
CC mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain
CC from another cell. Cadherins may thus contribute to the sorting of
CC heterogeneous cell types. Acts as a regulator of neural stem cells
CC quiescence by mediating anchorage of neural stem cells to ependymocytes
CC in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated
CC anchorage is affected, leading to modulate neural stem cell quiescence.
CC Plays a role in cell-to-cell junction formation between pancreatic beta
CC cells and neural crest stem (NCS) cells, promoting the formation of
CC processes by NCS cells (By similarity). CDH2 may be involved in
CC neuronal recognition mechanism. In hippocampal neurons, may regulate
CC dendritic spine density. {ECO:0000250|UniProtKB:P15116,
CC ECO:0000269|PubMed:31585109}.
CC -!- SUBUNIT: Homodimer (via extracellular region). Can also form
CC heterodimers with other cadherins (via extracellular region).
CC Dimerization occurs in trans, i.e. with a cadherin chain from another
CC cell (By similarity). Interacts with CDCP1 (PubMed:16007225). Interacts
CC with PCDH8; this complex may also include TAOK2 (By similarity). The
CC interaction with PCDH8 may lead to internalization through TAOK2/p38
CC MAPK pathway (By similarity). Identified in a complex containing FGFR4,
CC NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. May interact with
CC OBSCN (via protein kinase domain 2) (By similarity).
CC {ECO:0000250|UniProtKB:P15116, ECO:0000250|UniProtKB:Q9Z1Y3,
CC ECO:0000269|PubMed:16007225}.
CC -!- INTERACTION:
CC P19022; P35222: CTNNB1; NbExp=8; IntAct=EBI-2256711, EBI-491549;
CC P19022; P14923: JUP; NbExp=2; IntAct=EBI-2256711, EBI-702484;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15116};
CC Single-pass type I membrane protein {ECO:0000255}. Cell membrane,
CC sarcolemma {ECO:0000250|UniProtKB:P15116}. Cell junction
CC {ECO:0000269|PubMed:28169360}. Cell surface
CC {ECO:0000250|UniProtKB:P15116}. Note=Colocalizes with TMEM65 at the
CC intercalated disk in cardiomyocytes. Colocalizes with OBSCN at the
CC intercalated disk and at sarcolemma in cardiomyocytes.
CC {ECO:0000250|UniProtKB:P15116}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P19022-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P19022-2; Sequence=VSP_056448;
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. Calcium-binding sites are
CC occupied sequentially in the order of site 3, then site 2 and site 1.
CC {ECO:0000250|UniProtKB:P15116}.
CC -!- PTM: Cleaved by MMP24. Ectodomain cleavage leads to the generation of a
CC soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound
CC C-terminal fragment 1 (CTF1), which is further cleaved by gamma-
CC secretase into a 35 kDa (By similarity). Cleavage in neural stem cells
CC by MMP24 affects CDH2-mediated anchorage of neural stem cells to
CC ependymocytes in the adult subependymal zone, leading to modulate
CC neural stem cell quiescence (By similarity).
CC {ECO:0000250|UniProtKB:P15116}.
CC -!- PTM: May be phosphorylated by OBSCN. {ECO:0000250|UniProtKB:P15116}.
CC -!- DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 14
CC (ARVD14) [MIM:618920]: A congenital heart disease characterized by
CC infiltration of adipose and fibrous tissue into the right ventricle and
CC loss of myocardial cells, resulting in ventricular and supraventricular
CC arrhythmias. {ECO:0000269|PubMed:28280076,
CC ECO:0000269|PubMed:28326674}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Agenesis of corpus callosum, cardiac, ocular, and genital
CC syndrome (ACOGS) [MIM:618929]: An autosomal dominant, syndromic
CC neurodevelopmental disorder characterized by global developmental delay
CC and/or intellectual disability, corpus callosum agenesis or hypoplasia,
CC mirror movements, dysmorphic features, and ocular, cardiac, and genital
CC anomalies. {ECO:0000269|PubMed:31585109, ECO:0000269|PubMed:31650526}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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DR EMBL; X54315; CAA38213.1; -; mRNA.
DR EMBL; S42303; AAB22854.1; -; mRNA.
DR EMBL; AK302831; BAH13814.1; -; mRNA.
DR EMBL; AC006249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC015933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110015; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; EF444966; ACA05964.1; -; Genomic_DNA.
DR EMBL; CH471088; EAX01240.1; -; Genomic_DNA.
DR EMBL; BC036470; AAH36470.1; -; mRNA.
DR EMBL; M34064; AAA03236.1; -; mRNA.
DR EMBL; X57548; CAA40773.1; -; mRNA.
DR EMBL; Z27420; CAA81799.1; -; Genomic_DNA.
DR CCDS; CCDS11891.1; -. [P19022-1]
DR CCDS; CCDS77172.1; -. [P19022-2]
DR PIR; A38870; IJHUCN.
DR RefSeq; NP_001295105.1; NM_001308176.1. [P19022-2]
DR RefSeq; NP_001783.2; NM_001792.4. [P19022-1]
DR AlphaFoldDB; P19022; -.
DR SMR; P19022; -.
DR BioGRID; 107435; 92.
DR CORUM; P19022; -.
DR DIP; DIP-43894N; -.
DR IntAct; P19022; 27.
DR MINT; P19022; -.
DR STRING; 9606.ENSP00000269141; -.
DR BindingDB; P19022; -.
DR ChEMBL; CHEMBL1697669; -.
DR GlyConnect; 733; 11 N-Linked glycans (4 sites).
DR GlyGen; P19022; 10 sites, 12 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P19022; -.
DR PhosphoSitePlus; P19022; -.
DR BioMuta; CDH2; -.
DR DMDM; 116241277; -.
DR EPD; P19022; -.
DR jPOST; P19022; -.
DR MassIVE; P19022; -.
DR MaxQB; P19022; -.
DR PaxDb; P19022; -.
DR PeptideAtlas; P19022; -.
DR PRIDE; P19022; -.
DR ProteomicsDB; 2250; -.
DR ProteomicsDB; 53628; -. [P19022-1]
DR TopDownProteomics; P19022-1; -. [P19022-1]
DR ABCD; P19022; 4 sequenced antibodies.
DR Antibodypedia; 4558; 1714 antibodies from 53 providers.
DR CPTC; P19022; 5 antibodies.
DR DNASU; 1000; -.
DR Ensembl; ENST00000269141.8; ENSP00000269141.3; ENSG00000170558.10. [P19022-1]
DR Ensembl; ENST00000399380.7; ENSP00000382312.3; ENSG00000170558.10. [P19022-2]
DR GeneID; 1000; -.
DR KEGG; hsa:1000; -.
DR MANE-Select; ENST00000269141.8; ENSP00000269141.3; NM_001792.5; NP_001783.2.
DR UCSC; uc002kwg.3; human. [P19022-1]
DR CTD; 1000; -.
DR DisGeNET; 1000; -.
DR GeneCards; CDH2; -.
DR HGNC; HGNC:1759; CDH2.
DR HPA; ENSG00000170558; Tissue enhanced (heart).
DR MalaCards; CDH2; -.
DR MIM; 114020; gene.
DR MIM; 618920; phenotype.
DR MIM; 618929; phenotype.
DR neXtProt; NX_P19022; -.
DR OpenTargets; ENSG00000170558; -.
DR Orphanet; 293910; Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
DR PharmGKB; PA26293; -.
DR VEuPathDB; HostDB:ENSG00000170558; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000155981; -.
DR HOGENOM; CLU_005284_2_0_1; -.
DR InParanoid; P19022; -.
DR OMA; NVRFQSC; -.
DR PhylomeDB; P19022; -.
DR TreeFam; TF316817; -.
DR PathwayCommons; P19022; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-418990; Adherens junctions interactions.
DR Reactome; R-HSA-525793; Myogenesis.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; P19022; -.
DR SIGNOR; P19022; -.
DR BioGRID-ORCS; 1000; 52 hits in 1074 CRISPR screens.
DR ChiTaRS; CDH2; human.
DR GeneWiki; CDH2; -.
DR GenomeRNAi; 1000; -.
DR Pharos; P19022; Tbio.
DR PRO; PR:P19022; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P19022; protein.
DR Bgee; ENSG00000170558; Expressed in heart right ventricle and 168 other tissues.
DR ExpressionAtlas; P19022; baseline and differential.
DR Genevisible; P19022; HS.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0045177; C:apical part of cell; IBA:GO_Central.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016327; C:apicolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0016342; C:catenin complex; IDA:BHF-UCL.
DR GO; GO:0030054; C:cell junction; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005916; C:fascia adherens; IEA:Ensembl.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IBA:GO_Central.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IBA:GO_Central.
DR GO; GO:0014704; C:intercalated disc; ISS:BHF-UCL.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central.
DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR GO; GO:0045294; F:alpha-catenin binding; IPI:BHF-UCL.
DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0045295; F:gamma-catenin binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:Ensembl.
DR GO; GO:0048514; P:blood vessel morphogenesis; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl.
DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; ISS:UniProtKB.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0007043; P:cell-cell junction assembly; ISS:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0035995; P:detection of muscle stretch; TAS:BHF-UCL.
DR GO; GO:0010001; P:glial cell differentiation; ISS:UniProtKB.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IEA:Ensembl.
DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0090497; P:mesenchymal cell migration; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0014032; P:neural crest cell development; ISS:UniProtKB.
DR GO; GO:0060563; P:neuroepithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0097118; P:neuroligin clustering involved in postsynaptic membrane assembly; IEA:Ensembl.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:2000809; P:positive regulation of synaptic vesicle clustering; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0060019; P:radial glial cell differentiation; IEA:Ensembl.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0070445; P:regulation of oligodendrocyte progenitor proliferation; IEA:Ensembl.
DR GO; GO:1902897; P:regulation of postsynaptic density protein 95 clustering; IEA:Ensembl.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0007416; P:synapse assembly; IBA:GO_Central.
DR GO; GO:0003323; P:type B pancreatic cell development; ISS:UniProtKB.
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; IPR030051; CDH2.
DR PANTHER; PTHR24027; PTHR24027; 1.
DR PANTHER; PTHR24027:SF79; PTHR24027:SF79; 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; 5.
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 Alternative splicing; Calcium; Cardiomyopathy; Cell adhesion;
KW Cell junction; Cell membrane; Cleavage on pair of basic residues;
KW Disease variant; Glycoprotein; Intellectual disability; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..159
FT /id="PRO_0000003731"
FT CHAIN 160..906
FT /note="Cadherin-2"
FT /id="PRO_0000003732"
FT TOPO_DOM 160..724
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 725..745
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 746..906
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 160..267
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 268..382
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 383..497
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 498..603
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 604..714
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 863..884
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 864..883
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 226
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 260
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 261
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 263
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 293
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 295
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 301
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT BINDING 353
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P15116"
FT MOD_RES 96
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 135
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 572
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 1..57
FT /note="MCRIAGALRTLLPLLAALLQASVEASGEIALCKTGFPEDVYSAVLSKDVHEG
FT QPLLN -> MFLLRRYVCIFTEKLKNQAELYVFLS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056448"
FT VARIANT 21
FT /note="A -> T (in dbSNP:rs17495042)"
FT /id="VAR_028254"
FT VARIANT 118
FT /note="A -> T (in dbSNP:rs17445840)"
FT /id="VAR_028255"
FT VARIANT 162
FT /note="V -> D (in ACOGS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31650526"
FT /id="VAR_084438"
FT VARIANT 196
FT /note="S -> T (in dbSNP:rs1041970)"
FT /evidence="ECO:0000269|PubMed:2216790"
FT /id="VAR_028256"
FT VARIANT 212
FT /note="I -> L (in dbSNP:rs1041972)"
FT /evidence="ECO:0000269|PubMed:2384753"
FT /id="VAR_028257"
FT VARIANT 229
FT /note="Q -> P (in ARVD14; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28280076"
FT /id="VAR_084439"
FT VARIANT 353
FT /note="D -> N (in ACOGS; decreased function in cell-cell
FT adhesion; dbSNP:rs1599017933)"
FT /evidence="ECO:0000269|PubMed:31585109"
FT /id="VAR_084440"
FT VARIANT 407
FT /note="D -> N (in ARVD14; unknown pathological
FT significance; dbSNP:rs568089577)"
FT /evidence="ECO:0000269|PubMed:28280076,
FT ECO:0000269|PubMed:28326674"
FT /id="VAR_084441"
FT VARIANT 454
FT /note="T -> A (in dbSNP:rs17857112)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_048503"
FT VARIANT 525
FT /note="D -> G (in ACOGS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31650526"
FT /id="VAR_084442"
FT VARIANT 597
FT /note="D -> N (in ACOGS; decreased function in cell-cell
FT adhesion; dbSNP:rs1599011050)"
FT /evidence="ECO:0000269|PubMed:31585109"
FT /id="VAR_084443"
FT VARIANT 597
FT /note="D -> Y (in ACOGS; dbSNP:rs1599011050)"
FT /evidence="ECO:0000269|PubMed:31585109"
FT /id="VAR_084444"
FT VARIANT 601
FT /note="N -> T (in ACOGS; decreased function in cell-cell
FT adhesion; dbSNP:rs201775968)"
FT /evidence="ECO:0000269|PubMed:31585109"
FT /id="VAR_084445"
FT VARIANT 603
FT /note="P -> S (in ACOGS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31650526"
FT /id="VAR_084446"
FT VARIANT 613
FT /note="C -> W (in ACOGS; decreased function in cell-cell
FT adhesion; dbSNP:rs754880999)"
FT /evidence="ECO:0000269|PubMed:31585109"
FT /id="VAR_084447"
FT VARIANT 627
FT /note="D -> G (in ACOGS; decreased function in cell-cell
FT adhesion; dbSNP:rs1599010918)"
FT /evidence="ECO:0000269|PubMed:31585109"
FT /id="VAR_084448"
FT VARIANT 676
FT /note="Y -> C (in ACOGS; decreased function in cell-cell
FT adhesion; dbSNP:rs199984052)"
FT /evidence="ECO:0000269|PubMed:31585109"
FT /id="VAR_084449"
FT VARIANT 845
FT /note="N -> S (in dbSNP:rs2289664)"
FT /id="VAR_028258"
FT CONFLICT 12
FT /note="Missing (in Ref. 3; AAB22854)"
FT /evidence="ECO:0000305"
FT CONFLICT 16
FT /note="A -> L (in Ref. 1; CAA38213)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="P -> S (in Ref. 8; AAH36470)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="N -> I (in Ref. 1; CAA38213)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="P -> Q (in Ref. 8; AAH36470)"
FT /evidence="ECO:0000305"
FT CONFLICT 484
FT /note="V -> M (in Ref. 8; AAH36470)"
FT /evidence="ECO:0000305"
FT CONFLICT 629
FT /note="D -> G (in Ref. 8; AAH36470)"
FT /evidence="ECO:0000305"
FT CONFLICT 867
FT /note="A -> L (in Ref. 3; AAB22854)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 906 AA; 99809 MW; 7267E2A00489DF94 CRC64;
MCRIAGALRT LLPLLAALLQ ASVEASGEIA LCKTGFPEDV YSAVLSKDVH EGQPLLNVKF
SNCNGKRKVQ YESSEPADFK VDEDGMVYAV RSFPLSSEHA KFLIYAQDKE TQEKWQVAVK
LSLKPTLTEE SVKESAEVEE IVFPRQFSKH SGHLQRQKRD WVIPPINLPE NSRGPFPQEL
VRIRSDRDKN LSLRYSVTGP GADQPPTGIF IINPISGQLS VTKPLDREQI ARFHLRAHAV
DINGNQVENP IDIVINVIDM NDNRPEFLHQ VWNGTVPEGS KPGTYVMTVT AIDADDPNAL
NGMLRYRIVS QAPSTPSPNM FTINNETGDI ITVAAGLDRE KVQQYTLIIQ ATDMEGNPTY
GLSNTATAVI TVTDVNDNPP EFTAMTFYGE VPENRVDIIV ANLTVTDKDQ PHTPAWNAVY
RISGGDPTGR FAIQTDPNSN DGLVTVVKPI DFETNRMFVL TVAAENQVPL AKGIQHPPQS
TATVSVTVID VNENPYFAPN PKIIRQEEGL HAGTMLTTFT AQDPDRYMQQ NIRYTKLSDP
ANWLKIDPVN GQITTIAVLD RESPNVKNNI YNATFLASDN GIPPMSGTGT LQIYLLDIND
NAPQVLPQEA ETCETPDPNS INITALDYDI DPNAGPFAFD LPLSPVTIKR NWTITRLNGD
FAQLNLKIKF LEAGIYEVPI IITDSGNPPK SNISILRVKV CQCDSNGDCT DVDRIVGAGL
GTGAIIAILL CIIILLILVL MFVVWMKRRD KERQAKQLLI DPEDDVRDNI LKYDEEGGGE
EDQDYDLSQL QQPDTVEPDA IKPVGIRRMD ERPIHAEPQY PVRSAAPHPG DIGDFINEGL
KAADNDPTAP PYDSLLVFDY EGSGSTAGSL SSLNSSSSGG EQDYDYLNDW GPRFKKLADM
YGGGDD
